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C3 glomerulopathy associated to B-cell chronic lymphocytic leukemia
Glomerulopatía C3 asociada a leucemia linfocítica crónica de células B
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Lizeth Gallegos Durazo, Juana González Plascencia, Adriana Karina Mejía-Zárate" "autores" => array:6 [ 0 => array:2 [ "nombre" => "José Luis" "apellidos" => "Vázquez Castellanos" ] 1 => array:2 [ "nombre" => "Edgar Daniel" "apellidos" => "Copado Villagrana" ] 2 => array:2 [ "nombre" => "Blanca Miriam Guadalupe" "apellidos" => "Torres Mendoza" ] 3 => array:2 [ "nombre" => "Diana Lizeth" "apellidos" => "Gallegos Durazo" ] 4 => array:2 [ "nombre" => "Juana" "apellidos" => "González Plascencia" ] 5 => array:2 [ "nombre" => "Adriana Karina" "apellidos" => "Mejía-Zárate" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0211699520301740?idApp=UINPBA000064" "url" => "/02116995/0000004200000001/v4_202211260552/S0211699520301740/v4_202211260552/es/main.assets" ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta al Director</span>" "titulo" => "C3 glomerulopathy associated to B-cell chronic lymphocytic leukemia" "tieneTextoCompleto" => true "saludo" => "Dear Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "103" "paginaFinal" => "105" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Filipa Silva, Joana Tavares, Rita Pinho Peixeiro, João Oliveira, Diana Fernandes, Ana Castro, Sofia Santos, Rita Coutinho, Cristina Freitas, Josefina Santos, João Pedro Pimentel, Jorge Coutinho, António Cabrita" "autores" => array:13 [ 0 => array:4 [ "nombre" => "Filipa" "apellidos" => "Silva" "email" => array:1 [ 0 => "filipasofiasantossilva@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" => "Joana" "apellidos" => "Tavares" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => 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"apellidos" => "Cabrita" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Nephrology Department, Centro Hospitalar e Universitário do Porto, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Hematology Department, Centro Hospitalar e Universitário do Porto, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Internal Medicine Department, Unidade Local de Saúde do Nordeste, Portugal" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Glomerulopatía C3 asociada a leucemia linfocítica crónica de células B" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 405 "Ancho" => 1750 "Tamanyo" => 159269 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Glomerulus showing moderate mesangial widening and thickening of capillary walls, as well as double contours. (Periodic acid-Schiff stain (PAS) stain, 200×), (B) Immunofluorescence microscopy showing small granular deposits of complement (C3), mainly in the glomerula mesangium (×200). (C) Electron microscopy revealing electron dense deposits in the mesangial matrix (×8000).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">B-cell chronic lymphocytic leukemia (CLL-B) is the most commonly diagnosed leukemia in adults in Europe.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Kidney involvement has been described at diagnosis with an incidence of 7.5%<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2,3</span></a> and 16.2% during the course of the disease.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a> C3 glomerulonephritis (C3GN) is a rare disease characterized by accumulation of complement factors in the glomeruli due to overactivation and abnormal regulation of the alternative pathway of complement. One of the abnormalities commonly associated with this entity is the detection of a monoclonal gammopathy, being CLL one of the hematological diseases less commonly associated with C3GN.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">We present a case of a 68-year-old woman with overweight, hypertension and diabetes mellitus. She had non-proliferative diabetic retinopathy and hypertensive heart disease. Six months before she had the diagnosis of CLL-B with no clinical or laboratory criteria for targeted treatment.</p><p id="par0025" class="elsevierStylePara elsevierViewall">She presented with uncontrolled hypertension, anasarca and respiratory acidemia due to type 2 respiratory insufficiency, progressing rapidly to respiratory failure and mechanical ventilation. Biochemical investigation showed worsening anemia and leukocyte count, acute renal injury, hyperkalemia, hyperuricemia and hypoalbuminemia. The urine sediment had leukocyturia, erythrocyturia and hyaline and granulous casts and 24-h urine protein was 5.6<span class="elsevierStyleHsp" style=""></span>g. A renal ultrasound only showed discrete loss of cortical-medullary transition.