On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection.

BACKGROUND: Antiretroviral preexposure prophylaxis has been shown to reduce the risk of human immunodeficiency virus type 1 (HIV-1) infection in some studies, but conflicting results have been reported among studies, probably due to challenges of adherence to a daily regimen. METHODS: We conducted a double-blind, randomized trial of antiretroviral therapy for preexposure HIV-1 prophylaxis among men who have unprotected anal sex with men. Participants were randomly assigned to take a combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) or placebo before and after sexual activity. All participants received risk-reduction counseling and condoms and were regularly tested for HIV-1 and HIV-2 and other sexually transmitted infections. RESULTS: Of the 414 participants who underwent randomization, 400 who did not have HIV infection were enrolled (199 in the TDF-FTC group and 201 in the placebo group). All participants were followed for a median of 9.3 months (interquartile range, 4.9 to 20.6). A total of 16 HIV-1 infections occurred during follow-up, 2 in the TDF-FTC group (incidence, 0.91 per 100 person-years) and 14 in the placebo group (incidence, 6.60 per 100 person-years), a relative reduction in the TDF-FTC group of 86% (95% confidence interval, 40 to 98; P=0.002). Participants took a median of 15 pills of TDF-FTC or placebo per month (P=0.57). The rates of serious adverse events were similar in the two study groups. In the TDF-FTC group, as compared with the placebo group, there were higher rates of gastrointestinal adverse events (14% vs. 5%, P=0.002) and renal adverse events (18% vs. 10%, P=0.03). CONCLUSIONS: The use of TDF-FTC before and after sexual activity provided protection against HIV-1 infection in men who have sex with men. The treatment was associated with increased rates of gastrointestinal and renal adverse events. (Funded by the National Agency of Research on AIDS and Viral Hepatitis [ANRS] and others; ClinicalTrials.gov number, NCT01473472.).

Noninvasive ventilation and breathing-swallowing interplay in chronic obstructive pulmonary disease*.

OBJECTIVES: To investigate breathing-swallowing interactions in patients with chronic obstructive pulmonary disease requiring noninvasive mechanical ventilation and, if needed, to develop a technical modification of the ventilator designed to eliminate ventilator insufflations during swallowing. DESIGN: We conducted a prospective, open-label, interventional study. PATIENTS: Fifteen consecutive chronic obstructive pulmonary disease patients with exacerbations requiring ICU admission and NIV. INTERVENTIONS: Swallowing performance and breathing-swallowing interactions were investigated noninvasively by chin electromyography, cervical piezoelectric sensor, and inductive respiratory plethysmography. Two water-bolus sizes (5 and 10 mL) were tested in random order. Swallowing was tested with and without noninvasive mechanical ventilation, in random order. First, a standard mechanical ventilator capable of delivering noninvasive mechanical ventilation was used. Second, a marketed device was equipped with an off-switch for use during swallowing. MEASUREMENTS AND MAIN RESULTS: Swallowing performance and breathing-swallowing interactions were investigated noninvasively by chin electromyography, cervical piezoelectric sensor, and inductive respiratory plethysmography. Two water bolus sizes (5 and 10 mL) were tested in random order. Swallowing was tested with and without noninvasive mechanical ventilation in random order. First, a standard mechanical ventilator capable of delivering noninvasive mechanical ventilation was used. Swallowing efficiency, breathing-swallowing synchronization, and Borg Scale dyspnea scores improved significantly with noninvasive mechanical ventilation. However, swallowing induced ventilator triggering followed by autotriggering. To improve patient-ventilator synchrony, a marketed device was equipped with an off-switch for use during swallowing. This device completely eliminated swallowing-induced ventilator triggering and postswallow autotriggering. CONCLUSION: Patients with chronic obstructive pulmonary disease admitted to the ICU for acute exacerbations had abnormal breathing-swallowing interactions and dyspnea, which improved with noninvasive mechanical ventilation. Furthermore, a ventilator device with a simple switch-off pushbutton to eliminate insufflations during swallows prevented swallowing-induced ventilator triggering and postswallow autotriggering.

Challenges and opportunities for oral pre-exposure prophylaxis in the prevention of HIV infection: where are we in Europe?

