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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Atypical hemolytic-uremic syndrome &#40;aHUS&#41; is a rare&#44; life-threatening complement-mediated thrombotic microangiopathy&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Approximately half of cases have mutations in complement proteins but only 12&#37; have 2 or more mutations&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> Eculizumab is nowadays considered first-line therapy for aHUS&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">A 33-year-old female with unremarkable past medical history presented with a 3-day history of decreased urine output&#46; Physical examination showed hypertension &#40;160&#47;90<span class="elsevierStyleHsp" style=""></span>mmHg&#41; and lower limbs edema&#46; Investigations revealed an acute thrombotic microangiopathy &#40;ATM&#41;&#44; hematuria and nephrotic proteinuria &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Daily plasmapheresis &#40;PMP&#41; was started immediately&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Investigations for secondary causes of ATM revealed a low ADAMTS 13 activity&#44; decreased complement C4&#44; C3&#44; C1q and C2 levels and positive serum cryoglobulins &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Considering the hypothesis of an autoimmune disorder&#44; we started 3 daily pulses of 1000<span class="elsevierStyleHsp" style=""></span>mg methylprednisolone followed by oral prednisolone&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">PMP was stopped on the eighteenth day of admission &#40;D18&#41; due to normal platelet count during 3 consecutive days &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; On the D19 a renal biopsy was made&#46; It showed a &#8220;thrombotic microangiopathy with acute tubular necrosis&#8221; and &#8220;deposition of IgM&#44; C3 and C1q in the capillary wall&#8221;&#46; Due to increased hemolytic activity&#44; PMP was resumed on the D21&#46; On the D27&#44; rituximab was started to enhance immunosuppression&#46; PMP was stopped on the D35 based on the absence of schistocytosis&#44; hemoglobin stability and lactate dehydrogenase &#40;LDH&#41; normalization&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">On the D50&#44; LDH was high but hemoglobin and platelet count were stable&#46; A state of compensated hemolysis was assumed and the patient was discharged home&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Ten days later she was readmitted due to increased hemolytic activity &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; PMP was resumed and 1000<span class="elsevierStyleHsp" style=""></span>mg cyclophosphamide was given&#46; At that time ADAMTS13 and complement C4 levels were normal but complement C3 levels remained low&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">A genetic screening for mutations in complement regulatory proteins was made&#46; Two mutations were found in factor I &#40;C&#46; 452 A&#62;G&#44; pASN 151 Ser&#41; and C3 &#40;C193 A<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>C&#44; pLys 65 Gin&#41; proteins&#46; The process of eculizumab acquisition was lengthy&#44; wherefore this therapy was started only on the 98th day after readmission&#46; At that moment we were performing one PMP session&#47;week&#44; LDH remained high &#40;859<span class="elsevierStyleHsp" style=""></span>U&#47;L&#41; and moderate renal dysfunction &#40;creatinine 2&#46;08<span class="elsevierStyleHsp" style=""></span>mg&#47;dL and urea 60<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41; and nephrotic proteinuria persisted &#40;5&#46;2<span class="elsevierStyleHsp" style=""></span>g&#47;24<span class="elsevierStyleHsp" style=""></span>h&#41;&#46; Eculizumab was administered at a dose of 900<span class="elsevierStyleHsp" style=""></span>mg per week for 4 weeks followed by subsequent doses of 1200<span class="elsevierStyleHsp" style=""></span>mg every 2 weeks since the 5th week&#46; Complete hematologic remission was attained 2 days after eculizumab initiation&#46; The patient was discharged home on the 105th day after readmission&#46; Four weeks later&#44; proteinuria was only 0&#46;6<span class="elsevierStyleHsp" style=""></span>g&#47;24<span class="elsevierStyleHsp" style=""></span>h&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Currently&#44; 10 months after first infusion&#44; the patient remains under biweekly administration of eculizumab&#46; Hematologic remission persists and there is a significant recover of renal function &#40;urea 43<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; creatinine 1&#46;27<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Complement factor I &#40;CFI&#41; and C3 mutations account for 10&#37; and 4&#37; of the overall aHUS-associated mutations&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> C3 mutations are among the ones with the poorest prognosis&#58; 75&#37; risk of death or end stage renal failure &#40;ESRF&#41; at 3&#8211;5 years follow up and 50&#37; risk of recurrence&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> CFI mutations have a 50&#8211;60&#37; risk of death and ESRF at 3&#8211;5 years follow up and 10&#8211;30&#37; risk of recurrence&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Both mutations present in our patient were previously reported&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4&#44;5</span></a> The p&#46;Asn151Ser mutation causes a quantitative deficiency of factor I<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> and the p&#46;Lys65Gin mutation weakens the affinity of C3b to complement factor H&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Despite the growing importance of eculizumab&#44;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6&#44;7</span></a> PMP remains the mainstay of treatment while waiting for the immunoglobulin&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> Nonetheless&#44; its benefit depends on the underlying