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1.  Early non-invasive ventilation for acute respiratory failure in immunocompromised patients (IVNIctus): study protocol for a multicenter randomized controlled trial 
Trials  2014;15(1):372.
Background
Acute respiratory failure (ARF) remains the leading reason for intensive care unit (ICU) admission of immunocompromised patients. In the most severe cases, high-flow oxygen therapy may fail to ensure adequate gas exchange, and mechanical ventilation (MV) must be used. This scenario is associated with high mortality rates of 40 to 60%, depending on the cause of ARF and type of immune deficiency. The use of non-invasive ventilation (NIV) in this situation has been criticized as potentially delaying the initiation of optimal treatment. In contrast, early NIV used prophylactically in patients with ARF who do not meet the criteria for invasive MV (IMV) may obviate the need for IMV, thereby decreasing the morbidity and mortality rates. We aim to demonstrate that a management strategy including early NIV decreases 28-day mortality rates compared to oxygen therapy alone in immunocompromised patients with ARF.
Methods/Design
This is a multicenter parallel-group randomized controlled trial comparing early NIV to oxygen therapy alone in immunocompromised patients with ARF. All immunocompromised adult patients admitted to admission for ARF are eligible for randomization. Patient with ARF onset more than 72 hours earlier or ARF related to cardiogenic pulmonary edema or hypercapnia, or with a need for immediate endotracheal intubation or other organ failure are not eligible.
After inclusion patient are allocated to receive early NIV (intervention arm) or oxygen therapy only (control arm).
We plan to enroll 374 patients in 29 ICUs. An interim analysis is planned after the inclusion of 187 patients. The main objective is to demonstrate early NIV increases survival as compared to oxygen therapy alone. Other outcomes include the need of IMV, organ failure evolution, nosocomial infections rate, 6 months survival.
Discussion
This study is expected to demonstrate an improved 28-day survival in immunocompromised patients managed with early NIV.
Trial registration
Registration number: Clinicaltrials.gov NCT01915719. Registered on 26 July 2013.
Electronic supplementary material
The online version of this article (doi:10.1186/1745-6215-15-372) contains supplementary material, which is available to authorized users.
doi:10.1186/1745-6215-15-372
PMCID: PMC4190291  PMID: 25257210
Non-invasive ventilation; Immunocompromised patient; Acute respiratory failure
2.  Acute Respiratory Failure in Critically Ill Patients with Interstitial Lung Disease 
PLoS ONE  2014;9(8):e104897.
Background
Patients with chronic known or unknown interstitial lung disease (ILD) may present with severe respiratory flares that require intensive management. Outcome data in these patients are scarce.
Patients and Methods
Clinical and radiological features were collected in 83 patients with ILD-associated acute respiratory failure (ARF). Determinants of hospital mortality and response to corticosteroid therapy were identified by logistic regression.
Results
Hospital and 1-year mortality rates were 41% and 54% respectively. Pulmonary hypertension, computed tomography (CT) fibrosis and acute kidney injury were independently associated with mortality (odds ratio (OR) 4.55; 95% confidence interval (95%CI) (1.20–17.33); OR, 7.68; (1.78–33.22) and OR 10.60; (2.25–49.97) respectively). Response to steroids was higher in patients with shorter time from hospital admission to corticosteroid therapy. Patients with fibrosis on CT had lower response to steroids (OR, 0.03; (0.005–0.21)). In mechanically ventilated patients, overdistension induced by high PEEP settings was associated with CT fibrosis and hospital mortality.
Conclusion
Mortality is high in ILD-associated ARF. CT and echocardiography are valuable prognostic tools. Prompt corticosteroid therapy may improve survival.
doi:10.1371/journal.pone.0104897
PMCID: PMC4130629  PMID: 25115557
3.  Non-invasive mechanical ventilation in hematology patients: let's agree on several things first 
Critical Care  2012;16(6):175.