Following US Food and Drugs Administration approval in July 2012 of daily oral tenofovir and emtricitabine for pre-exposure prophylaxis (PrEP) to prevent HIV infection in high-risk individuals in the USA, there has been much controversy about the implementation of this PrEP regimen in other countries throughout the world, and in Europe in particular. In this review, we focus on the challenges and opportunities of a daily oral PrEP regimen to curb the rising incidence of HIV infection in high-risk groups, and particularly in men who have sex with men. A number of issues would need to be addressed before PrEP could be implemented, including assessing the real effectiveness and cost-effectiveness of daily PrEP, the sustainability of daily adherence, the risk of selecting resistance, the long-term safety, and the risk of change in sexual behavior that might offset the benefit of PrEP. Alternatives to a daily oral PrEP regimen are being explored.

Use of online blood volume and blood temperature monitoring during haemodialysis in critically ill patients with acute kidney injury: a single-centre randomized controlled trial.

BACKGROUND: Little is known about the clinical impact on cardiovascular stability during intermittent haemodialysis (IHD) for acute kidney injury (AKI) of online monitoring devices that control blood volume (BV) and blood temperature in the intensive care unit (ICU) setting. We compared different dialysis treatment modalities with or without these new systems among critically ill patients requiring IHD. METHODS: In a prospective single-centre three-arm randomized controlled trial, 600 dialysis sessions in 74 consecutive AKI critically ill patients were involved to assess intradialytic hypotension. Standard dialysis therapy with constant ultrafiltration (UF) rate, cool dialysate and high sodium conductivity (Treatment A) was compared to regimens with adjunctive interventions including BV control (Treatment B) and the combination of BV and active blood temperature control (Treatment C). Each dialysis session was randomly assigned to one of the three treatment arms and served as statistical unit. RESULTS: Five hundred and seventy-two dialysis sessions were analysed (188, 190 and 194 in Treatments A, B and C, respectively). Hypotension occurred in 16.6% treatments, with similar rates among the arms. Haemodynamic parameters and dialysis-related complications did not differ between therapies. Based on generalized estimating equation adjusted to dialysate sodium conductivity, higher Sequential Organ Failure Assessment the day of dialysis session, the need for vasopressors and lower systolic blood pressure at the onset of the session were identified as independent predictors of hypotensive episodes, whereas regimens containing the new online monitors were not. CONCLUSIONS: These results suggest that both actively controlled body temperature and UF profiled by online monitoring systems have no significant impact on the incidence of intradialytic hypotension in the ICU setting. Further research is needed before the use of these new sophisticated automatic methods can be applied routinely to the ICU setting.

Nicotine in Parkinson's Disease - a Therapeutic Track Gone up in Smoke?

In recent decades, numerous studies have found that smoking or the intake of any form of nicotine, such as smokeless tobacco, exposure to environmental tobacco smoke, or even dietary sources such as peppers, reduces the risk of developing Parkinson's disease.1 Such observations suggest a potential disease-modifying effect of nicotine in Parkinson's disease. Many experimental studies, some of them supported by grants from the tobacco industry, have lent support for such a hypothesis.

TMEM151A as an alternative to PRRT2 in paroxysmal kinesigenic dyskinesia: About three new cases.

Paroxysmal kinesigenic dyskinesia (PKD) are movement disorders triggered by sudden voluntary movement. Variants in the TMEM151A gene have recently been associated with the development of PKD. We report three patients presenting PKD with different TMEM151A mutations, two of which have not been described yet.

Admission of advanced lung cancer patients to intensive care unit: a retrospective study of 76 patients.

BACKGROUND: Criteria for admitting patients with incurable diseases to the medical intensive care unit (MICU) remain unclear and have ethical implications. METHODS: We retrospectively evaluated MICU outcomes and identified risk factors for MICU mortality in consecutive patients with advanced lung cancer admitted to two university-hospital MICUs in France between 1996 and 2006. RESULTS: Of 76 included patients, 49 had non-small cell lung cancer (stage IIIB n = 20; stage IV n = 29). In 60 patients, MICU admission was directly related to the lung cancer (complication of cancer management, n = 30; cancer progression, n = 14; and lung-cancer-induced diseases, n = 17). Mechanical ventilation was required during the MICU stay in 57 patients. Thirty-six (47.4%) patients died in the MICU. Three factors were independently associated with MICU mortality: use of vasoactive agents (odds ratio [OR] 6.81 95% confidence interval [95%CI] [1.77-26.26], p = 0.005), mechanical ventilation (OR 6.61 95%CI [1.44-30.5], p = 0.015) and thrombocytopenia (OR 5.13; 95%CI [1.17-22.5], p = 0.030). In contrast, mortality was lower in patients admitted for a complication of cancer management (OR 0.206; 95%CI [0.058-0.738], p = 0.015). Of the 27 patients who returned home, four received specific lung cancer treatment after the MICU stay. CONCLUSIONS: Patients with acute complications of treatment for advanced lung cancer may benefit from MCIU admission. Further studies are necessary to assess outcomes such as quality of life after MICU discharge.

