PubMed | Reanimation Medico Chirurgicale, Angers University Hospital Center, Bordeaux University Hospital Center, Saint Michaels Hospital and 7 more.
Type: Journal Article | Journal: Intensive care medicine | Year: 2016
Neurally adjusted ventilatory assist (NAVA) is a ventilatory mode that tailors the level of assistance delivered by the ventilator to the electromyographic activity of the diaphragm. The objective of this study was to compare NAVA and pressure support ventilation (PSV) in the early phase of weaning from mechanical ventilation.A multicentre randomized controlled trial of 128 intubated adults recovering from acute respiratory failure was conducted in 11 intensive care units. Patients were randomly assigned to NAVA or PSV. The primary outcome was the probability of remaining in a partial ventilatory mode (either NAVA or PSV) throughout the first 48h without any return to assist-control ventilation. Secondary outcomes included asynchrony index, ventilator-free days and mortality.In the NAVA and PSV groups respectively, the proportion of patients remaining in partial ventilatory mode throughout the first 48h was 67.2 vs. 63.3% (P=0.66), the asynchrony index was 14.7 vs. 26.7% (P<0.001), the ventilator-free days at day 7 were 1.0day [1.0-4.0] vs. 0.0days [0.0-1.0] (P<0.01), the ventilator-free days at day 28 were 21days [4-25] vs. 17days [0-23] (P=0.12), the day-28 mortality rate was 15.0 vs. 22.7% (P=0.21) and the rate of use of post-extubation noninvasive mechanical ventilation was 43.5 vs. 66.6% (P<0.01).NAVA is safe and feasible over a prolonged period of time but does not increase the probability of remaining in a partial ventilatory mode. However, NAVA decreases patient-ventilator asynchrony and is associated with less frequent application of post-extubation noninvasive mechanical ventilation.clinicaltrials.gov Identifier: NCT02018666.
Brochard L.,Saint Michaels Hospital |
Brochard L.,University of Toronto |
Brochard L.,University of Geneva |
Lefebvre J.-C.,University of Geneva |
And 7 more authors.
Seminars in Respiratory and Critical Care Medicine | Year: 2014
Noninvasive ventilation (NIV) has an established efficacy to improve gas exchange and reduce the work of breathing in patients with hypoxemic acute respiratory failure. The clinical efficacy in terms of meaningful outcome is less clear and depends very much on patient selection and assessment of the risks of the technique. The potential risks include an insufficient reduction of the oxygen consumption of the respiratory muscles in case of shock, an excessive increase in tidal volume in case of lung injury, and a risk of delayed or emergent intubation. With a careful selection of patients and a rapid decision regarding the need for intubation in case of failure, great benefits can be offered to patients. Emerging indications include its use in patients with treatment limitations, in the postoperative period, and in patients with immunosuppression. This last indication will necessitate reappraisal because the prognosis of the conditions associated with immunosuppression has improved over the years. In all cases, there is both a time window and a severity window for NIV to work, after which delaying endotracheal intubation may worsen outcome. The preventive use of NIV seems promising in this setting but needs more research. An emerging interesting new option is the use of high flow humidified oxygen, which seems to be intermediate between oxygen alone and NIV. © 2014 by Thieme Medical Publishers, Inc.
Lupia E.,University of Turin |
Goffi A.,Saint Michaels Hospital |
Bosco O.,University of Turin |
Montrucchio G.,University of Turin
Mediators of Inflammation | Year: 2012
Thrombopoietin (TPO) is a humoral growth factor originally identified for its ability to stimulate the proliferation and differentiation of megakaryocytes. In addition to its actions on thrombopoiesis, TPO directly modulates the homeostatic potential of mature platelets by influencing their response to several stimuli. In particular, TPO does not induce platelet aggregation per se but is able to enhance platelet aggregation in response to different agonists (priming effect). Our research group was actively involved, in the last years, in characterizing the effects of TPO in several human critical diseases. In particular, we found that TPO enhances platelet activation and monocyte-platelet interaction in patients with unstable angina, chronic cigarette smokers, and patients with burn injury and burn injury complicated with sepsis. Moreover, we showed that TPO negatively modulates myocardial contractility by stimulating its receptor c-Mpl on cardiomyocytes and the subsequent production of NO, and it mediates the cardiodepressant activity exerted in vitro by serum of septic shock patients by cooperating with TNF- and IL-1. This paper will summarize the most recent results obtained by our research group on the pathogenic role of elevated TPO levels in these diseases and discuss them together with other recently published important studies on this topic. Copyright 2012 Enrico Lupia et al.
