Scientific Letter
Two siblings with acute lymphoblastic leukaemia: Chance or genetics?
Dos hermanos con leucemia linfoblástica aguda: ¿casualidad o herencia?
Elena Carceller, David Ruano, Luis Madero López, Álvaro Lassaletta
Corresponding author
Hospital Infantil Universitario Niño Jesús, Madrid, Spain
Read
14443
Timeswas read the article
2305
Total PDF
12138
Total HTML
Share statistics
array:24 [ "pii" => "S2341287917301308" "issn" => "23412879" "doi" => "10.1016/j.anpede.2017.03.007" "estado" => "S300" "fechaPublicacion" => "2017-09-01" "aid" => "2241" "copyright" => "Asociación Española de Pediatría" "copyrightAnyo" => "2017" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "An Pediatr (Barc). 2017;87:170-1" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 3208 "formatos" => array:3 [ "EPUB" => 114 "HTML" => 2738 "PDF" => 356 ] ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S1695403317301546" "issn" => "16954033" "doi" => "10.1016/j.anpedi.2017.03.009" "estado" => "S300" "fechaPublicacion" => "2017-09-01" "aid" => "2241" "copyright" => "Asociación Española de Pediatría" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "An Pediatr (Barc). 2017;87:170-1" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 4788 "formatos" => array:3 [ "EPUB" => 166 "HTML" => 3882 "PDF" => 740 ] ] "es" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta científica</span>" "titulo" => "Dos hermanos con leucemia linfoblástica aguda: ¿casualidad o herencia?" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "170" "paginaFinal" => "171" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Two siblings with acute lymphoblastic leukaemia: chance or genetics?" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Elena Carceller, David Ruano, Luis Madero López, Álvaro Lassaletta" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Elena" "apellidos" => "Carceller" ] 1 => array:2 [ "nombre" => "David" "apellidos" => "Ruano" ] 2 => array:2 [ "nombre" => "Luis" "apellidos" => "Madero López" ] 3 => array:2 [ "nombre" => "Álvaro" "apellidos" => "Lassaletta" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2341287917301308" "doi" => "10.1016/j.anpede.2017.03.007" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287917301308?idApp=UINPBA00005H" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1695403317301546?idApp=UINPBA00005H" "url" => "/16954033/0000008700000003/v2_201708291307/S1695403317301546/v2_201708291307/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2341287917301382" "issn" => "23412879" "doi" => "10.1016/j.anpede.2016.10.014" "estado" => "S300" "fechaPublicacion" => "2017-09-01" "aid" => "2178" "copyright" => "Asociación Española de Pediatría" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "An Pediatr (Barc). 2017;87:171-3" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 2152 "formatos" => array:3 [ "EPUB" => 122 "HTML" => 1597 "PDF" => 433 ] ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific Letter</span>" "titulo" => "Early kidney damage in patients born with unilateral renal agenesis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "171" "paginaFinal" => "173" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Daño renal precoz en pacientes nacidos con agenesia renal unilateral" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ana Castellano-Martinez, Moises Rodriguez-Gonzalez, Virginia Roldan-Cano" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Ana" "apellidos" => "Castellano-Martinez" ] 1 => array:2 [ "nombre" => "Moises" "apellidos" => "Rodriguez-Gonzalez" ] 2 => array:2 [ "nombre" => "Virginia" "apellidos" => "Roldan-Cano" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S169540331630296X" "doi" => "10.1016/j.anpedi.2016.10.012" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S169540331630296X?idApp=UINPBA00005H" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287917301382?idApp=UINPBA00005H" "url" => "/23412879/0000008700000003/v2_201708291341/S2341287917301382/v2_201708291341/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2341287917301291" "issn" => "23412879" "doi" => "10.1016/j.anpede.2016.09.010" "estado" => "S300" "fechaPublicacion" => "2017-09-01" "aid" => "2169" "copyright" => "Asociación Española de Pediatría" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "An Pediatr (Barc). 2017;87:164-9" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1785 "formatos" => array:3 [ "EPUB" => 165 "HTML" => 1158 "PDF" => 462 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Clinical observation: A safe alternative to radiology in infants with mild traumatic brain injury" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "164" "paginaFinal" => "169" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Observación clínica: una alternativa segura a la radiología en lactantes con traumatismo craneoencefálico leve" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2235 "Ancho" => 1811 "Tamanyo" => 353777 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Algorithm for the management of mild head trauma in children aged less than 2 years in the hospital where the study was conducted (A: until July 2013; B: from July 2013).