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Background and purpose: Chloroquine (CLQ), an antimalarial drug, has a lysosomotropic effect associated with increased radiationsensibility, which is mediated by the leakage of hydrolytic enzymes, increased apoptosis, autophagy and increased oxidative stress in vitro. In this phase II study, we evaluated the efficacy and safety of radiosensibilization using CLQ concomitant with 30 Gray (Gy) of whole-brain irradiation (WBI) to treat patients with brain metastases (BM) from solid tumors. Methods: Seventy-three eligible patients were randomized. Thirty-nine patients received WBI (30 Gy in 10 fractions over 2 weeks) concomitant with 150 mg of CLQ for 4 weeks (the CLQ arm). Thirty-four patients received the same schedule of WBI concomitant with a placebo for 4 weeks (the control arm). All the patients were evaluated for quality of life (QoL) using the EORTC Quality of Life (QoL) Questionnaire (EORTC QLQ-C30) (Mexican version) beforebeginning radiotherapy and one month later. Results: The overall response rate (ORR) was 54% for the CLQ arm and 55% for the control arm (p=0.92). The progression-free survival of brain metastases (BMPFS) rates at one year were 83.9% (95% CI 69.4-98.4) for the CLQ arm and 55.1% (95% CI 33.6-77.6) for the control arm. Treatment with CLQ was independently associated with increased BMPFS (RR 0.31,95% CI [0.1-0.9], p=0.046).The only factor that was independently associated with increased overall survival (OS) was the presence of< 4 brain metastases (RR 1.9, 95% CI [1.12-3.3], p=0.017). WBI was associated with improvements in cognitive and emotional function but also with worsened nausea in both patients groups. No differences in QoL or toxicity were found between the study arms. Conclusion: Treatment with CLQ plus WBI improved the control of BM (compared with the control arm) with no increase in toxicity; however, CLQ did not improve the RR or OS. A phase III clinical trial is warranted to confirm these findings.

Abstract: BACKGROUND: Several drugs have been regarded as a possible aetiological factor for oral lichen planus (OLP). OBJECTIVE: To investigate the medication profile of patients with OLP and its possible association with the pathogenesis of OLP. METHODS: Data from 956 patients with OLP and 1029 controls were collected using a standardized registration method. All regular medications were recorded and classified according to the Anatomical Therapeutic Chemical Classification System. RESULTS: Patients with OLP used thyroid preparations (P < 0.001) and non-steroidal anti-inflammatory drugs (NSAIDs) (P < 0.01) in higher proportions compared to controls. A multivariate logistic regression model demonstrated that levothyroxine was associated with OLP (multivariate OR 3.39, 95% CI: 2.09-5.46, P < 0.001), even after controlling for confounders, including age, sex, smoking, allergies and systemic diseases. No statistical significance could be found between NSAIDs and OLP using the same model. CONCLUSION: In this study, the use of levothyroxine was associated with OLP, which in turn suggests a possible connection with hypothyroidism." Resumen: ANTECEDENTES: Muchos medicamentos han sido considerados posibles factores etiológicos del liquen plano oral (LPO). OBJETIVO: Investigar el perfil medicamentoso de pacientes con LPO y su posible asociación con la patogénesis del LPO. METODOS: Datos de 956 pacientes con LPO y 1029 controles fueron recolectados usando un método estandarizado de registro. Todos los medicamentos fueron registrados y clasificados de acuerdo al Sistema de Clasificación Anatómica, Terapéutica, Química. RESULTADOS: Los pacientes con LPO usan preparaciones para la tiroides (P < 0.001) y antiinflamatorios no esteroideos (AINEs) (P < 0.01) en mayores proporciones comparado con los controles. Una regresión logística multivariada demostró que la levotiroxina está asociada con LPO (OR multivariado 3.39, 95% CI: 2.09-5.46, P < 0.001), aún después de controlar para factores de confusión, incluyendo edad, sexo, tabaquismo, alergias y enfermedades sistémicas. No se encontró una significancia estadística entre los AINEs y el LPO usando el mismo modelo. CONCLUSION: En este estudio, el uso de levotiroxina está asociado con el LPO, lo cual a su vez sugiere una posible conexión con el hipotiroidismo."