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Pleural involvement by CLL was excluded. Serology studies for hepatitis B, C, VDRL and HIV 1 and 2 were negative. Immunologic studies showed decreased complement C3 levels with normal levels of C4. Anti-Neutrophilic Cytoplasmic Autoantibody (ANCA) were negative, cryoglobulins and anti-PLA2R (ELISA) were normal. Electroimmunosubtraction showed two bands with monoclonal characteristics (serum IgM/Lambda and IgG/Kappa and urinary IgG/Lambda type and free lambda light chains).</p><p id="par0035" class="elsevierStylePara elsevierViewall">Renal biopsy with seventeen glomeruli, two of which were globally sclerosed and the rest showed a membranoproliferative pattern (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). Renal tubules had thickened tubular basement membranes, there was interstitial mononuclear infiltration without significant fibrosis and moderate arteriolar hyalinosis. Immunofluorescence study revealed mesangial granular deposits for C3 (++), C4 (+) and vestigial IgM (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). There was no Congo red staining nor green birefringence on polarized light. Electron microscopy revealed electron dense mesangial deposits (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C). There was no evidence for deposits along the capillary walls and there was around 40% of foot process effacement.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">A final diagnosis of C3GN was made and renal disease as an underlying immunological phenomenon related to CLL was assumed. A deletion of the TP53 gene was detected and she started treatment with Rituximab and high dose methylprednisolone. After 6 cycles she achieved a complete hematological remission (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>) along with stabilization of renal function and marked improvement in the proteinuria.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">The first case of kidney disease in CLL was reported in 1957 by Scott et al. in a patient with nephrotic syndrome.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a> After that, several glomerular diseases have been associated with CLL and depending on the type and stage of the disease, the spectrum of kidney pathology can be particularly wide.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a> It can occur by diverse mechanisms such as parenchymal infiltration, extrarenal obstruction, tumor lysis syndrome, glomerulopathies, renovascular disease, electrolyte disorders and medication side effects.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">A chronological relationship with a suspected pathophysiological link and a parallel evolution of glomerulopathy and malignancy are suggested of paraneoplastic glomerulopathies.<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">8,9</span></a> Their pathophysiology is thought to be multifactorial<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a> since monoclonal protein secreted by B-cell clone can either be directly involved in the pathogenesis of the lesions, as is seen in fibrillary glomerulopathy, immunotactoid/microtubular glomerulonephritis, AL amyloidosis and type I/II cryoglobulinemia, or indirectly, as in cases of membranoproliferative glomerulonephritis (MPGN) not related to cryoglobulinemia.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">4,11</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">MPGN is by far the most common glomerular lesion described, followed by membranous nephropathy, minimal change disease and amyloidosis. Cases of MPGN presenting as C3GN, as the case here discussed, have also been reported.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a> One of the abnormalities commonly associated with C3GN is the detection of a monoclonal immunoglobulins. In this case, impaired regulation of the alternative pathway of complement is caused by monoclonal immunoglobulins and the MPGN pattern on kidney biopsy is the most frequent.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The presence of kidney disease can interfere with treatment strategies and outcomes. Therapy is only required for patients with active or symptomatic disease, or with advanced Binet or Rai stages.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Renal prognosis of C3GN remains poor, since 40% of patients progress to end stage renal disease 8–10 years after diagnosis and treatment is not well stablished.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">In conclusion, kidney involvement in patients with CLL could be more frequent than previously thought. Since it may present with a variety of pathology patterns and only a few of them predictable on clinical basis, kidney biopsy is essential. C3GN is rarely seen and renal prognosis as well as response to therapy is unknown. The report of these cases is of major role for better understanding the pathophysiology of this disease and in order to improve treatment and prognosis offered to this rare group of patients.