Case report
Fulminant myocarditis associated with pandemic H1N1 influenza A virus
Miocardite fulminante associada ao vírus influenza A pandémico H1N1
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The arrows indicate the days on which the device was implanted (left) and explanted (right). Admit: day admitted; D13 VAD, D18 VAD, D24 VAD: 13th, 18th, 24th day after implantation of the ventricular assist device; D2 post-VAD, D6 post-VAD, D13 post-VAD: 2nd, 6th, 13th day after explantation of the ventricular assist device. 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Left ventriculography at end-systole (A) and end-diastole (B) demonstrating typical apical ballooning and double outline apex suggestive of apical thrombus. Results of selective coronary angiography of the left main coronary artery (C) showing no significant stenosis.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ana Sofia Correia, Nuno Moreno, Alexandra Gonçalves, Vítor Araújo, Teresa Pinho, Rui André Rodrigues, Filipe Macedo, Maria Júlia Maciel" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Ana Sofia" "apellidos" => "Correia" ] 1 => array:2 [ "nombre" => "Nuno" "apellidos" => "Moreno" ] 2 => array:2 [ "nombre" => "Alexandra" "apellidos" => "Gonçalves" ] 3 => array:2 [ "nombre" => "Vítor" "apellidos" => "Araújo" ] 4 => array:2 [ "nombre" => "Teresa" "apellidos" => "Pinho" ] 5 => array:2 [ "nombre" => "Rui André" "apellidos" => "Rodrigues" ] 6 => array:2 [ "nombre" => "Filipe" "apellidos" => "Macedo" ] 7 => array:2 [ "nombre" => "Maria Júlia" "apellidos" => "Maciel" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204912001158?idApp=UINPBA00004E" "url" => "/21742049/0000003100000078/v1_201308021407/S2174204912001158/v1_201308021407/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case report</span>" "titulo" => "Fulminant myocarditis associated with pandemic H1N1 influenza A virus" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "517" "paginaFinal" => "520" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Marta Cabral, Maria J. Brito, Marta Conde, Mário Oliveira, Gonçalo C. Ferreira" "autores" => array:5 [ 0 => array:4 [ "nombre" => "Marta" "apellidos" => "Cabral" "email" => array:1 [ 0 => "mssr.cabral@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Maria J." "apellidos" => "Brito" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Marta" "apellidos" => "Conde" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Mário" "apellidos" => "Oliveira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "Gonçalo C." "apellidos" => "Ferreira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Pediatrics, Hospital Dona Estefânia – CHLC – EPE, Lisbon, Portugal" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Pathology, Hospital de São José – CHLC – EPE, Lisbon, Portugal" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Miocardite fulminante associada ao vírus influenza A pandémico H1N1" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1436 "Ancho" => 966 "Tamanyo" => 273912 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Intermediate (A) and high (B) magnification of myocardium with multifocal infiltrates composed mostly of lymphocytes but also some neutrophils, macrophages, plasma cells and eosinophils, associated with myocyte necrosis and ischemia.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Acute myocarditis, albeit rare and potentially lethal, is a well-recognized manifestation of numerous viral infections with a broad spectrum of symptoms and clinical features.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The etiological agents of viral myocarditis include enteroviruses, adenoviruses, parvoviruses, hepatitis C virus, human immunodeficiency virus, influenza, and others.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Coxsackie B virus has been described as the most common pathogen of viral myocarditis and hepatitis C virus is associated with many different forms of heart disease worldwide; however, influenza myocarditis is relatively rare.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a> Many people are affected by seasonal influenza every year, but the myocarditogenicity of this virus seems to be fairly low. The frequency of myocardial involvement in influenza infection is unclear,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> but some studies report that it ranges from 0 to 11%, depending on the diagnostic criteria used to define myocarditis.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Myocarditis is an inflammatory disorder characterized by myocyte necrosis and inflammatory infiltrate of the myocardium.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> The pathogenesis of influenza myocarditis is also unclear. Host immune response may play a role, as well as direct cytolysis by viral infection.