Predictors of mortality and short-term physical and cognitive dependence in critically ill persons 75 years and older: a prospective cohort study.

BACKGROUND: The purpose of this study was to identify predictors of 3-month mortality in critically ill older persons under medical care and to assess the clinical impact of an ICU stay on physical and cognitive dependence and subjective health status in survivors. METHODS: We conducted a prospective observational cohort study including all older persons 75 years and older consecutively admitted into ICU during a one-year period, except those admitted after cardiac arrest, All patients were followed for 3 months or until death. Comorbidities were assessed using the Charlson index and physical dependence was evaluated using the Katz index of Activity of Daily Living (ADL). Cognitive dependence was determined by a score based on the individual components of the Lawton index of Daily Living and subjective health status was evaluated using the Nottingham Health Profile (NHP) score. RESULTS: One hundred patients were included in the analysis. The mean age was 79.3 ± 3.4 years. The median Charlson index was 6 [IQR, 4 to 7] and the mean ADL and cognitive scores were 5.4 ± 1.1 and 1.2 ± 1.4, respectively, corresponding to a population with a high level of comorbidities but low physical and cognitive dependence. Mortality was 61/100 (61%) at 3 months. In multivariate analysis only comorbidities assessed by the Charlson index [Adjusted Odds Ratio, 1.6; 95% CI, 1.2-2.2; p < 0.003] and the number of organ failures assessed by the SOFA score [Adjusted Odds Ratio, 2.5; 95% CI, 1.1-5.2; p < 0.02] were independently associated with 3-month mortality. All 22 patients needing renal support after Day 3 died. Compared with pre-admission, physical (p = 0.04), and cognitive (p = 0.62) dependence in survivors had changed very little at 3 months. In addition, the mean NHP score was 213.1 ± 132.8 at 3 months, suggesting an acceptable perception of their quality of life. CONCLUSIONS: In a selected population of non surgical patients 75 years and older, admission into the ICU is associated with a 3-month survival rate of 38% with little impact on physical and cognitive dependence and subjective health status. Nevertheless, a high comorbidity level (ie, Charlson index), multi-organ failure, and the need for extra-renal support at the early phase of intensive care could be considered as predictors of death.

Serum neuron-specific enolase as predictor of outcome in comatose cardiac-arrest survivors: a prospective cohort study.

BACKGROUND: The prediction of neurological outcome in comatose patients after cardiac arrest has major ethical and socioeconomic implications. The purpose of this study was to assess the capability of serum neuron-specific enolase (NSE), a biomarker of hypoxic brain damage, to predict death or vegetative state in comatose cardiac-arrest survivors. METHODS: We conducted a prospective observational cohort study in one university hospital and one general hospital Intensive Care Unit (ICU). All consecutive patients who suffered cardiac arrest and were subsequently admitted from June 2007 to February 2009 were considered for inclusion in the study. Patients who died or awoke within the first 48 hours of admission were excluded from the analysis. Patients were followed for 3 months or until death after cardiopulmonary resuscitation. The Cerebral Performance Categories scale (CPC) was used as the outcome measure; a CPC of 4-5 was regarded as a poor outcome, and a CPC of 1-3 a good outcome. Measurement of serum NSE was performed at 24 h and at 72 h after the time of cardiac arrest using an enzyme immunoassay. Clinicians were blinded to NSE results. RESULTS: Ninety-seven patients were included. All patients were actively supported during the first days following cardiac arrest. Sixty-five patients (67%) underwent cooling after resuscitation. At 3 months 72 (74%) patients had a poor outcome (CPC 4-5) and 25 (26%) a good outcome (CPC 1-3). The median and Interquartile Range [IQR] levels of NSE at 24 h and at 72 h were significantly higher in patients with poor outcomes: NSE at 24 h: 59.4 ng/mL [37-106] versus 28.8 ng/mL [18-41] (p < 0.0001); and NSE at 72 h: 129.5 ng/mL [40-247] versus 15.7 ng/mL [12-19] (p < 0.0001). The Receiver Operator Characteristics (ROC) curve for poor outcome for the highest observed NSE value for each patient determined a cut-off value for NSE of 97 ng/mL to predict a poor neurological outcome with a specificity of 100% [95% CI = 87-100] and a sensitivity of 49% [95% CI = 37-60]. However, an approach based on a combination of SSEPs, NSE and clinical-EEG tests allowed to increase the number of patients (63/72 (88%)) identified as having a poor outcome and for whom intensive treatment could be regarded as futile. CONCLUSION: NSE levels measured early in the course of patient care for those who remained comatose after cardiac arrest were significantly higher in patients with outcomes of death or vegetative state. In addition, we provide a cut-off value for NSE (> 97 ng/mL) with 100% positive predictive value of poor outcome. Nevertheless, for decisions concerning the continuation of treatment in this setting, we emphasize that an approach based on a combination of SSEPs, NSE and clinical EEG would be more accurate for identifying patients with a poor neurological outcome.

