Therapeutic techniques based on the use of visible light

This article reviews different therapeutic strategies, which have in common the application of visible light to irradiate and thus activate photosensible substances, (PSs) of different nature, previously administered to the patients and distributed throughout their body. These therapies are: photodynamic therapy (PDT), photothermal therapy (PTT) and photoimmunotherapy (PIT). The advantage of these kinds of therapies, compared to the classical chemotherapy or radiotherapy, is that allow the possibility of destroying tumor tissue with less damage of the surrounding healthy tissue. Therapeutic effects of these phototherapies depend on the light-dependent activation of the PSs. The activated PSs induce either the local release of oxidative radicals (ROS) and the activation of immune responses (PDT and PIT), or the local generation of heat (PTT). In PIT, monoclonal antibodies (Mabs) are linked to PSs; thus, Mabs act as carriers to drive PSs to the target tissues. PDT also has antimicrobial effects and so is used as an alternative or adjuvant therapy together with antibiotic therapy since bacteria are unlikely to develop resistance to the ROS induced by PDT; furthermore, PDT enhances immune responses against bacterial pathogens. Although it is not yet a therapeutic technique, optogenetic, because of its promising future, has been included in this review. The common aspect among optogenetic, PDT, PIT and PTT is the all use of visible light. In optogenetic, different genes coding for photosensible membrane proteins with functions of ionic channels or protonic pumps (identified in single celled algae and bacteria), are transfected to mammalian cells which consequently will expresses these proteins. Then, it is possible the selective activation or silencing of cells by irradiation with light pulses of the specific wavelength corresponding to each exogenous protein. Future clinical applications of optogenetics could include treatment of epilepsy, development of new generations of heart pacemakers, treatment of neurodegenerative disorders and spinal cord sections, vision restoration in human subjects with retinal degeneration, etc.ABSTRACT: Este artículo revisa diferentes estrategias terapéuticas que tienen en común la aplicación de luz visible para irradiar y, de este modo, activar sustancias fotosensibles (PSs) de distinta naturaleza, previamente administradas a los pacientes y distribuidas por su cuerpo. Estas terapias son: fototerapia dinámica (PDT), terapia fototérmica (PTT) y terapia fotodinámica (PIT). La ventaja de este tipo de terapias, en comparación con la quimioterapia y radioterapia clásicas, es que permite la posibilidad de destruir tejido tumoral con mejor daño del tejido sano circundante. Los efectos terapéuticos de estas fototerapias dependen de la activación luz-dependiente de los PSs. Los PSs activados inducen bien la liberación de radicales oxidativos (ROS) y la activación de respuestas inmunes (PDT y PIT) o la generación local de calor (PTT). En PIT, se combinan anticuerpos monoclonales (Mabs) a los PSs; así los Mabs actúan como portadores para dirigir al PSs a los tejidos diana. La PDT tiene además efectos antimicrobianos y por tanto se emplea como una alternativa o tratamiento adyuvante junto con el tratamiento antibiótico ya que las bacterias difícilmente desarrollan resistencia a los ROS liberados por la PDT; además la PDT estimula la respuesta inmune frente a patógenos bacterianos. Aunque aún no es una técnica terapéutica, la optogenética, por su futuro prometedor, ha sido incluida en esta revisión. El rasgo común entre la optogenética, PDT, PIT y PTT es que todas ellas utilizan la luz visible. En optogenética, distintos genes codificantes para proteínas de membrana fotosensibles con funciones de canales iónicos o bombas de protones (identificados en ciertas algas y bacterias unicelulares) son transfectados a células de mamífero que consecuentemente expresarán estas proteínas. Entonces, es posible la activación o el silenciamiento selectivo de células mediante la irradiación con pulsos de luz de la luz de onda específica correspondiente para cada proteína exógena. La aplicación clínica futura de la optogenética podría incluir el tratamiento de la epilepsia, el desarrollo de nuevas generaciones de marcapasos cardiacos, el tratamiento de enfermedades neurodegenerativas y secciones medulares, restauración de la visión en sujetos con degeneración retiniana, etc.Grado en Medicin

Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. Conclusion: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective