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Empirical antibiotic treatment was started&#44; with fluid therapy and oxygen therapy&#44; followed by clinical improvement&#46; However&#44; 3<span class="elsevierStyleHsp" style=""></span>h later the patient presented acute lung edema followed by cardiac arrest&#46; The usual cardiopulmonary resuscitation maneuvers were applied during 5<span class="elsevierStyleHsp" style=""></span>min&#44; with the administration of 1<span class="elsevierStyleHsp" style=""></span>mg of adrenalin&#44; after which rhythm recovery in atrial fibrillation was observed&#44; and the patient was moved to the ICU&#46; The chest X-rays confirmed the diagnosis of acute lung edema&#44; exhibiting a &#8220;butterfly wing&#8221; pattern&#44; with perihilar redistribution and cardiomegalia&#46; The ECG tracing showed ST-segment depression on the inferolateral aspect &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#44; with no significant enzyme changes &#40;troponin T 53<span class="elsevierStyleHsp" style=""></span>ng&#47;l&#41;&#46; Coronary angiography was not performed&#44; since the patient referred no chest pain suggestive of ischemic heart disease&#44; and the electrocardiographic changes were set in the context of cardiac arrest&#46; Treatment was provided in the form of furosemide&#44; corticosteroids and antibiotics&#44; followed by good neurological&#44; hemodynamic and respiratory recovery&#46; Monitoring revealed no new electrocardiographic changes&#44; and discharge was therefore decided 48<span class="elsevierStyleHsp" style=""></span>h after admission&#46; The cardiac event was considered to probably constitute a side effect of carfilzomib&#46; Over the subsequent days the patient again suffered clinical worsening due to progression of his hematological disease&#46; The patient rejected the continuation of medical treatment and died in the Hematology ward 10 days later&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Carfilzomib&#44; authorized in 2012&#44; is a potent second-generation 20S proteasome chymotrypsin type activity inhibitor used to treat refractory multiple myeloma and other diseases such as Waldenstrom&#39;s macroglobulinemia&#44; lymphoma amyloidosis and certain autoimmune diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> The drug is administered via the intravenous route in an interval of about 10<span class="elsevierStyleHsp" style=""></span>min&#46; Dexamethasone premedication is advised in order to minimize the intensity of frequent symptoms such as fever&#44; nausea&#44; fatigue or headache&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> Carfilzomib has a broad range of adverse effects&#44; from transfusion reactions to both hematological &#40;thrombocytopenia and anemia&#41; and non-hematological complications&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> The PX-171-007 trial reported that a high dose of carfilzomib results in greater efficacy than the approved dose<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> of 27<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span>&#44; though higher doses also increase the risk of cardiovascular adverse events&#46; Carfilzomib is characterized by low peripheral neuropathy rates &#40;such complications being common with other therapeutic regimens based on bortezomib&#41;&#44; though recent case series and studies indicate that treatment with proteasome inhibitors can be associated to serious cardiac events&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> The initial clinical trials recorded episodes of heart problems with congestive heart failure&#44; lung edema and a decrease in left ventricular function in 7&#37; of the patients&#8211;the most frequently described adverse events being arrhythmias&#44; most of which were of a benign nature and of supraventricular origin&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> More recent publications report a large number of cardiac complications&#46; Danhof et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> described serious adverse effects in 50&#37; of the patients&#44; with left heart failure in 23&#37;&#46; The risk of cardiac adverse events was higher in patients concomitantly receiving doxorubicin or thoracic radiotherapy&#44; as in our case&#46; Careful patient selection is therefore advised&#44; with close monitoring of the population at risk&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> describes the adverse effects and risk factors for cardiac toxicity&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">It has been postulated that the cardiovascular effects can be mediated by different mechanisms derived from proteasome inhibition&#46; The most important of these mechanisms is the accumulation of damaged and non-degraded proteins within the myocytes&#44; which may prove toxic for the cells&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> In animal models the drug has been shown to induce ventricular dysfunction&#44; and at structural level cardiomyocyte enlargement and vacuolization have been observed&#44; as well as mitochondrial pleomorphism&#44; perivascular interstitial fibrosis and the induction of apoptosis&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> Furthermore&#44; proteasome