Letter to the Editor
Acute kidney injury secondary to diarrhea caused by “sprue-like” enteropathy associated with olmesartan
Daño renal agudo secundario a diarrea debido a enteropatía “sprue-like” asociada al olmesartan
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=> "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 6 => array:4 [ "nombre" => "Julio" "apellidos" => "Hernandez-Jaras" "email" => array:1 [ 0 => "Hernandez_jul@gva.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital Universitario y Politécnico La Fe, Valencia, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Gastroenterología, Servicio de Medicina Digestiva, Hospital Universitario y Politécnico La Fe, Valencia, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Daño renal agudo secundario a diarrea debido a enteropatía “sprue-like” asociada al olmesartan" ] ] "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" => 1104 "Ancho" => 2627 "Tamanyo" => 111770 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Serum creatinine levels prior to the diarrhea episode, at admission and at discharge in 19 olmesartan-related enteropathy patients classified by the Acute Kidney Injury Network (AKIN) stages. Bar height denotes median values while error bars denote range.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Olmesartan is an angiotensin II receptor antagonist used for managing hypertension. Despite being an effective and secure drug, several reports have shown that olmesartan treatment can induce “sprue-like” enteropathy.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Histological studies of kidney tissue from patients have often shown duodenal villous atrophy, increased intraepithelial lymphocytes and collagen depositions.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> The pathophysiological mechanisms causing the olmesartan-induced sprue-like enteropathy (OSLE) are not fully elucidated, but recent observations suggest a cell-mediated hypersensitivity reaction<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> possibly related to the haplotype DQ2/DQ8.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> Persistent diarrhea often accompanies enteropathy due to olmesartan use, which could have an impact on renal function. Indeed, three previous reports have shown renal involvement secondary to diarrhea due to olmesartan-related enteropathy.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5–7</span></a> Here we present a series of 19 cases of enteropathy related to olmesartan. Fourteen of these patients showed acute renal failure at admission, which was reverted after rehydration and discontinuing olmesartan.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Nineteen cases (9 females; median age 70, ranging from 56 to 88 years old) of OSLE were admitted to our hospital between September 2012 and June 2016. Patients went to the hospital due to persistent diarrhea that was non-responsive to conventional treatment. Prior to admission, patients had been treated with olmesartan for an average of 30 months (9–84 months). Most patients were taking 40<span class="elsevierStyleHsp" style=""></span>mg/day olmesartan (10–40<span class="elsevierStyleHsp" style=""></span>mg/day). OSLE was diagnosed after ruling out other possible causes for enteropathy (seronegative for tissular transglutaminase antibodies) and determining that the patient fulfilled the criteria set by Rubio et al.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Sixteen patients needed hospitalization for a time period ranging from 1 to 35 days and one was treated in the intensive care unit. Treatment consisted of rehydration therapy and olmesartan discontinuation, which reverted the enteropathy and associated diarrhea. At the time of this publication histological analyses in 12 patients showed full tissue recovery.</p><p id="par0015" class="elsevierStylePara elsevierViewall">None of the patients had previous history of chronic renal disease, and estimated glomerular filtrate was normal prior to injury (86.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>17.4<span class="elsevierStyleHsp" style=""></span>mL/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>). At admission, electrolyte imbalance was observed (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>) while serum creatinine was considerably higher in comparison to previous values (<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>). Acute Kidney Injury Network (AKIN) classification<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> showed 5 patients with no renal involvement, 3 patients at stage 1, 2 at stage 2 and 9 at stage 3. In addition, hypokalemia and metabolic acidosis was present in these patients (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">We have presented a series of cases (14 out of a total of 19) in which acute renal injury was secondary to dehydration due to OSLE. Renal involvement was severe in 11 patients (2 cases of AKIN stage 2 and 9 cases AKIN stage 3) accompanied by hypokalemia and metabolic acidosis.