RHBDD2 overexpression promotes a chemoresistant and invasive phenotype to rectal cancer tumors via modulating UPR and focal adhesion genes.

The current standard of care for locally advanced rectal cancer (RC) is neoadjuvant radio-chemotherapy (NRC) with 5-fluorouracil (5Fu) as the main drug, followed by surgery and adjuvant chemotherapy. While a group of patients will achieve a pathological complete response, a significant percentage will not respond to the treatment. The Unfolding Protein Response (UPR) pathway is generally activated in tumors and results in resistance to radio-chemotherapy. We previously showed that RHBDD2 gene is overexpressed in the advanced stages of colorectal cancer (CRC) and that it could modulate the UPR pathway. Moreover, RHBDD2 expression is induced by 5Fu. In this study, we demonstrate that the overexpression of RHBDD2 in CACO2 cell line confers resistance to 5Fu, favors cell migration, adhesion and proliferation and has a profound impact on the expression of both, the UPR genes BiP, PERK and CHOP, and on the cell adhesion genes FAK and PXN. We also determined that RHBDD2 binds to BiP protein, the master UPR regulator. Finally, we confirmed that a high expression of RHBDD2 in RC tumors after NRC treatment is associated with the development of local or distant metastases. The collected evidence positions RHBDD2 as a promising prognostic biomarker to predict the response to neoadjuvant therapy in patients with RC.

Conciliación de la medicación en atención primaria tras el alta hospitalaria / Medication reconciliation in primary care after hospital discharge

Objetivos: El objetivo primario de este estudio es comprobar si la información de los cambios propuestos en el tratamiento habitual de los pacientes al alta hospitalaria se traslada a su hoja de tratamiento activo cuando acuden a atención primaria. Se plantean objetivos secundarios como analizar la media de medicamentos por paciente al ingreso y al alta; identificar otros factores que pudieran influir en la modificación del tratamiento durante el ingreso (edad del paciente o número de fármacos previamente indicados, entre otros). También se analiza la relación entre el centro de salud al que pertenece el paciente y la probabilidad de que se concilie su medicación cuando acude a atención primaria. Material y métodos: Se trata de un estudio transversal observacional, desarrollado en la Organización Sanitaria Integrada Bidasoa. Se incluyó a todos los pacientes mayores de 65 años polimedicados (que tomaban 5 o más fármacos) de la organización, dados de alta en el Hospital Bidasoa entre el 15 de octubre y el 11 de noviembre de 2012. Las altas producidas en este periodo se enviaron desde el hospital a cada responsable de seguridad del paciente de los centros de atención primaria, y a través de la revisión de la historia clínica de cada paciente se obtuvo información relativa a si habían acudido a su centro en los 15 días posteriores al alta, así como de si se efectuó alguna modificación en la hoja de tratamiento activo. Resultados: Doscientos sesenta y un pacientes (n = 261) fueron dados de alta en el periodo de estudio, de los cuales 80 cumplían los criterios de inclusión. El informe de alta de 39 de ellos (49%) proponía algún cambio en su hoja de tratamiento activo. De ellos, 35 (90%) se pusieron en contacto con atención primaria, y en 24 pacientes los cambios fueron incluidos en su hoja de tratamiento activo, lo que supone el 68% de los que contactaron con atención primaria y el 61% de los que hubieran requerido cambios. Conclusiones: Los resultados observados en este estudio nos llevan a pensar en la necesidad de establecer un programa de conciliación de la medicación para los pacientes polimedicados al alta hospitalaria. Además, consideramos interesante ahondar en los motivos por los cuales los pacientes que a pesar de haber acudido a atención primaria tras el alta hospitalaria, no vieron trasladados los cambios de la medicación a su hoja de tratamiento activo (AU)

Objectives: The primary objective of this study was to determine if changes prescribed in the usual treatment of patients at discharge from the hospital were updated in their active treatment sheet when they came to the Primary Care clinic. The secondary objectives included, determining whether the drug average varies between the admission and discharge, as well as, identifying other factors related to the modification of treatment during hospital admission including, among others, patient age or the number of drugs previously indicated. Finally, the relationship between the Primary Care Unit to which the patient belonged and the probability that the medication was reconciled was also examined. Material and methods: This is an observational cross-sectional study conducted in the Bidasoa Integrated Healthcare Organization. The study included every patient over 65 years old with multiple medication (taking 5 or more drugs) belonging to this organization, and discharged from Bidasoa Hospital between 15th October and 11th November 2012. The information on hospital discharges during this period was sent from the hospital to those responsible for patient safety in the Primary Health Care Centers. Each patient clinical history was reviewed in order to confirm if a visit (at least once in the first two weeks after discharge) had been made to their Primary Care Unit, and whether there had been a change in their active treatment sheet. Results: Two hundred sixty-one patients (n = 261) were discharged from Bidasoa Hospital in the study period, and 80 met the inclusion criteria. The discharge report proposed a change in the active treatment in 39 of them (49%). Of these, 35 (90%) attended a Primary Care clinic, and the changes were included in their active treatment sheet in 24 patients, representing 68% of those who contacted Primary Care, and 61% of those who would have required changes. Conclusions: The results demonstrate the need to establish a reconciliation medication program for patients on multiple medications after hospital discharge. Moreover, further studies are needed to investigate what may be the reasons why the changes to active treatment sheets are not taking place for some patients, despite these having visited Primary Care after having been discharged from hospital

[Medication reconciliation in primary care after hospital discharge]. / Conciliación de la medicación en atención primaria tras el alta hospitalaria.