inhibition generates changes in endothelial nitric oxide synthase &#40;eNOS&#41; activity and in nitric oxide levels&#8211;this in turn leading to vasodilatation and endothelial dysfunction associated with arterial hypertension and coronary disease&#44; among other conditions&#46; Other drugs are also under study&#44; such as apremilast&#44; which exerts a protective effect against carfilzomib-induced cardiotoxicity&#44; and thus plays a key role in the modulation of oxidative stress&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Oncohematological patients are fragile and require very complex management&#46; Preventing serious adverse events in patients at risk though admission to intensive care for electrocardiographic and cardiorespiratory monitoring could prove necessary and constitute a new healthcare offer on the part of ICUs&#46; This would require the introduction of protocols involving multiple disciplines &#40;Clinical pharmacology&#44; Hematology and Intensive Care Medicine&#41; in order to select those patients considered to be at high risk and who could benefit from such monitoring&#44; in view of the limited number of ICU beds available&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0030" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Rodr&#237;guez-Garc&#237;a R&#44; Espina MJ&#44; Vi&#241;a L&#44; Astola I&#44; L&#243;pez-Amor L&#44; Escudero D&#46; Tratamiento con carfilzomib&#46; &#191;Deber&#237;an estos pacientes ingresar en la unidad de cuidados intensivos&#63; Med Intensiva&#46; 2018&#59;42&#58;60&#8211;62&#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  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Adverse events&#44; percentage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Cardiac toxicity risk factors&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" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Cardiovascular</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>Cardiac arrhythmia &#40;13&#46;3&#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">Previous cardiovascular disease&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>Heart failure &#40;7&#46;2&#8211;23&#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">Combination treatment with doxorubicin&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>Coronary disease &#40;3&#46;4&#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">Thoracic radiotherapy&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>Myocardiopathy &#40;1&#46;7&#37;&#41;&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>Dyspnea &#40;42&#46;2&#37;&#41;&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" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Hematological</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>Anemia &#40;46&#46;8&#37;&#41;&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>Thrombocytopenia &#40;36&#46;3&#37;&#41;&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>Neutropenia &#40;20&#46;7&#37;&#41;&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" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Others</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>Pneumonia &#40;12&#46;7&#37;&#41;&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>Serum creatinine elevation &#40;24&#46;1&#37;&#41;&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
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Scientific Letter
Treatment with carfilzomib. Should these patients be admitted to the Intensive Care Unit?
Tratamiento con carfilzomib. ¿Deberían estos pacientes ingresar en la unidad de cuidados intensivos?
R. Rodríguez-García
Corresponding author
rakel_20r@hotmail.com

Corresponding author.
, M.J. Espina, L. Viña, I. Astola, L. López-Amor, D. Escudero
Servicio de Medicina Intensiva, Hospital Universitario Central de Asturias, Oviedo, Spain
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Electrocardiogram&#58; sinus rhythm with ST-segment depression on inferolateral aspect&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The new drug treatments for different hematological neoplasms have improved the prognosis of these diseases by expanding the available therapeutic options&#46; However&#44; these drugs are not free from side effects that can be potentially life-threatening for the patient&#46; Considering the potential hazards&#44; it is necessary to determine whether the use of such drugs requires protocolized admission to the Intensive Care Unit &#40;ICU&#41; of patients considered to be at risk&#44; in order to guarantee strict vigilance and monitoring&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a 56-year-old male with multiple myeloma&#44; no other clinical antecedents of interest&#44; and no previous heart disease who suffered cardiac arrest following the administration of chemotherapy with carfilzomib &#40;Kyprolis<span class="elsevierStyleSup">&#174;</span>&#41;&#46; The patient was diagnosed with multiple myeloma &#40;IgG&#44; initial stage IIIA&#44; ISS-I&#41; in 2003 and received radiotherapy&#44; chemotherapy&#44; rescue therapy with hematopoietic stem cells&#44; and posterior consolidation in the form of autogenous transplantation&#46; Two transthoracic echocardiographic studies &#40;in 2011 and 2012&#41; revealed