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Fares I.,University of Montreal | Rivest-Khan L.,University of Montreal | Cohen S.,Maisonneuve Rosemont Hospital | Sauvageau G.,University of Montreal
Current Opinion in Hematology | Year: 2015

Purpose of review Hematopoietic stem and progenitor cell (HSPC) transplantation is frequently used in the treatment of hematological diseases. The outcome of the procedure is strongly influenced by the quantity of injected cells, especially if low cell numbers are infused as frequently encountered with cord blood transplants. Ex-vivo expansion of cord blood HSPCs would increase cell numbers, thus accelerating engraftment and reducing infectious complications and transplant-related mortality. In addition, expansion would maximize accessibility to better HLA-matched units, further improving patients' outcome. Similarly, in-vitro maintenance or expansion of leukemic stem cells (LSCs) would enable research into the much awaited targeted therapies that spare normal hematopoietic stem cells (HSCs). Here, we review recent findings on small molecules (excluding biologicals) regulating the activity of normal and leukemic stem cells and provide insights into basic science and clinical implications. Recent findings High-throughput screening of small molecules active on primary hematopoietic cells has led to the identification of two potent series of chemical compounds, best exemplified by StemRegenin1 and UM171, that both expand HSPCs. Current data suggest that the aryl hydrocarbon receptor antagonist StemRegenin1 is most active on primitive normal hematopoietic progenitors and LSCs and that UM171 expands long-term normal HSCs. Summary Small molecules are clinically useful and powerful tools for expanding HSPCs. They are also of potential value for dissecting the still elusive regulatory networks that govern self-renewal of human HSCs. Copyright © 2015 Wolters Kluwer Health, Inc. Source

Boukaram C.,Maisonneuve Rosemont Hospital | Boukaram C.,Antoine Lacassagne Cancer Center | Hannoun-Levi J.-M.,Antoine Lacassagne Cancer Center
Cancer Treatment Reviews | Year: 2010

The management of prostate cancer (PC) recurrence after definitive radiation therapy (RT) is shifting and there is no consensus regarding the optimal strategy. The major challenge is determining the anatomical site of relapse. In case of biochemical relapse (BR), androgen deprivation therapy (ADT) is a non-curative option commonly used, while patients with a local PC recurrence could be managed through a curative intent. Based on a Pubmed data search, this manuscript focused on the management of post-RT local PC recurrences. In case of BR (nadir + 2ng/ml), classical imaging work-up is not contributive for PSA levels <10. ng/ml while new imaging investigations (diffusion MRI, 11C-choline PET) are more sensitive to detect local and distant recurrences at lower PSA levels. Positive prostate biopsies are the only method for confirming local recurrence, although this technique presents limitations. Primary PC presentation as well as PSA-related features (interval to failure, PSA kinetic) and patient features (life expectancy, urinary, sexual status) are important to consider. Results of curative salvage options (radical prostatectomy, cryotherapy, brachytherapy and high-intensity focused ultrasound-HIFU) are analyzed and discussed. Each of these therapies appears feasible and has its own set of experience and toxicity profile. Other therapeutic options (photodynamic therapy, ADT, observation) are discussed. Longer follow-up and mature series are needed to evaluate the optimal strategy and prospective trials are warranted. Each clinical situation should be discussed in a multidisciplinary setting. Different options should be explained to the patient and decision should be taken after balancing treatment outcomes with life expectancy. © 2009 Elsevier Ltd. Source

Busque L.,University of Montreal | Patel J.P.,Sloan Kettering Cancer Center | Figueroa M.E.,University of Michigan | Vasanthakumar A.,University of Chicago | And 18 more authors.
Nature Genetics | Year: 2012

Aging is characterized by clonal expansion of myeloid-biased hematopoietic stem cells and by increased risk of myeloid malignancies. Exome sequencing of three elderly females with clonal hematopoiesis, demonstrated by X-inactivation analysis, identified somatic TET2 mutations. Recurrence testing identified TET2 mutations in 10 out of 182 individuals with X-inactivation skewing. TET2 mutations were specific to individuals with clonal hematopoiesis without hematological malignancies and were associated with alterations in DNA methylation. © 2012 Nature America, Inc. All rights reserved. Source