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Fulminant myocarditis is an uncommon complication, typically diagnosed in association with circulatory collapse or at autopsy in patients with influenza-associated fatal outcomes. It may present with fatal arrhythmias, atrioventricular block and/or varying degrees of heart failure, cardiogenic shock being the most severe.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">A few case reports and series present incidental diagnoses of influenza-associated acute fulminant myocarditis, but the true prevalence remains unknown.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> We present a case of rapidly fatal fulminant pandemic influenza A (H1N1) virus (H1N1v)-associated myocarditis, with no previous cardiac symptomatology.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Case report</span><p id="par0020" class="elsevierStylePara elsevierViewall">A previously healthy 10-year-old boy presented to the emergency department with a three-day history of a flu-like syndrome: fever, cough, headache, generalized myalgia, vomiting and diarrhea. He had no known risk factors for complications of influenza, he was not previously vaccinated for seasonal or pandemic influenza viruses and he was not receiving any antiviral treatment.</p><p id="par0025" class="elsevierStylePara elsevierViewall">At admission, he was pale and had signs of dehydration. Body temperature was 34.7<span class="elsevierStyleHsp" style=""></span>°C, pulse rate 120<span class="elsevierStyleHsp" style=""></span>beats/min and blood pressure 84/65<span class="elsevierStyleHsp" style=""></span>mmHg (median arterial pressure: 65<span class="elsevierStyleHsp" style=""></span>mmHg). Pulse oximetry showed oxygen saturation of 96–98% and cardiac physical examination was normal. Chest radiography revealed diffuse bilateral alveolar infiltrates. Laboratory findings included 11<span class="elsevierStyleHsp" style=""></span>300<span class="elsevierStyleHsp" style=""></span>leukocytes/mm<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> (84.5% neutrophils), C-reactive protein 2.41<span class="elsevierStyleHsp" style=""></span>mg/dl, and elevated creatinine (1.4<span class="elsevierStyleHsp" style=""></span>mg/dl), glucose (217<span class="elsevierStyleHsp" style=""></span>mg/dl) and phosphorus (8.1<span class="elsevierStyleHsp" style=""></span>mg/dl), with no other abnormalities. The patient's clinical condition improved significantly after intravenous fluid administration; however, when he was hemodynamically stable, sudden asystolic cardiac arrest occurred. Advanced life support was immediately started but was ineffective and the patient died.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Further investigation showed mild elevation of CK, CK-MB and myoglobin. Reverse transcriptase polymerase chain reaction assay from nasopharyngeal swab samples was positive for H1N1v. The autopsy showed multifocal infiltrates composed mostly of lymphocytes but also some neutrophils, macrophages, plasma cells and eosinophils, associated with myocyte necrosis and ischemia, which was compatible with myocarditis (<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>) and excluded the diagnosis of hypertrophic cardiomyopathy. The lung tissue specimen obtained at autopsy showed diffuse pulmonary vascular congestion and extensive alveolar hemorrhage (<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>). Additionally, multisystem histological changes including the cardiac and pulmonary alterations described above, and tracheobronchial and intestinal involvement associated with viral infection were evident, leading to a definite postmortem diagnosis of fulminant viral myocarditis.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0035" class="elsevierStylePara elsevierViewall">The prevalence of fulminant myocarditis associated with H1N1v is unknown because of the lack of comprehensive screening, with only a handful of case reports and autopsy findings in the literature.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Bratincsak et al. reported four fulminant myocarditis cases associated with H1N1v in children and suggested that the 2009 pandemic influenza virus was more commonly associated with myocarditis than seasonal influenza.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The Japanese pandemic influenza registry reported 15 patients with H1N1v-associated myocarditis, ranging from a child to a man over 70 years old.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> According to a report from Canada, only two of 505 children hospitalized with severe influenza infection had myocarditis.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> There are few individual case reports of fulminant myocarditis from the USA and Europe,<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8–12</span></a> and a single fatal case was reported in a multicenter pediatric study conducted in Spain.