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Invasive aspergillosis manifesting as retinal necrosis in a patient treated with ruxolitinib
Necrosis retiniana como manifestación de aspergilosis invasiva en un paciente tratado con ruxolitinib
A. Moruno-Rodrígueza,
, J.L. Sánchez-Vicenteb, T. Rueda-Ruedac, B. Lechón-Caballeroc, A. Muñoz-Moralesd, F. López-Herreroe
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a Sección de Uveítis, Departamento de Oftalmología, Hospital Universitario Virgen del Rocío, Sevilla, Spain
b Sección de Retina Quirúrgica, Departamento de Oftalmología, Hospital Universitario Virgen del Rocío, Sevilla, Spain
c Sección General, Departamento de Oftalmología, Hospital Universitario Virgen del Rocío, Sevilla, Spain
d Sección de Córnea, Departamento de Oftalmología, Hospital Universitario Virgen del Rocío, Sevilla, Spain
e Sección de Retina Médica, Departamento de Oftalmología, Hospital Universitario Virgen del Rocío, Sevilla, Spain
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B) Ojo izquierdo afectado con necrosis retiniana en el cuadrante nasal inferior, asociada a hemorragias y constricción focal de las arterias retinianas. C y D) Intensa oclusión arterial en la angiofluoresceingrafía.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. Moruno-Rodríguez, J.L. Sánchez-Vicente, T. Rueda-Rueda, B. Lechón-Caballero, A. Muñoz-Morales, F. López-Herrero" "autores" => array:6 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "Moruno-Rodríguez" ] 1 => array:2 [ "nombre" => "J.L." "apellidos" => "Sánchez-Vicente" ] 2 => array:2 [ "nombre" => "T." "apellidos" => "Rueda-Rueda" ] 3 => array:2 [ "nombre" => "B." "apellidos" => "Lechón-Caballero" ] 4 => array:2 [ "nombre" => "A." "apellidos" => "Muñoz-Morales" ] 5 => array:2 [ "nombre" => "F." 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(B) Axial CT section at the lower eyelid level showing periorbital tissues edema at the preseptal level. (C) CT coronal section showing edematization of periorbital soft tissues in the external canthus and right cheek. (D) Right eye eyelid photography showing fibrinoid necrosis plaques in both eyelids. (E) Appearance after surgical debridement of areas of fibrinoid necrosis and betadine net lining. (The authors have the informed consent of the patient for publishing the images that illustrate this article.).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "I.A. Placinta, E. España-Gregori, A. Rodrigo-Hernández, C. Martínez-Rubio, J. Safont-Albert, M.Á. Bort-Martí" "autores" => array:6 [ 0 => array:2 [ "nombre" => "I.A." "apellidos" => "Placinta" ] 1 => array:2 [ "nombre" => "E." "apellidos" => "España-Gregori" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Rodrigo-Hernández" ] 3 => array:2 [ "nombre" => "C." 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Moruno-Rodríguez, J.L. Sánchez-Vicente, T. Rueda-Rueda, B. Lechón-Caballero, A. Muñoz-Morales, F. López-Herrero" "autores" => array:6 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "Moruno-Rodríguez" "email" => array:1 [ 0 => "antoniomoruno_89@hotmail.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" => "J.L." "apellidos" => "Sánchez-Vicente" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "T." "apellidos" => "Rueda-Rueda" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "B." 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"apellidos" => "López-Herrero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Sección de Uveítis, Departamento de Oftalmología, Hospital Universitario Virgen del Rocío, Sevilla, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Sección de Retina Quirúrgica, Departamento de Oftalmología, Hospital Universitario Virgen del Rocío, Sevilla, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Sección General, Departamento de Oftalmología, Hospital Universitario Virgen del Rocío, Sevilla, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Sección de Córnea, Departamento de Oftalmología, Hospital Universitario Virgen del Rocío, Sevilla, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Sección de Retina Médica, Departamento de Oftalmología, Hospital Universitario Virgen del Rocío, Sevilla, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Necrosis retiniana como manifestación de aspergilosis invasiva en un paciente tratado con ruxolitinib" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1383 "Ancho" => 1255 "Tamanyo" => 151963 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Retinal compromise on day 11.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Invasive aspergillosis (IA) is a severe opportunistic infection that typically affects immunodepressed patients. Classic risk factors include chronic neutropenia, hematopoietic stem cell transplant, solid organ transplant, prolonged treatment with high corticoid doses, hematological tumors, cytotoxic chemotherapy, the acquired immunodeficiency syndrome and chronic granulomatous disease.