Phase 1 randomized trial of a plant-derived virus-like particle vaccine for COVID-19.

Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are being deployed, but the global need greatly exceeds the supply, and different formulations might be required for specific populations. Here we report Day 42 interim safety and immunogenicity data from an observer-blinded, dose escalation, randomized controlled study of a virus-like particle vaccine candidate produced in plants that displays the SARS-CoV-2 spike glycoprotein (CoVLP: NCT04450004 ). The co-primary outcomes were the short-term tolerability/safety and immunogenicity of CoVLP formulations assessed by neutralizing antibody (NAb) and cellular responses. Secondary outcomes in this ongoing study include safety and immunogenicity assessments up to 12 months after vaccination. Adults (18-55 years, n = 180) were randomized at two sites in Quebec, Canada, to receive two intramuscular doses of CoVLP (3.75 µg, 7.5 µg, and 15 µg) 21 d apart, alone or adjuvanted with AS03 or CpG1018. All formulations were well tolerated, and adverse events after vaccination were generally mild to moderate, transient and highest in the adjuvanted groups. There was no CoVLP dose effect on serum NAbs, but titers increased significantly with both adjuvants. After the second dose, NAbs in the CoVLP + AS03 groups were more than tenfold higher than titers in Coronavirus 2019 convalescent sera. Both spike protein-specific interferon-γ and interleukin-4 cellular responses were also induced. This pre-specified interim analysis supports further evaluation of the CoVLP vaccine candidate.

Neurally adjusted ventilatory assist in patients recovering spontaneous breathing after acute respiratory distress syndrome: physiological evaluation.

OBJECTIVE: Pressure-support ventilation is widely used during the weaning phase in patients with acute respiratory distress syndrome. The pressure-support level is adjusted to prevent ventilator-induced lung injury while limiting the patient's work of breathing. Neurally adjusted ventilatory assist is an assist mode that applies a positive pressure proportional to the integral of the electrical activity of the diaphragm. The objective was to assess the physiologic response to varying pressure-support ventilation and neurally adjusted ventilatory assist levels in selected acute respiratory distress syndrome patients and to evaluate the effect of neural triggering. METHODS: We prospectively assessed 11 consecutive patients with acute respiratory distress syndrome attributable to pulmonary diseases. Pressure-support ventilation and neurally adjusted ventilatory assist were used in random order. Neurally adjusted ventilatory assist was used with a low electrical activity of the diaphragm trigger (neurally adjusted ventilatory assist-electrical activity of the diaphragm) and with a high electrical activity of the diaphragm trigger that led to rescue triggering by inspiratory flow (neurally adjusted ventilatory assist-inspiratory flow). With each ventilation modality, four levels of assistance (100%, 120%, 140%, and 160%) were used in random order. Statistical analysis was performed using analysis of variance for repeated measurements and mixed models. MAIN RESULTS: Contrary to pressure-support ventilation, neurally adjusted ventilatory assist-electrical activity of the diaphragm and neurally adjusted ventilatory assist-inspiratory flow were associated with stable tidal volume levels despite increasing assistance. For the asynchrony index, an interaction was present between ventilation mode and assist level (p = .0076) because asynchrony index increased significantly with the pressure-support ventilation level (p = .004), but not with the neurally adjusted ventilatory assist-electrical activity of the diaphragm or neurally adjusted ventilatory assist-inspiratory flow level. The lowest asynchrony index was obtained with neurally adjusted ventilatory assist-electrical activity of the diaphragm. CONCLUSION: Compared to pressure-support ventilation, neurally adjusted ventilatory assist in acute respiratory distress syndrome patients holds promise for limiting the risk of overassistance, preventing patient-ventilator asynchrony, and improving overall patient-ventilator interactions. Neural triggering (neurally adjusted ventilatory assist-electrical activity of the diaphragm) considerably decreased patient-ventilator asynchrony.

