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Bars<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>mean gelsolin level; error bar<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>standard deviation. *<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.005.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. Rodríguez-Rodríguez, J.J. Egea-Guerrero, Z. Ruiz de Azúa-López, G. Rivera-Rubiales, Á. Vilches-Arenas, F. Murillo-Cabezas" "autores" => array:6 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "Rodríguez-Rodríguez" ] 1 => array:2 [ "nombre" => "J.J." "apellidos" => "Egea-Guerrero" ] 2 => array:2 [ "nombre" => "Z." "apellidos" => "Ruiz de Azúa-López" ] 3 => array:2 [ "nombre" => "G." "apellidos" => "Rivera-Rubiales" ] 4 => array:2 [ "nombre" => "Á." "apellidos" => "Vilches-Arenas" ] 5 => array:2 [ "nombre" => "F." 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Should these patients be admitted to the Intensive Care Unit?" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "60" "paginaFinal" => "62" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "R. Rodríguez-García, M.J. Espina, L. Viña, I. Astola, L. López-Amor, D. Escudero" "autores" => array:6 [ 0 => array:4 [ "nombre" => "R." "apellidos" => "Rodríguez-García" "email" => array:1 [ 0 => "rakel_20r@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "M.J." "apellidos" => "Espina" ] 2 => array:2 [ "nombre" => "L." "apellidos" => "Viña" ] 3 => array:2 [ "nombre" => "I." "apellidos" => "Astola" ] 4 => array:2 [ "nombre" => "L." "apellidos" => "López-Amor" ] 5 => array:2 [ "nombre" => "D." "apellidos" => "Escudero" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Medicina Intensiva, Hospital Universitario Central de Asturias, Oviedo, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tratamiento con carfilzomib. ¿Deberían estos pacientes ingresar en la unidad de cuidados intensivos?" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1092 "Ancho" => 3333 "Tamanyo" => 801152 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Electrocardiogram: sinus rhythm with ST-segment depression on inferolateral aspect.</p>" ] ] ] "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. However, these drugs are not free from side effects that can be potentially life-threatening for the patient. Considering the potential hazards, it is necessary to determine whether the use of such drugs requires protocolized admission to the Intensive Care Unit (ICU) of patients considered to be at risk, in order to guarantee strict vigilance and monitoring.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a 56-year-old male with multiple myeloma, no other clinical antecedents of interest, and no previous heart disease who suffered cardiac arrest following the administration of chemotherapy with carfilzomib (Kyprolis<span class="elsevierStyleSup">®</span>). The patient was diagnosed with multiple myeloma (IgG, initial stage IIIA, ISS-I) in 2003 and received radiotherapy, chemotherapy, rescue therapy with hematopoietic stem cells, and posterior consolidation in the form of autogenous transplantation. Two transthoracic echocardiographic studies (in 2011 and 2012) revealed mild tricuspid and mitral valve insufficiency, with no other relevant alterations. Following complete remission, biological progression was observed in 2012. Despite administration of a new chemotherapy cycle, a progressive increase in the monoclonal component was noted, with multiple hypermetabolic foci corresponding to tumor infiltration. Therapy was started with pomalidomide, dexamethasone and cyclophosphamide. Since this treatment proved ineffective and disease progression was observed, alternative treatment was considered in the form of carfilzomib, lenalidomide and dexamethasone (KRd). Treatment with carfilzomib was started with no prior echocardiographic study. The dosing scheme was 20<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span> on days 1 and 2 of the cycle, and 27<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span> on days 8, 9, 15 and 16. The first cycle proved uneventful, though during infusion of the second cycle, 28 days later, the patient suffered sudden dyspnea and febrile syndrome with the second dose, requiring admission to the Department of Hematology. Under conditions of hypotension, poor perfusion and acute respiratory failure, a brain CT scan and thoracic angioCT study were made, which discarded pulmonary embolism and brain disease. Echocardiography in turn revealed mild-moderate mitral valve insufficiency and mild tricuspid valve insufficiency, with the estimation of a systolic pulmonary artery pressure of 37<span class="elsevierStyleHsp" style=""></span>mmHg. Empirical antibiotic treatment was started, with fluid therapy and oxygen therapy, followed by clinical improvement. However, 3<span class="elsevierStyleHsp" style=""></span>h later the patient presented acute lung edema followed by cardiac arrest. The usual cardiopulmonary resuscitation maneuvers were applied during 5<span class="elsevierStyleHsp" style=""></span>min, with