genetic defect &#8211; only 25&#37; and 57&#37; of those with CFI and C3 mutations&#44; respectively&#44; achieve remission&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> In our patient&#44; PMP was critical to prevent further progression of renal failure and the development of other systemic involvement&#46; However&#44; as described by Loirat&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> it was unable to achieve complete and sustained remission&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">In our case&#44; the confounding presence of low ADAMTS13&#44; C4&#44; C2 and C1q levels&#44; the presence of cryoglobulins and the existence of immune deposits in the glomerular capillary wall led to the misdiagnosis of a thrombotic thrombocytopenic purpura secondary to an autoimmune disease&#46; It explains the preference for glucocorticoids&#44; rituximab and cyclophosphamide in relation to eculizumab&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Eculizumab is nowadays considered first-line therapy for aHUS&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> It is a humanized monoclonal immunoglobulin IgG that targets C5 and blocks the uncontrolled generation of the cytotoxic membrane attack complex&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> When we started Eculizumab&#44; our patient was still PMP dependent despite the 79 PMP sessions&#46; Contrariwise&#44; complete hematologic remission was attained two days after first infusion and a remarkable recover of renal function and reduction of proteinuria was evident&#46; These findings reinforce the benefits of eculizumab in aHUS&#44; even in cases of severe renal involvement&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">In conclusion&#44; our case highlights the diagnostic challenge of aHUS and emphasizes the notion that isolated PMP is no longer the best therapeutic option in aHUS&#44; in which cases a prompt switch to eculizumab is mandatory&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest related to the contents of this article&#46;</p></span>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Clinical course&#58; laboratory data and treatment&#46; Corticosteroid therapy was started with intravenous administration of methylprednisolone &#40;1000<span class="elsevierStyleHsp" style=""></span>mg&#47;day for 3 days&#41; followed by oral prednisolone and an initial dosage of 60<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46; This dosage was maintained until the 53rd day after admission&#44; with posterior tapering&#46; Rituximab &#40;arrows&#41; was administered at a dose of 600<span class="elsevierStyleHsp" style=""></span>mg &#40;375<span class="elsevierStyleHsp" style=""></span>mg&#47;m2&#41; on the 27th&#44; 34th&#44; 41st and 48th days after admission&#46; Cyclophosphamide &#40;arrowhead&#41; was administered in a single dose of 1000<span class="elsevierStyleHsp" style=""></span>mg on the 61st day after admission &#40;2nd day after readmission&#41;&#46; Eculizumab was administered at a dose of 900<span class="elsevierStyleHsp" style=""></span>mg for a week for 4 weeks&#44; started on the 158th day after admission&#44; followed by a dosage of 1200<span class="elsevierStyleHsp" style=""></span>mg 1 week later an then a maintenance dose of 1200<span class="elsevierStyleHsp" style=""></span>mg every 2 weeks&#46; This dosage is still being continued&#46; We performed a total of 79 plasma exchange sessions&#46; The last three laboratorial test results were done on the 270th&#44; 340th and 466th days following first admission&#46;</p>"
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                  <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  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">On admission</th></tr><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable&nbsp;\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">Result&nbsp;\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">Normal range&nbsp;\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">Hemoglobin &#40;g&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#8211;16&nbsp;\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">White-cell count &#40;&#215;10<span class="elsevierStyleSup">3</span>&#47;mm<span class="elsevierStyleSup">3</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#8211;10&nbsp;\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">Platelet count &#40;&#215;10<span class="elsevierStyleSup">3</span>&#47;mm<span class="elsevierStyleSup">3</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">150&#8211;400&nbsp;\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">Peripheral blood smear<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 schistocytes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;2 schistocytes&nbsp;\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">Haptoglobin &#40;g&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;0&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;3&#8211;2&nbsp;\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">Direct coombs tests&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Negative&nbsp;\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 &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">114&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&#8211;38&nbsp;\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">Creatinine &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;52&#8211;1&#46;04&nbsp;\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">Sodium &#40;mmol&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">135&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">137&#8211;145&nbsp;\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">Potassium &#40;mmol&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;5&#8211;5&#46;1&nbsp;\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">Lactate dehydrogenase &#40;U&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2827&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">313&#8211;618&nbsp;\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">c-Reactive