Hacia una medicina de excelencia en México: el protocolo Código Infarto, una visión desde la bioética traslacional / Towards medicine of excellence in Mexico: the "Código Infarto" protocol, a view from the perspective of translational bioethics

Resumen Introducción: México es el país con mayor mortalidad por infarto agudo de miocardio con elevación del segmento ST (IAM CEST), por lo que el Instituto Mexicano del Seguro Social desarrolló el protocolo de atención para los servicios de urgencias denominado Código Infarto. En este artículo se discuten aspectos de la medicina traslacional con una perspectiva bioética e integral. Objetivo: Analizar el protocolo Código Infarto desde la perspectiva de la bioética traslacional. Método: Se realizó una aproximación centrada en el problema a través del equilibrio reflexivo, así como la aplicación del método integral para el discernimiento ético. Resultados: El protocolo de atención para los servicios de urgencias Código Infarto se rige por la medicina basada en la evidencia y la medicina basada en valores; se orienta por el principio de integridad que considera las seis dimensiones de la calidad para la atención de pacientes con IAM CEST. Conclusión: El protocolo supera algunos determinantes sociales adversos que afectan la atención médica del IAM CEST, disminuye la mortalidad, la carga económica global de la enfermedad y desarrolla una medicina de excelencia de alto alcance social.

Abstract Introduction: Mexico is the country with the highest mortality due to ST-elevation acute myocardial infarction (STEMI), and the IMSS has therefore developed the protocol of care for emergency departments called Código Infarto (Infarction Code). In this article, aspects of translational medicine are discussed with a bioethical and comprehensive perspective. Objective: To analyze the Código Infarto protocol from the perspective of translational bioethics. Method: A problem-centered approach was carried out through reflective equilibrium (or Rawls' method), as well as by applying the integral method for ethical discernment. Results: The protocol of care for emergency services Código Infarto is governed by evidence-based medicine and value-based medicine; it is guided by a principle of integrity that considers six dimensions of quality for the care of patients with STEMI. Conclusion: The protocol overcomes some adverse social determinants that affect STEMI medical care, reduces mortality and global economic disease burden, and develops medicine of excellence with high social reach.

Joint Mexican position document on the treatment of atrial fibrillation / Posicionamiento conjunto acerca del tratamiento para fibrilación auricular

Abstract Atrial fibrillation (AF) is a frequent arrhythmia; its prevalence is near 2% in the general population; in Mexico, more than one-half million people are affected. AF needs to be considered as a public health problem. Because AF is an independent risk factor associated with mortality, due to embolic events, heart failure, or sudden death; early diagnosis is of utmost importance. In unstable patients with a recent onset of AF, electrical cardioversion should be practiced. In stable patients, once thromboembolic measures have been taken, it is necessary to assess whether it is reasonable to administer an antiarrhythmic drug to restore sinus rhythm or performed electrical cardioversion. For recidivating cases of paroxysmal and persistent presentation, the most effective strategy is performed pulmonary vein isolation with either radiofrequency or cryoballoon energy. Permanent AF is that in which recovery of sinus rhythm is not possible, the distinguishing feature of this phase is the uncontrollable variability of the ventricular frequency and could be treated pharmacologically with atrioventricular (AV) nodal blockers or with a VVIR pacemaker plus AV nodal ablation. The presence of AF has long been associated with the development of cerebral and systemic (pulmonary, limb, coronary, renal, and visceral) embolism. The prevention of embolisms in “valvular” AF should perform with Vitamin K antagonists (VKA). For patients with AF not associated with mitral stenosis or a mechanical valve prosthesis, a choice can be made between anticoagulant drugs, VKA, or direct oral anticoagulants. Antiplatelet agents have the weakest effect in preventing embolism.

Resumen La fibrilación auricular (FA) es una arritmia frecuente; su prevalencia es cercana al 2% en la población general, en México se ven afectados más de medio millón de personas por eso debe considerarse como un problema de salud pública. Debido a que la FA es un factor de riesgo independiente asociado a mortalidad, por eventos embólicos, insuficiencia cardíaca o muerte súbita, la identificación y diagnóstico temprano es de suma importancia. En el inicio reciente de FA en pacientes inestables, se debe practicar la cardioversión eléctrica. En pacientes estables, una vez que se han tomado medidas tromboembólicas, es necesario evaluar si es razonable administrar un medicamento antiarrítmico para restaurar el ritmo sinusal o realizar una cardioversión eléctrica. Para los casos que recidivan, ya sea paroxística o persistente, la estrategia más efectiva es realizar el aislamiento de la venas pulmonares con radiofrecuencia o crioablación con balón. La FA permanente es aquella en la que no es posible la recuperación del ritmo sinusal, la característica distintiva de esta fase de la FA es la variabilidad incontrolable de la frecuencia ventricular. Puede tratarse farmacológicamente con bloqueadores nodales AV o con un marcapasos VVIR mas ablación del nodo AV. La presencia de FA se ha asociado durante mucho tiempo con el desarrollo de embolia cerebral y sistémica (pulmonar, de extremidades, coronaria, renal y visceral). La prevención de embolias en la FA “valvular” debe realizarse con antagonistas de la vitamina K (AVK). Para los pacientes con FA no asociados con estenosis mitral o una prótesis valvular mecánica, se puede elegir entre medicamentos anticoagulantes, AVK o anticoagulantes orales directos (DOAC). Los agentes antiplaquetarios tienen el efecto más débil para prevenir la embolia.