the administration of 1<span class="elsevierStyleHsp" style=""></span>mg of adrenalin, after which rhythm recovery in atrial fibrillation was observed, and the patient was moved to the ICU. The chest X-rays confirmed the diagnosis of acute lung edema, exhibiting a “butterfly wing” pattern, with perihilar redistribution and cardiomegalia. The ECG tracing showed ST-segment depression on the inferolateral aspect (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), with no significant enzyme changes (troponin T 53<span class="elsevierStyleHsp" style=""></span>ng/l). Coronary angiography was not performed, since the patient referred no chest pain suggestive of ischemic heart disease, and the electrocardiographic changes were set in the context of cardiac arrest. Treatment was provided in the form of furosemide, corticosteroids and antibiotics, followed by good neurological, hemodynamic and respiratory recovery. Monitoring revealed no new electrocardiographic changes, and discharge was therefore decided 48<span class="elsevierStyleHsp" style=""></span>h after admission. The cardiac event was considered to probably constitute a side effect of carfilzomib. Over the subsequent days the patient again suffered clinical worsening due to progression of his hematological disease. The patient rejected the continuation of medical treatment and died in the Hematology ward 10 days later.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Carfilzomib, authorized in 2012, is a potent second-generation 20S proteasome chymotrypsin type activity inhibitor used to treat refractory multiple myeloma and other diseases such as Waldenstrom's macroglobulinemia, lymphoma amyloidosis and certain autoimmune diseases.<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. Dexamethasone premedication is advised in order to minimize the intensity of frequent symptoms such as fever, nausea, fatigue or headache.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> Carfilzomib has a broad range of adverse effects, from transfusion reactions to both hematological (thrombocytopenia and anemia) and non-hematological complications.<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/m<span class="elsevierStyleSup">2</span>, though higher doses also increase the risk of cardiovascular adverse events. Carfilzomib is characterized by low peripheral neuropathy rates (such complications being common with other therapeutic regimens based on bortezomib), though recent case series and studies indicate that treatment with proteasome inhibitors can be associated to serious cardiac events.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> The initial clinical trials recorded episodes of heart problems with congestive heart failure, lung edema and a decrease in left ventricular function in 7% of the patients–the most frequently described adverse events being arrhythmias, most of which were of a benign nature and of supraventricular origin.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> More recent publications report a large number of cardiac complications. Danhof et al.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> described serious adverse effects in 50% of the patients, with left heart failure in 23%. The risk of cardiac adverse events was higher in patients concomitantly receiving doxorubicin or thoracic radiotherapy, as in our case. Careful patient selection is therefore advised, with close monitoring of the population at risk. <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> describes the adverse effects and risk factors for cardiac toxicity.</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. The most important of these mechanisms is the accumulation of damaged and non-degraded proteins within the myocytes, which may prove toxic for the cells.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> In animal models the drug has been shown to induce ventricular dysfunction, and at structural level cardiomyocyte enlargement and vacuolization have been observed, as well as mitochondrial pleomorphism, perivascular interstitial fibrosis and the induction of apoptosis.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> Furthermore, proteasome inhibition generates changes in endothelial nitric oxide synthase (eNOS) activity and in nitric oxide levels–this in turn leading to vasodilatation and endothelial dysfunction associated with arterial hypertension and coronary disease, among other conditions. Other drugs are also under study, such as apremilast, which exerts a protective effect against carfilzomib-induced cardiotoxicity, and thus plays a key role in the modulation of oxidative stress.<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. 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. This would require the introduction of protocols involving multiple disciplines (Clinical pharmacology, Hematology and Intensive Care Medicine) in order to select those patients considered to be at high risk and who could benefit from such monitoring, in view of the limited number of ICU beds available.