protein &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;1&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">URINALYSIS</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Protein &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\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"><span class="elsevierStyleHsp" style=""></span>Leukocytes &#40;&#47;HPF&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;5&#47;c&nbsp;\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"><span class="elsevierStyleHsp" style=""></span>Red blood cells &#40;&#47;HPF&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;2&#47;c&nbsp;\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">Urinary protein to creatinine ratio &#40;mg&#47;mg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;0&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                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  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Additional studies</th></tr><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable&nbsp;\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">Result&nbsp;\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">Normal range&nbsp;\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">C3 &#40;g&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;9&#8211;1&#46;8&nbsp;\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">C4 &#40;g&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;1&#8211;0&#46;4&nbsp;\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">CH50 &#40;U&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23&#8211;46&nbsp;\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">C1q &#40;mg&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">118&#8211;244&nbsp;\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">C1q Inhibitor &#40;mg&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">197&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">180&#47;320&nbsp;\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">C2 &#40;mg&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&#8211;25&nbsp;\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">ADAMTS13 activity &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">40&#8211;130&nbsp;\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">Anti-ADAMTS13 antibody &#40;U&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;15&nbsp;\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">Serum cryoglobulins&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\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">Auto-immune antibodies<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&#44; Pregnancy test&#44; SPE&#44; Tumoral markers<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&#44; HIV&#44; HBV&#44; HCV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Negative&#47;Normal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\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">Blood&#44; urine and stool cultures&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\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">Upper endoscopy&#44; colonoscopy&#44; cervical&#44; thoracic and abdominopelvic CT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Irrelevant changes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab1381850.png"
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          "notaPie" => array:3 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar9005">Peripheral blood smear was done to evaluate presence of erythrocyte fragmentation and is reported as schistocytes count in a microscopic field at 100&#215; magnification&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Antinuclear antibodies&#44; extractable nuclear antigens&#44; anti-neutrophil cytoplasmic antibodies&#44; glomerular basement membrane&#44; rheumatoid factor&#44; cyclic citrullinated peptide&#44; anticardiolipin&#47;anti-&#946;2-glycoprotein&#44; Lupus anticoagulant&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Carcinoembryonic antigen&#44; carbohydrate antigen 19-9&#44; &#945;-fetoprotein&#44; cancer antigen 125&#44; neuron-specific enolase&#44; NSE&#46;</p> <p class="elsevierStyleNotepara" id="npar0020"><span class="elsevierStyleItalic">Abbreviations</span>&#58; ADAMTS13&#59; a disintegrin and metalloproteinase with a thrombospondin type 1 motif&#59; member 13&#46; CT&#59; computerized tomography&#46; HBV&#59; hepatitis B virus&#46; HCV&#59; hepatitis C virus&#46; HIV&#59; human immunodeficiency virus&#46; SPE&#59; serum protein electrophoresis&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Laboratorial results on admission and additional studies to establish the cause of the thrombotic microangiopathy&#46;</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" => "Treatment of atypical uraemic syndrome in the era of eculizumab"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "V&#46; Fremeaux-Bacchi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ckj/sfr177"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Kidney J"
                        "fecha" => "2012"
                        "volumen" => "5"
                        "paginaInicial" => "4"
                        "paginaFinal" => "6"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26069738"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "2"
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Letter to the Editor
Eculizumab for the treatment of an atypical hemolytic uremic syndrome with mutations in complement factor I and C3
Eculizumab para el tratamiento de un síndrome urémico hemolítico atípico con mutaciones en los factores I y C3 del sistema del complemento
Emanuel Ferreiraa,
Corresponding author
emanuelfeferreira@gmail.com

Corresponding author at: Servicio de Nefrología, Centro Hospitalar e Universitário de Coimbra–Hospital Geral., Rua do Buxo, lote 17, 3040-792 Coimbra, Portugal. Tel.: +351 916699039.
