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aorta; RC: right coronary artery; Cx: circumflex coronary artery; DA: anterior descending coronary artery; Dg: diagonal coronary artery.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Antonio Padilla-Serrano, José Antonio Fernández-Sánchez, Rafael De la Chica Ruíz-Ruano" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Antonio" "apellidos" => "Padilla-Serrano" ] 1 => array:2 [ "nombre" => "José Antonio" "apellidos" => "Fernández-Sánchez" ] 2 => array:2 [ "nombre" => "Rafael" "apellidos" => "De la Chica Ruíz-Ruano" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775323001124" "doi" => "10.1016/j.medcli.2023.02.012" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775323001124?idApp=UINPBA00004N" ] 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"gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S002577532300146X?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020623002425?idApp=UINPBA00004N" "url" => "/23870206/0000016100000001/v2_202311101438/S2387020623002425/v2_202311101438/en/main.assets" ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Immune-mediated diabetes associated with pembrolizumab" "tieneTextoCompleto" => true "saludo" => "<span class="elsevierStyleItalic">Dear Editor,</span>" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "39" "paginaFinal" => "40" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Javier Bodoque Cubas, Juan José Salazar González, Marcel.la Miret Llauradó" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Javier" "apellidos" => "Bodoque Cubas" "email" => array:1 [ 0 => "xavierbcubas.end@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Juan José" "apellidos" => "Salazar González" ] 2 => array:2 [ "nombre" => "Marcel.la" "apellidos" => "Miret Llauradó" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Hospital de Tortosa Verge de la Cinta, Tortosa, Tarragona, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Diabetes inmunomediada asociada a pembrolizumab" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">This article has been submitted in accordance with the indications of our centre's health care ethics committee after obtaining the patient's informed consent.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Immunotherapy has changed the course of the disease for many cancer patients.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> However, as it blocks immune checkpoints, it can be associated with autoimmune reactions, including immune-mediated diabetes.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">We report the case of a 66-year-old male, with a history of grade I obesity, diagnosed with stage IV lung squamous cell carcinoma treated with several courses of pembrolizumab, who was referred to the emergency department for severe diabetic ketoacidosis (DKA) after the 12th course of pembrolizumab.</p><p id="par0020" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Physical examination</span> revealed sinus tachycardia and Kussmaul's breathing. The patient remained afebrile, maintaining a BP of 135/87<span class="elsevierStyleHsp" style=""></span>mmHg with a heart rate of 110 bpm. He reported cardinal symptoms of diabetes with polydipsia and polyuria in previous months, but not weight loss.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">venous blood gases</span> on arrival at the ED showed a pH of 6.82 (NV: 7.35–7.45) with a blood glucose of 376<span class="elsevierStyleHsp" style=""></span>mg/dl, natraemia of 125 mEq/l (NV: 135–145 mEq/l), kalaemia of 4.1 mEq/l (NV: 3.5–5 mEq/L) and lactic acid of 4.01<span class="elsevierStyleHsp" style=""></span>mmol/l (NV: 0.36–1.33<span class="elsevierStyleHsp" style=""></span>mmol/l). The capillary ketonemia determination was 4.4<span class="elsevierStyleHsp" style=""></span>mmol/l (NV: <1<span class="elsevierStyleHsp" style=""></span>mmol/l). The <span class="elsevierStyleItalic">blood test</span> showed a blood glucose of 312<span class="elsevierStyleHsp" style=""></span>mg/dl, a glycosylated haemoglobin (Hb1Ac) of 9.4% (NV <<span class="elsevierStyleHsp" style=""></span>5.4%), creatinine of 0.79<span class="elsevierStyleHsp" style=""></span>mg/dl (NV: 0.7–1.3<span class="elsevierStyleHsp" style=""></span>mg/dl), natraemia of 136 mEq/l (NV: 135–145 mEq/l) and kalaemia of 3.4 mEq/l (NV: 3.5–5 mEq/l). After evaluation by Endocrinology, treatment was started with IV hydration therapy and intravenous insulin perfusion, with improvement of metabolic parameters and reversal of DKA.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Treatment was started on an outpatient basis with a basal bolus regimen and a new follow-up was requested one month after the onset of the symptoms. The <span class="elsevierStyleItalic">control CBC</span> showed a Hb1Ac of 8.7% with C-peptide levels <0.05<span class="elsevierStyleHsp" style=""></span>ng/ml (NV: 0.81–3.85<span class="elsevierStyleHsp" style=""></span>ng/ml), with anti-glutamate decarboxylase (GAD) antibodies <5 U/ml (positive if >5 U/ml) and pancreatic anti-slots (IA2) <7.5 U/ml (positive if >7.5<span class="elsevierStyleHsp" style=""></span>U/ml).</p><p id="par0035" class="elsevierStylePara elsevierViewall">A review of previous blood tests showed elevated fasting blood glucose levels since the eighth course of pembrolizumab. Subsequently, no blood glucose tests were performed until the tenth and eleventh courses of the drug were administered, when he already met the diagnostic criteria for diabetes, as he had fasting blood glucose levels of 146<span class="elsevierStyleHsp" style=""></span>mg/dl and 162<span class="elsevierStyleHsp" style=""></span>mg/dl, respectively.