Wirtz A.D.,Saint Michaels Hospital |
Willson J.D.,University of Wisconsin-La Crosse |
Kernozek T.W.,University of Wisconsin-La Crosse |
Hong D.-A.,University of Wisconsin-La Crosse
Knee | Year: 2012
Patellofemoral pain (PFP) is a common complaint among female runners. The etiology for PFP is frequently associated with increased patellofemoral joint stress (PFJS) and altered hip and knee joint kinematics during running. However, whether PFJS during running is increased among runners with PFP is unknown. The primary aim of this study was to compare PFJS during running among females with and without PFP. We also compared hip and knee transverse plane kinematics during running due to their potential influence on patellofemoral contact area and PFJS. Three dimensional hip and knee running kinematics and kinetics were obtained from 20 females with PFP and 20 females with no pain. Patellofemoral joint stress during running was estimated using patellofemoral contact area and a sagittal plane patellofemoral joint model previously described. Patellofemoral joint stress, PFJS-time integral, and hip and knee transverse plane kinematics at the time of impact peak and peak ground reaction force were compared between groups using a multivariate analysis of variance. The results show that peak PFJS and PFJS-time integral were similar between groups. Peak knee flexion angle and net knee extension moment were not different between groups. However, females with PFP demonstrated hip internal rotation that was 6° greater (P=0.04) when ground reaction forces were greatest. The extent these results are influenced by compensations for pain is unclear. However, if increased PFJS contributes to the etiology or exacerbation of PFP, interventions to minimize altered transverse plane hip kinematics may be indicated among runners who demonstrate this characteristic. © 2011 Elsevier B.V.
PubMed | Defence Research and Development Canada, Sunnybrook Health science Center, Saint Michaels Hospital and Montreal General Hospital
Type: Journal Article | Journal: British journal of anaesthesia | Year: 2016
Decreased plasma fibrinogen concentration shortly after injury is associated with higher blood transfusion needs and mortality. In North America and the UK, cryoprecipitate transfusion is the standard-of-care for fibrinogen supplementation during acute haemorrhage, which often occurs late during trauma resuscitation. Alternatively, fibrinogen concentrate (FC) can be beneficial in trauma resuscitation. However, the feasibility of its early infusion, efficacy and safety remain undetermined. The objective of this trial was to evaluate the feasibility, effect on clinical and laboratory outcomes and complications of early infusion of FC in trauma.Fifty hypotensive (systolic arterial pressure100mm Hg) adult patients requiring blood transfusion were randomly assigned to either 6g of FC or placebo, between Oct 2014 and Nov 2015 at a tertiary trauma centre. The primary outcome, feasibility, was assessed by the proportion of patients receiving the intervention (FC or placebo) within one h of hospital arrival. Plasma fibrinogen concentration was measured, and 28-day mortality and incidence of thromboembolic events were assessed.Overall, 96% (43/45) [95% CI 86-99%] of patients received the intervention within one h; 95% and 96% in the FC and placebo groups, respectively (P=1.00). Plasma fibrinogen concentrations remained higher in the FC group up to 12h after admission with the largest difference at three h (2.9mg dLEarly infusion of FC is feasible and increases plasma fibrinogen concentration during trauma resuscitation. Larger trials are justified.