</p> <p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">CSF, cerebrospinal fluid; CT, computed tomography; Fx, fracture; HT, head trauma; NSur: neurosurgery; Paed, paediatrics ward; PICU, paediatric intensive care unit; TBI, traumatic brain injury.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "David Muñoz-Santanach, Victoria Trenchs Sainz de la Maza, Sara Maya Gallego, Adriana Cuaresma González, Carles Luaces Cubells" "autores" => array:5 [ 0 => array:2 [ "nombre" => "David" "apellidos" => "Muñoz-Santanach" ] 1 => array:2 [ "nombre" => "Victoria" "apellidos" => "Trenchs Sainz de la Maza" ] 2 => array:2 [ "nombre" => "Sara" "apellidos" => "Maya Gallego" ] 3 => array:2 [ "nombre" => "Adriana" "apellidos" => "Cuaresma González" ] 4 => array:2 [ "nombre" => "Carles" "apellidos" => "Luaces Cubells" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S1695403316302764" "doi" => "10.1016/j.anpedi.2016.09.013" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1695403316302764?idApp=UINPBA00005H" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287917301291?idApp=UINPBA00005H" "url" => "/23412879/0000008700000003/v2_201708291341/S2341287917301291/v2_201708291341/en/main.assets" ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific Letter</span>" "titulo" => "Two siblings with acute lymphoblastic leukaemia: Chance or genetics?" "tieneTextoCompleto" => true "saludo" => "Dear Editor:" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "170" "paginaFinal" => "171" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Elena Carceller, David Ruano, Luis Madero López, Álvaro Lassaletta" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Elena" "apellidos" => "Carceller" ] 1 => array:2 [ "nombre" => "David" "apellidos" => "Ruano" ] 2 => array:2 [ "nombre" => "Luis" "apellidos" => "Madero López" ] 3 => array:4 [ "nombre" => "Álvaro" "apellidos" => "Lassaletta" "email" => array:1 [ 0 => "lassaalvaro@yahoo.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Hospital Infantil Universitario Niño Jesús, Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Dos hermanos con leucemia linfoblástica aguda: ¿casualidad o herencia?" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Acute lymphoblastic leukaemia (ALL) is the most frequent childhood cancer and accounts for 80% of cases of acute leukaemia.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> Its underlying mechanisms are largely unknown. There is growing evidence of the role of genetic factors in its aetiology. This statement is based on the following: (1) there is a strong association between ALL and some chromosomal translocations; (2) the incidence of acute leukaemia is greater in relatives of patients with acute leukaemia, and (3) there is a higher incidence of leukaemia in individuals with certain genetic syndromes (Down syndrome, Klinefelter syndrome, neurofibromatosis, Shwachman syndrome, etc.).<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> In recent years, genetic mutations associated with an increased risk of ALL have been reported, in spite of which its heritability remains uncertain. We present a case of ALL in a sibling of a patient that had received a diagnosis of ALL 4 years earlier.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The patient was a boy aged 18 months brought to the emergency department with fever of up to 39<span class="elsevierStyleHsp" style=""></span>°<span class="elsevierStyleSmallCaps">C</span> lasting 2 days and associated with cold symptoms and breathing difficulties. There had been no complications during pregnancy, delivery or the neonatal period. The boy had received vaccinations conforming to the official schedule. There were no other medical or surgical diseases. The complete blood count revealed pancytopenia. A bone marrow sample was obtained 48<span class="elsevierStyleHsp" style=""></span>h after admission whose analysis revealed infiltration with 60% of blast cells and markers compatible with common ALL (B-cell precursor). The relevant family history included an older brother aged 6 years with B-cell precursor ALL diagnosed 4 years earlier that had completed treatment 2 years after the diagnosis. The father had insulin-dependent diabetes mellitus since age 25 years, the mother was healthy, and a paternal aunt had died of cancer at age 40 years.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The 2 siblings were treated according to the PETHEMA BR protocol and responded well to chemotherapy. Both are in full remission at present, 6 and 10 years after diagnosis, respectively.