, Nuno Oliveiraa, Maria Marquesa, Luís Franciscob, Ana Santosa, Armando Carreiraa, Mário Camposc
a Servicio de Nefrología, Centro Hospitalar e Universitário de Coimbra–Hospital Geral, Coimbra, Portugal
b Servicio de Hematología, Centro Hospitalar e Universitário de Coimbra–Hospital Geral, Coimbra, Portugal
c Servicio de Nefrología, Centro Hospitalar e Universitário de Coimbra–Hospitais da Universidade de Coimbra, Coimbra, Portugal
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Clinical course&#58; laboratory data and treatment&#46; Corticosteroid therapy was started with intravenous administration of methylprednisolone &#40;1000<span class="elsevierStyleHsp" style=""></span>mg&#47;day for 3 days&#41; followed by oral prednisolone and an initial dosage of 60<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46; This dosage was maintained until the 53rd day after admission&#44; with posterior tapering&#46; Rituximab &#40;arrows&#41; was administered at a dose of 600<span class="elsevierStyleHsp" style=""></span>mg &#40;375<span class="elsevierStyleHsp" style=""></span>mg&#47;m2&#41; on the 27th&#44; 34th&#44; 41st and 48th days after admission&#46; Cyclophosphamide &#40;arrowhead&#41; was administered in a single dose of 1000<span class="elsevierStyleHsp" style=""></span>mg on the 61st day after admission &#40;2nd day after readmission&#41;&#46; Eculizumab was administered at a dose of 900<span class="elsevierStyleHsp" style=""></span>mg for a week for 4 weeks&#44; started on the 158th day after admission&#44; followed by a dosage of 1200<span class="elsevierStyleHsp" style=""></span>mg 1 week later an then a maintenance dose of 1200<span class="elsevierStyleHsp" style=""></span>mg every 2 weeks&#46; This dosage is still being continued&#46; We performed a total of 79 plasma exchange sessions&#46; The last three laboratorial test results were done on the 270th&#44; 340th and 466th days following first admission&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Atypical hemolytic-uremic syndrome &#40;aHUS&#41; is a rare&#44; life-threatening complement-mediated thrombotic microangiopathy&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Approximately half of cases have mutations in complement proteins but only 12&#37; have 2 or more mutations&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> Eculizumab is nowadays considered first-line therapy for aHUS&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">A 33-year-old female with unremarkable past medical history presented with a 3-day history of decreased urine output&#46; Physical examination showed hypertension &#40;160&#47;90<span class="elsevierStyleHsp" style=""></span>mmHg&#41; and lower limbs edema&#46; Investigations revealed an acute thrombotic microangiopathy &#40;ATM&#41;&#44; hematuria and nephrotic proteinuria &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Daily plasmapheresis &#40;PMP&#41; was started immediately&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Investigations for secondary causes of ATM revealed a low ADAMTS 13 activity&#44; decreased complement C4&#44; C3&#44; C1q and C2 levels and positive serum cryoglobulins &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Considering the hypothesis of an autoimmune disorder&#44; we started 3 daily pulses of 1000<span class="elsevierStyleHsp" style=""></span>mg methylprednisolone followed by oral prednisolone&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">PMP was stopped on the eighteenth day of admission &#40;D18&#41; due to normal platelet count during 3 consecutive days &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; On the D19 a renal biopsy was made&#46; It showed a &#8220;thrombotic microangiopathy with acute tubular necrosis&#8221; and &#8220;deposition of IgM&#44; C3 and C1q in the capillary wall&#8221;&#46; Due to increased hemolytic activity&#44; PMP was resumed on the D21&#46; On the D27&#44; rituximab was started to enhance immunosuppression&#46; PMP was stopped on the D35 based on the absence of schistocytosis&#44; hemoglobin stability and lactate dehydrogenase &#40;LDH&#41; normalization&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">On the D50&#44; LDH was high but hemoglobin and platelet count were stable&#46; A state of compensated hemolysis was assumed and the patient was discharged home&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Ten days later she was readmitted due to increased hemolytic activity &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; PMP was resumed and 1000<span class="elsevierStyleHsp" style=""></span>mg cyclophosphamide was given&#46; At that time ADAMTS13 and complement C4 levels were normal but complement C3 levels remained low&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">A genetic screening for mutations in complement regulatory proteins was made&#46; Two mutations were found in factor I &#40;C&#46; 452 A&#62;G&#44; pASN 151 Ser&#41; and C3 &#40;C193 A<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>C&#44; pLys 65 Gin&#41; proteins&#46; The process of eculizumab acquisition was lengthy&#44; wherefore this therapy was started only on the 98th day after readmission&#46; At that moment we were performing one PMP session&#47;week&#44; LDH remained high &#40;859<span class="elsevierStyleHsp" style=""></span>U&#47;L&#41; and moderate renal dysfunction &#40;creatinine 2&#46;08<span class="elsevierStyleHsp" style=""></span>mg&#47;dL and urea 60<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41; and nephrotic proteinuria persisted &#40;5&#46;2<span class="elsevierStyleHsp" style=""></span>g&#47;24<span