Transcranial Doppler as a screening test to exclude intracranial hypertension in brain-injured patients: the IMPRESSIT-2 prospective multicenter international study.

BACKGROUND: Alternative noninvasive methods capable of excluding intracranial hypertension through use of transcranial Doppler (ICPtcd) in situations where invasive methods cannot be used or are not available would be useful during the management of acutely brain-injured patients. The objective of this study was to determine whether ICPtcd can be considered a reliable screening test compared to the reference standard method, invasive ICP monitoring (ICPi), in excluding the presence of intracranial hypertension. METHODS: This was a prospective, international, multicenter, unblinded, diagnostic accuracy study comparing the index test (ICPtcd) with a reference standard (ICPi), defined as the best available method for establishing the presence or absence of the condition of interest (i.e., intracranial hypertension). Acute brain-injured patients pertaining to one of four categories: traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH) or ischemic stroke (IS) requiring ICPi monitoring, were enrolled in 16 international intensive care units. ICPi measurements (reference test) were compared to simultaneous ICPtcd measurements (index test) at three different timepoints: before, immediately after and 2 to 3 h following ICPi catheter insertion. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated at three different ICPi thresholds (> 20, > 22 and > 25 mmHg) to assess ICPtcd as a bedside real-practice screening method. A receiver operating characteristic (ROC) curve analysis with the area under the curve (AUC) was used to evaluate the discriminative accuracy and predictive capability of ICPtcd. RESULTS: Two hundred and sixty-two patients were recruited for final analysis. Intracranial hypertension (> 22 mmHg) occurred in 87 patients (33.2%). The total number of paired comparisons between ICPtcd and ICPi was 687. The NPV was elevated (ICP > 20 mmHg = 91.3%, > 22 mmHg = 95.6%, > 25 mmHg = 98.6%), indicating high discriminant accuracy of ICPtcd in excluding intracranial hypertension. Concordance correlation between ICPtcd and ICPi was 33.3% (95% CI 25.6-40.5%), and Bland-Altman showed a mean bias of -3.3 mmHg. The optimal ICPtcd threshold for ruling out intracranial hypertension was 20.5 mmHg, corresponding to a sensitivity of 70% (95% CI 40.7-92.6%) and a specificity of 72% (95% CI 51.9-94.0%) with an AUC of 76% (95% CI 65.6-85.5%). CONCLUSIONS AND RELEVANCE: ICPtcd has a high NPV in ruling out intracranial hypertension and may be useful to clinicians in situations where invasive methods cannot be used or not available. TRIAL REGISTRATION: NCT02322970 .

Cefiderocol as Rescue Therapy for Acinetobacter baumannii and Other Carbapenem-resistant Gram-negative Infections in Intensive Care Unit Patients.

Ten critically ill patients with either bacteremia or ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii, Stenotrophomonas maltophilia, or New Delhi metallo-ß-lactamase-producing Klebsiella pneumoniae received cefiderocol. All strains had minimum inhibitory concentration ≤2 µg/mL. Thirty-day clinical success and survival rates were 70% and 90%, respectively. Two patients had a microbiological failure. Future prospective studies are warranted.

Why and how to open intensive care units to family visits during the pandemic.

Since the lockdown because of the pandemic, family members have been prohibited from visiting their loved ones in hospital. While it is clearly complicated to implement protocols for the admission of family members, we believe precise strategic goals are essential and operational guidance is needed on how to achieve them. Even during the pandemic, we consider it a priority to share strategies adapted to every local setting to allow family members to enter intensive care units and all the other hospital wards.

Extremely drug-resistant NDM-9-producing ST147 Klebsiella pneumoniae causing infections in Italy, May 2020.

A large outbreak of New Delhi metallo-beta-lactamase (NDM)-1-producing Klebsiella pneumoniae sequence type (ST) 147 occurred in Tuscany, Italy in 2018-2019. In 2020, ST147 NDM-9-producing K. pneumoniae were detected at the University Hospital of Pisa, Tuscany, in two critically ill patients; one developed bacteraemia. Genomic and phylogenetic analyses suggest relatedness of 2018-2019 and 2020 strains, with a change from NDM-1 to NDM-9 in the latter and evolution by colistin, tigecycline and fosfomycin resistance acquisition.

Pulse oximeter to detect peripheral oxygen saturation in underwater rebreather ECCR diver: a preliminary study.

Hypoxia is one of the main problems an underwater diver may have to face. The probability of experiencing hypoxia is related to the type of dive and the equipment used. Hypoxia in diving is a potentially fatal event for the diver, as it can lead to the loss of brain functions and consequently to the loss of breathing control, all in the absence of specific premonitory symptoms. It is a risk that may be encountered more frequently by divers who use a closed-circuit rebreather (CCR). For those who use this type of equipment, hypoxia is usually the most frequent cause of death [1]. Our study was aimed at the detection of peripheral oxygen saturation in order to identify, in the future, a preclinical hypoxic condition. We combined the use of pulse oximetry with two forehead sensors on an underwater diver subject who was using an electronic closed-circuit rebreather (ECCR). Despite the known limits of this method and the preliminary status of these findings [2], the recorded data show a clear validity in the use of pulse oximetry in immersion for the detection of peripheral oxygen saturation. In the future, the pulse oximeter could become part of the instrumentation of the diver who uses CCR gear. The device could easily be implemented in these rebreathers. The possibility of being able to perform a basic instrumental analysis means that the diver can become more quickly aware of imminent hypoxia, characterized by the absence of clearly identifiable warning symptoms, and can put in place all the correct procedures for an emergency ascent, avoiding serious consequences.