OBJECTIVES: The primary objective of this study was to determine if changes prescribed in the usual treatment of patients at discharge from the hospital were updated in their active treatment sheet when they came to the Primary Care clinic. The secondary objectives included, determining whether the drug average varies between the admission and discharge, as well as, identifying other factors related to the modification of treatment during hospital admission including, among others, patient age or the number of drugs previously indicated. Finally, the relationship between the Primary Care Unit to which the patient belonged and the probability that the medication was reconciled was also examined. MATERIAL AND METHODS: This is an observational cross-sectional study conducted in the Bidasoa Integrated Healthcare Organization. The study included every patient over 65 years old with multiple medication (taking 5 or more drugs) belonging to this organization, and discharged from Bidasoa Hospital between 15th October and 11th November 2012. The information on hospital discharges during this period was sent from the hospital to those responsible for patient safety in the Primary Health Care Centers. Each patient clinical history was reviewed in order to confirm if a visit (at least once in the first two weeks after discharge) had been made to their Primary Care Unit, and whether there had been a change in their active treatment sheet. RESULTS: Two hundred sixty-one patients (n=261) were discharged from Bidasoa Hospital in the study period, and 80 met the inclusion criteria. The discharge report proposed a change in the active treatment in 39 of them (49%). Of these, 35 (90%) attended a Primary Care clinic, and the changes were included in their active treatment sheet in 24 patients, representing 68% of those who contacted Primary Care, and 61% of those who would have required changes. CONCLUSIONS: The results demonstrate the need to establish a reconciliation medication program for patients on multiple medications after hospital discharge. Moreover, further studies are needed to investigate what may be the reasons why the changes to active treatment sheets are not taking place for some patients, despite these having visited Primary Care after having been discharged from hospital.

Effects of exposure to Prestige-like heavy fuel oil and to perfluorooctane sulfonate on conventional biomarkers and target gene transcription in the thicklip grey mullet Chelon labrosus.

Thicklip grey mullets Chelon labrosus inhabit coastal and estuarine areas where they can be chronically exposed to commonly released pollutants such as polycyclic aromatic hydrocarbons (PAHs) and perfluorinated compounds. These pollutants can also originate from accidental spills, such as the Prestige oil spill in 2002, which resulted in the release of a heavy fuel oil that affected coastal ecosystems in the Bay of Biscay. Peroxisome proliferation (PP), induced biotransformation metabolism, immunosuppression and endocrine disruption are some of the possible biological effects caused by such chemicals. With the aim of studying the effects of organic toxic chemicals on such biological processes at the transcriptional and at the cell/tissue level, juvenile mullets were exposed to the typical mammalian peroxisome proliferator perfluorooctane sulfonate (PFOS), and to fresh (F) and weathered (WF) Prestige-like heavy fuel oil for 2 and 16 days. First, fragments of genes relevant to biotransformation, immune/inflammatory and endocrine disruption processes were cloned using degenerate primers. Fuel oil elicited a significant PP response as proved by the transcriptional upregulation of palmitoyl-CoA oxidase (aox1), peroxisome proliferator activated receptor alpha (pparalpha) and retinoic X receptor, by the AOX1 activity induction and by the increased peroxisomal volume density. PFOS only elicited a significant induction of AOX1 activity at day 2 and of PPARalpha mRNA expression at day 16. All treatments significantly increased catalase mRNA expression at day 16 in liver and at day 2 in gill. Cyp1a transcription (liver and gill) and EROD activity were induced in fuel oil treated organisms. In the case of phase II metabolism only hepatic glutathione S-transferase mRNA was overexpressed in mullets exposed to WF for 16 days. Functionally, this response was reflected in a significant accumulation of bile PAH metabolites. WF treated fish accumulated mainly high molecular weight metabolites while F exposure resulted in accumulation of mainly low molecular ones. Fuel oil significantly regulated immune response related complement component C3 and hepcidin transcription followed by a significant regulation of inflammatory response related apolipoprotein-A1 and fatty acid binding protein mRNAs at day 16. These responses were accompanied by a significant hepatic inflammatory response with lymphocyte accumulations (IRLA) and accumulation of melanomacrophage centers (MMC). PFOS did not elicit any transcriptional response in the studied biotransformation and immune related genes, although histologically significant effects were recorded in IRLA and MMC. A significant reduction of lysosomal membrane stability was observed in all exposed animals. No endocrine disruption effects were observed in liver while brain aromatase mRNA was overexpressed after all treatments at day 2 and estrogen receptor alpha was downregulated under WF exposure at day 16. These results show new molecular and cellular biomarkers of exposure to organic chemicals and demonstrate that in mullets PP could be regulated through molecular mechanisms similar to those in rodents, although the typical mammalian peroxisome proliferator PFOS and heavy fuel oil follow divergent mechanisms of action.