The safety and efficacy of tPA intravenous thrombolysis for treating acute ischemic stroke patients with a history of cerebral hemorrhage

Alteplase (tPA) intravenous thrombolysis is an effective treatment for acute ischemic stroke (AIS) when administered within 4.5 h of initial stroke symptoms. Here, its safety and efficacy were evaluated among AIS patients with a previous history of cerebral hemorrhage. Patients who arrived at the hospital within 4.5 h of initial stroke symptoms and who were treated with tPA intravenous thrombolysis or conventional therapies were analyzed. The 90-day modified Rankin scale (90-d mRS) was used alongside mortality and incidence of symptomatic intracerebral hemorrhage (SICH) rates to evaluate the curative effect of these therapies. Among 1,694 AIS patients, 805 patients were treated with intravenous thrombolysis, including patients with (n=793) or without (n=12) a history of cerebral hemorrhage, and the rate of incidence of SICH significantly differed between them (8.3 vs 4.3%, P=0.039). No significant difference was found in 90-d mRS measurements (41.7 vs 43.6%, P=0.530) and 90-d mortality rates (8.3 vs 6.5%, P=0.946). A total of 76 AIS patients with a history of cerebral hemorrhage received tPA thrombolytic therapy (n=12) or conventional therapy (n=64), and a significant difference was noted in the 90-d mRS scores between the two groups (41.7 vs 23.4%, P=0.029), while no significant difference was found in SICH measurements (8.3 vs 4.6%, P=0.610) and 90-d mortality rates (8.3 vs 9.4%, P=0.227). A history of cerebral hemorrhage is not an absolute contraindication for thrombolytic therapy; tPA intravenous thrombolysis does not increase SICH measurements and mortality rates in patients with a history of cerebral hemorrhage, and they may benefit from thrombolytic therapy.

Mobile device for thrombolysis decisions for telestroke / Dispositivo móvil para decisiones de trombólisis mediante Telestroke

Abstract Aim: This study compares the reliability of brain CT interpretations performed using a diagnostic workstation and a mobile tablet computer in a telestroke context. Methods: A factorial design with 1,452 interpretations was used. Reliability was evaluated using the Fleiss' kappa coefficient on the agreements of the interpretation results on the lesion classification, presence of imaging contraindications to the intravenous recombinant tissue-type plasminogen activator (t-PA) administration, and on the Alberta Stroke Program Early CT Score (ASPECTS). Results: The intra-observer agreements were as follows: good agreement on the overall lesion classification (κ= 0.63, p<0.001), very good agreement on hemorrhagic lesions (κ= 0.89, p<0.001), and moderate agreements on both without acute lesion classification and acute ischemic lesion classification (κ= 0.59 and κ= 0.58 respectively, p<0.001). There was good intra-observer agreement on the dichotomized-ASPECTS (κ= 0.65, p<0.001). Conclusions: The results of our study allow us to conclude that the reliability of the mobile solution for interpreting brain CT images of patients with acute stroke was assured, which would allow efficient and low-cost telestroke services.

Resumen Objetivo: Este estudio compara la confiabilidad de interpretaciones de TAC de cráneo simple realizadas utilizando una estación de trabajo de diagnóstico y un computador tableta en un contexto de teleACV. Métodos: Se utilizó un diseño factorial con 1,452 interpretaciones. La confiabilidad se evaluó utilizando el coeficiente kappa de Fleiss en las concordancias sobre los resultados de la interpretación en la clasificación de la lesión, la presencia de contraindicaciones en la imagen para la administración intravenosa del activador del plasminógeno tisular (AP-t) y con el Alberta Stroke Programme Early CT Score (ASPECTS). Resultados: Se obtuvieron las siguientes concordancias intraobservadores: buena concordancia en la clasificación general de la lesión (κ= 0.63, p<0.001), muy buena concordancia en lesiones hemorrágicas (κ= 0.89, p< 0.001), y concordancia moderada en ambos sin clasificación de lesión aguda y clasificación de lesión isquémica aguda (κ= 0.59 y κ= 0.58 respectivamente, p<0.001). Hubo una buena concordancia intraobservadores en el ASPECTS dicotomizado (κ= 0.65, p<0.001). Conclusiones: Los resultados de nuestro estudio permiten concluir que la confiabilidad de la solución móvil para la interpretación de imágenes de TAC de cráneo simple de pacientes con accidente cerebrovascular agudo (ACV) estaba garantizada, lo que permitiría servicios de teleACV eficientes y de bajo costo.