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> This is the first report in Portugal.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Common cardiac symptoms of myocarditis include dyspnea, chest discomfort, hypotension, peripheral edema and syncope.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> In the case of myocarditis caused by H1N1v, clinical manifestations vary greatly. Ukimura et al. reported that cardiac dysfunction had progressed rapidly in 12 out of 15 patients, and developed after recovery from flu-like symptoms in two patients. Ten patients with fulminant myocarditis had fatal arrhythmias and/or cardiogenic shock.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Cardiopulmonary arrest as the first cardiac symptom was described in only two patients, as happened with our patient.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Small autopsy-based studies have shown complication rates of myocarditis in fatal cases of 39.4% with Asian flu and 48% with Spanish flu.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> All these fatal cases with myocarditis had severe pneumonia and multiple organ involvement, implying that myocarditis was likely to be a terminally ill state of influenza infection,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> as could have been the case with our patient, according to the histopathological findings on autopsy (<a class="elsevierStyleCrossRefs" href="#fig0005">Figures 1 and 2</a>). By contrast, severe viral pneumonia did not precede myocarditis in the 15 cases reported by Ukimura et al.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Some patients complained only of high fever, without respiratory symptoms before the onset of myocarditis. The findings imply that the H1N1v may have a high affinity for heart tissue in some susceptible patients. In this patient there was initially thought to be an underlying cardiac disease (hypertrophic cardiomyopathy), which could have increased his susceptibility to cardiac complications, but this comorbidity was excluded by histopathology findings. Despite the presence of tachycardia, hypotension and hypothermia secondary to dehydration at admission, the patient was hemodynamically stable immediately before asystolic cardiac arrest and death.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Data on the clinical benefits of antiviral treatment for H1N1v are limited and different authorities have different recommendations. The Hong Kong Hospital Authority Central Committee on Infectious Disease and Emergency Responses (CCIDER) recommend that empirical antiviral treatment be started immediately in patients who are at higher risk for developing complications,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> including those younger than six years, morbidly obese, asthmatic, immunocompromised or pregnant subjects, patients showing no improvement in symptoms 48<span class="elsevierStyleHsp" style=""></span>h after medical treatment and in patients in whom H1N1v infection has been confirmed.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> There are compelling indications for the use of beta blockers and/or angiotensin-converting enzyme inhibitors for the treatment of a subacute phase of the illness; additional supportive intervention is essential as first-line therapy for myocarditis patients with heart failure.</p><p id="par0055" class="elsevierStylePara elsevierViewall">The recent application of intra-aortic balloon pump and/or veno-venous extracorporeal membrane oxygenation (ECMO) in serious cases has yielded good outcomes,<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,16,17</span></a> but in this case, despite aggressive management, circulatory resuscitation was not successful. This patient did not receive antiviral treatment, which has been convincingly shown to decrease morbidity and mortality in H1N1v infection. However, as this was a case of fulminant evolution, with rapid progression of inflammatory infiltration, antiviral treatment probably would not have had sufficient time to be effective.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Early detection of myocarditis in patients during influenza pandemics is difficult, as there are no specific symptoms or signs.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> To avoid misdiagnosis it is essential to determine the characteristic symptoms, signs and laboratory findings of acute myocarditis,<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> but it is also important to remember that it can occur suddenly, without any previous suspicious symptom or sign, as was seen in our patient.