46 years-old male with vertiginous syndrome and facial paralysis

Varón de 46 años que acude a servicio de urgencias por presentar vómitos alimentarios, mareo y fiebre de 38ºC de dos días de evolución. En la exploración física destacaban hipoestesia y paresia en lengua y hemicara izquierda, acompañado de presencia de vesículas en CAE. Tras una exploración física minuciosa llegamos al diagnóstico.A 46 year-old comes to the emergency department because of vomiting, dizziness and temperature of 38ºC. Physical examination revealed hypoesthesia and palsy of left facial side and tongue, accompanied by the presence of vesicles in CAE. After a meticulous physical examination we got the diagnosis

Zosteriform morphea: a exceptional pattern

La morfea (esclerodermia localizada) es una enfermedad de causa desconocida en la que se produce edema, esclerosis, induración y atrofia de la piel con desaparición de los pliegues cutáneos y de los folículos pilosos. Presentamos un paciente con una morfea de patrón clínico excepcional

Lemierre’s syndrome, a serious complication of acute sinusitis

Presentamos el caso clínico de una sinusitis aguda en un paciente joven con mala evolución y fatal desenlace, presentando como complicación un Síndrome de Lemierre. El Síndrome de Lemierre, caracterizado por una tromboflebitis de la vena yugular interna asociado a bacteriemia tiene una prevalencia baja (3,6 casos/millón/ año), si bien, el aumento de las resistencias a antibióticos está influyendo negativamente en la prevalencia de la enfermedad. Su diagnóstico se basa en pruebas de imagen que muestren la afectación venosa, así como el crecimiento de bacterias en sangre mediante cultivo. Su manejo es hospitalario, usando antibioticoterapia intravenosa prolongada a altas dosis, asociado a anticoagulación y cirugía dependiendo del caso.We report a case of acute sinusitis in a young patient with poor evolution and fatal outcome, presenting as a complication Lemierre syndrome. Lemierre syndrome, characterized by thrombophlebitis of the internal jugular vein associated with bacteremia has a low prevalence (3.6 cases / million / year), although the increase in antibiotic resistance is negatively influencing the prevalence of disease. Diagnosis is based on imaging tests showing the venous involvement, as well as the growth of bacteria in the blood by culture. Its handling is hospitable, prolonged intravenous antibiotic therapy using high doses associated with anticoagulation and surgery depending on the case

Signature-driven repurposing of Midostaurin for combination with MEK1/2 and KRASG12C inhibitors in lung cancer

Drug combinations are key to circumvent resistance mechanisms compromising response to single anti-cancer targeted therapies. The implementation of combinatorial approaches involving MEK1/2 or KRASG12C inhibitors in the context of KRAS-mutated lung cancers focuses fundamentally on targeting KRAS proximal activators or effectors. However, the antitumor effect is highly determined by compensatory mechanisms arising in defined cell types or tumor subgroups. A potential strategy to find drug combinations targeting a larger fraction of KRAS-mutated lung cancers may capitalize on the common, distal gene expression output elicited by oncogenic KRAS. By integrating a signature-driven drug repurposing approach with a pairwise pharmacological screen, here we show synergistic drug combinations consisting of multi-tyrosine kinase PKC inhibitors together with MEK1/2 or KRASG12C inhibitors. Such combinations elicit a cytotoxic response in both in vitro and in vivo models, which in part involves inhibition of the PKC inhibitor target AURKB. Proteome profiling links dysregulation of MYC expression to the effect of both PKC inhibitor-based drug combinations. Furthermore, MYC overexpression appears as a resistance mechanism to MEK1/2 and KRASG12C inhibitors. Our study provides a rational framework for selecting drugs entering combinatorial strategies and unveils MEK1/2- and KRASG12C-based therapies for lung cancer