Fibrinolíticos en tromboembolismo de pulmón: Nuevas alternativas para una indicación controvertida / Fibrinolytics in lung thromboembolism. New alternatives for a controversial prescription

El uso de fibrinolíticos en el tromboembolismo de pulmón (TEP) es un tema de debate que ha sufrido idas y venidas desde su primera descripción en la década del 60. Esta terapia que puede liberar rápidamente la obstrucción mecánica en la arteria pulmonar, tiene la limitante del alto riesgo hemorrágico. Justamente por la incidencia prohibitiva de sangrado mayor y cerebral, y por la falta de beneficio en la supervivencia, es que solo está indicado el uso de fibrinolíticos sistémicos en el reducido número de pacientes con TEP grave y descompensación hemodinámica. En el TEP de moderado riesgo, aun con sufrimiento del ventículo derecho (VD), no están indicados. En los últimos años ha surgido la alternativa de combinar bajas dosis de fibrinolíticos liberados localmente en la arteria pulmonar mediante un catéter que puede adjuntarse o no a ultrasonidos en el sitio de la trombosis. Esta forma de administrar los trombolíticos permite corregir la hipertensión pulmonar aguda y liberar el trombo prácticamente sin sangrados mayores o del SNC. Los estudios publicados son muy alentadores, pero la evidencia aún es muy escasa, se requiere un laboratorio de hemodinamia disponible en todo momento y no está exento de riesgos, con un costo considerable. Por el momento solo un reducido número de pacientes con TEP moderado y parámetros de mal pronóstico parece tener indicación para esta alternativa.

The use of fibrinolytics in lung thromboembolism (PTE) is a subject under debate since its first description in the 1960s. This therapy, which can rapidly resolve the mechanical obstruction in the pulmonary artery, has the limiting of a high hemorrhagic risk. Precisely because of the prohibitive incidence of major and cerebral bleeding and the lack of benefit in survival, the use of systemic thrombolytics is only indicated in the small number of patients with severe PE and hemodynamic instability. In moderate-risk PE, even with right ventricular (RV) dysfunction, they are not indicated. In recent years, an alternative has arisen, by combining low doses of fibrinolytics released locally into the pulmonary artery through a catheter that may, or may not, be attached to ultrasound at the site of thrombosis. This way of administering thrombolytics can correct acute pulmonary hypertension and eliminate the thrombus without major or CNS bleeds. Although the published studies are very encouraging, the evidence is still poor, a laboratory of hemodynamics is required at all times and this procedure is not free of risks, with a considerable cost. At the moment, only a small number of patients with moderate PE and poor prognosis seem to have an indication for this new alternative.

Hemoptise maciça tratada com oxigenação por membrana extracorpórea e trombolítico endobrônquico com sucesso / Massive hemoptysis successfully treated with extracorporeal membrane oxygenation and endobronchial thrombolysis

RESUMO A oxigenação por membrana extracorpórea tem sido utilizada para tratamento de hipoxemia refratária em muitos cenários clínicos. Os princípios fundamentais do manejo do paciente com hemoptise maciça são a proteção da via aérea e do pulmão sadio, a localização da fonte de sangramento e o controle da hemorragia. Relatamos o caso de uma paciente com insuficiência respiratória aguda associada à hemoptise maciça secundária à laceração pulmonar durante cirurgia cardíaca. O uso da oxigenação por membrana extracorpórea venoarterial permitiu a sobrevivência da paciente, porém, devido à grande dificuldade no manejo dos coágulos pulmonares após hemoptise, foi necessário o uso de terapia incomum, com infusão endobrônquica de trombolítico, conforme descrito em raros casos na literatura.

ABSTRACT Extracorporeal membrane oxygenation has been used to treat refractory hypoxemia in numerous clinical scenarios. The fundamental principles for the management of massive hemoptysis patients include protecting the airway and healthy lung, locating the source of bleeding and controlling the hemorrhage. We report the case of a patient with acute respiratory failure associated with massive hemoptysis secondary to lung laceration during cardiac surgery. The use of extracorporeal membrane oxygenation allowed patient survival. However, due to the great difficulty in managing pulmonary clots after hemoptysis, it was necessary to use an unusual therapy involving endobronchial infusion of a thrombolytic agent as described in rare cases in the literature.

Evaluación de la estrategia de terapia antitrombótica posterior al cambio valvular aórtico con válvulas biológicas en pacientes de bajo riesgo trombótico / Evaluation of the antithrombotic strategy in low thrombotic risk patients who underwent aortic valve replacement with a bioprosthesis

Resumen De acuerdo a las guías actuales, aún es materia de debate el uso de anticoagulación en los primeros 3 meses en pacientes de bajo riesgo trombótico sometidos a cambio valvular aórtico con prótesis biológicas. En base a la evidencia actual, la aspirina a dosis bajas es razonable como alternativa a los antagonistas de la vitamina K (AVK) durante el posquirúrgico temprano en pacientes con prótesis biológicas en posición aórtica. Se comparó la incidencia de complicaciones trombóticas o hemorrágicas de acuerdo a la estrategia de terapia antitrombótica en los pacientes de bajo riesgo trombótico sometidos a cambio valvular aórtico con válvulas biológicas en el Instituto Nacional de Cardiología Ignacio Chávez. La hipótesis: la aspirina como monoterapia antitrombótica tiene un efecto benéfico comparado con los AVK. Se estudiaron los pacientes de bajo riesgo trombótico sometidos a cambio valvular aórtico con válvulas biológicas en el Instituto Nacional de Cardiología Ignacio Chávez. Se incluyeron los pacientes operados del año 2011 al 2015. Se identificó en el seguimiento a un año la presencia de complicaciones trombóticas o hemorrágicas y si se manejaron con cualquiera de las siguientes: aspirina únicamente, AVK solo y la combinación aspirina más AVK. Se analizaron 231 pacientes. Solo se presentó una complicación hemorrágica en un paciente tratado con AVK. No hubo complicaciones trombóticas. No se presentaron complicaciones trombóticas en pacientes que no recibieron anticoagulación oral formal durante los primeros 3 meses posquirúrgicos, lo que indica que es seguro el uso de aspirina como monoterapia en estos pacientes de bajo riesgo trombótico.