</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.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Rodríguez-García R, Espina MJ, Viña L, Astola I, López-Amor L, Escudero D. Tratamiento con carfilzomib. ¿Deberían estos pacientes ingresar en la unidad de cuidados intensivos? Med Intensiva. 2018;42:60–62.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1092 "Ancho" => 3333 "Tamanyo" => 801152 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Electrocardiogram: sinus rhythm with ST-segment depression on inferolateral aspect.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Adverse events, percentage \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 \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 (13.3%) \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 \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 (7.2–23%) \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 \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 (3.4%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Thoracic radiotherapy \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 (1.7%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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 (42.2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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 (46.8%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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 (36.3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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 (20.7%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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 (12.7%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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 (24.1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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 (5.3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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>Hyperglycemia (12%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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>Water-electrolyte alterations: hypopotassemia (14%), hypomagnesemia (14%), hypercalcemia (11%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1662623.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Cardiovascular adverse effects of carfilzomib and cardiac toxicity risk factors.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Carfilzomib" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "K.M. 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Year/Month | Html | Total | |
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2024 November | 6 | 5 | 11 |
2024 October | 68 | 50 | 118 |
2024 September | 96 | 37 | 133 |
2024 August | 135 | 52 | 187 |
2024 July | 90 | 26 | 116 |
2024 June | 123 | 48 | 171 |
2024 May | 74 | 28 | 102 |
2024 April | 99 | 45 | 144 |
2024 March | 89 | 33 | 122 |
2024 February | 100 | 38 | 138 |
2024 January | 97 | 33 | 130 |
2023 December | 123 | 38 | 161 |
2023 November | 102 | 32 | 134 |
2023 October | 85 | 31 | 116 |
2023 September | 84 | 32 | 116 |
2023 August | 62 | 14 | 76 |
2023 July | 82 | 30 | 112 |
2023 June | 81 | 16 | 97 |
2023 May | 65 | 42 | 107 |
2023 April | 56 | 29 | 85 |
2023 March | 117 | 35 | 152 |
2023 February | 94 | 38 | 132 |
2023 January | 88 | 22 | 110 |
2022 December | 82 | 48 | 130 |
2022 November | 112 | 34 | 146 |
2022 October | 82 | 46 | 128 |
2022 September | 92 | 40 | 132 |
2022 August | 105 | 44 | 149 |
2022 July | 101 | 30 | 131 |
2022 June | 48 | 29 | 77 |
2022 May | 61 | 34 | 95 |
2022 April | 56 | 49 | 105 |
2022 March | 69 | 72 | 141 |
2022 February | 49 | 31 | 80 |
2022 January | 90 | 38 | 128 |
2021 December | 64 | 44 | 108 |
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2021 October | 89 | 89 | 178 |
2021 September | 51 | 43 | 94 |
2021 August | 76 | 42 | 118 |
2021 July | 69 | 34 | 103 |
2021 June | 52 | 31 | 83 |
2021 May | 70 | 58 | 128 |
2021 April | 157 | 100 | 257 |
2021 March | 125 | 39 | 164 |
2021 February | 141 | 33 | 174 |
2021 January | 94 | 25 | 119 |
2020 December | 66 | 15 | 81 |
2020 November | 76 | 23 | 99 |
2020 October | 60 | 26 | 86 |
2020 September | 61 | 22 | 83 |
2020 August | 67 | 23 | 90 |
2020 July | 64 | 37 | 101 |
2020 June | 46 | 16 | 62 |
2020 May | 50 | 10 | 60 |
2020 April | 36 | 18 | 54 |
2020 March | 42 | 19 | 61 |
2020 February | 122 | 40 | 162 |
2020 January | 53 | 25 | 78 |
2019 December | 65 | 25 | 90 |
2019 November | 42 | 29 | 71 |
2019 October | 60 | 24 | 84 |
2019 September | 52 | 31 | 83 |
2019 August | 55 | 28 | 83 |
2019 July | 52 | 32 | 84 |
2019 June | 42 | 19 | 61 |
2019 May | 51 | 48 | 99 |
2019 April | 40 | 19 | 59 |
2019 March | 19 | 23 | 42 |
2019 February | 67 | 37 | 104 |
2019 January | 46 | 42 | 88 |
2018 December | 44 | 37 | 81 |
2018 November | 51 | 76 | 127 |
2018 October | 76 | 18 | 94 |
2018 September | 69 | 14 | 83 |
2018 August | 27 | 11 | 38 |
2018 July | 38 | 14 | 52 |
2018 June | 38 | 17 | 55 |
2018 May | 12 | 4 | 16 |
2018 January | 0 | 1 | 1 |