Molecular mechanisms of autophagy and its role in cancer development / Mecanismos moleculares de la autofagia y su papel en el cáncer

Abstract Autophagy is an evolutionary process preserved in eukaryotes, which removes harmful components and maintains cell homeostasis in response to a variety of extracellular stimuli. It is involved in both physiological and pathological conditions, including cancer. The role of autophagy in the treatment of cancer is described as a "double-edged sword", which reflects its involvement in tumor suppression, survival and subsequent proliferation of tumor cells. Recent advances are useful for planning appropriate adjustments to inhibit or promote autophagy in order to obtain therapeutic efficacy in cancer patients. The objectives of this review are to clarify the role of autophagy in cancer and to highlight the need for more research in the field.

Resumen La autofagia es un proceso conservado evolutivamente en eucariotas que elimina componentes dañinos y mantiene la homeostasis celular en respuesta a una serie de estímulos extracelulares. Está implicada tanto en condiciones fisiológicas como patológicas, incluyendo el cáncer. El papel de la autofagia en el tratamiento del cáncer se describe como un "arma de doble filo", un término que refleja su participación en la supresión tumoral, la supervivencia y la proliferación de células tumorales. Los avances recientes ayudan a proyectar los ajustes apropiados en la inhibición o la promoción de la autofagia con el objetivo de conferir eficacia terapéutica en los pacientes con cáncer. Esta revisión tiene como objetivo aclarar los roles de la autofagia en el cáncer y destacar la necesidad de una mayor investigación en el campo.

High Resolution Esophageal Manometry in Patients with Chagas Disease: A Cross-Sectional Evaluation.

INTRODUCTION: Gastrointestinal involvement affects 30-40% of the patients with chronic Chagas disease. Esophageal symptoms appear once the structural damage is established. Little is known about the usefulness of high resolution manometry to early identification of esophageal involvement. METHOD: We performed a cross-sectional study at the Vall d'Hebron University Hospital (Barcelona, Spain) between May 2011 and April 2012. Consecutive patients diagnosed with Chagas disease in the chronic phase were offered to participate. All patients underwent a structured questionnaire about digestive symptoms, a barium esophagogram (Rezende classification) and an esophageal high resolution manometry (HRM). A control group of patients with heartburn who underwent an esophageal HRM in our hospital was selected. RESULTS: 62 out of 73 patients that were included in the study fulfilled the study protocol. The median age of the Chagas disease group (CG) was 37 (IQR 32-45) years, and 42 (67.7%) patients were female. Twenty-seven (43.5%) patients had esophageal symptoms, heartburn being the most frequent. Esophagogram was abnormal in 5 (8.77%). The esophageal HRM in the CG showed a pathological motility pattern in 14 patients (22.6%). All of them had minor disorders of the peristalsis (13 with ineffective esophageal motility and 1 with fragmented peristalsis). Hypotonic lower esophageal sphincter was found more frequently in the CG than in the control group (21% vs 3.3%; p<0.01). Upper esophageal sphincter was hypertonic in 22 (35.5%) and hypotonic in 1 patient. When comparing specific manometric parameters or patterns in the CG according to the presence of symptoms or esophagogram no statistically significant association were seen, except for distal latency. CONCLUSION: The esophageal involvement measured by HRM in patients with chronic Chagas disease in our cohort is 22.6%. All the patients with esophageal alterations had minor disorders of the peristalsis. Symptoms and esophagogram results did not correlate with the HRM results.

Assessment of rectocolonic morphology and function in patients with Chagas disease in Barcelona (Spain).