Abstract According to current guidelines, in patients without additional risk factors who have undergone aortic valve replacement with a bioprosthesis, anticoagulation in the first 3 months after surgery is still a matter of debate. According to current evidence, aspirin in low doses is a reasonable alternative to vitamin K antagonists (VKA). A comparison is made between the incidence of thrombotic and haemorrhagic complications in patients with low thrombotic risk who underwent aortic valve replacement with a bioprosthesis in the National Institute of Cardiology of Ignacio Chávez of Mexico. The hypothesis: aspirin as monotherapy has a beneficial effect compared to VKA. The studied patients were the low thrombotic risk patients who underwent aortic valve replacement with a bioprosthesis in the National Institute of Cardiology of Ignacio Chávez of Mexico from 2011 to 2015. The groups studied were: aspirin only, VKA only, and the combination of VKA plus aspirin. The patients were retrospectively followed-up for 12 months, and the thrombotic and haemorrhagic complications were documented. Of the 231 patients included in the study, only one patient in the VKA only group presented with a haemorrhagic complication. No thrombotic complications were observed. In the present study no thrombotic complications were observed in patients who did not receive anticoagulation in the first 3 months after an aortic valve replacement with a bioprosthesis after a follow up period of 12 months. This suggests that the use of aspirin only is safe during this period.

Intra-arterial fibrinolysis for the management of acute ischemia on a below-knee amputation stump. Case report / Fibrinólise intra-arterial para tratamento da isquemia aguda em coto de amputação infrapatelar. Relato de caso

ABSTRACT Preservation of the knee joint has enormous advantages in terms of mobility and rehabilitation of an amputee. Any cause of breakdown requiring revision to an above-knee amputation is a major setback because it reduces the patient's rehabilitative potential. We report a case of intra-arterial thrombolysis use to save a below-knee amputation stump with acute ischemia. A 56-year-old man who sought the emergency department with 1-day history of acute pain on his right below-knee stump. The angiography confirmed popliteal artery occlusion. Pharmacomechanical thrombectomy, with Aspirex (rotational catheter to restore blood flow in occluded vessel, by removing occlusion material from the vessel) and recombinant tissue plasminogen activator, was performed. After 9 years of follow-up the patient remained asymptomatic, capable of independent ambulation with prosthetic limb. Intra-arterial fibrinolysis seems to be a safe and effective treatment for cases of acutely ischemic amputation stump.

RESUMO A preservação da articulação do joelho tem grandes vantagens para a mobilidade e a reabilitação de um amputado. Qualquer causa que exija revisão para uma amputação acima do joelho é um grande revés, porque reduz o potencial de reabilitação do paciente. O objetivo aqui foi descrever o uso de trombólise intra-arterial para salvar um coto de amputação abaixo do joelho com isquemia aguda. Homem, 56 anos, procurou pronto atendimento de nosso hospital com histórico de 1 dia de dor aguda em seu coto de amputação infrapatelar direito. A angiografia confirmou oclusão da artéria poplítea. Foi realizada trombectomia farmacomecânica com Aspirex (cateter rotativo para restabelecer o fluxo sanguíneo em vasos ocluídos, removendo material de oclusão do vaso) e ativador do plaminogênio tecidual recombinante. Após 9 anos de seguimento, o paciente permanecia assintomático, capaz de deambulação independente com membro protético. A fibrinólise intra-arterial parece ser um tratamento seguro e eficaz para casos selecionados de coto de amputação com isquêmica aguda.

Evolución del protocolo de trombolisis endovenosa en ataque cerebrovascular isquémico agudo / Intravenous thrombolysis for acute ischemic stroke. A four years’ experience in a Chilean public hospital

Background: Intravenous thrombolysis (IVT) with alteplase (tissue plasminogen activator) is the standard pharmacological treatment in acute ischemic stroke (AIS), reducing disability in patients. Aim: To report the results a thrombolysis protocol during four years in a regional public hospital. Material and Methods: Data from 106 consecutive patients aged 68 ± 13 years (57% men) who were treated with IVT, from May 2012 until April 2016, was analyzed. Results: The median door-to-needle time was 80 minutes (interquartile range = 57-113). The median National Institute of Health Stroke Scale (NIHSS) scores on admission and at discharge were was 11.5 and 5 points respectively. At discharge, 27% of hospitalized patients had a favorable outcome (n = 99), defined as having 0 to 1 points in the modified Rankin scale. Symptomatic intracerebral hemorrhage and mortality rates were 5.7 and 13.1%, respectively. The thrombolysis rate rose from 0.7% in 2012 to 6% in 2016. Conclusions: The implementation of 24/7 neurology shifts in the Emergency Department allowed us to increase the amount and quality of IVT in our hospital, as measured by the rate of thrombolysis and by process indicators such as door-to-needle time.

