Robinson J.G.,University of Iowa |
Farnier M.,Point Medical |
Krempf M.,University of Nantes |
Bergeron J.,Clinique des Maladies Lipidiques de Quebec |
And 9 more authors.
New England Journal of Medicine | Year: 2015
Background: Alirocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin- kexin type 9 (PCSK9), has been shown to reduce low-density lipoprotein (LDL) cholesterol levels in patients who are receiving statin therapy. Larger and longer-term studies are needed to establish safety and efficacy. Methods: We conducted a randomized trial involving 2341 patients at high risk for cardiovascular events who had LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or more and were receiving treatment with statins at the maximum tolerated dose (the highest dose associated with an acceptable side-effect profile), with or without other lipid-lowering therapy. Patients were randomly assigned in a 2:1 ratio to receive alirocumab (150 mg) or placebo as a 1-ml subcutaneous injection every 2 weeks for 78 weeks. The primary efficacy end point was the percentage change in calculated LDL cholesterol level from baseline to week 24. Results: At week 24, the difference between the alirocumab and placebo groups in the mean percentage change from baseline in calculated LDL cholesterol level was -62 percentage points (P<0.001); the treatment effect remained consistent over a period of 78 weeks. The alirocumab group, as compared with the placebo group, had higher rates of injection-site reactions (5.9% vs. 4.2%), myalgia (5.4% vs. 2.9%), neurocognitive events (1.2% vs. 0.5%), and ophthalmologic events (2.9% vs. 1.9%). In a post hoc analysis, the rate of major adverse cardiovascular events (death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization) was lower with alirocumab than with placebo (1.7% vs. 3.3%; hazard ratio, 0.52; 95% confidence interval, 0.31 to 0.90; nominal P = 0.02). Conclusions: Over a period of 78 weeks, alirocumab, when added to statin therapy at the maximum tolerated dose, significantly reduced LDL cholesterol levels. In a post hoc analysis, there was evidence of a reduction in the rate of cardiovascular events with alirocumab. (Funded by Sanofi and Regeneron Pharmaceuticals; ODYSSEY LONG TERM ClinicalTrials.gov number, NCT01507831.) Copyright © 2015 Massachusetts Medical Society.
News Article | November 10, 2016
There are not a lot of things that could bring together people as far apart on the US political spectrum as Republican Newt Gingrich and Democrat Bob Kerrey. But in 2007, after leading a three-year commission that looked into the costs of care for elderly people, the political rivals came to full agreement on a common enemy: dementia. At the time, there were fewer than 30 million people worldwide diagnosed with the condition, but it was clear that the numbers were set to explode. By 2050, current predictions suggest, it could reach more than 130 million, at which point the cost to US health care alone from diseases such as Alzheimer’s will probably hit US$1 trillion per year in today’s dollars. “We looked at each other and said, ‘You know, if we don’t get a grip on Alzheimer’s, we can’t get anything done because it’s going to drown the system,’” recalls Gingrich, the former speaker of the US House of Representatives. He still feels that sense of urgency, and for good reason. Funding has not kept pace with the scale of the problem; targets for treatments are thin on the ground and poorly understood; and more than 200 clinical trials for Alzheimer’s therapies have been terminated because the treatments were ineffective. Of the few treatments available, none addresses the underlying disease process. “We’re faced with a tsunami and we’re trying to deal with it with a bucket,” says Gingrich. But this message has begun to reverberate around the world, which gives hope to the clinicians and scientists. Experts say that the coming wave can be calmed with the help of just three things: more money for research, better diagnostics and drugs, and a victory — however small — that would boost morale. “What we really need is a success,” says Ronald Petersen, a neurologist at Mayo Clinic in Rochester, Minnesota. After so many failures, one clinical win “would galvanize people’s interest that this isn’t a hopeless disorder”. Dementia is the fifth-biggest cause of death in high-income countries, but it is the most expensive disease to manage because patients require constant, costly care for years. And yet, research funding for dementia pales in comparison with that for many other diseases. At