class="elsevierStyleHsp" style=""></span>h&#41;&#46; Eculizumab was administered at a dose of 900<span class="elsevierStyleHsp" style=""></span>mg per week for 4 weeks followed by subsequent doses of 1200<span class="elsevierStyleHsp" style=""></span>mg every 2 weeks since the 5th week&#46; Complete hematologic remission was attained 2 days after eculizumab initiation&#46; The patient was discharged home on the 105th day after readmission&#46; Four weeks later&#44; proteinuria was only 0&#46;6<span class="elsevierStyleHsp" style=""></span>g&#47;24<span class="elsevierStyleHsp" style=""></span>h&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Currently&#44; 10 months after first infusion&#44; the patient remains under biweekly administration of eculizumab&#46; Hematologic remission persists and there is a significant recover of renal function &#40;urea 43<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; creatinine 1&#46;27<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Complement factor I &#40;CFI&#41; and C3 mutations account for 10&#37; and 4&#37; of the overall aHUS-associated mutations&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> C3 mutations are among the ones with the poorest prognosis&#58; 75&#37; risk of death or end stage renal failure &#40;ESRF&#41; at 3&#8211;5 years follow up and 50&#37; risk of recurrence&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> CFI mutations have a 50&#8211;60&#37; risk of death and ESRF at 3&#8211;5 years follow up and 10&#8211;30&#37; risk of recurrence&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Both mutations present in our patient were previously reported&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4&#44;5</span></a> The p&#46;Asn151Ser mutation causes a quantitative deficiency of factor I<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> and the p&#46;Lys65Gin mutation weakens the affinity of C3b to complement factor H&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Despite the growing importance of eculizumab&#44;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6&#44;7</span></a> PMP remains the mainstay of treatment while waiting for the immunoglobulin&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> Nonetheless&#44; its benefit depends on the underlying genetic defect &#8211; only 25&#37; and 57&#37; of those with CFI and C3 mutations&#44; respectively&#44; achieve remission&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> In our patient&#44; PMP was critical to prevent further progression of renal failure and the development of other systemic involvement&#46; However&#44; as described by Loirat&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> it was unable to achieve complete and sustained remission&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">In our case&#44; the confounding presence of low ADAMTS13&#44; C4&#44; C2 and C1q levels&#44; the presence of cryoglobulins and the existence of immune deposits in the glomerular capillary wall led to the misdiagnosis of a thrombotic thrombocytopenic purpura secondary to an autoimmune disease&#46; It explains the preference for glucocorticoids&#44; rituximab and cyclophosphamide in relation to eculizumab&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Eculizumab is nowadays considered first-line therapy for aHUS&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> It is a humanized monoclonal immunoglobulin IgG that targets C5 and blocks the uncontrolled generation of the cytotoxic membrane attack complex&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> When we started Eculizumab&#44; our patient was still PMP dependent despite the 79 PMP sessions&#46; Contrariwise&#44; complete hematologic remission was attained two days after first infusion and a remarkable recover of renal function and reduction of proteinuria was evident&#46; These findings reinforce the benefits of eculizumab in aHUS&#44; even in cases of severe renal involvement&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">In conclusion&#44; our case highlights the diagnostic challenge of aHUS and emphasizes the notion that isolated PMP is no longer the best therapeutic option in aHUS&#44; in which cases a prompt switch to eculizumab is mandatory&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest related to the contents of this article&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Ferreira E&#44; Oliveira N&#44; Marques M&#44; Francisco L&#44; Santos A&#44; Carreira A&#44; et al&#46; Eculizumab for the treatment of an atypical hemolytic uremic syndrome with mutations in complement factor I and C3&#46; Nefrologia&#46; 2016&#59;36&#58;72&#8211;75&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Clinical course&#58; laboratory data and treatment&#46; Corticosteroid therapy was started with intravenous administration of methylprednisolone &#40;1000<span class="elsevierStyleHsp" style=""></span>mg&#47;day for 3 days&#41; followed by oral prednisolone and an initial dosage of 60<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46; This dosage was maintained until the 53rd day after admission&#44; with posterior tapering&#46; Rituximab &#40;arrows&#41; was administered at a dose of 600<span class="elsevierStyleHsp" style=""></span>mg &#40;375<span class="elsevierStyleHsp" style=""></span>mg&#47;m2&#41; on the 27th&#44; 34th&#44; 41st and 48th days after admission&#46; Cyclophosphamide &#40;arrowhead&#41; was administered in a single dose of 1000<span class="elsevierStyleHsp" style=""></span>mg on the 61st day after admission &#40;2nd day after readmission&#41;&#46; Eculizumab was administered at a dose of 900<span