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Cerebral aspergillosis in an HIV-infected patient: Unsuccessful outcome despite combined antifungal therapy
Aspergilosis cerebral en un paciente con infección por el VIH: evolución desfavorable a pesar de tratamiento antifúngico combinado
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"identificador" => "aff1" ] ] ] 1 => array:3 [ "nombre" => "Nuria" "apellidos" => "Fernández" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff1" ] ] ] 2 => array:3 [ "nombre" => "Josefina" "apellidos" => "Ayats" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff2" ] ] ] 3 => array:4 [ "nombre" => "Miguel" "apellidos" => "Santin" "email" => array:1 [ 0 => "msantin@bellvitgehospital.cat" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor1" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Enfermedades Infecciosas, IDIBELL, Hospital Universitari de Bellvitge, Universidad de Barcelona, L’Hospitalet de Llobregat, Barcelona, España" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff1" ] 1 => array:3 [ "entidad" => "Servicio de Microbiología, IDIBELL, Hospital Universitari de Bellvitge, Universidad de Barcelona, L’Hospitalet de Llobregat, Barcelona, España" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff2" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "⁎" "correspondencia" => "Autor para correspondencia." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "<span class="elsevierStyleItalic">Aspergilosis cerebral en un paciente con infección por el VIH: evolución desfavorable a pesar de tratamiento antifúngico combinado</span>" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig1" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 555 "Ancho" => 1300 "Tamanyo" => 122555 ] ] "descripcion" => array:1 [ "es" => "<p class="elsevierStyleSimplePara elsevierViewall">Evolution. A: RMI at PML+IRIS diagnosis. B: CT scan showing one ring-enhancing lesion with perifocal edema in the left parieto-occipital lobe. C: multiple lesions illustrating therapeutic failure.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p class="elsevierStylePara elsevierViewall">Central nervous system (CNS) aspergillosis is the most serious clinical form of invasive aspergillosis and results in substantial mortality, approaching 100% of affected persons<a class="elsevierStyleCrossRef" href="#bib1"><span class="elsevierStyleSup">1</span></a>. The introduction of new antifungal agents, such as voriconazole, a novel triazole, and echinocandins, a new family of antifungals, has generated new treatment expectancies for invasive aspergillosis. Here we report a fatal case of CNS aspergillosis in an AIDS patient treated unsuccessfully with a combination of systemic voriconazole and caspofungin, as well as intralesional amphotericin B.</p><p class="elsevierStylePara elsevierViewall">A 47-year-old HIV-seropositive man, former intravenous drug-user, was admitted for bilateral cavitated pneumonia. He had been treated with combined antiretroviral therapy (cART) for the previous 6 months (emtricitabine, tenofovir and lopinavir/ritonavir). Six weeks earlier he had been diagnosed with progressive multifocal leukoencephalopathy (PML) as an expression of immune reconstitution inflammatory syndrome (IRIS) (<a class="elsevierStyleCrossRef" href="#fig1">Figure 1</a>A). High-dose corticosteroid treatment was initiated. After 4 weeks of treatment with tapered doses of corticosteroids, chest pain, shortness of breath, and bradypsychia developed. Physical examination on admission revealed temperature 38.3<span class="elsevierStyleHsp" style=""></span>°C, respiratory rate of 32 per min, lethargy, global aphasia and slight upper right limb paresis. A chest radiograph showed bilateral cavitated pulmonary consolidations. The patient's CD4 count was 22<span class="elsevierStyleHsp" style=""></span>cells/μl. Unenhanced brain CT study showed no changes with respect to a scan carried out at previous admission. Levofloxacin (500<span class="elsevierStyleHsp" style=""></span>mg/day IV) and ceftriaxone (1<span class="elsevierStyleHsp" style=""></span>g/day IV) were given empirically. Blood cultures and pneumococcal and legionella antigen testing in urine were negative. Three days later the patient presented seizures. A new contrast-enhanced CT scan revealed a ring-enhancing lesion with perifocal edema in the left parieto-occipital lobe (<a class="elsevierStyleCrossRef" href="#fig1">Figure 1</a>B). CT-guided needle puncture of one pulmonary lesion was performed, but pathology and cultures of the specimen