Catheter dysfunction and dialysis performance according to vascular access among 736 critically ill adults requiring renal replacement therapy: a randomized controlled study.

OBJECTIVE: To compare dialysis catheter function according to catheter site. DESIGN: Multicenter, open, randomized controlled trial. SETTING: Nine university-affiliated hospitals and three general hospitals in France. PATIENTS: Seven hundred thirty-six patients in intensive care units who required a first venous catheterization to perform either intermittent hemodialysis (470 patients with 1275 sessions) or continuous renal replacement therapy (266 patients with 1003 days). INTERVENTION: Patients randomly received either femoral (n = 370) or jugular (n = 366) catheterization. For the jugular site, right-side position (n = 252) was recommended. MEASUREMENTS AND MAIN RESULTS: Time to catheter ablation for dysfunction, urea reduction ratio (intermittent hemodialysis), and downtime (continuous renal replacement therapy) were assessed for all participants and evaluated by randomly assigned catheterization site (femoral or jugular). Baseline demography and dialysis prescriptions were similar between the site arms. In modified intent-to-treat, catheter dysfunction occurred in 36 of 348 (10.3%) and 38 of 342 (11.1%) patients in the femoral and jugular groups, respectively. The risk of catheter dysfunction did not significantly differ between randomized groups (hazard ratio, 1.06; 95% confidence interval, 0.67-1.68; p = .80). Compared to the femoral site, the observed risk of dysfunction decreased in the right jugular position (15 of 226; 6.6%; adjusted hazard ratio, 0.58; 95% confidence interval, 0.31-1.07; p = .09) and significantly increased in the left jugular position (23 of 118; 19.5%; adjusted hazard ratio, 1.89; 95% confidence interval, 1.12-3.21; p < .02). The postintermittent hemodialysis mean urea reduction ratio per session was 50.8% (standard deviation, 16.1) for femoral vs. 52.8% (standard deviation, 15.8) for jugular (p = .30) sites, and the median continuous renal replacement therapy downtime per patient-day was 1.17 hrs (interquartile range, 0.75-1.50) for both sites (p = .98). CONCLUSIONS: In terms of catheter dysfunction and dialysis performance among critically ill adults requiring acute renal replacement therapy, jugular site did not significantly outperform femoral site placement.

Nicotine withdrawal and agitation in ventilated critically ill patients.

INTRODUCTION: Smoking is highly addictive, and nicotine abstinence is associated with withdrawal syndrome in hospitalized patients. In this study, we aimed to evaluate the impact of sudden nicotine abstinence on the development of agitation and delirium, and on morbidities and outcomes in critically ill patients who required respiratory support, either noninvasive ventilation or intubation, and mechanical ventilation. METHODS: We conducted a prospective, observational study in two intensive care units (ICUs). The 144 consecutive patients admitted to ICUs and requiring mechanical ventilation for >48 hours were included. Smoking status was assessed at ICU admission by using the Fagerström Test of Nicotine Dependence (FTND). Agitation, with the Sedation-Agitation Scale (SAS), and delirium, with the Intensive Care Delirium Screening Checklist (ICDSC), were tested twice daily during the ICU stay. Agitation and delirium were defined by SAS >4 and ICDSC >4, respectively. Nosocomial complications and outcomes were evaluated. RESULTS: Smokers (n = 44) were younger and more frequently male and were more likely to have a history of alcoholism and to have septic shock as the reason for ICU admission than were nonsmokers. The incidence of agitation, but not delirium, increased significantly in the smoker group (64% versus 32%; P = 0.0005). Nicotine abstinence was associated with higher incidences of self-removal of tubes and catheters, and with more interventions, including the need for supplemental sedatives, analgesics, neuroleptics, and physical restraints. Sedation-free days, ventilator-free days, length of stay, and mortality in ICUs did not differ between groups. Multivariate analysis identified active smoking (OR, 3.13; 95% CI, 1.45-6.74; P = 0.003) as an independent risk factor for agitation. Based on a subgroup of 56 patients, analysis of 28 pairs of patients (smokers and nonsmokers in a 1:1 ratio) matched for age, gender, and alcoholism status found similar results regarding the role of nicotine withdrawal in increasing the risk of agitation during an ICU stay. CONCLUSIONS: Nicotine withdrawal was associated with agitation and higher morbidities in critically ill patients. These results suggest the need to look specifically at those patients with tobacco dependency by using the FTND in ICU settings. Identifying patients at risk of behavioral disorders may lead to earlier interventions in routine clinical practice.