mild tricuspid and mitral valve insufficiency&#44; with no other relevant alterations&#46; Following complete remission&#44; biological progression was observed in 2012&#46; Despite administration of a new chemotherapy cycle&#44; a progressive increase in the monoclonal component was noted&#44; with multiple hypermetabolic foci corresponding to tumor infiltration&#46; Therapy was started with pomalidomide&#44; dexamethasone and cyclophosphamide&#46; Since this treatment proved ineffective and disease progression was observed&#44; alternative treatment was considered in the form of carfilzomib&#44; lenalidomide and dexamethasone &#40;KRd&#41;&#46; Treatment with carfilzomib was started with no prior echocardiographic study&#46; The dosing scheme was 20<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span> on days 1 and 2 of the cycle&#44; and 27<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span> on days 8&#44; 9&#44; 15 and 16&#46; The first cycle proved uneventful&#44; though during infusion of the second cycle&#44; 28 days later&#44; the patient suffered sudden dyspnea and febrile syndrome with the second dose&#44; requiring admission to the Department of Hematology&#46; Under conditions of hypotension&#44; poor perfusion and acute respiratory failure&#44; a brain CT scan and thoracic angioCT study were made&#44; which discarded pulmonary embolism and brain disease&#46; Echocardiography in turn revealed mild-moderate mitral valve insufficiency and mild tricuspid valve insufficiency&#44; with the estimation of a systolic pulmonary artery pressure of 37<span class="elsevierStyleHsp" style=""></span>mmHg&#46; Empirical antibiotic treatment was started&#44; with fluid therapy and oxygen therapy&#44; followed by clinical improvement&#46; However&#44; 3<span class="elsevierStyleHsp" style=""></span>h later the patient presented acute lung edema followed by cardiac arrest&#46; The usual cardiopulmonary resuscitation maneuvers were applied during 5<span class="elsevierStyleHsp" style=""></span>min&#44; with the administration of 1<span class="elsevierStyleHsp" style=""></span>mg of adrenalin&#44; after which rhythm recovery in atrial fibrillation was observed&#44; and the patient was moved to the ICU&#46; The chest X-rays confirmed the diagnosis of acute lung edema&#44; exhibiting a &#8220;butterfly wing&#8221; pattern&#44; with perihilar redistribution and cardiomegalia&#46; The ECG tracing showed ST-segment depression on the inferolateral aspect &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#44; with no significant enzyme changes &#40;troponin T 53<span class="elsevierStyleHsp" style=""></span>ng&#47;l&#41;&#46; Coronary angiography was not performed&#44; since the patient referred no chest pain suggestive of ischemic heart disease&#44; and the electrocardiographic changes were set in the context of cardiac arrest&#46; Treatment was provided in the form of furosemide&#44; corticosteroids and antibiotics&#44; followed by good neurological&#44; hemodynamic and respiratory recovery&#46; Monitoring revealed no new electrocardiographic changes&#44; and discharge was therefore decided 48<span class="elsevierStyleHsp" style=""></span>h after admission&#46; The cardiac event was considered to probably constitute a side effect of carfilzomib&#46; Over the subsequent days the patient again suffered clinical worsening due to progression of his hematological disease&#46; The patient rejected the continuation of medical treatment and died in the Hematology ward 10 days later&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Carfilzomib&#44; authorized in 2012&#44; is a potent second-generation 20S proteasome chymotrypsin type activity inhibitor used to treat refractory multiple myeloma and other diseases such as Waldenstrom&#39;s macroglobulinemia&#44; lymphoma amyloidosis and certain autoimmune diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> The drug is administered via the intravenous route in an interval of about 10<span class="elsevierStyleHsp" style=""></span>min&#46; Dexamethasone premedication is advised in order to minimize the intensity of frequent symptoms such as fever&#44; nausea&#44; fatigue or headache&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> Carfilzomib has a broad range of adverse effects&#44; from transfusion reactions to both hematological &#40;thrombocytopenia and anemia&#41; and non-hematological complications&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> The PX-171-007 trial reported that a high dose of carfilzomib results in greater efficacy than the approved dose<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> of 27<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span>&#44; though higher doses also increase the risk of cardiovascular adverse events&#46; Carfilzomib is characterized by low peripheral neuropathy rates &#40;such complications being common with other therapeutic regimens based on bortezomib&#41;&#44; though recent case series and studies indicate that treatment with proteasome inhibitors can be associated to serious cardiac events&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> The initial clinical trials recorded episodes of heart problems with congestive heart failure&#44; lung edema and a decrease in left