Abstract: Proliferation, differentiation and apoptosis are tightly regulated by extracellular stimuli including hormones, growth factors and cytokines. A balance between these processes is a critical requirement for tissue homeostasis and loss of this balance can result in development of disease. The binding of such mediators to their cognate receptors induces activation of intracellular signal transduction cascades that, through regulation of transcription, eventually results in altered gene expression and changes in cell fate decisions. Constitutive activation of oncogenic signalling pathways by loss of tumor suppressors and activation of oncogenes causes malignant transformation, which is characterized by a differentiation block and the ability of the cancer cells to proliferate and survive independent of growth factor signals. Recently both oncogenes and tumor suppressors have been shown to be critical regulators of autophagy in response to cellular stress. In this review current data concerning a novel role for FoxO transcription factors in regulating autophagy will be discussed. Resumen: La proliferación, diferenciación y apoptosis son procesos estrictamente regulados por estímulos extracelulares que incluyen hormonas, factores de crecimiento y citoquinas. El equilibrio entre dichos procesos es crítico para la homeostasis del tejido y su perdida puede resultar en el desarrollo de enfermedades. La unión de estos mediadores a sus receptores induce la activación de cascadas intracelulares que a través de la regulación de la transcripción, se traducen en la expresión de genes alterados. La activación constitutiva de rutas de señalización oncogénicas por la pérdida de supresores tumorales y la activación de oncogenes provoca la transformación maligna, que se caracteriza por un bloqueo en la diferenciación y por la capacidad de las células cancerosas de proliferar y sobrevivir independiente de las señales del factor de crecimiento. Recientemente se ha demostrado que oncogenes y supresores tumorales son reguladores críticos de la autofagia en respuesta al estrés celular. En esta revisión bibliográfica se analiza el nuevo rol del factor de trascripción FOXO en la regulación de la autofagia.

Publicado por vez primera en 1979, «Terminología médica» ha proporcionado tanto al estudiante de medicina como al médico propiamente forma¬do, un amplio panorama acerca de síntomas, signos, tratamientos, nómina anatómica y demás aspectos cuya definición e identificación se han modificado con el paso de los años.

Esa fue la inmensa tarea que se propuso un destacado grupo de académicos y especialistas bajo la batuta del Dr. Hernán D. Aguirre con el libro que contemplan en sus manos. Desde los problemas más comunes de la medicación ambulatoria hasta las complejidades de la alteración de la esfera mental, pasando por las consultas más frecuentes en los servicios de urgencias y de consulta externa, los lectores podrán apreciar esos enfoques que esperan ayudarles a orientar y facilitar su práctica médica. El tiempo, implacable como siempre, les permitirá juzgar a ustedes y a sus pacientes si la tarea se cumplió a cabalidad ¡Yo espero que así sea!

La hipertensión arterial es un problema de salud pública en el mundo, constituye un factor importante en el 35% de los eventos cardiovasculares ateroscleróticos y hasta el 49% en los casos de falla cardíaca; además, está involucrada en el incremento de la tasa de eventos cerebrovasculares y, después de la diabetes mellitus, es la causa más frecuente de enfermedad renal crónica. La enfermedad cobra mayor importancia cuando las cifras de presión arterial no solo están relacionadas con aumento de la mortalidad, sino con años de vida perdidos ajustados por discapacidad