the US National Institutes of Health (NIH), for example, annual funding for dementia in 2015 was only around $700 million, compared with some $2 billion for cardiovascular disease and more than $5 billion for cancer. One problem is visibility. Other disease communities — most notably, people affected by breast cancer and HIV/AIDS — have successfully advocated for large pots of dedicated research funding. But “there simply wasn’t any comparable upswell of attention to Alzheimer’s”, says George Vradenburg, chair and co-founder of UsAgainstAlzheimer’s, a non-profit organization in Chevy Chase, Maryland. The biggest reason, he says, is that “the victims of the disease hide out”. Dementia mostly affects elderly people and is often misconstrued as a normal part of ageing; there is a stigma attached to the condition, and family care-givers are often overworked and exhausted. Few are motivated enough to speak up. However, social and political awareness has increased in the past five years. “We all started to work together a lot more, and that helps,” says Susan Peschin, chief executive at the Alliance for Aging Research in Washington DC, one of more than 50 non-profit groups in the Accelerate Cure/Treatments for Alzheimer’s Disease coalition. The impact can be seen in government investments. France took action first, creating a national plan for Alzheimer’s in 2008 that included €200 million (US$220 million) over five years for research. In 2009, the German Centre for Neurodegenerative Diseases in Bonn was created with a €66-million annual budget. And UK spending on dementia research more than doubled between 2010 and 2015, to £66 million (US$82 million). The European Union has been dishing out tens of millions of euros each year for dementia studies through the Innovative Medicines Initiative and the Joint Programming process, and Australia is now about halfway through doling out its Aus$200-million (US$150-million), five-year dementia-research fund. “This is a global challenge, and no one country will be able to solve the problem,” says Philippe Amouyel, a neurologist and geneticist at the University Hospital of Lille in France. Yet it’s the United States that has been the biggest backer by far, thanks in part to efforts by Gingrich and Kerrey. The NIH’s annual budget for Alzheimer’s and other dementias jumped in the past year to around $1 billion, and there is support for a target to double that figure in the next few years — even in the fractious US political landscape. “Alzheimer’s doesn’t care what political party you’re in,” says Kerrey. Two billion dollars is “a reasonable number”, says Petersen, who chairs the federal advisory board that came up with the target in 2012. Now, he adds, the research community just needs to work out “what are we going to do with it if in fact we get it?”. The answer could depend in large part on the fate of a drug called solanezumab, developed by Eli Lilly of Indianapolis, Indiana. This antibody-based treatment removes the protein amyloid-β, which clumps together to form sticky plaques in the brains of people with Alzheimer’s. By the end of this year, Lilly is expected to announce the results of a 2,100-person clinical trial testing whether the drug can slow cognitive decline in people with mild Alzheimer’s. It showed preliminary signs of cognitive benefit in this patient population in earlier trials (R. S. Doody et al. N. Engl. J. Med. 370, 311–321; 2014), but the benefits could disappear in this final stage of testing, as has happened for practically every other promising compound. No one is expecting a cure. If solanezumab does delay brain degradation, at best it might help people to perform 30–40% better on cognitive tests than those on a placebo. But even such a marginal gain would be a triumph. It would show scientists and the drug industry that a disease-modifying therapy is at least possible. By contrast, another setback could bring recent momentum in therapeutic development to a halt. “This is a fork in the road,” says John Hardy, a neurogeneticist at University College London. “This is going to be a very important outcome, way beyond the importance for Lilly and this particular drug.” On a scientific level, success for solanezumab could lend credence to the much-debated amyloid hypothesis, which posits that the build-up of amyloid-β in the brain is one of the triggers of Alzheimer’s disease. The previous failure of amyloid-clearing agents led many to conclude that plaques were a consequence of a process in the disease, rather than the cause of it. But those