class="elsevierStyleHsp" style=""></span>mg for a week for 4 weeks&#44; started on the 158th day after admission&#44; followed by a dosage of 1200<span class="elsevierStyleHsp" style=""></span>mg 1 week later an then a maintenance dose of 1200<span class="elsevierStyleHsp" style=""></span>mg every 2 weeks&#46; This dosage is still being continued&#46; We performed a total of 79 plasma exchange sessions&#46; The last three laboratorial test results were done on the 270th&#44; 340th and 466th days following first admission&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">On admission</th></tr><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable&nbsp;\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">Result&nbsp;\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">Normal range&nbsp;\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">Hemoglobin &#40;g&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#8211;16&nbsp;\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">White-cell count &#40;&#215;10<span class="elsevierStyleSup">3</span>&#47;mm<span class="elsevierStyleSup">3</span>&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#8211;10&nbsp;\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">Platelet count &#40;&#215;10<span class="elsevierStyleSup">3</span>&#47;mm<span class="elsevierStyleSup">3</span>&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">150&#8211;400&nbsp;\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">Peripheral blood smear<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 schistocytes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;2 schistocytes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;0&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;3&#8211;2&nbsp;\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">Direct coombs tests&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Negative&nbsp;\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 &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">114&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&#8211;38&nbsp;\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">Creatinine &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;52&#8211;1&#46;04&nbsp;\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">Sodium &#40;mmol&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">135&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">137&#8211;145&nbsp;\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">Potassium &#40;mmol&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;5&#8211;5&#46;1&nbsp;\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">Lactate dehydrogenase &#40;U&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2827&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">313&#8211;618&nbsp;\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">c-Reactive protein &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;1&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">URINALYSIS</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Protein &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\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"><span class="elsevierStyleHsp" style=""></span>Leukocytes &#40;&#47;HPF&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;5&#47;c&nbsp;\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"><span class="elsevierStyleHsp" style=""></span>Red blood cells &#40;&#47;HPF&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;2&#47;c&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;0&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  \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">CH50 &#40;U&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23&#8211;46&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">118&#8211;244&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">197&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">180&#47;320&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">40&#8211;130&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\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">Auto-immune antibodies<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&#44; Pregnancy test&#44; SPE&#44; Tumoral markers<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&#44; HIV&#44; HBV&#44; HCV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Negative&#47;Normal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\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">Blood&#44; urine and stool cultures&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\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">Upper endoscopy&#44; colonoscopy&#44; cervical&#44; thoracic and abdominopelvic CT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Irrelevant changes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar9005">Peripheral blood smear was done to evaluate presence of erythrocyte fragmentation and is reported as schistocytes count in a microscopic field at 100&#215; magnification&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Antinuclear antibodies&#44; extractable nuclear antigens&#44; anti-neutrophil cytoplasmic antibodies&#44; glomerular basement membrane&#44; rheumatoid factor&#44; cyclic citrullinated peptide&#44; anticardiolipin&#47;anti-&#946;2-glycoprotein&#44; Lupus anticoagulant&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Carcinoembryonic antigen&#44; carbohydrate antigen 19-9&#44; &#945;-fetoprotein&#44; cancer antigen 125&#44; neuron-specific enolase&#44; NSE&#46;</p> <p class="elsevierStyleNotepara" id="npar0020"><span class="elsevierStyleItalic">Abbreviations</span>&#58; ADAMTS13&#59; a disintegrin and metalloproteinase with a thrombospondin type 1 motif&#59; member 13&#46; CT&#59; computerized tomography&#46; HBV&#59; hepatitis B virus&#46; HCV&#59; hepatitis C virus&#46; HIV&#59; human immunodeficiency virus&#46; SPE&#59; serum protein electrophoresis&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Laboratorial results on admission and additional studies to establish the cause of the thrombotic microangiopathy&#46;</p>"