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 405 "Ancho" => 1750 "Tamanyo" => 159269 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Glomerulus showing moderate mesangial widening and thickening of capillary walls, as well as double contours. (Periodic acid-Schiff stain (PAS) stain, 200×), (B) Immunofluorescence microscopy showing small granular deposits of complement (C3), mainly in the glomerula mesangium (×200). (C) Electron microscopy revealing electron dense deposits in the mesangial matrix (×8000).</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">B2M: beta-2 microglobulin; DHL: lactate desidrogenase; Hg: hemoglobina; sCr: serum creatinine; sU: serum urea.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Hematologic and biochemical parameters \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Leukocytes (×10<span class="elsevierStyleSup">3</span>/μL) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Lymphocytes (×10<span class="elsevierStyleSup">3</span>/μL) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Hg (g/dL) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Platelet (×10<span class="elsevierStyleSup">3</span>/μL) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">sCR (<0.9<span class="elsevierStyleHsp" style=""></span>mg/dL) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">sU (10–50<span class="elsevierStyleHsp" style=""></span>mg/mL) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Albumin (3.4–4.8<span class="elsevierStyleHsp" style=""></span>g/dL) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">24-h protein (g/day) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Urine protein (mg/g crea) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">DHL (U/L) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">B2 M (mg/L) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">C3 levels (mg/dL) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">At diagnosis of CLL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">174 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7700 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">416 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">At hospital admission \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">63.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">131 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9200 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">178 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">After treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">140 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3076 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">182 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">78.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3047878.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Biochemical variations along the disease curse.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0080" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Weltgesundheitsorganisation" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:4 [ "editores" => "S.H.Swerdlow, E.Campo, N.L.Harris, E.S.Jaffe, S.A.Pileri, H.Stein" "titulo" => "WHO classification of tumours of haematopoietic and lymphoid tissues" "edicion" => "Revised 4th ed." 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 4 | 0 | 4 |
| 2024 Octubre | 48 | 21 | 69 |
| 2024 Septiembre | 41 | 24 | 65 |
| 2024 Agosto | 62 | 52 | 114 |
| 2024 Julio | 41 | 31 | 72 |
| 2024 Junio | 48 | 45 | 93 |
| 2024 Mayo | 63 | 42 | 105 |
| 2024 Abril | 47 | 48 | 95 |
| 2024 Marzo | 47 | 26 | 73 |
| 2024 Febrero | 39 | 30 | 69 |
| 2024 Enero | 27 | 26 | 53 |
| 2023 Diciembre | 28 | 31 | 59 |
| 2023 Noviembre | 68 | 43 | 111 |
| 2023 Octubre | 62 | 26 | 88 |
| 2023 Septiembre | 85 | 35 | 120 |
| 2023 Agosto | 71 | 27 | 98 |
| 2023 Julio | 78 | 29 | 107 |
| 2023 Junio | 44 | 30 | 74 |
| 2023 Mayo | 43 | 28 | 71 |
| 2023 Abril | 35 | 12 | 47 |
| 2023 Marzo | 50 | 34 | 84 |
| 2023 Febrero | 28 | 24 | 52 |
| 2023 Enero | 39 | 32 | 71 |
| 2022 Diciembre | 61 | 34 | 95 |
| 2022 Noviembre | 50 | 39 | 89 |
| 2022 Octubre | 65 | 49 | 114 |
| 2022 Septiembre | 48 | 32 | 80 |
| 2022 Agosto | 45 | 56 | 101 |
| 2022 Julio | 42 | 52 | 94 |
| 2022 Junio | 52 | 71 | 123 |
| 2022 Mayo | 51 | 29 | 80 |
| 2022 Abril | 73 | 60 | 133 |
| 2022 Marzo | 86 | 77 | 163 |
| 2022 Febrero | 88 | 50 | 138 |
| 2022 Enero | 59 | 56 | 115 |
| 2021 Diciembre | 73 | 49 | 122 |
| 2021 Noviembre | 64 | 42 | 106 |
| 2021 Octubre | 93 | 38 | 131 |
| 2021 Septiembre | 50 | 35 | 85 |
| 2021 Agosto | 48 | 51 | 99 |
| 2021 Julio | 32 | 26 | 58 |
| 2021 Junio | 39 | 41 | 80 |
| 2021 Mayo | 47 | 49 | 96 |
| 2021 Abril | 76 | 69 | 145 |
| 2021 Marzo | 39 | 36 | 75 |
| 2021 Febrero | 22 | 24 | 46 |
| 2021 Enero | 41 | 31 | 72 |
| 2020 Diciembre | 14 | 11 | 25 |
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