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In recent years, a significant increase in the risk population has occurred<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2,3</span></a> as a consequence of the use of new medicaments and treatment strategies as well as the increase of chronic diseases.</p><p id="par0015" class="elsevierStylePara elsevierViewall">IA mortality depends on the clinic form and the type of host, although it could exceed 50%.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Ruxolitinib (Jakavi<span class="elsevierStyleSup">®</span>, Novartis Pharmaceutical, Nuremberg, Germany) is a selective Janus kinase inhibitor (JAK 1 and 2) recently approved for treating myeloproliferative diseases.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Several cases have been published recently reporting opportunistic infections in patients treated with ruxolitinib, constituting increasing evidence that says drug could have an immunosuppressive effect, diminishing control over latent infections and increasing the risk of reactivating opportunistic infections.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The case of a 30-year-old male with acute myeloblastic leukemia and secondary myelodysplastic syndrome is presented. The patient developed a graft-versus-host disease treated with ruxolitinib. The patient developed IA with cerebral and ocular compromise in the form of sudden retinal necrosis.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Clinic case report</span><p id="par0035" class="elsevierStylePara elsevierViewall">Male, 30, with acute myeloblastic leukemia in complete remission with minimum negative residual disease and secondary myelodysplastic syndrome. In July 2017 (3 months before being admitted) he developed a cutaneous and digestive graft-versus-host disease in second line treatment with ruxolitinib from August 1, 2017 (tacrolimus/ruxolitinib/budesonide/prednisone/mesenchymal cells). In addition to said treatment, the patient was being administered loperamide hydrochloride (Fortasec<span class="elsevierStyleSup">®</span>), trimethoprim sulfamethoxazole (Cotrimoxazol<span class="elsevierStyleSup">®</span>) (400<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>80<span class="elsevierStyleHsp" style=""></span>mg, Monday, Wednesday and Friday), posaconazole 300<span class="elsevierStyleHsp" style=""></span>mg/day, omeprazole 20<span class="elsevierStyleHsp" style=""></span>mg/day and insulin.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The patient was admitted October 6, 2017 due to bilateral mixed etiology pneumonia by <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> (isolated in blood culture and sputum) and <span class="elsevierStyleItalic">Aspergillus</span> sp. (positive culture isolation and AGA), treated with cefepime and ciprofloxacin (on the basis of antibiogram). In addition, the patient received amphotericin B.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The fourth day of admission the patient consulted due to temporal visual field loss in the left eye. Ocular fundus showed periarteial homogeneous whitish edema extending from the optic disk toward the nasal-inferior periphery. In addition, numerous flame hemorrhages and filiform arteries with focal constrictions could be observed. Macular compromise or vitritis were absent. The right eye had normal appearance (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). As the patient had low risk for cytomegalovirus which, in addition, had never been replicated, viral herpetic retinitis was suspected, accordingly intravenous acyclovir was added and study of clinic was carried out with polymerase chain reaction (PCR) for herpes simplex, herpes zoster, Epstein-Barr virus and cytomegalovirus, all of which gave negative results.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Fluorescein angiography (FAG) taken the following day showed intense ischemia mainly compromising the nasal and inferior retina with associated intraretinal hemorrhages (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><p id="par0055" class="elsevierStylePara elsevierViewall">One week after the first examination (11th day of hospital stay), an extension of the ischemia area was observed involving the papilla and central macular, without detecting vitritis by means of ophthalmoscopy (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The right eye remained unaffected. Optical coherence tomography (OCT) revealed compromise of the inner retinal layers, presence of subretinal hypopyon and cells in the vitreous (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). Due to the lack of response to systemic treatment, intravitreal treatment was initiated with gancyclovir, foscarnet and amphotericin B. Aqueous humor samples were taken through aspiration as well as vitreous samples through vitrectomy for PCR and culturing, which gave negative results for herpes simplex, herpes zoster, Epstein-Barr virus, cytomegalovirus and <span class="elsevierStyleItalic">Aspergillus.