Uso perioperatorio de la ecografía de la vía aérea en un paciente con infección profunda del cuello. Reporte de caso / Perioperative use of airway ultrasound in a patient with a deep neck infection. Case Report

Introducción: las infecciones profundas del cuello son patologías complejas con gran potencial de complicaciones graves, que, debido a su ubicación pueden ser de difícil reconocimiento y manejo. Es de gran importancia realizar un diagnóstico asertivo y ofrecer el tratamiento adecuado para poder disminuir las complicaciones que se pudieran presentar. La ecografía es una ayuda diagnóstica cada vez más utilizada que nos puede ayudar a guiar nuestras conductas de manera rápida y efectiva. Caso clínico: presentamos un caso de un paciente con un absceso en cuello, en el que la utilización de la ecografía de manera intraoperatoria facilitó la toma de decisiones y evitó procedimientos invasivos innecesarios. Conclusiones: el Point of Care Ultrasound (PoCUS) es una forma rápida y práctica de resolver preguntas y facilitar la toma de decisiones objetivas en el entorno perioperatorio.

Introduction: Deep neck infections are a complex group of pathologies with great potential for serious complications due to their location. Therefore, recognition and management can be a challenge. To reduce the risk of complications it is extremely important to have an assertive diagnosis y and offer the proper treatment. An ultrasound is a diagnosis tool that is being used more often because it can help us guide our medical decisions in a quick and effective way. Clinical case: We present a case of a patient who had an intraoperative ultrasound which helped in the decision making and avoided any further invasive procedures. Conclusions: The Point of Care Ultrasound (PoCUS) is a quick and practical way to solve questions and facilitate objective decisions in the perioperative environment.

Estudios genéticos del metabolismo de la warfarina y su utilidad en la toma de decisiones / Genetic studies of warfarin metabolism and its usefulness in decision making

Resumen Introducción: Al momento de valorar la necesidad de realizar un reemplazo quirúrgico valvular cardiaco es posible elegir entre una válvula mecánica o una bioprotésica; la elección debe tener presentes los riesgos de la terapia anticoagulante y la necesidad potencial o el riesgo de nuevas intervenciones. La anticoagulación se realiza con antagonistas de la vitamina K, y de estos, la warfarina es el que se prescribe con mayor frecuencia. Por su metabolismo hepático (P450), dicho medicamento tiene múltiples interacciones farmacológicas y no farmacológicas que en ocasiones se convierten en un verdadero problema en la práctica clínica. Hasta la fecha no se recomienda realizar de forma rutinaria una dosificación guiada por genotipo; sin embargo, se requieren estudios genéticos para definir conductas médicas cuando se hace difícil su manejo. Caso clínico: Se describe el caso de una mujer de 37 años portadora de una válvula mitral mecánica por enfermedad reumática, anticoagulada de forma crónica con warfarina; sin embargo, durante el seguimiento tuvo múltiples consultas a urgencias (entre dos y tres veces por mes) por niveles de anticoagulación en rangos subterapéuticos, como valores elevados de INR. Presentó infarto agudo de miocardio con coronarias sanas e isquemia cerebral transitoria en contexto de INR bajo, considerados así de etiología tromboembólica. Por estas dificultades se decidió realizar la medición de los niveles de factor II de la coagulación, el cual fue normal a pesar del uso del medicamento, por lo que se sospechó resistencia al fármaco. Se solicitó estudio genético que mostró genotipo asociado con actividad enzimática reducida o normal de la CYP2C9, además un genotipo WARF CYP2C9 *1/*2 y WARF VKORC1 A/A, con lo cual se concluyó que la paciente presentaba un comportamiento metabólico divergente para warfarina. Se decidió realizar un reemplazo de válvula mecánica por válvula bioprotésica, con el objetivo de suspender el uso de la warfarina. La paciente presentó una evolución clínica satisfactoria. Conclusiones: La farmacogenética ha logrado identificar polimorfismos en los genes implicados en el metabolismo de la warfarina, los cuales están relacionados con riesgo de sangrado. Estas variantes se encuentran relacionadas con los genes CYP2C9, CYP4F2 y VKORC1. Si bien no se ha demostrado un impacto clínico en los ajustes de warfarina guiados por genotipo, dichos exámenes se hacen necesarios en algunos casos para sugerir un cambio en la dosis del medicamento o su suspensión definitiva.

