Checkpoint inhibitor-induced fulminant myocarditis, complete atrioventricular block and myasthenia gravis-a case report.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy over the last decade. Pembrolizumab, a humanized monoclonal IgG4 antibody, binds to the programmed death 1 (PD-1) receptor, blocking its interaction with programmed death-ligand 1 (PD-L1) and thereby increasing the anti-tumor activity of the host immune system. These drugs are associated with immune-mediated side effects that can be life threatening, and myocarditis is among the most serious events. We present a 48-year-old woman with a history of progressive thymoma who developed complete atrioventricular block associated with fulminant myocarditis and myasthenia gravis 2 weeks after starting treatment with pembrolizumab. She had also presented a couple of days before to the emergency department due to dyspnea that was related to pleural effusion. Electrocardiogram (ECG) and echocardiogram were unremarkable, but she had very mildly increased troponin levels that were attributed to acute respiratory compromise, so she was discharged after successful thoracentesis. Despite aggressive treatment combination of high-dose corticosteroids, immunosuppressive agents and anti-thymocyte globulin, the disease rapidly progressed to the fatal outcome. This report remarks on the importance of rapid consideration of ICI-induced myocarditis even if cardiac biomarkers are slightly elevated, as a mild presentation can go unnoticed and progress to a severe case. Therefore, a high index of suspicion is warranted in these patients and cardiac imaging techniques such as magnetic resonance could have a role diagnosing incipient cardiac inflammation.

[High frequency of endoluminal thrombus in patients with ischaemic stroke following COVID-19]. / Alta Frecuencia de Trombo Endoluminal en pacientes con ictus isquémico tras la infección por Coronavirus 2019.

BACKGROUND: Ischaemic stroke may be a major complication of SARS-CoV-2 infection.Studying and characterising the different aetiological subtypes, clinical characteristics, and functional outcomes may be valuable in guiding patient selection for optimal management and treatment. METHODS: Data were collected retrospectively on consecutive patients with COVID-19 who developed acute focal brain ischaemia (between 1 March and 19 April 2020) at a tertiary university hospital in Madrid (Spain). RESULTS: During the study period, 1594 patients were diagnosed with COVID-19. We found 22 patients with ischaemic stroke (1.38%), 6 of whom did not meet the inclusion criteria. The remaining 16 patients were included in the study (15 cases of ischaemic stroke and one case of transient ischaemic attack).Median baseline National Institutes of Health Stroke Scale score was 9 (interquartile range: 16), and mean (standard deviation) age was 73 years (12.8). Twelve patients (75%) were men. Mean time from COVID-19 symptom onset to stroke onset was 13 days. Large vessel occlusion was identified in 12 patients (75%).We detected elevated levels of D-dimer in 87.5% of patients and C-reactive protein in 81.2%. The main aetiology was atherothrombotic stroke (9 patients, 56.3%), with the predominant subtype being endoluminal thrombus (5 patients, 31.2%), involving the internal carotid artery in 4 cases and the aortic arch in one. The mortality rate in our series was 44% (7 of 16 patients). CONCLUSIONS: In patients with COVID-19, the most frequent stroke aetiology was atherothrombosis, with a high proportion of endoluminal thrombus (31.2% of patients). Our clinical and laboratory data support COVID-19-associated coagulopathy as a relevant pathophysiological mechanism for ischaemic stroke in these patients.

Transplantation of a heart donated after circulatory death via thoraco-abdominal normothermic regional perfusion and results from the first Spanish case.

BACKGROUND: Controlled donation after circulatory death (cDCD) has emerged as one of the main strategies for increasing the organ donor pool. Because of the ischemic injury that follows the withdrawal of life-sustaining therapies, hearts from cDCD donors have not been considered for transplantation until recently. The ex-situ perfusion of hearts directly procured from cDCD donors has been used to allow the continuous perfusion of the organ and the assessment of myocardial viability prior to transplantation. Based on our experience with abdominal normothermic regional perfusion in cDCD, we designed a protocol to recover and validate hearts from cDCD donors using thoraco-abdominal normothermic regional perfusion without the utilization of an ex-situ device. CASE PRESENTATION: We describe the first case of a cDCD heart transplant performed with this approach in Spain. The donor was a 43-year-old asthmatic female diagnosed with severe hypoxic encephalopathy. She was considered a potential cDCD donor and a suitable candidate for multiorgan procurement including the heart via thoraco-abdominal normothermic regional perfusion. The heart recipient was a 60-year-old male diagnosed with amyloid cardiomyopathy. Cold ischemia time was 55 min. The surgery was uneventful. CONCLUSIONS: This case report, the first of its kind in Spain, supports the feasibility of evaluating and successfully transplanting cDCD hearts without the need for ex-situ perfusion based on the use of thoraco-abdominal normothermic regional perfusion opening the way for multiorgan donation in cDCD.

[New antiepileptic drugs and neuropathic pain. From molecular medicine to clinical practice]. / Nuevos fármacos antiepilépticos y dolor neuropático. De la medicina molecular a la clínica.

Neuropathic pain is a phenomenon characterized by a high prevalence in population that may be originated by very different etiologies. In contrast to nociceptive pain, painful signal is originated in the nervous system, it presents poor responses to conventional treatments and may worsen the quality of life. Antiepileptic drugs have demonstrated its effectiveness in the treatment of this pathology, and owing to the important development of these drugs in the last years, they may become a very effective tool. On the other hand, the best knowledge of the physiopathology of nociception is providing new channels and receptors as targets to treat. In this paper we try to review the different potential therapeutical targets and antiepileptic drugs in the treatment of this pathology.

Nuevos fármacos antiepilépticos y dolor neuropático. De la medicina molecular a la clínica / New antiepileptic drugs and neuropathic pain. From molecular medicine to clinical practice

El dolor neuropático, que es un fenómeno con una elevada prevalencia en la población general, puede estar originado por muy diversas etiologías. A diferencia del dolor nociceptivo, la señal algésica se origina en el propio sistema nervioso, suele responder mal al tratamiento convencional y puede tener un importante impacto en la calidad de vida. Los fármacos antiepilépticos han demostrado ser efectivos en el tratamiento de este síntoma y, dado el importante avance que se ha producido en los últimos años, pueden llegar a ser una herramienta muy eficaz. Por su parte, el mejor conocimiento de la fisiopatología de la nocicepción está proporcionando nuevos canales y receptores sobre los que es posible actuar. En este artículo pretendemos revisar las dianas terapéuticas sobre las que se podría intervenir, así como los diversos estudios realizados de los distintos fármacos antiepilépticos en el tratamiento de este síntoma

Neuropathic pain is a phenomenon characterized by a high prevalence in population that may be originated by very different etiologies. In contrast to nociceptive pain, painful signal is originated in the nervous system, it presents poor responses to conventional treatments and may worsen the quality of life. Antiepileptic drugs have demonstrated its effectiveness in the treatment of this pathology, and owing to the important development of these drugs in the last years, they may become a very effective tool. On the other hand, the best knowledge of the physiopathology of nociception is providing new channels and receptors as targets to treat. In this paper we try to review the different potential therapeutical targets and antiepileptic drugs in the treatment of this pathology

Nuevos fármacos antiepilépticos en la profilaxis de la migraña / New antiepileptic drugs in migraine prevention

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