Cina C.S.,Saint Michaels Hospital
Journal of Vascular Surgery | Year: 2010
Endovascular repair is an established modality of treatment for abdominal aortic aneurysms. It is therefore reasonable to expect its application to other less common aneurysmal conditions, including isolated iliac and popliteal artery aneurysms (PAA). There are, however, essential differences between aortic aneurysms and peripheral aneurysms: smaller arterial caliber, mobility of the arterial segment, associated occlusive disease, and devices that have not been specifically designed for peripheral applications. Due to these differences, results obtained in abdominal aortic aneurysms cannot be extrapolated to peripheral aneurysms. The attraction of the endovascular repair for PAA is its minimally invasive nature. The literature, however, provides only case reports, case series and small cohorts, and one small randomized, controlled trial. A cumulative summary of these studies provides the clinician with information upon which to base the choice of treatment on a specific patient. Endovascular repair for PAA with suitable anatomy and good run-off can be considered safe, and medium term results appear comparable with those of open repair. © 2010 Society for Vascular Surgery.
Guettler S.,Samuel Lunenfeld Research Institute |
Guettler S.,King's College |
Larose J.,Ontario Cancer Institute |
Petsalaki E.,Samuel Lunenfeld Research Institute |
And 9 more authors.
Cell | Year: 2011
The poly(ADP-ribose)polymerases Tankyrase 1/2 (TNKS/TNKS2) catalyze the covalent linkage of ADP-ribose polymer chains onto target proteins, regulating their ubiquitylation, stability, and function. Dysregulation of substrate recognition by Tankyrases underlies the human disease cherubism. Tankyrases recruit specific motifs (often called RxxPDG "hexapeptides") in their substrates via an N-terminal region of ankyrin repeats. These ankyrin repeats form five domains termed ankyrin repeat clusters (ARCs), each predicted to bind substrate. Here we report crystal structures of a representative ARC of TNKS2 bound to targeting peptides from six substrates. Using a solution-based peptide library screen, we derive a rule-based consensus for Tankyrase substrates common to four functionally conserved ARCs. This 8-residue consensus allows us to rationalize all known Tankyrase substrates and explains the basis for cherubism-causing mutations in the Tankyrase substrate 3BP2. Structural and sequence information allows us to also predict and validate other Tankyrase targets, including Disc1, Striatin, Fat4, RAD54, BCR, and MERIT40. © 2011 Elsevier Inc.
Stelfox H.T.,Medicine and Community Health science |
Bobranska-Artiuch B.,University of Calgary |
Nathens A.,Saint Michaels Hospital |
Straus S.E.,University of Toronto
Critical Care Medicine | Year: 2010
Objective: Trauma care provides injured children with life-and limb-saving treatment, but it is unclear if the proper tools have been developed to measure the quality of care delivered. We sought to systematically review the literature on quality indicators for evaluating pediatric trauma care. DATA SOURCES AND STUDY SELECTION: We searched MEDLINE (1950-January 14, 2009), EMBASE (1980-week 2, 2009), CINAHL (1982-week 2, 2009) and The Cochrane Library (4th Quarter 2008) from the earliest available date to January 14, 2009, plus the Gray Literature, select journals by hand, reference lists, and articles recommended by experts in the field. Studies were selected that used one or more quality indicators to evaluate the quality of care delivered to patients 18 yrs of age or younger with a major traumatic injury. Data Extraction and data synthesis: The literature search identified 6869 citations. Review of abstracts led to the retrieval of 538 full-text articles for assessment; 12 articles were selected for review. Of these, five (42%) articles were case series and five (42%) articles were cohort studies. Two articles included control groups, a before-and-after case series, and a nonrandomized controlled trial. A total of 120 quality indicators in pediatric trauma care were identified, predominantly measures of prehospital and hospital processes and outcomes of care. We did not identify any prehospital structure or posthospital or secondary injury prevention quality indicators. Among multiple trauma patients, deficiencies in the quality of care ranged from 8% to 45% of patients, with 6% to 32% of deaths in hospital judged to be preventable on peer review. Conclusions: There is limited experimental research regarding quality indicators in pediatric trauma care, but the literature suggests that deficiencies exist in the quality of care. Future research is needed to develop and evaluate patient-centered pediatric-specific indicators that cover the full spectrum of trauma care. © 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.