Abstract Introduction: When assessing the need for a cardiac valvular surgical replacement, it is possible to choose between a mechanical or bioprosthetic valve; The choice must take into account the risks of anticoagulant therapy and the potential need and/or risk of new interventions. Anticoagulation is performed with vitamin K antagonists and warfarin is the most commonly prescribed of these. This medicine due to its hepatic metabolism (P450) has multiple pharmacological and non-pharmacological interactions that sometimes become a real problem in clinical practice. To date, it is not recommended to routinely perform a genotype-guided dosage. However, such genetic studies are necessary to define medical behaviors when handling is difficult. Case report: It is described a case of a 37-year-old woman with a mechanical mitral valve due to rheumatic disease, chronically anticoagulated with warfarin; however, during the follow-up with multiple emergency consultations (2-3 times per month) for anticoagulation levels in subtherapeutic ranges such as elevated INR levels. She presented acute myocardial infarction with healthy coronary arteries and transient cerebral ischemia in the context of low INR thus considered thromboembolic etiology. Due to these difficulties, it was decided to measure coagulation factor II levels, which was normal despite the use of the drug, suspecting drug resistance. A genetic study was requested that showed genotype associated with reduced or normal CYP2C9 enzymatic activity, plus a WARF CYP2C9 * 1/* 2 and WARF VKORC1 A/A genotype concluding that the patient presented a divergent metabolic behavior for warfarin. It was decided to perform a mechanical valve replacement with a bioprosthetic valve, in order to suspend the use of warfarin. The patient presented a satisfactory clinical evolution. Conclusions: Pharmacogenetics has managed to identify polymorphisms in the genes involved in warfarin metabolism, which are related to bleeding risk. These variants are related to the CYP2C9, CYP4F2 and VKORC1 genes. Although no clinical impact has been demonstrated in genotype-guided warfarin adjustments, such tests are necessary in some cases to suggest a change in the dose of the medication or the definitive suspension.

Rational Design of Copper(II)-Uracil Nanoprocessed Coordination Polymers to Improve Their Cytotoxic Activity in Biological Media.

This work is focused on the rational structural design of two isostructural Cu(II) nano-coordination polymers (NCPs) with uracil-1-acetic acid (UAcOH) (CP1n) and 5-fluorouracil-1-acetic acid (CP2n). Suitable single crystals for X-ray diffraction studies of CP1 and CP2 were prepared under hydrothermal conditions, enabling their structural determination as 1D-CP ladder-like polymeric structures. The control of the synthetic parameters allows their processability into water colloids based on nanoplates (CP1n and CP2n). These NCPs are stable in water at physiological pHs for long periods. However, interestingly, CP1n is chemically altered in culture media. These transformations provoke the partial release of its building blocks and the formation of new species, such as [Cu(UAcO)2(H2O)4]·2H2O (Cu(II)-complex), and species corresponding to the partial reduction of the Cu(II) centers. The cytotoxic studies of CP1n versus human pancreatic adenocarcinoma and human uveal melanoma cells show that CP1n produces a decrease in the cell viability, while their UAcOH and Cu(II)-complex are not cytotoxic under similar conditions. The copper reduction species detected in the hydrolysis of CP1n are closely related to the formation of the reactive oxygen species (ROS) detected in the cytotoxic studies. These results prompted us to prepare CP2n that was designed to improve the cytotoxicity by the substitution of UAcO by 5-FUAcO, taking into account the anticancer activity of the 5-fluorouracil moiety. The new CP2n has a similar behavior to CP1n both in water and in biological media. However, its subtle structural differences are vital in improving its cytotoxic activity. Indeed, the release during the hydrolysis of species containing the 5-fluorouracil moiety provokes a remarkable increase in cellular toxicity and a significant increase in ROS species formation.

TRPA1-FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p.

Recent evidence suggests that the ion channel TRPA1 is implicated in lung adenocarcinoma (LUAD), where its role and mechanism of action remain unknown. We have previously established that the membrane receptor FGFR2 drives LUAD progression through aberrant protein-protein interactions mediated via its C-terminal proline-rich motif. Here we report that the N-terminal ankyrin repeats of TRPA1 directly bind to the C-terminal proline-rich motif of FGFR2 inducing the constitutive activation of the receptor, thereby prompting LUAD progression and metastasis. Furthermore, we show that upon metastasis to the brain, TRPA1 gets depleted, an effect triggered by the transfer of TRPA1-targeting exosomal microRNA (miRNA-142-3p) from brain astrocytes to cancer cells. This downregulation, in turn, inhibits TRPA1-mediated activation of FGFR2, hindering the metastatic process. Our study reveals a direct binding event and characterizes the role of TRPA1 ankyrin repeats in regulating FGFR2-driven oncogenic process; a mechanism that is hindered by miRNA-142-3p.TRPA1 has been reported to contribute lung cancer adenocarcinoma (LUAD), but the mechanisms are unclear. Here the authors propose that TRPA1/FGFR2 interaction is functional in LUAD and show that astrocytes oppose brain metastasis by mediating the downregulation of TRPA1 through exosome-delivered miRNA-142-3p.

DNA adduct formation by the anticancer drug ellipticine in human leukemia HL-60 and CCRF-CEM cells.

Ellipticine induces formation of two DNA adducts in leukemia HL-60 and CCRF-CEM cells, identical with deoxyguanosine adducts generated by ellipticine metabolites 13-hydroxyellipticine and 12-hydroxyellipticine in vitro and in vivo. The ellipticine cytotoxicity to HL-60 (IC(50)=0.64microM) and CCRF-CEM cells (IC(50)=4.7microM) correlates with levels of DNA adducts. The different expressions of enzymes activating ellipticine in cells explain this finding. While cytochrome P450 1A1 and cyclooxygenase-1 are expressed in both cells, HL-60 cells express also high levels of another activator, myeloperoxidase. The results suggest the adduct formation as a new mode of antitumor action of ellipticine for leukemia.