Patterns of complex emergency general surgery in Canada.

BACKGROUND: Most of the literature on emergency general surgery (EGS) has investigated appendiceal and biliary disease; however, EGS surgeons manage many other complex conditions. This study aimed to describe the operative burden of these conditions throughout Canada. METHODS: This multicentre retrospective cohort study evaluated EGS patients at 7 centres across Canada in 2014. Adult patients (aged ≥ 18 yr) undergoing nonelective operative interventions for nonbiliary, nonappendiceal diseases were included. Data collected included information on patients' demographic characteristics, diagnosis, procedure details, complications and hospital length of stay. Logistic regression was used to identify predictors of morbidity and mortality. RESULTS: A total of 2595 patients were included, with a median age of 60 years (interquartile range 46-73 yr). The most common principal diagnoses were small bowel obstruction (16%), hernia (15%), malignancy (11%) and perianal disease (9%). The most commonly performed procedures were bowel resection (30%), hernia repair (15%), adhesiolysis (11%) and débridement of skin and soft tissue infections (10%). A total of 47% of cases were completed overnight (between 5 pm and 8 am). The overall inhospital mortality rate was 8%. Thirty-three percent of patients had a complication, with independent predictors including increasing age (p = 0.001), increasing American Society of Anesthesiologists score (p = 0.02) and transfer from another centre (p = 0.001). CONCLUSION: This study characterizes the epidemiology of nonbiliary, nonappendiceal EGS operative interventions across Canada. Canadian surgeons are performing a large volume of EGS, and conditions treated by EGS services are associated with a substantial risk of morbidity and mortality. Results of this study will be used to guide future research efforts and set benchmarks for quality improvement.

CONTEXTE: La plupart des études sur les services de chirurgie générale d'urgence (CGU) s'intéressent seulement aux atteintes de l'appendice et de la vésicule biliaire. Pourtant, les chirurgiens du domaine traitent beaucoup d'autres problèmes complexes. L'objectif de l'étude était de décrire le travail chirurgical associé à ces problèmes dans l'ensemble du Canada. MÉTHODES: Notre étude de cohorte rétrospective multicentrique inclut les patients adultes (≥ 18 ans) qui ont subi en 2014 une opération non planifiée pour une atteinte qui ne touchait ni l'appendice ni la vésicule biliaire dans 1 des 7 centres sélectionnés, répartis un peu partout au pays. Nous avons recueilli les données suivantes : renseignements de base des patients, diagnostic, détails de l'intervention, nature des complications et durée d'hospitalisation. Puis nous avons dégagé les facteurs prédictifs de morbidité et de mortalité en appliquant un modèle de régression logistique. RÉSULTATS: L'échantillon totalisait 2595 patients, pour un âge médian de 60 ans (écart interquartile 46­73 ans). Les diagnostics principaux les plus courants étaient l'occlusion de l'intestin grêle (16 %), la hernie (15 %), la tumeur maligne (11 %) et les lésions périanales (9 %). Les interventions les plus fréquentes étaient la résection de l'intestin (30 %), la réparation d'une hernie (15 %), le débridement (11 %) et le débridement de tissus mous ou cutanés infectés (10 %). L'opération a eu lieu le soir ou la nuit (entre 17 h et 8 h) dans 47 % des cas. Le taux global de mortalité à l'hôpital était de 8 %. Des complications sont survenues chez 33 % des patients, dont les facteurs prédictifs indépendants étaient l'âge avancé (p = 0,001), un score ASA (de l'American Society of Anesthesiologists) élevé (p = 0,02) et le transfert à partir d'un autre centre (p = 0,001). CONCLUSION: Cette étude dresse le profil épidémiologique des interventions effectuées par les services de CGU du Canada en présence d'atteintes autres que celles de l'appendice et de la vésicule biliaire. Les chirurgiens du pays font beaucoup d'interventions générales urgentes, pour traiter des affections associées à un risque élevé de morbidité et de mortalité. Les résultats de l'étude guideront les prochaines recherches et serviront de points de référence en matière d'amélioration de la qualité.

Melatonin induces histone hyperacetylation in the rat brain.

We have reported that melatonin induces histone hyperacetylation in mouse neural stem cells, suggesting an epigenetic role for this pleiotropic hormone. To support such a role, it is necessary to demonstrate that melatonin produces similar effects in vivo. Histone acetylation, following chronic treatment with melatonin (4µg/ml in drinking water for 17 days), was examined by western blotting in selected rat brain regions. Melatonin induced significant increases in histone H3 and histone H4 acetylation in the hippocampus. Histone H4 was also hyperacetylated in the striatum, but there were no significant changes in histone H3 acetylation in this brain region. No significant changes in the acetylation of either histone H3 or H4 were observed in the midbrain and cerebellum. An examination of kinase activation, which may be related to these changes, revealed that melatonin treatment increased the levels of phospho-ERK (extracellular signal-regulated kinase) in the hippocampus and striatum, but phospho-Akt (protein kinase B) levels were unchanged. These findings suggest that chromatin remodeling and associated changes in the epigenetic regulation of gene expression underlie the multiple physiological effects of melatonin.

HDAC inhibitor M344 suppresses MCF-7 breast cancer cell proliferation.

Histone deacetylase (HDAC) inhibitors represent a novel class of drugs that selectively induce cell cycle arrest and apoptosis in transformed cells. This study examined, for the first time, the effects of the relatively new HDAC inhibitor, M344 [4-dimethylamino-N-(6-hydroxycarbamoylhexyl)-benzamide], on the proliferation of MCF-7 breast cancer cells. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays revealed significant concentration- and time-dependent decreases in MCF-7 cell proliferation following treatment with M344 (1-100µM). In contrast to the significant induction of p21(waf1/cip1) mRNA expression following treatment with M344 (10µM) for 1 or 3 days, there was a significant decrease in p53 mRNA expression, although p53 protein levels were unchanged. Similar treatment with M344 also induced expression of the pro-apoptotic genes, Puma and Bax, together with the morphological features of apoptosis, in MCF-7 cells. The results of this study reinforce previous findings indicating that HDAC inhibitors are an important group of oncostatic drugs, and show that M344 is a potent suppressor of breast cancer cell proliferation.