Acute respiratory failure is a dreaded and life-threatening event that represents the main reason for ICU admission. Respiratory events occur in up to 50% of hematology patients, including one-half of those admitted to the ICU. Mortality from acute respiratory failure in hematology patients depends on the patient's general status, acute respiratory failure etiology, need for mechanical ventilation and associated organ dysfunction. Non-invasive mechanical ventilation is clearly beneficial for chronic obstructive pulmonary disease exacerbation and cardiogenic pulmonary edema. These benefits are based mainly on the avoidance of invasive mechanical ventilation complications. Non-invasive mechanical has also been recommended in hematology patients with acute respiratory failure but its real benefits remain unclear in these settings. There is growing concern about the safety of non-invasive mechanical ventilation to treat hypoxemic acute respiratory failure overall, but also in hematology patients. Prophylactic non-invasive mechanical ventilation in patients with acute respiratory failure but not respiratory distress seems to be effective in hematology patients with a reduced rate of intubation. However, curative non-invasive mechanical ventilation should be restricted to those patients with isolated respiratory failure, with fast improvement of respiratory distress under non-invasive mechanical ventilation, and with rapid switch to intubation to avoid deleterious delays in optimal invasive mechanical ventilation.
doi:10.1186/cc11830
PMCID: PMC3672579  PMID: 23167945
4.  Adjunctive steroid in HIV-negative patients with severe Pneumocystis pneumonia 
Respiratory Research  2013;14(1):87.
Background
High-dose steroid therapy has been proven effective in AIDS-related Pneumocystis pneumonia (PCP) but not in non-AIDS-related cases. We evaluated the effects on survival of steroids in HIV-negative patients with PCP.
Methods
Retrospective study patients admitted to the ICU with hypoxemic PCP. We compared patients receiving HDS (≥1 mg/Kg/day prednisone equivalent), low-dose steroids (LDS group, <1 mg/Kg/day prednisone equivalent), and no steroids (NS group). Variables independently associated with ICU mortality were identified.
Results
139 HIV-negative patients with PCP were included. Median age was 48 [40–60] years. The main underlying conditions were hematological malignancies (n=55, 39.6%), cancer (n=11, 7.9%), and solid organ transplantation (n=73, 52.2%). ICU mortality was 26% (36 deaths). The HDS group had 72 (51.8%) patients, the LDS group 35 (25%) patients, and the NS group 32 (23%) patients. Independent predictors of ICU mortality were SAPS II at ICU admission (odds ratio [OR], 1.04/point; [95%CI], 1.01-1.08, P=0.01), non-hematological disease (OR, 4.06; [95%CI], 1.19-13.09, P=0.03), vasopressor use (OR, 20.31; 95%CI, 6.45-63.9, P<0.001), and HDS (OR, 9.33; 95%CI, 1.97-44.3, P=0.02). HDS was not associated with the rate of ICU-acquired infections.
Conclusions
HDS were associated with increased mortality in HIV-negative patients with PCP via a mechanism independent from an increased risk of infection.
doi:10.1186/1465-9921-14-87
PMCID: PMC3765749  PMID: 23981859
Pneumocystis jiroveci infection; Immunocompromised host; Mortality
5.  Plasma thioredoxin levels during post-cardiac arrest syndrome: relationship with severity and outcome 
Critical Care  2013;17(1):R18.
Introduction
Despite experimental evidence, clinical demonstration of acute state of oxidative stress and inflammation during post-cardiac arrest syndrome is lacking. Plasma level of thioredoxin (TRX), a redox-active protein induced under conditions of oxidative stress and inflammation, is increased in various critical care conditions. We determined plasma TRX concentrations after cardiac arrest and assessed relationships with severity and outcome.
Methods
Retrospective study of consecutive patients admitted to a single academic intensive care unit (ICU) for out-of-hospital cardiac arrest (between July 2006 and March 2008). Plasma levels of TRX were measured at admission, day (D) 1, 2 and 3.