Poley R.A.,Queen's University |
Poley R.A.,Saint Michaels Hospital |
Newbigging J.L.,Queen's University |
Sivilotti M.L.A.,Queen's University
Academic Emergency Medicine | Year: 2014
Objectives: Deep vein thrombosis (DVT) is both common and serious, yet the desire to never miss the diagnosis, coupled with the low specificity of D-dimer testing, results in high imaging rates, return visits, and empirical anticoagulation. The objective of this study was to evaluate a new approach incorporating bedside limited-compression ultrasound (LC US) by emergency physicians (EPs) into the workup strategy for DVT. Methods: This was a cross-sectional observational study of emergency department (ED) patients with suspected DVT. Patients on anticoagulants; those with chronic DVT, leg cast, or amputation; or when the results of comprehensive imaging were already known were excluded. All patients were treated in the usual fashion based on the protocol in use at the center, including comprehensive imaging based on the modified Wells score and serum D-dimer testing. Seventeen physicians were trained and performed LC US in all subjects. The authors identified a priori an alternate workup strategy in which DVT would be ruled out in "DVT unlikely" (Wells score < 2) patients if the LC US was negative and in "DVT likely" (Wells score ≥ 2) patients if both the LC US and the D-dimer were negative. The criterion standard was based on comprehensive imaging interpreted by radiologists blinded to LC US findings and by structured medical record review at 6 months in patients without comprehensive imaging. Results: A total of 227 patients were enrolled (47% DVT likely), of whom 24 had DVT. The LC US was positive in 27 cases (21 actually DVT positive), indeterminate in 28 (one DVT positive), and negative in 172 (two DVT positive). Of 130 patients deemed DVT negative by the new strategy, one had confirmed DVT (miss rate = 0.8%; 95% confidence interval [CI] = 0.1% to 4.0%), but this patient had been misclassified by the treating physician as low risk by Wells criteria. The stand-alone sensitivity and specificity of LC US were 91% (95% CI = 70% to 98%) and 97% (95% CI = 92% to 99%), respectively. Incorporating LC US into the diagnostic approach would have reduced the rate of comprehensive imaging from 70% to 43%, D-dimer testing from 100% to 33%, and the mean time to diagnostic certainty by 5.0 hours and avoided 24 (11%) return visits for imaging and 10 (4.4%) cases of unnecessary anticoagulation. In 19% of cases, the treating and scanning physician disagreed whether the patient was DVT likely or DVT unlikely based on Wells score (κ = 0.62; 95% CI = 0.48 to 0.77). Conclusions: Limited-compression US holds promise as one component of the diagnostic approach to DVT, but should not be used as a stand-alone test due to imperfect sensitivity. Tradeoffs in diagnostic efficiency for the sake of perfect sensitivity remain a difficult issue collectively in emergency medicine (EM), but need to be scrutinized carefully in light of the costs of overinvestigation, delays in diagnosis, and risks of empirical anticoagulation. © 2014 by the Society for Academic Emergency Medicine.
Levaot N.,Ontario Cancer Institute |
Voytyuk O.,Ontario Cancer Institute |
Dimitriou I.,Ontario Cancer Institute |
Sircoulomb F.,Ontario Cancer Institute |
And 12 more authors.
Cell | Year: 2011
Cherubism is an autosomal-dominant syndrome characterized by inflammatory destructive bony lesions resulting in symmetrical deformities of the facial bones. Cherubism is caused by mutations in Sh3bp2, the gene that encodes the adaptor protein 3BP2. Most identified mutations in 3BP2 lie within the peptide sequence RSPPDG. A mouse model of cherubism develops hyperactive bone-remodeling osteoclasts and systemic inflammation characterized by expansion of the myelomonocytic lineage. The mechanism by which cherubism mutations alter 3BP2 function has remained obscure. Here we show that Tankyrase, a member of the poly(ADP-ribose)polymerase (PARP) family, regulates 3BP2 stability through ADP-ribosylation and subsequent ubiquitylation by the E3-ubiquitin ligase RNF146 in osteoclasts. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the SRC, SYK, and VAV signaling pathways. © 2011 Elsevier Inc.