yielded no positive results. A specimen obtained by CT-guided stereotaxic biopsy of the cerebral abscess revealed septated hyphae on KOH stain; <span class="elsevierStyleItalic">Aspergillus fumigatus</span> grew in culture. A diagnosis of necrotizing bilateral pneumonia with CNS involvement by <span class="elsevierStyleItalic">A. fumigatus</span> was established. The paraventricular location of the abscess precluded surgical excision; voriconazole and caspofungin at doses of 400<span class="elsevierStyleHsp" style=""></span>mg/12<span class="elsevierStyleHsp" style=""></span>h and 70<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h, respectively, were started. A new CT scan performed 11 days after starting treatment showed new lesions, and <span class="elsevierStyleItalic">A. fumigatus</span> was recovered from the aspirated material. One ml (0.5<span class="elsevierStyleHsp" style=""></span>mg) of amphotericin B deoxycholate was instilled into the two largest lesions, but the patient's condition deteriorated and new lesions were seen in another CT scan (<a class="elsevierStyleCrossRef" href="#fig1">Figure 1</a>C). Thus, treatment was finally withdrawn and the patient died 78 days after the diagnosis. An autopsy was not performed.</p><elsevierMultimedia ident="fig1"></elsevierMultimedia><p class="elsevierStylePara elsevierViewall">The results of treatment for CNS aspergillosis are usually discouraging, and short-term outcome is fatal<a class="elsevierStyleCrossRef" href="#bib1"><span class="elsevierStyleSup">1</span></a>. In a retrospective review of invasive aspergillosis, only 9% of patients with CNS involvement achieved partial or complete response with amphotericin B- or itraconazole-based therapy<a class="elsevierStyleCrossRef" href="#bib2"><span class="elsevierStyleSup">2</span></a>.</p><p class="elsevierStylePara elsevierViewall">Voriconazole is a new broad-spectrum triazole with good in vitro activity against <span class="elsevierStyleItalic">Aspergillus</span> species<a class="elsevierStyleCrossRefs" href="#bib3"><span class="elsevierStyleSup">3,4</span></a>. The favorable CNS penetration in humans makes voriconazole a promising option for the treatment of aspergillosis affecting the CNS<a class="elsevierStyleCrossRef" href="#bib5"><span class="elsevierStyleSup">5</span></a>. The largest study of voriconazole for CNS aspergillosis reported to date is a retrospective study of 81 patients from clinical trials and compassionate-use programs<a class="elsevierStyleCrossRef" href="#bib6"><span class="elsevierStyleSup">6</span></a>. Overall, partial or complete response was achieved in 35% of patients. The prognosis of CNS aspergillosis among AIDS patients seems to be even worse. Thirty-six cases, including ours, have been reported to date in the English literature<a class="elsevierStyleCrossRefs" href="#bib7"><span class="elsevierStyleSup">7–9</span></a>. Antifungal treatment failed in all but one case. Three patients were treated with voriconazole: 2 did not respond, and although the other did, he ultimately died of invasive cytomegalovirus infection. Our patient was treated with a combination of voriconazole and caspofungin, based on favorable published data<a class="elsevierStyleCrossRef" href="#bib10"><span class="elsevierStyleSup">10</span></a>; despite this combined treatment, the disease progressed and the patient's clinical condition deteriorated. There were no overt factors, such as under-dosage, drug interactions, or poor gastrointestinal absorption that might have compromised the response to treatment. Unfortunately, plasma and CSF voriconazole concentrations, which might have been of value in evaluating this case, were not available.</p><p class="elsevierStylePara elsevierViewall">In summary, the case reported illustrates the dismal prognosis of CNS aspergillosis. Despite the promising results reported with the newest antifungal agents, treatment of CNS aspergillosis remains ineffective in the majority of cases. Lastly, it is important to underline the limitations of case reports to gather medical evidence; cohort series or randomized clinical trials should be designed for this purpose, although in the case of cerebral aspergillosis, these studies are difficult to perform.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig1" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 555 "Ancho" => 1300 "Tamanyo" => 122555 ] ] "descripcion" => array:1 [ "es" => "<p class="elsevierStyleSimplePara elsevierViewall">Evolution. A: RMI at PML+IRIS diagnosis. B: CT scan showing one ring-enhancing lesion with perifocal edema in the left parieto-occipital lobe. C: multiple lesions illustrating therapeutic failure.