</p><p id="par0065" class="elsevierStylePara elsevierViewall">This was the first death in the Portuguese pediatric population during the 2009 H1N1v pandemic, and provided arguments for more stringent indications for antiviral therapy in the context of influenza pandemics.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conclusion</span><p id="par0070" class="elsevierStylePara elsevierViewall">The fulminant form of myocarditis associated with H1N1v may present in the form of fatal arrhythmia, atrioventricular block and/or cardiogenic shock, usually diagnosed in the context of circulatory collapse or autopsy in patients with H1N1v infection, as occurred in this patient.</p><p id="par0075" class="elsevierStylePara elsevierViewall">As the incidence of H1N1v infection continues to rise, physicians should be aware of this rare and potentially fatal complication, since early diagnosis and aggressive supportive measures are essential.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of interest</span><p id="par0080" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "xres251840" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec239439" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres251841" "titulo" => "Resumo" ] 3 => array:2 [ "identificador" => "xpalclavsec239440" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case report" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Conclusion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2011-10-01" "fechaAceptado" => "2011-11-30" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec239439" "palabras" => array:4 [ 0 => "Influenza" 1 => "H1N1" 2 => "Fulminant" 3 => "Myocarditis" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec239440" "palabras" => array:4 [ 0 => "Influenza" 1 => "H1NI" 2 => "Fulminante" 3 => "Miocardite" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Fulminant myocarditis associated with influenza A virus is exceedingly rare, with only a few cases reported in the literature. We describe a previously healthy 10-year-old boy, with a three-day history of flu-like symptoms without antiviral treatment. He was hospitalized with dehydration and hypothermia in the context of persistent vomiting, when he suddenly developed heart failure secondary to fulminant myocarditis. Despite aggressive management, including circulatory support and cardiopulmonary resuscitation measures, the patient died of cardiogenic shock. The postmortem histopathology was compatible with a multisystem viral infection with myocarditis and pulmonary involvement, and H1N1v polymerase chain reaction was positive.</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The prevalence of influenza-associated fulminant myocarditis remains unknown. Findings reported in the literature raise the possibility that the novel H1N1 influenza A virus is more commonly associated with a severe form of myocarditis than previously encountered influenza strains.</p>" ] "pt" => array:2 [ "titulo" => "Resumo" "resumen" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A miocardite fulminante associada ao vírus Influenza A é extremamente rara, com apenas alguns casos relatados na literatura. Descrevemos um rapaz de 10 anos, previamente saudável, com história de sintomas gripais com 3 dias de evolução, sem terapêutica antiviral. Foi internado por desidratação e hipotermia, no contexto de vómitos persistentes após o que, subitamente, desenvolveu insuficiência cardíaca secundária a miocardite fulminante. Apesar da intervenção imediata, incluindo suporte circulatório e reanimação cardiorrespiratória, o doente faleceu por choque cardiogénico. O exame histopatológico <span class="elsevierStyleItalic">post-mortem</span> foi compatível com o diagnóstico de infecção viral multissistémica, com miocardite e envolvimento pulmonar e a PCR para o H1N1<span class="elsevierStyleHsp" style=""></span>v foi positiva.</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A prevalência de miocardite fulminante associada ao vírus Influenza permanece desconhecida. Relatos na literatura levantam a hipótese de o vírus Influenza A H1N1 estar mais frequentemente associado a formas graves de miocardite do que as estirpes sazonais anteriores.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1451 "Ancho" => 966 "Tamanyo" => 374058 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Low (A) and intermediate (B) magnification of pulmonary parenchyma with vascular congestion and multiple foci of alveolar hemorrhage, without associated inflammation.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1436 "Ancho" => 966 "Tamanyo" => 273912 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Intermediate (A) and high (B) magnification of myocardium with multifocal infiltrates composed mostly of lymphocytes but also some neutrophils, macrophages, plasma cells and eosinophils, associated with myocyte necrosis and ischemia.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:17 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fulminant myocarditis associated with pandemic H1N1 influenza A virus in children" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 4 | 12 |