Blood volume- and blood temperature-controlled hemodialysis in critically ill patients: a 6-month, case-matched, open-label study.

BACKGROUND/AIMS: Online monitoring devices for intermittent hemodialysis have been developed to improve intradialytic cardiovascular stability in chronic dialysis patients. We propose to test blood volume and blood temperature biofeedback control systems in critically ill patients with acute kidney injury (AKI). METHODS: Twenty patients were prospectively dialyzed with machines equipped with online monitoring new devices and compared with 42 historical controls. In addition to feasibility and safety appraisals, efficacy was assessed by the intradialytic hypotension rate. RESULTS: During the study period, controlled temperature was assessed by a mean Delta(max) body temperature of -0.3 +/- 0.2 degrees C, and all but 7% of dialysis sessions achieved relative blood volume-guided ultrafiltration profiling without increased dialysis-related complications. This was associated with decreased intradialytic hypotension rate. CONCLUSION: The combination of active controlled body temperature and profiled ultrafiltration by online monitoring systems is feasible and safe in critically ill AKI patients, and suggests possibilities for improvement in intradialytic hemodynamic stability.

Procalcitonin levels and bacterial aetiology among COPD patients admitted to the ICU with severe pneumonia: a prospective cohort study.

BACKGROUND: Serum procalcitonin (PCT) is considered useful in predicting the likeliness of developing bacterial infections in emergency setting. In this study, we describe PCT levels overtime and their relationship with bacterial infection in chronic obstructive pulmonary disease (COPD) critically ill patients with pneumonia. METHODS: We conducted a prospective cohort study in an ICU of a University Hospital. All consecutive COPD patients admitted for pneumonia between September 2005 and September 2006 were included. Respiratory samples were tested for the presence of bacteria and viruses. Procalcitonin was sequentially assessed and patients classified according to the probability of the presence of a bacterial infection. RESULTS: Thirty four patients were included. The PCT levels were assessed in 32/34 patients, median values were: 0.493 microg/L [IQR, 0.131 to 1.471] at the time of admission, 0.724 microg/L [IQR, 0.167 to 2.646] at six hours, and 0.557 microg/L [IQR, 0.123 to 3.4] at 24 hours. The highest PCT (PCTmax) levels were less than 0.1 microg/L in 3/32 (9%) patients and greater than 0.25 microg/L in 22/32 (69%) patients, suggesting low and high probability of bacterial infection, respectively. Fifteen bacteria and five viruses were detected in 15/34 (44%) patients. Bacteria were not detected in patients with PCTmax levels < 0.1 microg/L. In contrast, bacteria were detected in 4/7 (57%) patients estimated unlikely to have a bacterial infection by PCT levels (PCTmax > 0.1 and < 0.25 microg/L). CONCLUSION: Based on these results we suggest that a PCT level cut off > 0.1 microg/L may be more appropriate than 0.25 microg/L (previously proposed for non severe lower respiratory tract infection) to predict the probability of a bacterial infection in severe COPD patients with pneumonia. Further studies testing procalcitonin-based antibiotic strategies are needed in COPD patients with severe pneumonia.

Extracorporeal life support in severe drug intoxication: a retrospective cohort study of seventeen cases.