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Aspergillosis case-fatality rate" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S.-J. Lin" 1 => "J. Schranz" 2 => "S.M. Teutsch" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/318483" "Revista" => array:6 [ "tituloSerie" => "Clin Infect Dis" "fecha" => "2001" "volumen" => "32" "paginaInicial" => "358" "paginaFinal" => "366" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11170942" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Invasive aspergillosis: disease spectrum, treatment practices, and outcomes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "T.F. Patterson" 1 => "W.R. Kirkpatrick" 2 => "M. White" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Medicine" "fecha" => "2000" "volumen" => "79" "paginaInicial" => "250" "paginaFinal" => "260" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10941354" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "D.W. Denning" 1 => "P. Ribaud" 2 => "N. Milpied" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/324620" "Revista" => array:6 [ "tituloSerie" => "Clin Infect Dis" "fecha" => "2002" "volumen" => "34" "paginaInicial" => "563" "paginaFinal" => "571" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11807679" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib4" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Voriconazole versus amphotenicin B for primary therapy of invasive aspergillosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "R. Herbrecht" 1 => "W.D. Denning" 2 => "T.F. Patterson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa020191" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2002" "volumen" => "347" "paginaInicial" => "408" "paginaFinal" => "415" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12167683" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib5" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Voriconazole concentrations in the cerebrospinal fluid and brain tissue of guinea pigs and immunocompromised patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "I. Lutsar" 1 => "S. Roffey" 2 => "P. Troke" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/377131" "Revista" => array:6 [ "tituloSerie" => "Clin Infect Dis" "fecha" => "2003" "volumen" => "37" "paginaInicial" => "728" "paginaFinal" => "732" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12942409" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib6" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Improved outcome in central nervous system aspergillosis using voriconazole treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "S. Schwartz" 1 => "M. Ruhnke" 2 => "P. Ribaud" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Blood" "fecha" => "2005" "volumen" => "106" "paginaInicial" => "2641" "paginaFinal" => "2645" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib7" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Central nervous system aspergillosis in patients with human immunodeficiency virus infection: report of six cases and review" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "E. Mylonakis" 1 => "M. Paliou" 2 => "P. Sax" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Medicine" "fecha" => "2000" "volumen" => "79" "paginaInicial" => "269" "paginaFinal" => "280" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib8" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Emergence of invasive cerebral aspergillosis in an HIV-positive patient on voriconazole therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "S.J. Van Hal" 1 => "K. Clezy" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1468-1293.2005.00256.x" "Revista" => array:6 [ "tituloSerie" => "HIV Medicine" "fecha" => "2005" "volumen" => "6" "paginaInicial" => "45" "paginaFinal" => "46" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15670252" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib9" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cerebral aspergillosis due to <span class="elsevierStyleItalic">Aspergillus fumigatus</span> in AIDS patient: first culture-proven case reported in Brazil" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "J. Vidal" 1 => "R. Dauar" 2 => "M. Melhem" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "/S0036-46652005000300009" "Revista" => array:6 [ "tituloSerie" => "Rev Inst Med Trop S