ventricular function in 7&#37; of the patients&#8211;the most frequently described adverse events being arrhythmias&#44; most of which were of a benign nature and of supraventricular origin&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> More recent publications report a large number of cardiac complications&#46; Danhof et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> described serious adverse effects in 50&#37; of the patients&#44; with left heart failure in 23&#37;&#46; The risk of cardiac adverse events was higher in patients concomitantly receiving doxorubicin or thoracic radiotherapy&#44; as in our case&#46; Careful patient selection is therefore advised&#44; with close monitoring of the population at risk&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> describes the adverse effects and risk factors for cardiac toxicity&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">It has been postulated that the cardiovascular effects can be mediated by different mechanisms derived from proteasome inhibition&#46; The most important of these mechanisms is the accumulation of damaged and non-degraded proteins within the myocytes&#44; which may prove toxic for the cells&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> In animal models the drug has been shown to induce ventricular dysfunction&#44; and at structural level cardiomyocyte enlargement and vacuolization have been observed&#44; as well as mitochondrial pleomorphism&#44; perivascular interstitial fibrosis and the induction of apoptosis&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> Furthermore&#44; proteasome inhibition generates changes in endothelial nitric oxide synthase &#40;eNOS&#41; activity and in nitric oxide levels&#8211;this in turn leading to vasodilatation and endothelial dysfunction associated with arterial hypertension and coronary disease&#44; among other conditions&#46; Other drugs are also under study&#44; such as apremilast&#44; which exerts a protective effect against carfilzomib-induced cardiotoxicity&#44; and thus plays a key role in the modulation of oxidative stress&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Oncohematological patients are fragile and require very complex management&#46; Preventing serious adverse events in patients at risk though admission to intensive care for electrocardiographic and cardiorespiratory monitoring could prove necessary and constitute a new healthcare offer on the part of ICUs&#46; This would require the introduction of protocols involving multiple disciplines &#40;Clinical pharmacology&#44; Hematology and Intensive Care Medicine&#41; in order to select those patients considered to be at high risk and who could benefit from such monitoring&#44; in view of the limited number of ICU beds available&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0030" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Rodr&#237;guez-Garc&#237;a R&#44; Espina MJ&#44; Vi&#241;a L&#44; Astola I&#44; L&#243;pez-Amor L&#44; Escudero D&#46; Tratamiento con carfilzomib&#46; &#191;Deber&#237;an estos pacientes ingresar en la unidad de cuidados intensivos&#63; Med Intensiva&#46; 2018&#59;42&#58;60&#8211;62&#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  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Adverse events&#44; percentage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Cardiac toxicity risk factors&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" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Cardiovascular</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>Cardiac arrhythmia &#40;13&#46;3&#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">Previous cardiovascular disease&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>Heart failure &#40;7&#46;2&#8211;23&#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">Combination treatment with doxorubicin&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>Coronary disease &#40;3&#46;4&#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">Thoracic radiotherapy&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>Myocardiopathy &#40;1&#46;7&#37;&#41;&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>Dyspnea &#40;42&#46;2&#37;&#41;&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" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Hematological</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>Anemia &#40;46&#46;8&#37;&#41;&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>Thrombocytopenia &#40;36&#46;3&#37;&#41;&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>Neutropenia &#40;20&#46;7&#37;&#41;&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" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Others</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>Pneumonia &#40;12&#46;7&#37;&#41;&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>Serum creatinine elevation &#40;24&#46;1&#37;&#41;&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>Acute renal failure &#40;5&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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          "identificador" => "bibs0015"
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ISSN: 21735727
Original language: English
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