in favour of the amyloid hypothesis say that the failed drugs were given too late, or to people with no amyloid build-up — possibly those with a different form of dementia. For its latest solanezumab trial, Lilly sought out participants with mild cognitive impairment, and used brain scans and spinal-fluid analyses to confirm the presence of amyloid-β in their brains. Another company, Biogen in Cambridge, Massachusetts, took the same approach to screening participants in a trial of its amyloid-targeting drug aducanumab. Earlier this year, a 165-person study reported early signs that successfully clearing amyloid-β with the Biogen therapy correlated with slower cognitive decline (J. Sevigny et al. Nature 537, 50–56; 2016). If those results hold up to further scrutiny, “that will at least tell us that amyloid is sufficiently upstream in the cascade that it deserves being targeted and tackled pharmacologically”, says Giovanni Frisoni, a clinical neuroscientist at the University of Geneva in Switzerland who is involved in the drug’s testing. Although debate over the amyloid hypothesis continues, interest is growing in earlier intervention with drugs that clear the protein. Reisa Sperling, a neurologist at Brigham and Women’s Hospital in Boston, Massachusetts, worries that even mild dementia is a sign of irreparable brain-cell death. “You can suck all the amyloid out of the brain or stop it from further accumulating, but you’re not going to grow those neurons back.” That is why she is leading Anti-Amyloid Treatment in Asymptomatic Alzheimer’s, or A4, a $140-million, placebo-controlled solanezumab study that aims to treat people with elevated amyloid levels before they show any signs of cognitive impairment. And A4 is not her only trial. In March, she and neurologist Paul Aisen of the University of Southern California’s Alzheimer’s Therapeutic Research Institute in San Diego launched a trial in 1,650 asymptomatic people with early signs of amyloid-β build-up. It will test a pill from Johnson & Johnson that blocks β-secretase, an enzyme responsible for producing the toxic protein. These interventions are known as secondary prevention because they target people who are already developing amyloid plaques. Sperling and Aisen also plan to test what’s called primary prevention. In August, they received NIH funding to start treating people who have normal brain levels of amyloid-β and no signs of cognitive decline, but who have a high risk of developing Alzheimer’s — because of a combination of factors such as age and genetics. “The biggest impact we can have is in delaying the onset of the diseases,” says David Holtzman, a neurologist at Washington University School of Medicine in St. Louis, Missouri, and an investigator in the Dominantly Inherited Alzheimer Network, which is testing the benefits of giving either solanezumab or another anti-amyloid therapy to people who inherit gene mutations that predispose them to develop Alzheimer’s at an early age. Secondary prevention could eventually mean screening everyone past middle age for signs of amyloid-β, although the current testing methods are either expensive ($3,000 brain scans) or invasive (spinal taps). Researchers have flagged a dozen possible blood-based biomarkers, but none has yet panned out, says Dennis Selkoe, a Brigham and Women’s Hospital neurologist. Yet a cheap and easy diagnostic test for amyloid-β could ultimately prove unnecessary. In the same way that some have suggested giving cholesterol-lowering drugs to anyone at risk of heart disease, clinicians might eventually give anti-amyloid drugs to a broad set of people prone to Alzheimer’s — even if they are not already amyloid positive, says Sperling. Just as cholesterol is not the sole cause of heart disease, amyloid-β is not the only driver of Alzheimer’s. There’s also tau, a protein that causes tangles in the brains of most people with Alzheimer’s. Several pharmaceutical companies are targeting tau, but few large drug-makers have clinical candidates directed at other types of target. “They know how to modulate a specific target and keep looking under that lamp post, rather than venturing away from their comfort zones,” says Bernard Munos, an industry consultant and former Eli Lilly executive. That’s a problem, says Howard Fillit, chief science officer of the Alzheimer’s Drug Discovery Foundation in New York City. “We really need to increase the diversity of targets we’re tackling.” After amyloid and tau, the only target receiving much attention from researchers is neuroinflammation — the “third leg of the stool” in treating Alzheimer’s, according to neurogeneticist Rudy Tanzi at Massachusetts General Hospital in Boston. He likens Alzheimer’s disease to a wildfire in the brain. Plaques and tangles provide the initial brush fires, but it’s the accompanying neuroinflammation that fans the flames. Once the blaze is raging, Tanzi says, “putting out those brush fires that got you there isn’t good enough”. This could explain why anti-amyloid drugs failed when given to people with full-blown dementia. For these individuals, perhaps reducing the inflammatory activity of brain immune cells called microglia could help. Drug researchers are now focusing on two genes, CD33 and TREM2, that are involved in microglial function. But, says Tanzi, “there are two dozen other genes that deserve attention. Who knows if one of these new genes that no one is working on might lead to drug clues?” Many Alzheimer’s experts emphasize the need to develop better low-cost interventions that don’t require drug research. At the University of New South Wales in Sydney, Australia, for example, geriatric psychiatrist Henry Brodaty is testing whether an Internet coaching tool that focuses on diet, exercise, cognitive training and mood can postpone disease development. “We know that two-thirds of the world’s dementia is going to be in developing countries,” he says (see ‘The approaching wave’). Lifestyle interventions, he argues, could be more broadly scalable than expensive drugs. Researchers also need to look beyond Alzheimer’s, to the many other types of dementia. Injuries to the vessels that supply blood to the brain cause a form called vascular dementia. Clumps of a protein called α-synuclein underlie cognitive problems in people with Parkinson’s disease and also what’s called Lewy body dementia. Tau deposits are often behind the nerve-cell loss responsible for frontotemporal dementia. And there are many other, equally devastating, drivers of serious mental decline. “We should not be ignoring these other diseases,” says Nick Fox, a neurologist at University College London, especially given that many types of dementia share biological mechanisms. Tackling one disease could help inform treatment strategies for another. But perhaps the biggest hindrance to drug development today is more logistical than scientific, with clinical trials for dementia taking years to complete as investigators struggle to recruit sufficient numbers of study participants. “We need to get answers more quickly,” says Marilyn Albert, director of the Johns Hopkins Alzheimer’s Disease Research Center in Baltimore, Maryland. One solution is trial-ready registries. By enrolling people who are interested in taking part in a study before it actually exists, investigators can start a trial as soon as a drug comes along for testing. “We have to register humanity in the task of defeating this disease,” says Aisen. The 1,600-person COMPASS-ND registry is being funded through the Canadian Consortium on Neurodegeneration in Aging. Member Serge Gauthier, a neurologist at McGill University in Montreal, says that finding participants can be challenging. But he adds that around one-third of the people who come to memory clinics such as his have what’s known as subjective cognitive impairment — they might forget names or suffer from other ‘senior moments’, but they do not meet the clinical definition of dementia. They are perfect for trial-ready registries, says Gauthier: they are at an elevated risk of the disease, and they’ve demonstrated concern. Gauthier wants to find more people like them. He fits the profile himself, so he joined the Brain Health Registry, which has more than 40,000 participants so far and is led by researchers at the University of California, San Francisco. He takes regular cognitive tests, and could be asked to do more once potential diagnostic tools or therapies are ready for testing. “It’s a fun thing to do,” he says. Voluntarily or not, people will need to face up to dementia, because in just a few short decades, pretty much everyone is going to have a friend or loved one affected by the disease. It’s an alarming idea, and it should spur action, says Robert Egge, chief public policy officer of the Alzheimer’s Association in Chicago, Illinois. “We know where we’re heading,” he says. “The question is: are we going to get in front of it or not?”
Adhikari N.K.J.,Li Ka Shing Knowledge Institute |
Dellinger R.P.,Cooper University Hospital |
Lundin S.,Sahlgrenska University Hospital |
Payen D.,University Paris Diderot |
And 6 more authors.