Results
Of 176 patients included, median TRX values measured in ICU survivors and non-survivors were, respectively: 22 ng/mL (7.8 to 77) vs. 72.4 (21.9 to 117.9) at admission (P < 0.001); 5.9 (3.5 to 25.5) vs. 23.2 (5.8 to 81.4) at D1 (P = 0.003); 10.8 (3.6 to 50.8) vs. 11.7 (4.5 to 66.4) at D2 (P = 0.22); and 16.7 (5.3 to 68.3) vs. 17 (4.3 to 62.9) at D3 (P = 0.96). Patients dying within 24 hours had significantly (P < 0.001) higher TRX levels (118.6 ng/mL (94.8 to 280)) than those who died after 24 hours or survived (50.8 (13.9 to 95.7) and 22 (7.8 to 77)). The area under the ROC curve to predict early death was 0.84 (0.76 to 0.91).
TRX levels on admission were significantly correlated with 'low-flow' duration (P = 0.003), sequential organ failure assessment (SOFA) score (P < 0.001), and blood lactate concentration (P < 0.001), but not with 'no-flow' duration or simplified acute physiology score (SAPS) II score. TRX levels and admission arterial pO2 correlated negatively (r = -0.17, P = 0.03). Finally, cardiac arrest with cardiac etiology exhibited lower levels of TRX than in cases of extra-cardiac cause (46 ng/mL (11 to 104) vs. 68 (42 to 137), P = 0.01).
Conclusions
Our data show for the first time that TRX levels were elevated early following cardiac arrest, suggestive of oxidative stress and inflammation occurring with this condition. Highest values were found in the most severe patients. TRX could be a useful tool for further exploration and comprehension of post-cardiac arrest syndrome.
doi:10.1186/cc12492
PMCID: PMC4056807  PMID: 23356570
6.  Epidemiology and outcome of severe pneumococcal pneumonia admitted to intensive care unit: a multicenter study 
Critical Care  2012;16(4):R155.
Introduction
Community-acquired pneumonia (CAP) account for a high proportion of ICU admissions, with Streptococcus pneumoniae being the main pathogen responsible for these infections. However, little is known on the clinical features and outcomes of ICU patients with pneumococcal pneumonia. The aims of this study were to provide epidemiological data and to determine risk factors of mortality in patients admitted to ICU for severe S. pneumoniae CAP.
Methods
We performed a retrospective review of two prospectively-acquired multicentre ICU databases (2001-2008). Patients admitted for management of severe pneumococcal CAP were enrolled if they met the 2001 American Thoracic Society criteria for severe pneumonia, had life-threatening organ failure and had a positive microbiological sample for S. pneumoniae. Patients with bronchitis, aspiration pneumonia or with non-pulmonary pneumococcal infections were excluded.
Results
Two hundred and twenty two patients were included, with a median SAPS II score reaching 47 [36-64]. Acute respiratory failure (n = 154) and septic shock (n = 54) were their most frequent causes of ICU admission. Septic shock occurred in 170 patients (77%) and mechanical ventilation was required in 186 patients (84%); renal replacement therapy was initiated in 70 patients (32%). Bacteraemia was diagnosed in 101 patients. The prevalence of S. pneumoniae strains with decreased susceptibility to penicillin was 39.7%. Although antibiotherapy was adequate in 92.3% of cases, hospital mortality reached 28.8%. In multivariate analysis, independent risk factors for mortality were age (OR 1.05 (95% CI: 1.02-1.08)), male sex (OR 2.83 (95% CI: 1.16-6.91)) and renal replacement therapy (OR 3.78 (95% CI: 1.71-8.36)). Co-morbidities, macrolide administration, concomitant bacteremia or penicillin susceptibility did not influence outcome.
Conclusions
In ICU, mortality of pneumococcal CAP remains high despite adequate antimicrobial treatment. Baseline demographic data and renal replacement therapy have a major impact on adverse outcome.
doi:10.1186/cc11471
PMCID: PMC3580745  PMID: 22894879
7.  Clinical features of H1N1 2009 infection in critically ill immunocompromised patients 
Critical Care  2010;14(2):139.