</p><p id="par0040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Literature</span> cases of immune-mediated diabetes mellitus secondary to the use of PDL-1 inhibitors (pembrolizumab and ipilimumab) have been reported.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Although the frequency of presentation is low (0.1-0.2%), most patients start as DKA.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> However, in most of the cases described, fasting blood glucose or Hb1Ac levels were altered in the months prior to onset, demonstrating that pancreatic beta cell destruction possibly occurs progressively.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The responsible mechanism is a destruction of pancreatic cells by the T cells, which are no longer inhibited by PDL1.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The destruction of beta cells results in the release of intracellular proteins, such as glutamic acid decarboxylase or GAD, and a percentage of these patients may be found to have positive anti-GAD antibodies at diagnosis.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a> However, in approximately 50% of the cases reported, pancreatic immunology is negative, and we must rely primarily on C-peptide levels to confirm the diagnosis.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">It should be noted that, due to its low incidence, it has not been clearly established which patients are most susceptible to developing immune-mediated diabetes, so serial fasting blood glucose, glycosylated haemoglobin and C-peptide monitoring is recommended prior to the administration of each course of treatment.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> At the same time, the warning signs of diabetic onset should be explained.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> On the other hand, it is recommended that patients with a history of autoimmune diseases should be provided with a glucometer for self-testing of capillary blood glucose in case of having compatible symptoms.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Based on these findings, we consider it important to keep in mind the possibility of developing immune-mediated diabetes in patients treated with PDL-1 inhibitors because most of the described cases start as DKA that could have been avoided if the referral endocrinology unit had been consulted and treatment had been optimised based on simple fasting serum/capillary blood glucose, Hb1Ac and C-peptide tests.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0060" class="elsevierStylePara elsevierViewall">No private or public funding source has been obtained.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflict of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflict of interest" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A paradigm shift in cancer immunotherapy: From enhancement to normalization" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.F. Sanmamed" 1 => "L. Chen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cell.2018.09.035" "Revista" => array:6 [ "tituloSerie" => "Cell" "fecha" => "2018" "volumen" => "175" "paginaInicial" => "313" "paginaFinal" => "326" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30290139" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens: A systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Barroso-Sousa" 1 => "W.T. Barry" 2 => "A.C. Garrido-Castro" 3 => "F.S. Hodi" 4 => "L. Min" 5 => "I.E. Krop" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jamaoncol.2017.3064" "Revista" => array:6 [ "tituloSerie" => "JAMA Oncol" "fecha" => "2018" "volumen" => "4" "paginaInicial" => "173" "paginaFinal" => "182" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28973656" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Programmed cell death-1 inhibitor-induced type 1 diabetes mellitus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "K. Clotman" 1 => "K. Janssens" 2 => "P. Specenier" 3 => "I. Weets" 4 => "C.E. De Block" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/jc.2018-00728" "Revista" => array:6 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "2018" "volumen" => "103" "paginaInicial" => "3144" "paginaFinal" => "3154" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29955867" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Precipitation of autoimmune diabetes with anti-pd-1 immunotherapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Hughes" 1 => "N. Vudattu" 2 => "M. Sznol" 3 => "S. Gettinger" 4 => "H. Kluger" 5 => "B. Lupsa" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2337/dc14-2349" "Revista" => array:6 [ "tituloSerie" => "Diabetes Care" "fecha" => "2015" "volumen" => "38" "paginaInicial" => "e55" "paginaFinal" => "e57" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25805871" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autoimmune diabetes associated with pembrolizumabs: a review of published case reports" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A. Cheema" 1 => "B. Makadia" 2 => "T. Kawardia" 3 => "R. Bajwa" 4 => "M. Hossain" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.14740/wjon1085w" "Revista" => array:6 [ "tituloSerie" => "World J Oncol" "fecha" => "2018" "volumen" => "9" "paginaInicial" => "1" "paginaFinal" => "4" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29581809" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000016100000001/v2_202311101438/S2387020623002371/v2_202311101438/en/main.assets" "Apartado" => array:4 [ "identificador" => "43309" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000016100000001/v2_202311101438/S2387020623002371/v2_202311101438/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020623002371?idApp=UINPBA00004N" ]