Evidencias para el uso combinado de ácido acetilsalicílico (aspirina) y clopidogrel en síndromes coronarios agudos / Evidences about combination use of acetylsalicylic acid (aspirin) and clopidogrel in acute coronary syndrome

Las enfermedades tromboembólicas siguen siendo una de las causas más importantes de morbilidad y mortalidad en todo el mundo. El mecanismo fisiopatológico subyacente en los síndromes coronarios agudos es la trombosis coronaria. Por eso, la base de su tratamiento se ha centrado en los fármacos antiplaquetarios, fibrinolíticos y anticoagulantes. En un número importante de individuos deben emplearse medidas adicionales como, por ejemplo, el intervencionismo percutáneo coronario (angioplastia y la colocación de los llamados stentsintracoronarios). La aspirina se ha considerado como el fármaco de primera elección en la prevención de las afecciones tromboembólicas. La combinación aspirina-clopidogrel ha representado una terapéutica sumamente eficiente en el tratamiento de los eventos tromboembólicos. La introducción de tabletas de combinación fija representa un avance para facilitar el cumplimiento de la terapia.

Thromboembolic diseases remain one of the most important causes of morbidity and mortality worldwide. The pathophysiologic mechanism underlying the acute coronary syndromes is coronary thrombosis. That is why the basis of its treatment has focused on antiplatelet, fibrinolytic and anticoagulant drugs. In a significant number of individuals, additional measures must be used, such as, for example, the coronary percutaneous intervention (angioplasty and placement of the so-called intracoronary stents). Aspirin has been regarded as the drug of first choice in the prevention of thromboembolic diseases. The combination aspirin-clopidogrel has represented a highly efficient therapeutic measure for thromboembolic events. The introduction of fixed combination tablets represents a step forward in order to facilitate therapeutic compliance.

Brazilian guidelines for endovascular treatment of patients with acute ischemic stroke / Diretrizes brasileiras para o tratamento endovascular de pacientes com acidente vascular cerebral isquêmico agudo

ABSTRACT These guidelines are the result of a joint effort from writing groups of the Brazilian Stroke Society, the Scientific Department of Cerebrovascular Diseases of the Brazilian Academy of Neurology, the Brazilian Stroke Network and the Brazilian Society of Diagnostic and Therapeutic Neuroradiology. Members from these groups participated in web-based discussion forums with predefined themes, followed by videoconference meetings in which controversies and position statements were discussed, leading to a consensus. This guidelines focuses on the implications of the recent clinical trials on endovascular therapy for acute ischemic stroke due to proximal arterial occlusions, and the final text aims to guide health care providers, health care managers and public health authorities in managing patients with this condition in Brazil.

RESUMO Estas diretrizes são o resultado de um esforço conjunto de membros da Sociedade Brasileira de Doenças Cerebrovasculares (SBDCV), Departamento científico de Doenças Cerebrovasculares da Academia Brasileira de Neurologia (ABN), Rede Brasil AVC (RBAVC) e da Sociedade Brasileira de Neurorradiologia Diagnóstica e Terapêutica (SBNR). Membros destas 4 entidades participaram de fórum de discussões por internet de temas pré-definidos, seguidos de encontros de videoconferência para discussão de pontos controversos e das recomendações, em busca de um consenso final. Estas diretrizes tem seu foco sobre as implicações dos recentes ensaios clínicos de tratamento endovascular do acidente vascular cerebral (AVC) isquêmico agudo relacionado a oclusão de artérias proximais. O texto final foi elaborado para servir de orientação no manejo destes pacientes AVC isquêmico pelos diferentes profissionais de saúde, gestores de saúde pública e de saúde complementar no Brasil.

Simple prediction model for unfavorable outcome in ischemic stroke after intravenous thrombolytic therapy / Modelo simples de predição de desfecho desfavorável em acidente vascular cerebral isquêmico tratado após terapia trombolítica intravenosa

ABSTRACT Objective We aimed to develop a model to predict unfavorable outcome in patients with acute ischemic stroke treated with intravenous thrombolytic therapy (IVT), based on simple variables present on admission. Methods Retrospective analysis of acute ischemic stroke patients treated with IVT in a hospital in Rio de Janeiro. Clinical and radiographic variables were selected for analysis. Multivariate logistic regression was used to develop a predictive model. Results We analyzed a total of 82 patients. Median National Institutes of Health Stroke Scale (NIHSS) on admission was 9 (3–22), 40.2% presented with a hyperdense artery sign (HAS), 62% had identifiable early parenchymal changes and 61.6% experienced a favorable outcome. An NIHSS score of > 12 on arrival, age > 70 and the presence of HAS were associated with the outcome, even after correction in a logistic regression model. Conclusion An NIHSS > 12 on arrival, presence of HAS and age > 70 years were predictors of unfavorable outcome at three months in patients with acute ischemic stroke treated with IVT.

RESUMO Objetivo Desenvolver um modelo para predizer desfecho desfavorável em pacientes com acidente vascular cerebral isquêmico (AVCi) agudo tratados com terapia trombolítica intravenosa (TTI), baseado em variáveis simples presentes à admissão. Métodos Análise retrospectiva de casos de AVCi tratados com TTI em um hospital no Rio de Janeiro. Variáveis clínicas e radiográficas foram selecionadas para análise. Foi utilizada regressão logística para desenvolver modelo preditivo. Resultados 82 casos foram analisados. A mediana de escore de National Institutes of Health Stroke Scale (NIHSS) na admissão foi 9 (3–22), 40,2% se apresentaram com sinal da artéria hiperdensa (SAH), 62% possuíam alterações parenquimatosas precoces e 61,6% obtiveram um desfecho favorável. NIHSS > 12, idade > 70 e a presença de SAH foram associados com o desfecho, mesmo após correção em modelo de regressão logística. Conclusão NIHSS > 12, a presença de SAH e idade maior que 70 anos foram preditores de desfecho desfavorável em 3 meses em pacientes com AVCi tratados com TTI.