</span></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Cerebral magnetic resonance (MR) identified focal ischemic lesions in various evolution stages, with subcortical location in both brain hemispheres with parietal predominance. Some of said lesions exhibited cortical hemorrhagic transformation evidencing probable septic embolism (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). The microbiological study of the cerebrospinal fluid obtained through lumbar puncture was negative.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Despite treatment, on the 20th day after admission the ophthalmological clinic worsened, compromising the posterior pole and the 4 retinal quadrants, respecting some isolated areas in the periphery. A new sputum culture identified <span class="elsevierStyleItalic">Aspergillus niger</span> and <span class="elsevierStyleItalic">Aspergillus flavus.</span></p><p id="par0070" class="elsevierStylePara elsevierViewall">In the absence of a certainty diagnostic for the ocular disorder, a diagnostic vitrectomy with retinal biopsy was performed on the 24th day after admission which confirmed the presence of <span class="elsevierStyleItalic">Aspergillus</span> in the retina. It was then decided to associate systemic and intravitreal voriconazole.</p><p id="par0075" class="elsevierStylePara elsevierViewall">One week after vitrectomy (31st day after admission), the patient exhibited an extensive frontal lobe acute lobar hematoma without analytic justification and therefore probably related to the systemic fungal infection. Despite surgical evacuation, re-bleedings occurred. Computerized axial tomography (CAT) showed a new ischemic lesions with mass effect and subfalcine herniation. The patient died 2 days after the cerebral hemorrhagic process.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0080" class="elsevierStylePara elsevierViewall">Ruxolitinib is an oral inhibitor of JAK1 and JAK2 approved for treatment of high and medium risk myelofibrosis and high risk polycythemia. Association between the use of ruxolitinib and the risk of infections could be explained by several pathophysiological mechanisms. On the one hand, it interferes with cytokins signaling and growth factors involved in immunological mechanisms. In addition, it diminishes pro-inflammatory cytokins levels in patients with myelofibrosis. On the other hand, it interferes with T-cell regulation and alters dendritic cell function, altering CD4+ and CD8+ activation. Similarly, it inhibits the function of the <span class="elsevierStyleItalic">natural killer</span> cells in patients with Philadelphia-negative myeloproliferative neoplasia.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6,7</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Some authors reported lower efficacy of anti-infectious medicaments in patients treated with ruxolitinib.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Recently, reports on opportunistic infections are increasing, including mycosis, in patients treated with medicaments that interfere with the immune system signaling pathways such as BTK, JAK/STAT and P13K.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">The most frequent local clinic forms of IA take place in lungs and paranasal sinuses. With vascular dissemination, the skin, central nervous system, eyes, liver and other structures could be compromised. When the central nervous system is thus compromised, mortality is above 80%.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">After reviewing the literature and barring errors, the present is the first described case of retinal necrosis due to <span class="elsevierStyleItalic">Aspergillus</span> in patients treated with ruxolitinib. Clinic exhibited extremely fast evolution with rapid extension of necrosis regardless of systemic and intravitreal treatment as well as prophylactic treatment with posaconazole. This lead the authors to think that treatments with ruxolitinib could compromise the efficacy of anti-infectious medicaments.</p><p id="par0105" class="elsevierStylePara elsevierViewall">The intense ischemia of the clinic and the alteration of arterial perfusion demonstrated in FAG evidenced the hematogenous extension of the fungus. An additional characteristic of the infection was the presence of subretinal hypopyon observed in OCT, and when the retinal biopsy was taken, abundant inflammatory content was observed in the subretinal space. The retinal biopsy provided the confirmation diagnostic due to the fact that cultures as well as PCR in aqueous humor and vitreous were negative.</p><p id="par0110" class="elsevierStylePara elsevierViewall">In addition to the ocular clinic, the patient exhibited central nervous system compromise, where septic focal points arose and subsequently caused the hemorrhages that led to demise.</p><p id="par0115" class="elsevierStylePara elsevierViewall">Recently, there has been an increase of publications reporting fungal infections in patients with hematological cancers regarded as low risk for this type of infections and were being treated with JAK inhibitors.