Guay J.,Maisonneuve Rosemont Hospital
Journal of Cardiothoracic and Vascular Anesthesia | Year: 2011

Objective: To compare carotid artery stenting with open carotid surgery for the treatment of symptomatic or asymptomatic carotid artery stenosis in terms of stroke, myocardial infarction, and death at 30 days. Design: A meta-analysis of parallel randomized clinical trials (RCTs) (blind or open) published (full article available) in English. Setting: University-based electronic search. Interventions: Patients were submitted to carotid artery stenting or open carotid artery surgery. Measurements and Main Results: Ten RCTs including 6,950 patients were found. There was a moderate amount of heterogeneity (I 2 = 49.8%) in stroke at 30 days when all available data were added together. Heterogeneity fell to 0% when only studies (n = 4) in which cerebral protection devices were used in a high percentage of the patients in the stenting groups were retained. Those 4 studies included 5,012 patients. Carotid endarterectomy reduced the risk ratio (RR) of stroke at 30 days compared with stenting (RR = 0.50; 95% confidence interval (CI), 0.38-0.67; p = 0.000002; event rate 2.8% and 5.6%). Carotid endarterectomy increases the risk of myocardial infarction (RR = 2.16 [95% CI, 1.32-3.54], p = 0.002, heterogeneity 0%, event rate 1.8% and 0.9%). There was no difference in death at 30 days (RR = 0.72 [0.42-1.24] (random effects model), p = 0.23, I 2 = 2.45%, p value for heterogeneity = 0.41; event rate 0.7% and 1.1% for carotid endarterectomy and stenting, respectively). Conclusions: Compared with stenting, carotid endarterectomy decreases the risk of stroke at 30 days, increases the risk of myocardial infarction, and does not affect the risk of death. © 2011 Elsevier Inc. All rights reserved. Source

Awissi D.-K.,Maisonneuve Rosemont Hospital | Begin C.,Maisonneuve Rosemont Hospital | Moisan J.,Hopital du Sacre Coeur de Montreal | Lachaine J.,University of Montreal | Skrobik Y.,Intensive Care Unit
Annals of Pharmacotherapy | Year: 2012

Background: Intensive care units (ICUs) account for considerable health care costs. Adequate pain and sedation management is important to clinical care. Objective: To determine whether implementing a protocol for management of analgesia, sedation, and delirium in the ICU would save costs. Methods:With data from the I-SAVE (Impact of Sedation, Analgesia and Delirium Protocols Evaluated in the Intensive Care Unit: an Economic Evaluation) study, a prospective pre- and postprotocol design was used. Between the 2 periods, protocols for systematic management of sedation, analgesia, and delirium were implemented. Cost-effectiveness was calculated by associating the variation of cost and effectiveness measures (proportion of patients within targeted pain, sedation, and delirium goals). Total costs (in 2004 Canadian dollars), by patient, consisted of the sum of sedation, analgesia, and delirium drug acquisition costs during the ICU stay and the cost of the ICU stay. Results: A total of 1214 patients, 604 in the preprotocol group and 610 in the postprotocol group, were included. The mean (SD) ICU length of stay and the duration of mechanical ventilation were shorter among patients of the postprotocol group compared with those of the preprotocol group (5.43 [6.43] and 6.39 [8.05] days, respectively; p = 0.004 and 5.95 [6.80] and 7.27 [9.09] days, respectively; p < 0.009). The incidence of delirium remained the same. The proportion of patients with Richmond Agitation and Sedation (RASS) scores between -1 and +1 increased from 57.0% to 66.2% (p = 0.001), whereas the proportion of patients with a numeric rating scale (NRS) score of 1 or less increased from 56.3% to 66.6% (p < 0.001). The mean total cost of ICU hospitalization decreased from $6212.64 (7846.86) in the preprotocol group to $5279.90 (6263.91) in the postprotocol group (p = 0.022). The cost analyses for pain and agitation management improved; the proportion of patients with RASS scores between -1 and +1 or NRS scores of 1 or less increased significantly in the postprotocol group while costing, on average, $932.74 less per hospitalization. Conclusions: Establishing protocols for patient-driven management of sedation, analgesia, and delirium is a cost-effective practice and allows savings of nearly $1000 per hospitalization. Source

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