Trombolisis intravenosa en cuadros imitadores de isquemia cerebral: experiencia de un centro / Thrombolysis in stroke mimics: experience in 10 cases

Background: The effectiveness of intravenous thrombolysis (IVT) in cerebral ischemia is time dependent. Stroke mimics (SM) are frequent in emergency rooms. The effort to reduce door to needle time, can lead to administer thrombolytics to SM. Aim: To describe the frequency and prognosis of SM treated with IVT. Material and Methods: Prospective analysis of all patients evaluated in a Chilean private clinic between December 2004 and July 2015 with a suspected acute ischemic stroke (AIS). We calculated the number of SM that were treated with IVT. In these patients, we analyzed the presence of symptomatic cerebral hemorrhage defined as the presence of a neurological deterioration of four points or more on the National Institute of Health Stroke Scale, the presence of extracranial bleeding according to Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries criteria and the patient’s functional status at three months by modified Rankin scale (MRS). Results: We evaluated 1,417 patients with suspected AIS, of which 240 (16.9%) were finally diagnosed as SM. A total of 197 patients were treated with IVT, of these 10 (5%) corresponded to SM. All SM patients treated with thrombolytic drugs were functionally independent at 3 months and showed no bleeding complications. Conclusions: Occasionally SM patients were treated with IVT. This treatment was not associated with bleeding complications and the prognosis of these patients at three months was favorable.

Time-To-Treatment of Acute Coronary Syndrome and Unit of First Contact in the ERICO Study / Tempo para Tratamento durante Síndrome Coronariana Aguda e Unidade de Primeiro Contato no Estudo ERICO

Abstract Background: To the best of our knowledge, there are no studies evaluating the influence of the unit of the first contact on the frequency and time of pharmacological treatment during an acute coronary syndrome (ACS) event. Objectives: The main objective was to investigate if the unit of first contact influenced the frequency and time of aspirin treatment in the Strategy of Registry of Acute Coronary Syndrome (ERICO) study. Methods: We analyzed the pharmacological treatment time in 830 ERICO participants - 700 individuals for whom the hospital was the unit of first contact and 130 who initially sought primary care units. We built logistic regression models to study whether the unit of first contact was associated with a treatment time of less than three hours. Results: Individuals who went to primary care units received the first aspirin dose in those units in 75.6% of the cases. The remaining 24.4% received aspirin at the hospital. Despite this finding, individuals from primary care still had aspirin administered within three hours more frequently than those who went to the hospital (76.8% vs 52.6%; p<0.001 and 100% vs. 70.7%; p=0.001 for non ST-elevation ACS and ST-elevation myocardial infarction, respectively). In adjusted models, individuals coming from primary care were more likely to receive aspirin more quickly (odds ratio: 3.66; 95% confidence interval: 2.06-6.51). Conclusions: In our setting, individuals from primary care were more likely to receive aspirin earlier. Enhancing the ability of primary care units to provide early treatment and safe transportation may be beneficial in similar settings.

Resumo Fundamento: Em nosso conhecimento, não há estudos que avaliam a influência da unidade de primeiro contato na frequência e tempo para o tratamento farmacológico durante um evento de síndrome coronariana aguda (SCA). Objetivos: O principal objetivo foi investigar se a unidade de primeiro contato influencia a frequência e o tempo para tratamento com aspirina no estudo "Estratégia de Registro de Insuficiência Coronariana" (ERICO). Métodos: Analisamos o tempo para o tratamento farmacológico em 830 participantes do estudo ERICO - 700 indivíduos cuja primeira unidade de contato foi o hospital, e 130 que procuraram, num primeiro momento, unidades de atenção primária. Construímos modelos de regressão logística para estudar se a unidade de primeiro contato estava associada a um tempo de tratamento de menos de três horas. Resultados: Indivíduos que buscaram unidades de atenção primária receberam a primeira dose de aspirina nestas unidades em 75,6% dos casos. Os outros 24,4% receberam a aspirina no hospital. Apesar deste achado, indivíduos de unidades de atenção primária receberam aspirina em três horas mais frequentemente do que aqueles que foram ao hospital (76,8% vs 52,6%; p<0,001 e 100% vs, 70,7%; p=0,001 para SCA sem elevação do segmento ST e infarto agudo do miocárdio com elevação do ST, respectivamente). Em modelos ajustados, indivíduos vindos de unidades de atenção primária tinham mais probabilidade de receber aspirina mais rapidamente (razão de chances: 3,66; 95% intervalo de confiança: 2,06-6,51). Conclusões: Neste contexto, indivíduos provenientes de unidades de atenção primária tinham maior chance de receber aspirina mais rapidamente. O aprimoramento da capacidade das unidades de atenção primária para proporcionar tratamento precoce e transporte seguro pode ser benéfico em contextos similares.