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The data obtained in this case series is similar to 2 cases in Spain with high creatinine and low potassium levels associated with enteropathy in patients treated with olmesartan, which reverted after drug discontinuation.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> Along the same lines, another case of enteropathy related to olmesartan with high serum creatinine and hypokalemia has been reported.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> Chronic enteropathy could be associated with severe dehydration and weight loss by diarrhea, which would explain the renal involvement observed in these patients.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Olmesartan is commonly used for hypertension treatment. Although it is a safe and reliable drug, the Food and Drug Administration has recommended suspending treatment if intestinal problems occur.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> Our data highlight the severe effects on renal tissue due to chronic diarrhea secondary to OSLE. More than half of the patients had stage 2 or 3 AKIN, in which kidney tissue was affected. It is likely that the duration and severity of the diarrhea episodes and the patient's hydration pattern contribute to the extent of kidney injury. Rehydration therapy and suspension of olmesartan treatment reverted symptoms and renal function was normal at discharge. However, in some cases, the extent of kidney tissue damage was high, which in turn could jeopardize patients’ renal function.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Besides weight loss, dehydration and other complications secondary to diarrhea, the renal involvement shown in this case series highlights the necessity of including olmesartan treatment in the differential diagnosis of chronic diarrhea in order to minimize the effects on kidney tissue and preserve patients’ renal function.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1104 "Ancho" => 2627 "Tamanyo" => 111770 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Serum creatinine levels prior to the diarrhea episode, at admission and at discharge in 19 olmesartan-related enteropathy patients classified by the Acute Kidney Injury Network (AKIN) stages. Bar height denotes median values while error bars denote range.</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">Hypokalemia (K<span class="elsevierStyleSup">+</span> <3.5<span class="elsevierStyleHsp" style=""></span>mEq/L) data has been reported as count (percentage). The rest of the data is reported as median (max–min). Hb, hemoglobin.</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="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">AKIN<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0<br>(<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>5) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">AKIN<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1<br>(<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">AKIN<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2<br>(<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">AKIN<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3<br>(<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>9) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypokalemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (40%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (33%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 (89%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Urea (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38.0 (57.0–30.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70.0 (87.0–44.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60.5 (78.0–43.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">129.0 (242.0–38.0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cl<span class="elsevierStyleSup">−</span> (mEq/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">105.0 (107.0–102.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">102.0 (108.0–98.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">103.5 (104.0–103.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">103.0 (116.0–95.0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Na<span class="elsevierStyleSup">+</span> (mEq/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">139 (141–136) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">139 (139–136) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">137 (138–136) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">136 (139–130) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">K<span class="elsevierStyleSup">+</span> (mEq/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.0 (4.3–2.