Paulo" "fecha" => "2005" "volumen" => "47" "paginaInicial" => "161" "paginaFinal" => "165" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16021291" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib10" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Combination antifungal therapy for invasive aspergillosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "K.A. Marr" 1 => "M. Boeckh" 2 => "R.A. Carter" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Infect Dis" "fecha" => "2004" "volumen" => "39" "paginaInicial" => "797" "paginaFinal" => "802" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "es" "url" => "/0213005X/0000002700000003/v1_201305090133/S0213005X0800044X/v1_201305090133/es/main.assets" "Apartado" => array:4 [ "identificador" => "8691" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Cartas científicas" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/0213005X/0000002700000003/v1_201305090133/S0213005X0800044X/v1_201305090133/es/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0213005X0800044X?idApp=UINPBA00004N" ]
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| 2022 Diciembre | 24 | 4 | 28 |
| 2022 Noviembre | 24 | 11 | 35 |
| 2022 Octubre | 13 | 5 | 18 |
| 2022 Septiembre | 20 | 8 | 28 |
| 2022 Agosto | 24 | 8 | 32 |
| 2022 Julio | 18 | 9 | 27 |
| 2022 Junio | 15 | 7 | 22 |
| 2022 Mayo | 11 | 6 | 17 |
| 2022 Abril | 26 | 11 | 37 |
| 2022 Marzo | 27 | 9 | 36 |
| 2022 Febrero | 24 | 3 | 27 |
| 2022 Enero | 29 | 7 | 36 |
| 2021 Diciembre | 21 | 8 | 29 |
| 2021 Noviembre | 16 | 8 | 24 |
| 2021 Octubre | 25 | 5 | 30 |
| 2021 Septiembre | 13 | 6 | 19 |
| 2021 Agosto | 9 | 7 | 16 |
| 2021 Julio | 17 | 5 | 22 |
| 2021 Junio | 19 | 5 | 24 |
| 2021 Mayo | 17 | 7 | 24 |
| 2021 Abril | 21 | 7 | 28 |
| 2021 Marzo | 32 | 8 | 40 |
| 2021 Febrero | 23 | 5 | 28 |
| 2021 Enero | 17 | 6 | 23 |
| 2020 Diciembre | 11 | 11 | 22 |
| 2020 Noviembre | 11 | 12 | 23 |
| 2020 Octubre | 8 | 6 | 14 |
| 2020 Septiembre | 18 | 6 | 24 |
| 2020 Agosto | 9 | 6 | 15 |
| 2020 Julio | 11 | 7 | 18 |
| 2020 Junio | 11 | 12 | 23 |
| 2020 Mayo | 9 | 3 | 12 |
| 2020 Abril | 14 | 4 | 18 |
| 2020 Marzo | 15 | 1 | 16 |
| 2020 Febrero | 12 | 5 | 17 |
| 2020 Enero | 12 | 3 | 15 |
| 2019 Diciembre | 18 | 10 | 28 |
| 2019 Noviembre | 8 | 5 | 13 |
| 2019 Octubre | 7 | 1 | 8 |
| 2019 Septiembre | 6 | 4 | 10 |
| 2019 Agosto | 10 | 2 | 12 |
| 2019 Julio | 13 | 9 | 22 |
| 2019 Junio | 36 | 24 | 60 |
| 2019 Mayo | 80 | 29 | 109 |
| 2019 Abril | 42 | 8 | 50 |
| 2019 Marzo | 6 | 5 | 11 |
| 2019 Febrero | 8 | 9 | 17 |
| 2019 Enero | 8 | 1 | 9 |
| 2018 Diciembre | 11 | 5 | 16 |
| 2018 Noviembre | 19 | 12 | 31 |
| 2018 Octubre | 32 | 6 | 38 |
| 2018 Septiembre | 9 | 4 | 13 |
| 2018 Agosto | 5 | 1 | 6 |
| 2018 Julio | 11 | 0 | 11 |
| 2018 Junio | 20 | 3 | 23 |
| 2018 Mayo | 11 | 0 | 11 |
| 2018 Abril | 13 | 1 | 14 |
| 2018 Marzo | 35 | 0 | 35 |
| 2018 Febrero | 10 | 0 | 10 |
| 2018 Enero | 7 | 2 | 9 |
| 2017 Diciembre | 10 | 0 | 10 |
| 2017 Noviembre | 11 | 2 | 13 |
| 2017 Octubre | 8 | 2 | 10 |
| 2017 Septiembre | 17 | 0 | 17 |
| 2017 Agosto | 12 | 3 | 15 |
| 2017 Julio | 20 | 1 | 21 |
| 2017 Junio | 14 | 24 | 38 |
| 2017 Mayo | 37 | 8 | 45 |
| 2017 Abril | 57 | 4 | 61 |
| 2017 Marzo | 68 | 37 | 105 |
| 2017 Febrero | 37 | 0 | 37 |
| 2017 Enero | 35 | 0 | 35 |
| 2016 Diciembre | 32 | 5 | 37 |
| 2016 Noviembre | 36 | 6 | 42 |
| 2016 Octubre | 70 | 5 | 75 |
| 2016 Septiembre | 105 | 7 | 112 |
| 2016 Agosto | 40 | 3 | 43 |
| 2016 Julio | 19 | 2 | 21 |
| 2016 Junio | 28 | 8 | 36 |
| 2016 Mayo | 20 | 12 | 32 |
| 2016 Abril | 14 | 32 | 46 |
| 2016 Marzo | 18 | 10 | 28 |
| 2016 Febrero | 25 | 11 | 36 |
| 2016 Enero | 19 | 6 | 25 |
| 2015 Diciembre | 25 | 6 | 31 |
| 2015 Noviembre | 22 | 3 | 25 |
| 2015 Octubre | 23 | 2 | 25 |
| 2015 Septiembre | 17 | 7 | 24 |
| 2015 Agosto | 30 | 3 | 33 |
| 2015 Julio | 19 | 5 | 24 |
| 2015 Junio | 17 | 1 | 18 |
| 2015 Mayo | 18 | 5 | 23 |
| 2015 Abril | 24 | 8 | 32 |
| 2015 Marzo | 18 | 8 | 26 |
| 2015 Febrero | 19 | 4 | 23 |
| 2015 Enero | 33 | 2 | 35 |
| 2014 Diciembre | 44 | 2 | 46 |
| 2014 Noviembre | 32 | 2 | 34 |
| 2014 Octubre | 48 | 2 | 50 |
| 2014 Septiembre | 30 | 4 | 34 |
| 2014 Agosto | 26 | 4 | 30 |
| 2014 Julio | 41 | 4 | 45 |
| 2014 Junio | 39 | 1 | 40 |
| 2014 Mayo | 19 | 1 | 20 |
| 2014 Abril | 17 | 1 | 18 |
| 2014 Marzo | 26 | 2 | 28 |
| 2014 Febrero | 18 | 2 | 20 |
| 2014 Enero | 22 | 1 | 23 |
| 2013 Diciembre | 14 | 5 | 19 |
| 2013 Noviembre | 19 | 2 | 21 |
| 2013 Octubre | 29 | 5 | 34 |
| 2013 Septiembre | 23 | 5 | 28 |
| 2013 Agosto | 28 | 6 | 34 |
| 2013 Julio | 21 | 1 | 22 |
| 2009 Marzo | 1251 | 0 | 1251 |
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