Eficacia y seguridad del uso de agentes trombopoyeticos (romiplostim y eltrombopag) en el tratamiento de púrpura trombocitopénica idiopática refractaria / Efficacy and safety of the use of thrombopoietic agents (romiplostim and eltrombopag) in the treatment of idiopathic refractory thrombocytopenic purpura

INTRODUCCIÓN: Antecedentes: El presente dictamen presenta la evaluación de tecnología de la eficacia y seguridad del uso de agentes trombopoyéticos (romiplostim y eltrombopag) en el tratamiento de púrpura \r\ntrombocitopénica idiopática. Aspectos Generales: La trombocitopenia inmune primaria o púrpura trombocitopénica idiopática (PTI) es una condición autoinmune usualmente benigna caracterizada por el aumento de la destrucción plaquetaria y la sub-optima producción plaquetaria. Tecnología Sanitaria de Interés: Romiplostim y Eltrombopag: Romiplostim es una proteína sintética agonista del receptor de trombopoyetina. Al actuar como un imitador de la trombopoyetina, romiplostim estimula la diferenciación y proliferación de células de la médula ósea, las cuales son responsables de la producción de plaquetas. De esta manera, éste fármaco aumenta la producción plaquetaria y por lo tanto los recuentos de plaquetas. Eltrombopag es una molécula pequeña no-peptídica que activa el receptor de trombopoyetina al unirse a su dominio transmembrana. Dado su mecanismo de acción, eltrombopag, a diferencia de romiplostim, no compite con las trombopoyetinas circulantes por los sitios de unión. METODOLOGÍA: Estrategia de Búsqueda: Se llevó a cabo una búsqueda de la literatura con respecto a la eficacia y seguridad de romiplostim y eltrombopag en el tratamiento de púrpura trombocitopénica idiopática en las bases de datos de PubMed, TRIPDATABASE y www.clinicaltrials.gov. Adicionalmente, se realizó una búsqueda de evaluaciones de tecnologías y guías de práctica clínica en las páginas web de grupos dedicados a la investigación y educación en salud en general como The National Institute for Health and Care Excellence (NICE), the American Society of Hematology (ASH), Sociedad Española de Hematología y Hemoterapia (SEHH) y la Sociedad Española de Hematología y Oncología Pediátrica (SEHOP). RESULTADOS: Sinopsis de la Evidencia: se llevó a cabo una búsqueda de evidencia científica relacionada al uso de romiplostim y eltrombopag en el tratamiento de pacientes con PTI. En la presente sinopsis se describe la evidencia disponible según el tipo de publicación, siguiendo lo indicado en los criterios de elegibilidad (GPC, ETS, RS, MA y ECA fase III). Guías de práctica clínica: Se incluyeron recomendaciones de dos GPC, una de la American Society of Haematology del 2011, y una de los expertos españoles de la SEHH y la SEHOP del 2012. Ambas responden directamente a la pregunta de interés del presente dictamen. Evaluaciones de tecnología sanitaria: Se incluyeron dos ETS del National Institude for Health and Care Excellence. Estas ETS responden directamente a la pregunta de investigación del presente dictamen. Ensayos clínicos: Se incluyeron dos ECA donde se evaluó el uso de romiplostim y eltrompobag, de manera independiente, en el tratamiento de adultos con PTI crónica. CONCLUSIONES: Las GPC concuerdan en sus recomendaciones sobre el uso de agentes trombopoyéticos (romiplostim y eltrombopag) en el tratamiento de PTI crónica en pacientes que han mostrado refractariedad a los tratamiento de primera línea y en quienes la esplenectomía no ha funcionado o está contraindicada. Las ETS recomiendan tanto el uso de romiplostim como el de eltrombopag en pacientes adultos con PTI crónica en quienes la esplenectomía no ha surgido efecto o en quienes ésta está contraindicada, y que son refractarios a las terapias de primera línea. Sin embargo, ésta recomendación esta circunscrita a un descuento en el costo del tratamiento por parte de la empresa comercializadora. Los ECA muestran la eficacia y seguridad del el uso de romiplostim y eltrombopag, por separado, en el tratamiento de PTI crónica en pacientes refractarios a terapias de primera y segunda línea. Se observa un efecto positivo de ambos medicamentos sobre el conteo plaquetario, y un perfil de seguridad aceptable. En ausencia de una comparación head-to-head, no es posible concluir con certeza sobre la eficacia de eltrombopag vs romiplostim. Sin embargo, una apreciación cualitativa de los ECA que evalúan a dichos fármacos por separado sugiere que estos muestran similar beneficio y perfil de seguridad, lo cual concuerda con la opinión de expertos. Frente a un beneficio similar por parte de ambos fármacos, los costos de los mismos toman relevancia en la toma de decisión de su empleo en un sistema de prestación de servicios de salud como EsSalud. Así, el tratamiento mensual con romiplostim tiene un costo aproximado de S/.12, 000, mientras que el costo del tratamiento mensual con eltrombopag puede variar entre S1.4,404.9 - 8,809.8, dependiendo de la dosis. Con lo que se establece que el costo de eltrombopag es menor al de romiplostim para lograr un mismo beneficio por paciente en cuanto a conteo plaquetario. El Instituto de Evaluación de Tecnologías en Salud e Investigación - IETSI, aprueba el uso de eltrombopag para el manejo de púrpura trombocitopénica idiopática como tercera línea, según lo establecido en el Anexo 1. La vigencia del presente dictamen preliminar es de dos años.