Seasonal influenza virus has been described as an emerging and severe pathogen in immunocompromised hosts. Since the beginning of the 2009 influenza A novel H1N1 pandemic, several series have described the clinical course of the disease in various populations. We report the clinical course of H1N1 2009 infection in 10 immunocompromised patients. Half of the patients received long-term steroid therapy. Disease was characterized by a clinical picture similar to that of non-immunocompromised patients but with prolonged course and higher mortality.
doi:10.1186/cc8927
PMCID: PMC2887153  PMID: 20392286
8.  Predictive Features of Severe Acquired ADAMTS13 Deficiency in Idiopathic Thrombotic Microangiopathies: The French TMA Reference Center Experience 
PLoS ONE  2010;5(4):e10208.
Severe ADAMTS13 deficiency occurs in 13% to 75% of thrombotic microangiopathies (TMA). In this context, the early identification of a severe, antibody-mediated, ADAMTS13 deficiency may allow to start targeted therapies such as B-lymphocytes-depleting monoclonal antibodies. To date, assays exploring ADAMTS13 activity require skill and are limited to only some specialized reference laboratories, given the very low incidence of the disease. To identify clinical features which may allow to predict rapidly an acquired ADAMTS13 deficiency, we performed a cross-sectional analysis of our national registry from 2000 to 2007. The clinical presentation of 160 patients with TMA and acquired ADAMTS13 deficiency was compared with that of 54 patients with detectable ADAMTS13 activity. ADAMTS13 deficiency was associated with more relapses during treatment and with a good renal prognosis. Patients with acquired ADAMTS13 deficiency had platelet count <30×109/L (adjusted odds ratio [OR] 9.1, 95% confidence interval [CI] 3.4–24.2, P<.001), serum creatinine level ≤200 µmol/L (OR 23.4, 95% CI 8.8–62.5, P<.001), and detectable antinuclear antibodies (OR 2.8, 95% CI 1.0–8.0, P<.05). When at least 1 criteria was met, patients with a severe acquired ADAMTS13 deficiency were identified with positive predictive value of 85%, negative predictive value of 93.3%, sensitivity of 98.8%, and specificity of 48.1%. Our criteria should be useful to identify rapidly newly diagnosed patients with an acquired ADAMTS13 deficiency to better tailor treatment for different pathophysiological groups.
doi:10.1371/journal.pone.0010208
PMCID: PMC2859048  PMID: 20436664
10.  Changes in Human Immunodeficiency Virus Type 1 Populations after Treatment Interruption in Patients Failing Antiretroviral Therapy 
Journal of Virology  2001;75(14):6410-6417.
Mutations in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase and protease that confer resistance to antiretroviral agents are usually accompanied by a reduction in the viral replicative capacity under drug-free conditions. Consequently, when antiretroviral treatment is interrupted in HIV-1-infected patients harboring drug-resistant virus, resistant quasi-species appear to be most often replaced within several weeks by wild-type virus. Using a real-time PCR-based technique for the selective quantification of resistant viral sequences in plasma, we have studied the kinetics of the switch from mutant to wild-type virus and evaluated the extent to which minority populations of resistant viruses not detected by genotyping persist in these individuals. Among 12 patients with viruses expressing the V82A or L90M resistance mutation who had undergone a 3-month interruption of therapy and for whom conventional genotyping had revealed an apparent total reconversion to wild-type virus, minority populations expressing these mutations, representing 0.1 to 21% of total virus, were still detectable in 9 cases. Kinetic studies demonstrated that viruses expressing resistance mutations could be detected for >5 months after the discontinuation of treatment in some patients. Most of the minority resistant genomes detected more than 3 months after the interruption of therapy carried only part of the mutations present in the resistant viruses prior to treatment interruption and appeared to result from the emergence of existing strains selected at earlier stages in the development of drug resistance. Thus, following the interruption of treatment, viral populations containing resistance mutations can persist for several months after the time when conventional genotyping techniques detect only wild-type virus. These populations include viral strains with only some of the resistance mutations initially present, strains that presumably express better fitness under drug-free conditions.
doi:10.1128/JVI.75.14.6410-6417.2001
PMCID: PMC114364  PMID: 11413308

Results 1-10 (10)