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6–9</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Accordingly, the possibility of said types of infections should be considered in said patients, utilizing invasive diagnostic methods like retinal biopsy and establishing early and intensive treatment due to the possibility of extremely fast evolution with grave consequences. In addition, efficient prophylactic treatments preventing the appearance of said infections should be carried out. A further option would be the possibility of suspending said medicaments if the baseline clinic allows.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conflict of interests</span><p id="par0125" class="elsevierStylePara elsevierViewall">No conflict of interests was declared by the authors.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres1184808" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1104919" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1184809" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1104918" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Clinic case report" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Conflict of interests" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-10-15" "fechaAceptado" => "2018-12-15" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1104919" "palabras" => array:6 [ 0 => "<span class="elsevierStyleItalic">Aspergillus</span>" 1 => "Retinal necrosis" 2 => "Ruxolitinib" 3 => "Graft-versus-host disease" 4 => "Acute myeloblastic leukemia" 5 => "Myelodysplastic syndrome" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1104918" "palabras" => array:6 [ 0 => "<span class="elsevierStyleItalic">Aspergillus</span>" 1 => "Necrosis retiniana" 2 => "Ruxolitinib" 3 => "Enfermedad injerto contra huésped" 4 => "Leucemia mieloblástica aguda" 5 => "Síndrome mielodisplásico" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A 30 year-old man with acute myeloblastic leukemia and secondary myelodysplastic syndrome developed graft-versus-host disease. The patient was treated with ruxolitinib. After being treated for 3 months with ruxolitinib, an inhibitor of Janus kinase, he developed <span class="elsevierStyleItalic">Aspergillus</span> retinal necrosis resistant to common treatment.</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Treatment with Janus kinase inhibitors may lead to an increased incidence of opportunistic infections. Janus kinase inhibitor administration may result in poor treatment efficacy.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Varón de 30 años de edad con leucemia mieloblástica aguda y síndrome mielodisplásico secundario que desarrolló una enfermedad injerto contra huésped. El paciente fue tratado con ruxolitinib, un inhibidor de la Janus quinasa. A los 3 meses de haber iniciado el tratamiento se produjo una necrosis retiniana por <span class="elsevierStyleItalic">Aspergillus</span>, sin respuesta al tratamiento.</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El tratamiento con inhibidores de la Janus quinasa favorecería un aumento en la incidencia de infecciones oportunistas. El uso de estos fármacos podría dar lugar a una menor eficacia de los tratamientos empleados.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Moruno-Rodríguez A, Sánchez-Vicente JL, Rueda-Rueda T, Lechón-Caballero B, Muñoz-Morales A, López-Herrero F. Necrosis retiniana como manifestación de aspergilosis invasiva en un paciente tratado con ruxolitinib. Arch Soc Esp Oftalmol. 2019;94:237–241.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 980 "Ancho" => 1305 "Tamanyo" => 111902 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">(A) Uncompromised right eye. (B) Left eye compromised with retinal necrosis in the inferior lower quadrant, associated to hemorrhages and focal constriction of retinal arteries. (C and D) Intense arterial occlusion in angiofluoresceingraph.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1383 "Ancho" => 1255 "Tamanyo" => 151963 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Retinal compromise on day 11.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1070 "Ancho" => 1305 "Tamanyo" => 166960 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">(A) Nuclear magnetic resonance showing lesions in both hemisphere indicating septic focal points. (B) Left eye OCT showing the presence of cells in the posterior vitreous (+), compromise of inner retinal layers (×) due to the hematogenous dispersion of the infection, and subretinal hypopyon (−).