Transplanted human bone marrow (BM) and umbilical cord blood (UCB) progenitor cells activate islet-regenerative or revascularization programs depending on the progenitor subtypes administered. Using purification of multiple progenitor subtypes based on a conserved stem cell function, high aldehyde dehydrogenase (ALDH) activity (ALDH(hi)), we have recently shown that transplantation of BM-derived ALDH(hi) progenitors improved systemic hyperglycemia and augmented insulin secretion by increasing islet-associated proliferation and vascularization, without increasing islet number. Conversely, transplantation of culture-expanded multipotent-stromal cells (MSCs) derived from BM ALDH(hi) cells augmented total beta cell mass via formation of beta cell clusters associated with the ductal epithelium, without sustained islet vascularization. To identify paracrine effectors produced by islet-regenerative MSCs, culture-expanded BM ALDH(hi) MSCs were transplanted into streptozotocin-treated nonobese diabetic/severe combine immune deficient (SCID) mice and segregated into islet-regenerative versus nonregenerative cohorts based on hyperglycemia reduction, and subsequently compared for differential production of mRNA and secreted proteins. Regenerative MSCs showed increased expression of matrix metalloproteases, epidermal growth factor receptor (EGFR)-activating ligands, and downstream effectors of Wnt signaling. Regenerative MSC supernatant also contained increased levels of pro-angiogenic versus pro-inflammatory cytokines, and augmented the expansion of ductal epithelial but not beta cells in vitro. Conversely, co-culture with UCB ALDH(hi) cells induced beta cell but not ductal epithelial cell proliferation. Sequential transplantation of MSCs followed by UCB ALDH(hi) cells improved hyperglycemia and glucose tolerance by increasing beta cell mass associated with the ductal epithelium and by augmenting intra-islet capillary densities. Thus, combinatorial human progenitor cell transplantation stimulated both islet-regenerative and revascularization programs. Understanding the progenitor-specific pathways that modulate islet-regenerative and revascularization processes may provide new approaches for diabetes therapy.

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, non appendiceal 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 46-73 ans). Les diagnostics principaux les plus ...