| 2024 October | 55 | 37 | 92 |
| 2024 September | 77 | 22 | 99 |
| 2024 August | 44 | 30 | 74 |
| 2024 July | 40 | 29 | 69 |
| 2024 June | 45 | 23 | 68 |
| 2024 May | 40 | 20 | 60 |
| 2024 April | 28 | 23 | 51 |
| 2024 March | 52 | 16 | 68 |
| 2024 February | 51 | 23 | 74 |
| 2024 January | 62 | 29 | 91 |
| 2023 December | 32 | 27 | 59 |
| 2023 November | 39 | 32 | 71 |
| 2023 October | 33 | 13 | 46 |
| 2023 September | 38 | 24 | 62 |
| 2023 August | 37 | 25 | 62 |
| 2023 July | 31 | 18 | 49 |
| 2023 June | 37 | 15 | 52 |
| 2023 May | 67 | 33 | 100 |
| 2023 April | 44 | 13 | 57 |
| 2023 March | 50 | 22 | 72 |
| 2023 February | 41 | 10 | 51 |
| 2023 January | 46 | 14 | 60 |
| 2022 December | 59 | 31 | 90 |
| 2022 November | 51 | 32 | 83 |
| 2022 October | 34 | 15 | 49 |
| 2022 September | 30 | 27 | 57 |
| 2022 August | 35 | 40 | 75 |
| 2022 July | 44 | 43 | 87 |
| 2022 June | 25 | 24 | 49 |
| 2022 May | 28 | 33 | 61 |
| 2022 April | 42 | 27 | 69 |
| 2022 March | 28 | 35 | 63 |
| 2022 February | 34 | 32 | 66 |
| 2022 January | 42 | 25 | 67 |
| 2021 December | 39 | 30 | 69 |
| 2021 November | 35 | 35 | 70 |
| 2021 October | 51 | 48 | 99 |
| 2021 September | 31 | 23 | 54 |
| 2021 August | 40 | 32 | 72 |
| 2021 July | 34 | 23 | 57 |
| 2021 June | 33 | 19 | 52 |
| 2021 May | 29 | 48 | 77 |
| 2021 April | 66 | 60 | 126 |
| 2021 March | 53 | 15 | 68 |
| 2021 February | 57 | 20 | 77 |
| 2021 January | 32 | 14 | 46 |
| 2020 December | 46 | 17 | 63 |
| 2020 November | 24 | 16 | 40 |
| 2020 October | 34 | 11 | 45 |
| 2020 September | 31 | 12 | 43 |
| 2020 August | 33 | 8 | 41 |
| 2020 July | 63 | 6 | 69 |
| 2020 June | 46 | 9 | 55 |
| 2020 May | 46 | 10 | 56 |
| 2020 April | 59 | 18 | 77 |
| 2020 March | 44 | 19 | 63 |
| 2020 February | 92 | 57 | 149 |
| 2020 January | 41 | 14 | 55 |
| 2019 December | 45 | 8 | 53 |
| 2019 November | 40 | 12 | 52 |
| 2019 October | 45 | 6 | 51 |
| 2019 September | 555 | 7 | 562 |
| 2019 August | 27 | 3 | 30 |
| 2019 July | 41 | 8 | 49 |
| 2019 June | 19 | 8 | 27 |
| 2019 May | 30 | 11 | 41 |
| 2019 April | 29 | 16 | 45 |
| 2019 March | 60 | 7 | 67 |
| 2019 February | 90 | 9 | 99 |
| 2019 January | 65 | 10 | 75 |
| 2018 December | 83 | 7 | 90 |
| 2018 November | 137 | 8 | 145 |
| 2018 October | 222 | 26 | 248 |
| 2018 September | 66 | 7 | 73 |
| 2018 August | 60 | 4 | 64 |
| 2018 July | 35 | 5 | 40 |
| 2018 June | 45 | 8 | 53 |
| 2018 May | 67 | 5 | 72 |
| 2018 April | 44 | 7 | 51 |
| 2018 March | 60 | 7 | 67 |
| 2018 February | 29 | 7 | 36 |
| 2018 January | 55 | 2 | 57 |
| 2017 December | 69 | 3 | 72 |
| 2017 November | 51 | 7 | 58 |
| 2017 October | 43 | 14 | 57 |
| 2017 September | 36 | 18 | 54 |
| 2017 August | 33 | 16 | 49 |
| 2017 July | 20 | 15 | 35 |
| 2017 June | 41 | 33 | 74 |
| 2017 May | 33 | 9 | 42 |
| 2017 April | 22 | 9 | 31 |
| 2017 March | 31 | 15 | 46 |
| 2017 February | 39 | 7 | 46 |
| 2017 January | 34 | 1 | 35 |
| 2016 December | 38 | 10 | 48 |
| 2016 November | 25 | 5 | 30 |
| 2016 October | 20 | 4 | 24 |
| 2016 September | 19 | 2 | 21 |
| 2016 August | 4 | 5 | 9 |
| 2016 July | 4 | 3 | 7 |
| 2016 June | 8 | 1 | 9 |
| 2016 May | 14 | 3 | 17 |
| 2016 April | 13 | 29 | 42 |
| 2016 March | 7 | 9 | 16 |
| 2016 February | 9 | 11 | 20 |
| 2016 January | 12 | 11 | 23 |
| 2015 December | 14 | 10 | 24 |
| 2015 November | 11 | 8 | 19 |
| 2015 October | 16 | 12 | 28 |
| 2015 September | 22 | 3 | 25 |
| 2015 August | 21 | 5 | 26 |
| 2015 July | 10 | 1 | 11 |
| 2015 June | 14 | 3 | 17 |
| 2015 May | 9 | 2 | 11 |
| 2015 April | 20 | 4 | 24 |
| 2015 March | 10 | 2 | 12 |
| 2015 February | 14 | 0 | 14 |
| 2015 January | 10 | 5 | 15 |
| 2014 December | 20 | 7 | 27 |
| 2014 November | 6 | 2 | 8 |
| 2014 October | 16 | 7 | 23 |
| 2014 September | 26 | 15 | 41 |
| 2014 August | 20 | 4 | 24 |
| 2014 July | 21 | 7 | 28 |
| 2014 June | 20 | 5 | 25 |
| 2014 May | 11 | 4 | 15 |
| 2014 April | 14 | 3 | 17 |
| 2014 March | 28 | 11 | 39 |
| 2014 February | 37 | 6 | 43 |
| 2014 January | 30 | 10 | 40 |
| 2013 December | 28 | 8 | 36 |
| 2013 November | 28 | 8 | 36 |
| 2013 October | 30 | 10 | 40 |
| 2013 September | 29 | 9 | 38 |
| 2013 August | 33 | 15 | 48 |
| 2013 July | 43 | 16 | 59 |
| 2013 June | 39 | 6 | 45 |
| 2013 May | 44 | 9 | 53 |
| 2013 April | 45 | 16 | 61 |
| 2013 March | 31 | 10 | 41 |
| 2013 February | 35 | 12 | 47 |
| 2013 January | 33 | 10 | 43 |
| 2012 December | 26 | 10 | 36 |
| 2012 November | 18 | 7 | 25 |
| 2012 October | 2 | 2 | 4 |
| 2012 September | 3 | 3 | 6 |
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