INTRODUCTION: Cardiovascular failure is the leading cause of death in severe acute drug intoxication. In this setting, we report the feasibility, complications, and outcome of emergency extracorporeal life support (ECLS) in refractory shock or cardiac arrest following a drug overdose. METHODS: This is a retrospective cohort study of 17 patients admitted over a 10-year period for prolonged cardiac arrest or refractory shock following a drug overdose and not responding to optimal conventional treatment. Patients were evaluated in the medical ICU and cardiovascular surgery department of a university hospital. ECLS implantation used a centrifugal pump connected to a hollow-fiber membrane oxygenator and was performed in the operating room (n = 13), intensive care unit (n = 3), or emergency department (n = 1). ECLS was employed for refractory shock and prolonged cardiac arrest in 10 and 7 cases, respectively. RESULTS: The mean duration of external cardiac massage was 101 +/- 55 minutes. Fifteen patients had ingested cardiotoxic drugs, including 11 cases of drugs with membrane stabilizing activity. Time from hospital admission to initiation of ECLS was 6.4 +/- 7.0 hours. Time to ECLS implant was 58 +/- 11 minutes. The mean ECLS flow rate was 3.45 +/- 0.45 L/min. The average ECLS duration was 4.5 +/- 2.4 days. Early complications included limb ischemia (n = 6), femoral thrombus (n = 1), cava inferior thrombus (n = 1), and severe bleeding at the site of cannulation (n = 2). Fifteen patients were weaned off ECLS support and 13 (76%) were discharged to hospital without sequelae. CONCLUSIONS: Based on our experience, we consider ECLS as a last resort, efficient, and relatively safe therapeutic option in this population. However, the uncontrolled nature of our data requires careful interpretation.

Angiotensin converting enzyme insertion/deletion genetic polymorphism: its impact on renal function in critically ill patients.

OBJECTIVE: Previous clinical studies have suggested an association between the insertion/deletion (I/D) genetic polymorphism of angiotensin converting enzyme and acute or chronic diseases. We aimed to test the prognostic value of the I-allele, which is associated with lower angiotensin converting enzyme activity, on acute kidney injury. DESIGN: Prospective 6-month noninterventional study. SETTING: Intensive care unit of a University Hospital. PATIENTS AND METHODS: One hundred eighty consecutive admitted white patients for an expected intensive care unit stay >48 hr. Angiotensin converting enzyme genetic polymorphism was screened for genotype (I/D polymorphism analysis by polymerase chain reaction amplification) and phenotype (measurement of the circulating rate of angiotensin converting enzyme by spectrophotometry). Acute kidney injury was assessed according to Risk, Injury, Failure, Loss, and End-stage Kidney classification. INTERVENTION: None. RESULTS: II, ID, and DD genotype frequencies were 25%, 48%, and 27%, respectively. II and ID genotypes were associated with lower baseline circulating rates of angiotensin converting enzyme (20 +/- 14 and 22 +/- 18 U/L, respectively, vs. 30 +/- 23 U/L for DD genotype; p = 0.04). Repartition of angiotensin converting enzyme genotypes were different in patients with and without acute kidney injury (p < 0.0001), with greater II genotype proportion in acute kidney injury patients (42% vs. 13% for those without acute kidney injury). After adjustment on the identified prognostic factors, II genotype was independently associated with increased risk of acute kidney injury (adjusted odds ratio, 6.5; 95% confidence interval, 2.4-17.7; p = 0.0002), then death among patients with acute kidney injury (adjusted odds ratio, 1.7; 95% confidence ratio, 1.1-2.6; p = 0.02). CONCLUSION: These data confirm the key role of the renin-angiotensin system to maintain glomerular filtration rate, and highlight an association between a genetic factor and susceptibility to and prognosis of acute kidney disease.

Hyperreninemic hypoaldosteronism syndrome, plasma concentrations of interleukin-6 and outcome in critically ill patients with liver cirrhosis.

OBJECTIVE: To investigate the relation between the adrenal production of gluco- and mineralocorticoids, the inflammatory status and the outcome in critically ill patients with liver cirrhosis. DESIGN: Prospective descriptive study. SETTING: Medical intensive care unit (ICU) in a university hospital. PATIENTS: Fifty consecutive patients with liver cirrhosis. INTERVENTIONS: A corticotropin stimulation test within 12h following ICU admission. Plasma cortisol concentration was measured before and after the test. Renin and aldosterone concentrations, as well as interleukin-6 (IL-6) level to assess the pro-inflammatory status, were measured only before the test. Impaired adrenal function was defined as cortisol response to the test less than 9microg/dl. Hyperreninemic hypoaldosteronism syndrome was defined as basal renin over aldosterone ratio (RRA) higher than 2. MEASUREMENTS AND RESULTS: Forty-one (82%) patients had impaired adrenal function, and 26 patients (52%) presented with RRA > 2. Patients with RRA > 2 exhibited greater disease severity and organ dysfunction scores at baseline, higher levels of serum renin and IL-6, and a greater ICU mortality rate, but risk-adjusted mortality rates were not different between the two groups. Renin and IL-6 plasma concentrations were positively correlated. Finally, in a Cox regression analysis, independent predictors of 30-day mortality were hyperreninemic hypoaldosteronism syndrome, IL-6 higher than 400pg/ml and severe renal failure. CONCLUSIONS: Adrenal dysfunction was common in critically ill cirrhotic patients. Hyperreninemic hypoaldosteronism syndrome was related to a greater pro-inflammatory status and degree of acute organ failure, and was independently associated with a worse prognosis.