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Most cases of ALL in children are sporadic, and ALL is not considered an inherited disease. Direct evidence of a genetic heritable predisposition to ALL due to certain genetic syndromes, such as Bloom syndrome, neurofibromatosis, ataxia-telangiectasia and trisomy 21 is only found in a small percentage of ALL cases (<5%). The genetic basis of the heritable susceptibility to ALL outside these syndromes has not been elucidated. However, there have been advances on this matter in recent years: genomic studies have found that somatic variants of <span class="elsevierStyleItalic">ARD5B</span>, <span class="elsevierStyleItalic">IKZF1</span> and <span class="elsevierStyleItalic">CDKN2A</span> are associated with an increased risk of ALL (odds ratio, 1.3–1.9).<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">2,3</span></a> Other rare germline mutations in <span class="elsevierStyleItalic">PAX5</span>, <span class="elsevierStyleItalic">ETV6</span> and especially p53 may also predispose to leukaemia.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a> Despite all these findings, there is no sufficient evidence to prove a familial risk of ALL in children, which may be due, in part, to the low incidence of the disease. A Scandinavian study that included 3.994 patients with ALL identified 36 cases of ALL in siblings: 10 cases in singleton siblings and 26 in twins. The study showed that compared to the general population, twins of children with ALL had an increased risk of developing leukaemia (standardised incidence ratio [SIR], 163; 95% CI, 70–320), while the increase in risk in singleton siblings was small (SIR, 3; 95% CI, 2–6).<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">5</span></a> It is believed that the high risk found in twins results from sharing the prenatal blood circulation.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a> The increased risk in singleton siblings is not associated with the aforementioned genomic findings, so the authors suggested that other germline mutations or polymorphisms yet unknown may underlie this familial effect. To date, this is the first study in the literature that attributes an increased risk of developing ALL in siblings of patients with the disease.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In the case of our patient, in whom none of the findings suggested the presence of a genetic syndrome associated with an increased predisposition for ALL, and based on the data currently available in the literature, we did not have sufficient evidence to establish whether this familial aggregation was hereditary in nature. On the other hand, since the incidence of ALL is low in the general population and the mild increase in the relative risk of siblings of patients with ALL does not result in a high probability of developing leukaemia, we do not recommend routine screening of siblings of patients with leukaemia.</p><p id="par0030" class="elsevierStylePara elsevierViewall">It is important that research on the genetic basis of ALL continues, not only to establish its heritability, but also to learn its potential impact on prognosis and treatment.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Carceller E, Ruano D, Madero López L, Lassaletta Á. Dos hermanos con leucemia linfoblástica aguda: ¿casualidad o herencia? An Pediatr (Barc). 2017;87:170–171.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib0035" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Leucemias. Leucemia linfoblástica aguda" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "A. Lassaletta" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Pediatr Integral" "fecha" => "2016" "volumen" => "20" "paginaInicial" => "380" "paginaFinal" => "389" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0040" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Germline genomic variants associated with childhood acute lymphoblastic leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L.R. Treviño" 1 => "W. Yang" 2 => "D. French" 3 => "S.P. Hunger" 4 => "W.L. Carroll" 5 => "M. Devidas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng.432" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "2009" "volumen" => "41" "paginaInicial" => "1001" "paginaFinal" => "1005" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19684603" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0045" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Papaemmanuil" 1 => "F.J. Hosking" 2 => "J. Vijayakrishnan" 3 => "A. Price" 4 => "B. Olver" 5 => "E. Sheridan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng.430" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "2009" "volumen" => "41" "paginaInicial" => "1006" "paginaFinal" => "1010" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19684604" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0050" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Germline mutations in predisposition genes in pediatric cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Zhang" 1 => "M.F. Walsh" 2 => "G. Wu" 3 => "M.N. Edmonson" 4 => "T.A. Gruber" 5 => "J. Easton" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1508054" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2015" "volumen" => "373" "paginaInicial" => "2336" "paginaFinal" => "2346" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26580448" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0055" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Familial risks for childhood acute lymphocytic leukaemia in Sweden and Finland: far exceeding the effects of known germline variants" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "E. Kharazmi" 1 => "M.I. da Silva Filho" 2 => "E. Pukkala" 3 => "K. Sundquist" 4 => "H. Thomsen" 5 => "K. Hemminki" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/bjh.12069" "Revista" => array:6 [ "tituloSerie" => "Br J Haematol" "fecha" => "2012" "volumen" => "159" "paginaInicial" => "585" "paginaFinal" => "588" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23025517" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0060" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Infection, immune responses and the aetiology of childhood leukaemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M. Greaves" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nrc1816" "Revista" => array:6 [ "tituloSerie" => "Nat Rev Cancer" "fecha" => "2006" "volumen" => "6" "paginaInicial" => "193" "paginaFinal" => "203" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16467884" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23412879/0000008700000003/v2_201708291341/S2341287917301308/v2_201708291341/en/main.assets" "Apartado" => array:4 [ "identificador" => "38181" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Scientific letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23412879/0000008700000003/v2_201708291341/S2341287917301308/v2_201708291341/en/main.pdf?idApp=UINPBA00005H&text.app=https://analesdepediatria.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287917301308?idApp=UINPBA00005H" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 26 | 10 | 36 |
| 2024 October | 148 | 42 | 190 |
| 2024 September | 159 | 35 | 194 |
| 2024 August | 229 | 55 | 284 |
| 2024 July | 316 | 42 | 358 |
| 2024 June | 273 | 36 | 309 |
| 2024 May | 216 | 45 | 261 |
| 2024 April | 212 | 44 | 256 |
| 2024 March | 185 | 23 | 208 |
| 2024 February | 262 | 39 | 301 |
| 2024 January | 195 | 35 | 230 |
| 2023 December | 275 | 34 | 309 |
| 2023 November | 206 | 30 | 236 |
| 2023 October | 173 | 32 | 205 |
| 2023 September | 140 | 18 | 158 |
| 2023 August | 126 | 21 | 147 |
| 2023 July | 147 | 34 | 181 |
| 2023 June | 137 | 30 | 167 |
| 2023 May | 157 | 26 | 183 |
| 2023 April | 105 | 21 | 126 |
| 2023 March | 113 | 23 | 136 |
| 2023 February | 95 | 18 | 113 |
| 2023 January | 110 | 15 | 125 |
| 2022 December | 132 | 26 | 158 |
| 2022 November | 146 | 34 | 180 |
| 2022 October | 160 | 59 | 219 |
| 2022 September | 138 | 27 | 165 |
| 2022 August | 115 | 48 | 163 |
| 2022 July | 111 | 47 | 158 |
| 2022 June | 80 | 36 | 116 |
| 2022 May | 96 | 48 | 144 |
| 2022 April | 125 | 44 | 169 |
| 2022 March | 184 | 49 | 233 |
| 2022 February | 151 | 29 | 180 |
| 2022 January | 152 | 30 | 182 |
| 2021 December | 120 | 54 | 174 |
| 2021 November | 111 | 45 | 156 |
| 2021 October | 146 | 80 | 226 |
| 2021 September | 128 | 36 | 164 |
| 2021 August | 125 | 51 | 176 |
| 2021 July | 123 | 27 | 150 |
| 2021 June | 164 | 35 | 199 |
| 2021 May | 195 | 44 | 239 |
| 2021 April | 394 | 84 | 478 |
| 2021 March | 228 | 33 | 261 |
| 2021 February | 190 | 25 | 215 |
| 2021 January | 382 | 26 | 408 |
| 2020 December | 152 | 25 | 177 |
| 2020 November | 137 | 32 | 169 |
| 2020 October | 123 | 28 | 151 |
| 2020 September | 154 | 16 | 170 |
| 2020 August | 121 | 12 | 133 |
| 2020 July | 147 | 28 | 175 |
| 2020 June | 132 | 10 | 142 |
| 2020 May | 163 | 21 | 184 |
| 2020 April | 159 | 12 | 171 |
| 2020 March | 135 | 29 | 164 |
| 2020 February | 181 | 18 | 199 |
| 2020 January | 181 | 10 | 191 |
| 2019 December | 142 | 19 | 161 |
| 2019 November | 117 | 13 | 130 |
| 2019 October | 223 | 16 | 239 |
| 2019 September | 179 | 10 | 189 |
| 2019 August | 138 | 20 | 158 |
| 2019 July | 119 | 15 | 134 |
| 2019 June | 154 | 21 | 175 |
| 2019 May | 221 | 29 | 250 |
| 2019 April | 185 | 32 | 217 |
| 2019 March | 123 | 16 | 139 |
| 2019 February | 127 | 13 | 140 |
| 2019 January | 116 | 36 | 152 |
| 2018 December | 89 | 23 | 112 |
| 2018 November | 115 | 29 | 144 |
| 2018 October | 135 | 13 | 148 |
| 2018 September | 68 | 20 | 88 |
| 2018 August | 2 | 0 | 2 |
| 2018 July | 3 | 0 | 3 |
| 2018 June | 4 | 0 | 4 |
| 2018 May | 6 | 0 | 6 |
| 2018 April | 19 | 0 | 19 |
| 2018 March | 32 | 0 | 32 |
| 2018 February | 25 | 0 | 25 |
| 2018 January | 23 | 0 | 23 |
| 2017 December | 27 | 0 | 27 |
| 2017 November | 31 | 0 | 31 |
| 2017 October | 28 | 0 | 28 |
| 2017 September | 1 | 0 | 1 |
| 2017 August | 0 | 7 | 7 |
| 2017 July | 0 | 7 | 7 |
Show all