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Invasive pulmonary aspergillosis in a patient with metastatic non-small cell lung cancer after treatment with gefitinib" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Park" 1 => "S. Park" 2 => "H. Choi" 3 => "J.Y. Park" 4 => "H.S. Lim" 5 => "M.J. Park" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3904/kjim.2015.276" "Revista" => array:6 [ "tituloSerie" => "Korean J Intern Med" "fecha" => "2018" "volumen" => "33" "paginaInicial" => "211" "paginaFinal" => "213" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27889954" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0060" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Galactomannan use in clinical practice: providing free testing is not the answer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.S. Dos Santos" 1 => "D.M. Hermes" 2 => "A.C. Pasqualotto" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bjid.2017.11.002" "Revista" => array:6 [ "tituloSerie" => "Braz J Infect Dis" "fecha" => "2018" "volumen" => "22" "paginaInicial" => "37" "paginaFinal" => "40" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29172032" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0065" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Advances in the serological diagnosis of invasive <span class="elsevierStyleItalic">Aspergillus</span> infections in patients with haematological disorders" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J. Maertens" 1 => "K. Theunissen" 2 => "T. Lodewyck" 3 => "K. Lagrou" 4 => "J. van Eldere" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Mycoses" "fecha" => "2007" "volumen" => "50" "numero" => "Suppl. 1" "paginaInicial" => "2" "paginaFinal" => "17" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0070" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Aspergillosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "B.H. Segal" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "N Engl J Med" "fecha" => "2009" "volumen" => "360" "paginaInicial" => "1870" "paginaFinal" => "1884" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0075" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Activity of therapeutic JAK 1/2 blockade in graft-versus-host disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Spoerl" 1 => "N.R. Mathew" 2 => "M. Bscheider" 3 => "A. Schmitt-Graeff" 4 => "S. Chen" 5 => "T. Mueller" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Blood" "fecha" => "2014" "volumen" => "123" "paginaInicial" => "3832" "paginaFinal" => "3842" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0080" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ruxolitinib-associated infections: a systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "F. Lussana" 1 => "M. Cattaneo" 2 => "A. Rambaldi" 3 => "A. Squizzato" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ajh.24976" "Revista" => array:5 [ "tituloSerie" => "Am J Hematol" "fecha" => "2018" "volumen" => "93" "paginaInicial" => "339" "paginaFinal" => "347" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0085" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ruxolitinib is a potent immunosuppressive compound: is it time for anti-infective prophylaxis?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. Heine" 1 => "P. Brossart" 2 => "D. Wolf" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Blood" "fecha" => "2013" "volumen" => "122" "paginaInicial" => "3843" "paginaFinal" => "3844" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0090" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pulmonary cryptococcosis in a ruxolitinib-treated patient with primary myelofibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Hirano" 1 => "M. Yamasaki" 2 => "N. Saito" 3 => "K. Iwato" 4 => "W. Daido" 5 => "K. Funaishi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.rmcr.2017.06.015" "Revista" => array:6 [ "tituloSerie" => "Respir Med Case Rep" "fecha" => "2017" "volumen" => "22" "paginaInicial" => "87" "paginaFinal" => "90" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28721333" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0095" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fulminant <span class="elsevierStyleItalic">Cryptococcus neoformans</span> infection with fatal pericardial tamponade in a patient with chronic myelomonocytic leukaemia who was treated with ruxolitinib: case report and review of fungal pericarditis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J. Liu" 1 => "E. Mouhayar" 2 => "J.J. Tarrand" 3 => "D.P. Kontoyiannis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/myc.12735" "Revista" => array:6 [ "tituloSerie" => "Mycoses" "fecha" => "2018" "volumen" => "61" "paginaInicial" => "245" "paginaFinal" => "255" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29280197" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0100" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "[in Spanish]" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "[Aspergillosis. Clinical forms and treatment]" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J. Fortún" 1 => "Y. Meije" 2 => "G. Fresco" 3 => "S. Moreno" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Enferm Infecc Microbiol Clin" "fecha" => "2012" "volumen" => "30" "paginaInicial" => "201" "paginaFinal" => "208" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735794/0000009400000005/v1_201904290704/S2173579419300350/v1_201904290704/en/main.assets" "Apartado" => array:4 [ "identificador" => "5812" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Short communications" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735794/0000009400000005/v1_201904290704/S2173579419300350/v1_201904290704/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173579419300350?idApp=UINPBA00004N" ]
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