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.6 (4.0–3.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.3 (4.6–3.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.3 (4.4–2.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">pH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.38 (7.46–7.37) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.32 (7.32–7.32) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.24 (7.29–7.18) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.14 (7.29–6.98) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CO<span class="elsevierStyleInf">2</span> (mEq/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">39.4 (47.3–19.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">49.0 (49.0–49.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45.1 (47.2–43.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13.7 (48.0–4.6) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HCO<span class="elsevierStyleInf">3</span><span class="elsevierStyleSup">−</span> (mEq/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22.2 (27.5–16.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22.9 (24.7–21.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18.6 (20.1–17.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.0 (16.0–4.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hb (g/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13.3 (14.5–12.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13.9 (14.6–10.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15.9 (16.6–15.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14.8 (18.1–12.0) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1536011.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Incidence of hypokalemia and serum biochemical values at hospital admission in olmesartan-related enteropathy patients classified by the Acute Kidney Injury Network (AKIN) stages.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Severe sprue like enteropathy associated with olmesartan" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 7 | 7 | 14 |
| 2024 October | 49 | 41 | 90 |
| 2024 September | 57 | 30 | 87 |
| 2024 August | 71 | 57 | 128 |
| 2024 July | 37 | 23 | 60 |
| 2024 June | 76 | 40 | 116 |
| 2024 May | 60 | 33 | 93 |
| 2024 April | 62 | 33 | 95 |
| 2024 March | 58 | 33 | 91 |
| 2024 February | 59 | 41 | 100 |
| 2024 January | 56 | 26 | 82 |
| 2023 December | 54 | 26 | 80 |
| 2023 November | 83 | 40 | 123 |
| 2023 October | 103 | 31 | 134 |
| 2023 September | 74 | 39 | 113 |
| 2023 August | 79 | 21 | 100 |
| 2023 July | 82 | 34 | 116 |
| 2023 June | 71 | 26 | 97 |
| 2023 May | 94 | 35 | 129 |
| 2023 April | 73 | 13 | 86 |
| 2023 March | 110 | 25 | 135 |
| 2023 February | 85 | 25 | 110 |
| 2023 January | 44 | 21 | 65 |
| 2022 December | 58 | 30 | 88 |
| 2022 November | 83 | 31 | 114 |
| 2022 October | 60 | 37 | 97 |
| 2022 September | 54 | 41 | 95 |
| 2022 August | 62 | 49 | 111 |
| 2022 July | 47 | 42 | 89 |
| 2022 June | 58 | 36 | 94 |
| 2022 May | 91 | 25 | 116 |
| 2022 April | 96 | 43 | 139 |
| 2022 March | 103 | 33 | 136 |
| 2022 February | 105 | 45 | 150 |
| 2022 January | 103 | 43 | 146 |
| 2021 December | 86 | 40 | 126 |
| 2021 November | 113 | 32 | 145 |
| 2021 October | 107 | 53 | 160 |
| 2021 September | 113 | 34 | 147 |
| 2021 August | 114 | 49 | 163 |
| 2021 July | 86 | 29 | 115 |
| 2021 June | 81 | 22 | 103 |
| 2021 May | 65 | 50 | 115 |
| 2021 April | 218 | 54 | 272 |
| 2021 March | 148 | 35 | 183 |
| 2021 February | 138 | 36 | 174 |
| 2021 January | 110 | 19 | 129 |
| 2020 December | 106 | 18 | 124 |
| 2020 November | 91 | 25 | 116 |
| 2020 October | 89 | 23 | 112 |
| 2020 September | 81 | 20 | 101 |
| 2020 August | 74 | 24 | 98 |
| 2020 July | 78 | 11 | 89 |
| 2020 June | 57 | 21 | 78 |
| 2020 May | 81 | 15 | 96 |
| 2020 April | 96 | 12 | 108 |
| 2020 March | 121 | 22 | 143 |
| 2020 February | 99 | 19 | 118 |
| 2020 January | 84 | 19 | 103 |
| 2019 December | 101 | 28 | 129 |
| 2019 November | 117 | 26 | 143 |
| 2019 October | 66 | 23 | 89 |
| 2019 September | 53 | 15 | 68 |
| 2019 August | 45 | 26 | 71 |
| 2019 July | 51 | 20 | 71 |
| 2019 June | 41 | 16 | 57 |
| 2019 May | 42 | 24 | 66 |
| 2019 April | 62 | 27 | 89 |
| 2019 March | 44 | 24 | 68 |
| 2019 February | 25 | 20 | 45 |
| 2019 January | 30 | 21 | 51 |
| 2018 December | 119 | 39 | 158 |
| 2018 November | 218 | 21 | 239 |
| 2018 October | 136 | 31 | 167 |
| 2018 September | 83 | 22 | 105 |
| 2018 August | 37 | 11 | 48 |
| 2018 July | 42 | 11 | 53 |
| 2018 June | 51 | 5 | 56 |
| 2018 May | 77 | 19 | 96 |
| 2018 April | 48 | 11 | 59 |
| 2018 March | 95 | 6 | 101 |
| 2018 February | 50 | 6 | 56 |
| 2018 January | 49 | 4 | 53 |
| 2017 December | 71 | 7 | 78 |
| 2017 November | 33 | 16 | 49 |
| 2017 October | 32 | 6 | 38 |
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