The aim of this study was to determine the relationship between colonic symptoms, radiological abnormalities, and anorectal dysfunction in patients with Chagas disease. We performed a cross-sectional study of untreated patients diagnosed with Chagas disease. All patients were evaluated clinically (by a questionnaire for colonic symptoms based on Rome III criteria) and underwent a barium enema and anorectal manometry. A control group of patients with functional constipation and without Chagas disease was included in the study. Overall, 69 patients were included in the study: 42 patients were asymptomatic and 27 patients had abdominal symptoms according to Rome III criteria. Anorectal manometry showed a higher proportion of abnormalities in symptomatic patients than in asymptomatic ones (73% versus 21%, respectively; P < 0.0001). Megarectum was detected in a similar proportion in the different subgroups regardless of the presence of symptoms or abnormalities in anorectal functions. Among non-Chagas disease patients with functional constipation, 90% had an abnormal anorectal manometry study. Patients with Chagas disease present a high proportion of constipation with dyssynergic defecation in anorectal manometry but a low prevalence of impaired rectoanal inhibitory reflex, although these abnormalities may be nonspecific for Chagas disease. The presence of megarectum is a nonspecific finding.

Incidencia y mortalidad de bacteriemia en un hospital clínico docente en Santiago de Chile / Incidence and mortality of bacteremia in a public hospital in Santiago

Background:The incidence of bacteremia has increased over the last decade due to the aging of the population and the wide implementation of invasive nosocomial procedures and wide-spectrum antimicrobial treatments. Aim: To assess the epidemiology of hospital and ambulatory bacteremias in a public hospital in Santiago. Material and Methods: A prospective longitudinal cohort study of laboratory-confirmed adult patients with bacteremia was undertaken at a public hospital in Santiago, between June 1, 2007 and April 30, 2008. Demographic, clinical, and laboratory data was collected into a standardized study-specific form. Results: In the study period, 253 cases of true bacteremia were identified, with an incidence of 11 per 1,000 patient discharges (63.6% nosocomial, 36.7% fatal). Only 2/3 of the cohort was alive at day 28 of hospitalization. Variables associated with mortality were age with a hazard ratio (HR) of 2.31; (95% confidence intervals (CI) 1.42- 3.77); female gender (HR, 1.70; 95% CI 1.06- 2.71); shock (HR, 3.24; 95%CI 2.01-5.22); and C reactive protein (HR, 2.10; 95% CI 1.17- 3.78). The variable associated with lower mortality was surgery (HR, 0.43; 95% CI 0.25-0.75). Selective empiric treatment did not improve survival. Conclusions: Besides age and gender, survival can be influenced by modifiable variables such as presence of shock and surgical intervention, which may provide an opportunity to improve outcomes.

[Incidence and mortality of bacteremia in a public hospital in Santiago]. / Incidencia y mortalidad de bacteriemia en un hospital clínico docente en Santiago de Chile.

BACKGROUND: The incidence of bacteremia has increased over the last decade due to the aging of the population and the wide implementation of invasive nosocomial procedures and wide-spectrum antimicrobial treatments. AIM: To assess the epidemiology of hospital and ambulatory bacteremias in a public hospital in Santiago. MATERIAL AND METHODS: A prospective longitudinal cohort study of laboratory-confirmed adult patients with bacteremia was undertaken at a public hospital in Santiago, between June 1, 2007 and April 30, 2008. Demographic, clinical, and laboratory data was collected into a standardized study-specific form. RESULTS: In the study period, 253 cases of true bacteremia were identified, with an incidence of 11 per 1,000 patient discharges (63.6% nosocomial, 36.7% fatal). Only 2/3 of the cohort was alive at day 28 of hospitalization. Variables associated with mortality were age with a hazard ratio (HR) of 2.31; (95% confidence intervals (CI) 1.42- 3.77); female gender (HR, 1.70; 95% CI 1.06- 2.71); shock (HR, 3.24; 95%CI 2.01-5.22); and C reactive protein (HR, 2.10; 95% CI 1.17- 3.78). The variable associated with lower mortality was surgery (HR, 0.43; 95% CI 0.25-0.75). Selective empiric treatment did not improve survival. CONCLUSIONS: Besides age and gender, survival can be influenced by modifiable variables such as presence of shock and surgical intervention, which may provide an opportunity to improve outcomes.