Procalcitonin levels in acute exacerbation of COPD admitted in ICU: a prospective cohort study.

BACKGROUND: Antibiotics are recommended for severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) admitted to intensive care units (ICU). Serum procalcitonin (PCT) could be a useful tool for selecting patients with a lower probability of developing bacterial infection, but its measurement has not been investigated in this population. METHODS: We conducted a single center prospective cohort study in consecutive COPD patients admitted to the ICU for AECOPD between September 2005 and September 2006. Sputum samples or tracheal aspirates were tested for the presence of bacteria and viruses. PCT levels were measured at the time of admittance, six hours, and 24 hours using a sensitive immunoassay. RESULTS: Thirty nine AECOPD patients were included, 31 of which (79%) required a ventilator support at admission. The median [25%-75% interquartile range] PCT level, assessed in 35/39 patients, was: 0.096 microg/L [IQR, 0.065 to 0.178] at the time of admission, 0.113 microg/L [IQR, 0.074 to 0.548] at six hours, and 0.137 microg/L [IQR, 0.088 to 0.252] at 24 hours. The highest PCT (PCTmax) levels were less than 0.1 microg/L in 14/35 (40%) patients and more than 0.25 microg/L in 10/35 (29%) patients, suggesting low and high probability of bacterial infection, respectively. Five species of bacteria and nine species of viruses were detected in 12/39 (31%) patients. Among the four patients positive for Pseudomonas aeruginosa, one had a PCTmax less than 0.25 microg/L and three had a PCTmax less than 0.1 microg/L. The one patient positive for Haemophilus influenzae had a PCTmax more than 0.25 microg/L. The presence or absence of viruses did not influence PCT at time of admission (0.068 vs 0.098 microg/L respectively, P = 0.80). CONCLUSION: The likelihood of bacterial infection is low among COPD patients admitted to ICU for AECOPD (40% with PCT < 0.1 microg/L) suggesting a possible inappropriate use of antibiotics. Further studies are necessary to assess the impact of a procalcitonin-based therapeutic strategy in critically ill COPD patients.

Mild hypothermia during advanced life support: a preliminary study in out-of-hospital cardiac arrest.

INTRODUCTION: Induction of mild hypothermia after cardiac arrest may confer neuroprotection. We assessed the feasibility, safety and effectiveness of therapeutic infusion of 2 l of normal saline at 4 degrees C before return of spontaneous circulation during cardiopulmonary resuscitation after out of hospital cardiac arrest. METHODS: This was a prospective, observational, multicenter clinical trial conducted in Emergency Medical Services units and in a medical intensive care unit at Caen University Hospital, Cen, France. RESULTS: In patients who had suffered out of hospital cardiac arrest, hypothermia was induced by infusing 2 l of 4 degrees C NaCl 0.9% over 30 minutes during advanced life support prior to arrival at the hospital. A total of 33 patients were included in the study. Eight patients presented with ventricular fibrillation as the initial cardiac rhythm. Mild hypothermia was achieved after a median of 16 minutes (interquartile range 11.5 to 25.0 minutes) after return of spontaneous circulation. After intravenous cooling, the temperature decreased by 2.1 degrees C (P < 0.0001) to a mean body temperature of 33.3 degrees C (interquartile range 32.3 to 34.3 degrees C). The only observed adverse event was pulmonary oedema, which occurred in one patient. CONCLUSION: We concluded that prehospital induction of therapeutic hypothermia using infusion of 2 l of 4 degrees C normal saline during advanced life support was feasible, effective and safe. Larger studies are required to assess the impact that this early cooling has on neurological outcomes after cardiac arrest.