Estratégia invasiva nas síndromes coronarianas agudas sem supradesnivelamento do segmento st / Invasive strategy in acute coronary syndrome without st segment elevation

As doenças cardiovasculares representam uma das principais causas de morbimortalidade no mundo ocidental. Neste cenário, as síndromes coronarianas agudas respondempela grande maioria dos eventos fatais. Em pacientes acometidos por síndrome coronariana sem supra-desnivelamento do segmento ST a estratificação invasiva (cinecoronariografia) ocupa papel central na tomada de conduta terapêutica, tendo como méritos: 1) determinara presença de doença arterial coronária obstrutiva, confirmando o diagnóstico clínico e laboratorial de SCA; 2) identificar a lesão “culpada” ou responsável pelo quadro clínicoapresentado; 3) fornecer informações prognósticas a respeito da ocorrência de eventos cardiovasculares como óbito e infarto, intimamente relacionados à severidade e extensão da doença coronária, à função ventricular esquerda e à presença de condições associadas(como valvopatias); 4) e estabelecer a necessidade e o tipo de revascularizaçãomiocárdica a ser empregado, seja percutânea ou cirúrgica. O momento ideal de realizar a estratificação invasiva varia de acordo com a estratificação de risco do paciente avaliado, devendo em geral ser realizada em até 72h. Estratégias muito precoces (<2h) ou precoces (<24h) são plausíveis em cenários de mais alto risco clínico...

Cardiovascular diseases represent one of the main causes of morbidity and mortality in the western world. In this scenario, acute coronary syndromes represent the vast majority of fatal events. In patients affected by coronary syndrome without ST segment elevation,the invasive strategy (cinecoronariography) plays a central role in the choice of therapeuticconduct, as it has several merits: 1) determining the presence of obstructive coronary arterial disease, confirming the clinical and laboratory diagnosis of ACS; 2) identifying the lesion responsible for the clinical symptoms presented; 3) providing prognostic information on the occurrence of cardiovascular events with such as death or stroke, which are closely related to the severity and extent of the coronary disease, the left ventricle function, and the presence of associated conditions (such as valve disease); and 4) establishing the need for and type of myocardial revascularization to be used, whether percutaneous or surgical. The ideal moment to conduct invasive stratification varies, depending on therisk level of the patient being evaluated, but in general, it should be performed within 72 hours. Very early strategies (< 2 hours) or early strategies (< 24 hours) are plausible in scenarios of greater clinical risk...

Terapia antitrombótica na fase aguda das síndromes coronarianas aguda / Antithrombotic therapy in acute phase of acute coronary syndrome

A morbidade e a mortalidade nas síndromes coronarianas agudas – causadas principalmente pela instabilidade da placa aterosclerótica, levando à formação de trombos – foi bastante reduzida com o advento de antiplaquetários, antitrombóticos e revascularização precoce. Hoje, dispomos de quatro antitrombóticos para uso nestas condições: a heparina não fracionada, a de baixo peso molecular, o fondaparinux e a bivalirudina – sendo apenas as três primeiras disponíveis no Brasil. Como são agentes antiocoagulantes, o risco de sangramento não é desprezível e deve ser apropriadamente dosado com o fim de trazer o máximo benefício antitrombótico, sem grande risco hemorrágico. Nesta revisão sumarizamos o atual estado da arteno uso de antitrombóticos no Brasil...

Morbidity and mortality in the acute coronary syndromes – caused in the majorly by atherosclerotic plaque instability, with consequent thrombus formation – was drastically reduced by the advent of antiplatelet and antithrombotic agents, and by early revascularization. Nowadays, we have 4 antithrombotic agents: unfractionated heparin, low molecular weight heparin, fondaparinux and bivalirudin – with only the first 3 available in Brazil. As they comprise anticoagulant effects, the risk of bleedingis high and must be taken into account when prescribed, in order to bring the greater benefits without higher bleeding risk. In this review we summarized the current state of the art about the use of these agents in our country...

Initial experience with ocriplasmin in the treatment of vitreomacular traction / Experiência inicial com ocriplasmina no tratamento da tração vitreorretiniana

ABSTRACT This study aimed to report the clinical and structural outcomes of intravitreal ocriplasmin in the treatment of vitreomacular interface disorders in two tertiary centers in Brazil. A retrospective study was performed by reviewing medical records and spectral domain optical coherence tomography (SD-OCT) findings of seven patients who were treated with a single ocriplasmin injection. A total of 57.14% of patients achieved resolution of vitreomacular traction as evidenced by SD-OCT. Regarding our functional results, 87.71% maintained or improved visual acuity after follow-up. To the best of our knowledge, this is the first study reporting initial results of ocriplasmin therapy in Brazil.

RESUMO O objetivo desse estudo é relatar os resultados iniciais, tanto do ponto de vista funcional quanto anatômico, no tratamento das doenças da interface vítreo-macular com a ocriplasmina em 2 serviços terciários no Brasil. Um estudo retrospectivo foi realizado através de revisão de prontuários, além de análise de achados em tomografia de coerência óptica de domínio espectral (SD-OCT) em 7 pacientes tratados com uma única injeção intravítrea de ocriplasmina. Em nosso estudo 57,14% dos pacientes apresentaram resolução da tração vítreo-macular no SD-OCT. Em relação aos resultados funcionais, 87,71% dos pacientes mantiveram, ou melhoraram sua acuidade visual durante o acompanhamento. Para nosso conhecimento, trata-se do primeiro estudo em nosso país, mostrando resultados iniciais com ocriplasmina em pacientes tratados no Brasil.