Critical Care Medicine | Year: 2014
OBJECTIVE:: Treatment with inhaled nitric oxide improves oxygenation but not survival in mechanically ventilated patients with acute respiratory distress syndrome, but the effect may depend on the severity of hypoxemia. Our objective was to determine whether nitric oxide reduces hospital mortality in patients with severe acute respiratory distress syndrome (PaO2/FIO2 ≤ 100 mm Hg) but not in patients with mild-moderate acute respiratory distress syndrome (100 < PaO2/FIO2 ≤ 300 mm Hg) at the time of randomization. DATA SOURCES:: Data were collected from Medline, Embase, and Cochrane CENTRAL electronic databases (inception to May 2013); proceedings from five conferences (to May 2013); and trial registries (http://www.clinicaltrials.gov and http://www.controlled- trials.com). No language restrictions were applied. STUDY SELECTION:: Two authors independently selected parallel-group randomized controlled trials comparing nitric oxide with control (placebo or no gas) in mechanically ventilated adults or postneonatal children with acute respiratory distress syndrome. DATA EXTRACTION:: Two authors independently extracted data from included trials. Trial investigators provided subgroup data. Meta-analyses used within-trial subgroups and random-effects models. DATA SYNTHESIS:: Nine trials (n = 1,142 patients) met inclusion criteria. Overall methodological quality was good. Nitric oxide did not reduce mortality in patients with severe acute respiratory distress syndrome (risk ratio, 1.01 [95% CI, 0.78-1.32]; p = 0.93; n = 329, six trials) or mild-moderate acute respiratory distress syndrome (risk ratio, 1.12 [95% CI, 0.89-1.42]; p = 0.33; n = 740, seven trials). Risk ratios were similar between subgroups (interaction p = 0.53). There was no between-trial heterogeneity in any analysis (I = 0%). Varying the PaO2/FIO2 threshold between 70 and 200 mm Hg, in increments of 10 mm Hg, did not identify any threshold at which the nitric oxide-treated patients had lower mortality relative to controls. CONCLUSIONS:: Nitric oxide does not reduce mortality in adults or children with acute respiratory distress syndrome, regardless of the degree of hypoxemia. Given the lack of related ongoing or recently completed randomized trials, new data addressing the effectiveness of nitric oxide in patients with acute respiratory distress syndrome and severe hypoxemia will not be available for the foreseeable future. © 2013 by the Society of Critical Care Medicine and Lippincott.
Nseir S.,Intensive Care Unit |
Nseir S.,Lille University |
Zerimech F.,University Hospital of Lille |
Fournier C.,Calmette Hospital |
And 6 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2011
Rationale: Underinflation of the tracheal cuff frequently occurs in critically ill patients and represents a risk factor for microaspiration of contaminated oropharyngeal secretions and gastric contents that plays a major role in the pathogenesis of ventilator-associated pneumonia (VAP). Objectives: To determine the impact of continuous control of tracheal cuff pressure (P cuff) on microaspiration of gastric contents. Methods: Prospective randomized controlled trial performed in a single medical intensive care unit. A total of 122 patients expected to receive mechanical ventilation for at least 48 hours through a tracheal tube were randomized to receive continuous control of P cuffusing a pneumatic device (intervention group, n = 61) or routine care of P cuff (control group, n = 61). Measurements and Main Results: The primary outcome was microaspiration of gastric contents as defined by the presence of pepsin at a significant level in tracheal secretions collected during the 48 hours after randomization. Secondary outcomes included incidence of VAP, tracheobronchial bacterial concentration, and tracheal ischemic lesions. The pneumatic device was efficient in controlling P cuff. Pepsin was measured in 1,205 tracheal aspirates. Percentage of patients with abundant microaspiration (18 vs. 46%; P = 0.002; OR [95% confidence interval], 0.25 [0.11-0.59]), bacterial concentration in tracheal aspirates (mean ± SD 1.6 ± 2.4 vs. 3.1 ± 3.7 log 10 cfu/ml, P = 0.014), and VAP rate (9.8 vs. 26.2%; P = 0.032; 0.30 [0.11-0.84]) were significantly lower in the intervention group compared with the control group. However, no significant difference was found in tracheal ischemia score between the two groups. Conclusions: Continuous control of P cuff is associated with significantly decreased microaspiration of gastric contents in critically ill patients.