Background Retinopathy of prematurity is the major cause of blindness in children in Colombia. This cause of childhood blindness is irreversible when stablished, but 100% preventable with the adequate strategies put in place. This raises important questions concerning strategies to reduce the incidence of blindness as a result of ROP, which should ensure that all infants who are at risk of blinding ROP are examined in screening programmes. Aim The aim was to collect data in the neonatal intensive care units. This was used to evaluate the existing human and material resources for preventing, screening and treating ROP and rehabilitation of children suffering from ROP. The data helped to do an analysis of gaps in the service and allowed to present a proposal for a programme to prevent blindness due to ROP in the cities of Manizales, Pereira and Armenia, Colombia. Methods 7 NICUs were visited in the three cities. The study collected quantitative data on neonatal intensive care units, admission and survival of premature babies during 2010, human resources and infrastructure and data on knowledge of the Colombian guidelines on ROP. Results The survival rates vary according to the provider. They are higher in the private sector, and lower in the public sector. Overall, the available data allowed us to estimate that there are approximately 45,000 births per year (2010) in the region (95% occur in hospital) and 1.8% of all the births are less than 2,000g. Therefore, in the region, 810 babies per year weighing less than 2,000g are at risk of developing any type of ROP. The number of places, ventilators and monitors is sufficient. Staffing is adequate in the private NICUs, with a shortage of neonatologists in the public NICUs. The number of nurses monitoring babies is universally adequate, but the lack of knowledge in controlling risk factors of developing ROP such as monitoring oxygen in a constraint. An ROP screening programme is not available in public NICUs and in some of the mixed providers. The Kangaroo Mother programme lack of screening for ROP. Conclusions The unstable health system has allowed (i) unsustainable NICUs and programmes for ROP (ii) If available, programmes running without being monitored or evaluated, and, (iii) no screening in public and some mixed NICUs in Manizales, Pereira and Armenia. (iv) no screening for ROP in the Kangaroo Mother Programe As access and survival rates improve in the NICUS of these cities, ROP is likely to continue to be a significant cause of blindness in the region, despite the progress that has been achieved with the 2010 Colombian guidelines for screening and treating ROP. Recommendations The results suggest that the prevention of blinding ROP is a complex task in Colombia that requires concomitant strategies to be put in place: Firstly, national policies in screening for ROP and oxygen delivery for the babies in the NICUs are needed. Secondly, as a primary preventive strategy, training nurses in the NICUs to control and monitor the delivery of oxygen; as a secondary preventive strategy, ROP programmes offered to the public, mixed, private NICUs and to the Kangaro Mother Programme; as a tertiary strategy, rehabilitation providing a low vision centre for these children Thirdly, running ROP programmes need to be monitored and evaluated.

Background: Health care–associated infections (HAIs) are a public health problem that increase health care costs. This article aimed to systematically review the literature and meta-analyze studies investigating risk factors (RFs) independently associated with HAIs in hospitalized adults. Methods: Electronic databases (MEDLINE, Embase, and LILACS) were searched to identify studies from 2009-2016. Pooled risk ratios (RRs) or odds ratios (ORs) or mean differences (MDs) and 95% confidence intervals (CIs) were calculated and compared across the groups. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Results: Of 867 studies, 65 met the criteria for review, and the data of 18 were summarized in the meta-analysis. The major RFs independently associated with HAIs were diabetes mellitus (RR, 1.76; 95% CI, 1.27-2.44), immunosuppression (RR, 1.24; 95% CI, 1.04-1.47), body temperature (MD, 0.62; 95% CI, 0.41-0.83), surgery time in minutes (MD, 34.53; 95% CI, 22.17-46.89), reoperation (RR, 7.94; 95% CI, 5.49-11.48), cephalosporin exposure (RR, 1.77; 95% CI, 1.30-2.42), days of exposure to central venous catheter (MD, 5.20; 95% CI, 4.91-5.48), intensive care unit (ICU) admission (RR, 3.76; 95% CI, 1.79-7.92), ICU stay in days (MD, 21.30; 95% CI, 19.81-22.79), and mechanical ventilation (OR, 12.95; 95% CI, 6.28-26.73). Conclusions: Identifying RFs that contribute to develop HAIs may support the implementation of strategies for their prevention, therefore maximizing patient safety.

To improve cardiovascular implant success, metal-based stents are designated to modulate endothelial cells adhesion and migration in order to prevent restenosis and late thrombosis diseases. Biomimetic coatings with extra-cellular matrix adhesive biomolecules onto stents surfaces are a strategy to recover a healthy endothelium. However, the appropriate bioactive sequences to selective promote growth of endothelium and the biomolecules surface immobilization strategy remains to be elucidated. In this study, biofunctionalization of cobalt chromium, CoCr, alloy surfaces with elastin-like recombinamers, ELR, genetically modified with an REDV sequence, was performed to enhance metal surfaces endothelialization. Moreover, physical adsorption and covalent bonding were used as biomolecules binding strategies onto CoCr alloy. Surfaces were activated with plasma and etched with sodium hydroxide previous to silanization with 3-chloropropyltriethoxysilane and functionalized with the ELR. CoCr alloy surfaces were successfully biofunctionalized and the use of an ELR with an REDV sequence, allows conferring bioactivity to the biomaterials surface, demonstrating a higher cell adhesion and spreading of HUVEC cells on the different CoCr surfaces. This effect is emphasized as increases the amount of immobilized biomolecules and directly related to the immobilization technique, covalent bonding, and the increase of surface charge electronegativity. Our strategy of REDV elastin-like recombinamers immobilization onto CoCr alloy surfaces via covalent bonding through organosilanes provides a bioactive surface that promotes endothelial cell adhesion and spreading.