        ]
      ]
    ]
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      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:10 [
            0 => array:3 [
              "identificador" => "bib0055"
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              "referencia" => array:1 [
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                  "contribucion" => array:1 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                            0 => "V&#46; Fremeaux-Bacchi"
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                        ]
                      ]
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                  ]
                  "host" => array:1 [
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                      "Revista" => array:6 [
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            1 => array:3 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                            0 => "C&#46; Loirat"
                            1 => "V&#46; Fr&#233;meaux-Bacchi"
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1750-1172-6-60"
                      "Revista" => array:5 [
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            2 => array:3 [
              "identificador" => "bib0065"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Actualizaci&#243;n en s&#237;ndrome hemol&#237;tico ur&#233;mico at&#237;pico&#58; diagn&#243;stico y tratamiento&#46; Documento de consenso"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
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                            0 => "J&#46;M&#46; Campistol"
                            1 => "M&#46; Arias"
                            2 => "G&#46; Ariceta"
                            3 => "M&#46; Blasco"
                            4 => "M&#46; Espinosa"
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                          ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3265/Nefrologia.pre2012.Nov.11781"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nefrologia"
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            3 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "Mutations in components of complement influence the outcome of Factor I-associated atypical hemolytic uremic syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; Bienaime"
                            1 => "M&#46;A&#46; Dragon-Durey"
                            2 => "C&#46;H&#46; Regnier"
                            3 => "S&#46;C&#46; Nilsson"
                            4 => "W&#46;H&#46; Kwan"
                            5 => "J&#46; Blouin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ki.2009.472"
                      "Revista" => array:6 [
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            ]
            4 => array:3 [
              "identificador" => "bib0075"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Novel C3 mutation p&#46;Lys65Gln in aHUS affects complement factor H binding"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "E&#46; Volokhina"
                            1 => "D&#46; Westra"
                            2 => "X&#46; Xue"
                            3 => "P&#46; Gros"
                            4 => "N&#46; van de Kar"
                            5 => "L&#46; van den Heuvel"
                          ]
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00467-012-2183-z"
                      "Revista" => array:6 [
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              ]
            ]
            5 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A systematic review of eculizumab for atypical haemolytic uraemic syndrome &#40;aHUS&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "J&#46; Rathbone"
                            1 => "E&#46; Kaltenthaler"
                            2 => "A&#46; Richards"
                            3 => "P&#46; Tappenden"
                            4 => "A&#46; Bessey"
                            5 => "A&#46; Cantrell"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/bmjopen-2013-003573"
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              ]
            ]
            6 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46;M&#46; Legendre"
                            1 => "C&#46; Licht"
                            2 => "P&#46; Muus"
                            3 => "L&#46;A&#46; Greenbaum"
                            4 => "S&#46; Babu"
                            5 => "C&#46; Bedrosian"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1208981"
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                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Noris"
                            1 => "J&#46; Caprioli"
                            2 => "E&#46; Bresin"
                            3 => "C&#46; Mossali"
                            4 => "G&#46; Pianetti"
                            5 => "S&#46; Gamba"
                          ]
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Article information
ISSN: 20132514
Original language: English
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