Van Meerbeeck J.P.,Ghent University |
Scherpereel A.,University Hospital of Lille |
Surmont V.F.,Ghent University |
Baas P.,Netherlands Cancer Institute
Critical Reviews in Oncology/Hematology | Year: 2011
This review addresses the management of MPM. In an introductory section, the etiology, epidemiology, presentation, diagnosis and staging of MPM will be reviewed. The evidence was collected by a systematic analysis of the literature (2000-2009) using the databases Medline (National Library of Medicine, USA), Embase (Elsevier, Netherlands), Cochrane Library (Great Britain), National Guideline Clearinghouse (USA), HTA Database (International Network of Agencies for Health Technology Assessment - INAHTA), NIH database (USA), International Pleural Mesothelioma Program - WHOLIS (WHO Database) with the following keywords and filters: pleura, cancer, mesothelioma, guidelines, treatment, surgery, chemotherapy, radiotherapy, palliation, supportive care, pleurodesis, review. © 2010 Elsevier Ireland Ltd.
Florin V.,University Hospital of Lille |
Desmedt E.,University Hospital of Lille |
Vercambre-Darras S.,University Hospital of Lille |
Mortier L.,Service de Dermatologie
Investigational New Drugs | Year: 2012
Background Despite multiple available options, the treatment of cutaneous melanoma metastases is often unsuccessful. Based on the hypothesis that imiquimod and 5-fluorouracil have synergistic antitumor properties, we used this topical combination to treat several patients. Aim Our objective was to investigate the treatment combination in a small cohort of patients with surgically non-resectable melanoma metastases. Methods The lesions of 5 patients with multiple cutaneous metastases were treated topically, 5 days per week, with 5-fluorouracil in the morning and imiquimod at night. Results 45 lesions were treated. A clinical response was seen in 44 lesions, with a complete response in 19 lesions and a partial response in 25. Stable disease was confirmed in the 1 remaining lesion. No patients developed new lesions during treatment. However, one patient had a recurrence 6 months after treatment discontinuation, followed by a partial response when rechallenged. Conclusions The imiquimod and 5-fluorouracil combination is effective. That patients did not develop new, distant lesions suggests the achievement of locoregional control, probably by the induction of antitumor immune response. © Springer Science+Business Media, LLC 2011.
Nseir S.,University Hospital of Lille |
Makris D.,University of Thessaly |
Mathieu D.,University Hospital of Lille |
Durocher A.,University Hospital of Lille |
Marquette C.,University Hospital of Nice
Critical Care | Year: 2010
Introduction: Sedative and analgesic medications are routinely used in mechanically ventilated patients. The aim of this review is to discus epidemiologic data that suggest a relationship between infection and sedation, to review available data for the potential causes and pathophysiology of this relationship, and to identify potential preventive measures.Methods: Data for this review were identified through searches of PubMed, and from bibliographies of relevant articles.Results: Several epidemiologic studies suggested a link between sedation and ICU-acquired infection. Prolongation of exposure to risk factors for infection, microaspiration, gastrointestinal motility disturbances, microcirculatory effects are main mechanisms by which sedation may favour infection in critically ill patients. Furthermore, experimental evidence coming from studies both in humans and animals suggest that sedatives and analgesics present immunomodulatory properties that might alter the immunologic response to exogenous stimuli. Clinical studies comparing different sedative agents do not provide evidence to recommend the use of a particular agent to reduce ICU-acquired infection rate. However, sedation strategies aiming to reduce the duration of mechanical ventilation, such as daily interruption of sedatives or nursing-implementing sedation protocol, should be promoted. In addition, the use of short acting opioids, propofol, and dexmedetomidine is associated with shorter duration of mechanical ventilation and ICU stay, and might be helpful in reducing ICU-acquired infection rates.Conclusions: Prolongation of exposure to risk factors for infection, microaspiration, gastrointestinal motility disturbances, microcirculatory effects, and immunomodulatory effects are main mechanisms by which sedation may favour infection in critically ill patients. Future studies should compare the effect of different sedative agents, and the impact of progressive opioid discontinuation compared with abrupt discontinuation on ICU-acquired infection rates. © 2010 Nseir et al.; licensee BioMed Central Ltd.
Vallet B.,University Hospital of Lille |
Robin E.,University Hospital of Lille |
Lebuffe G.,University Hospital of Lille
Critical Care | Year: 2010
This article is one of ten reviews selected from the Yearbook of Intensive Care and Emergency Medicine 2010 (Springer Verlag) and co-published as a series in Critical Care. Other articles in the series can be found online at http://ccforum.com/series/yearbook. Further information about the Yearbook of Intensive Care and Emergency Medicine is available from http://www.springer.com/series/2855. © 2010 Springer-Verlag Berlin Heidelberg 2010.
Yakoub-Agha I.,Lille 2 University of Health and Law |
Yakoub-Agha I.,University Hospital of Lille
Seminars in Hematology | Year: 2016
The clinical outcome after allogeneic stem cell transplantation from a human leukocyte antigen (HLA)-matched sibling donor as well as an HLA-matched unrelated donor has clearly improved due in part to the progress made in the domains of HLA-typing techniques. Although HLA-matched sibling transplantation is still held as the "gold standard," transplantation from HLA-A, -B, -C, -DRB1, and -DQB1-matched unrelated donors (so called 10/10) represent the first choice for patients without a suitable related donor. Several studies have shown that unmanipulated marrow transplantation from an HLA allele-matched unrelated donor resulted in similar outcomes to those observed following sibling transplantation. However, incorporating anti-thymocyte globulin (ATG) within graft-versus-host disease (GVHD) prophylaxis should be considered for peripheral blood stem cell grafts in order to decrease the risk of developing chronic GVHD. © 2016 Elsevier Inc.
Vallet B.,University Hospital of Lille |
Futier E.,University Hospital of Clermont Ferrand
Current Opinion in Critical Care | Year: 2010
Purpose of review: Tissue hypoxia is a key trigger for organ dysfunction. The maintenance of adequate tissue oxygenation is therefore of particular importance during major surgery. In this review, we discuss the physiological basis and the rationale underlying the recent concepts of perioperative oxygen therapy. Recent findings: Adequate tissue oxygenation is vital for optimal tissue healing in the surgical context. Nevertheless, the definitive proof for a beneficial effect of perioperative oxygen therapy with an increase in inspired oxygen has not been established. In contrast, optimization of oxygen delivery (DO2), using either or both fluid loading and inotropic supports, to prevent tissue hypoxia in relation to an increased oxygen consumption (VO2) could improve outcome. In this context, the use of central venous oxygen saturation (ScvO2), which reflects important changes in the DO2/VO2 relationship and of central venous-to-arterial carbon dioxide difference, to address adequacy of oxygen utilization, has shown promising results. Summary: Adequacy of oxygen delivery to tissue oxygen metabolic demand is essential during the perioperative period. The benefit of perioperative oxygen therapy is rather optimizing the DO2 than increasing inspired oxygen. Improving DO2 has been demonstrated in the perioperative period to reduce both morbidity and mortality. Adaptation of DO2 to O2 consumption using specific goals seems promising. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.