Impact of hyperhydration on the mortality risk in critically ill patients admitted in intensive care units: comparison between bioelectrical impedance vector analysis and cumulative fluid balance recording.

BACKGROUND: Studies have demonstrated a positive correlation between fluid overload (FO) and adverse outcomes in critically ill patients. The present study aims at defining the impact of hyperhydration on the Intensive Care Unit (ICU) mortality risk, comparing Bioelectrical Impedance Vector Analysis (BIVA) assessment with cumulative fluid balance (CFB) recording. METHODS: We performed a prospective, dual-centre, clinician-blinded, observational study of consecutive patients admitted to ICU with an expected length of ICU stay of at least 72 hours. During observational period (72-120 hours), CFB was recorded and cumulative FO was calculated. At the admission and daily during the observational period, BIVA was performed. We considered FO between 5% and 9.99% as moderate and a FO ≥ 10% as severe. According to BIVA hydration scale of lean body mass, patients were classified as normohydrated (>72.7%-74.3%), mild (>71%-72.7%), moderate (>69%-71%) and severe (≤ 69%) dehydrated and mild (>74.3%-81%), moderate (>81%-87%) and severe (>87%) hyperhydrated. Two multivariate logistic regression models were performed: the ICU mortality was the response variable, while the predictor variables were hyperhydration, measured by BIVA (BIVA model), and FO (FO model). A p-value <0.05 was considered to indicate statistical significance. RESULTS: One hundred and twenty-five patients were enrolled (mean age 64.8 ± 16.0 years, 65.6% male). Five hundred and fifteen BIVA measurements were performed. The mean CFB recorded at the end of the observational period was 2.7 ± 4.1 L, while the maximum hydration of lean body mass estimated by BIVA was 83.67 ± 6.39%. Severe hyperhydration measured by BIVA was the only variable found to be significantly associated with ICU mortality (OR 22.91; 95% CI 2.38-220.07; p < 0.01). CONCLUSIONS: The hydration status measured by BIVA seems to predict mortality risk in ICU patients better than the conventional method of fluid balance recording. Moreover, it appears to be safe, easy to use and adequate for bedside evaluation. Randomized clinical trials with an adequate sample size are needed to validate the diagnostic properties of BIVA in the goal-directed fluid management of critically ill patients in ICU.

Carbapenem-sparing antibiotic regimens for infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae in intensive care unit.

A carbapenem-sparing regimen of tigecycline plus gentamicin or colistin was effective for treating 24 of 26 (92%) Klebsiella pneumoniae carbapenemase-producing K. pneumoniae infectious episodes in 22 polytrauma intensive care unit patients without comorbidities. The 30-day crude mortality rate was 14%. Regimens were considered appropriate in 12% of episodes according to the Vitek 2 System and in 100% based on E-test.

Colistin and rifampicin compared with colistin alone for the treatment of serious infections due to extensively drug-resistant Acinetobacter baumannii: a multicenter, randomized clinical trial.

BACKGROUND: Extensively drug-resistant (XDR) Acinetobacter baumannii may cause serious infections in critically ill patients. Colistin often remains the only therapeutic option. Addition of rifampicin to colistin may be synergistic in vitro. In this study, we assessed whether the combination of colistin and rifampicin reduced the mortality of XDR A. baumannii infections compared to colistin alone. METHODS: This multicenter, parallel, randomized, open-label clinical trial enrolled 210 patients with life-threatening infections due to XDR A. baumannii from intensive care units of 5 tertiary care hospitals. Patients were randomly allocated (1:1) to either colistin alone, 2 MU every 8 hours intravenously, or colistin (as above), plus rifampicin 600 mg every 12 hours intravenously. The primary end point was overall 30-day mortality. Secondary end points were infection-related death, microbiologic eradication, and hospitalization length. RESULTS: Death within 30 days from randomization occurred in 90 (43%) subjects, without difference between treatment arms (P = .95). This was confirmed by multivariable analysis (odds ratio, 0.88 [95% confidence interval, .46-1.69], P = .71). A significant increase of microbiologic eradication rate was observed in the colistin plus rifampicin arm (P = .034). No difference was observed for infection-related death and length of hospitalization. CONCLUSIONS: In serious XDR A. baumannii infections, 30-day mortality is not reduced by addition of rifampicin to colistin. These results indicate that, at present, rifampicin should not be routinely combined with colistin in clinical practice. The increased rate of A. baumannii eradication with combination treatment could still imply a clinical benefit. CLINICAL TRIALS REGISTRATION: NCT01577862.

Necrotizing Fasciitis and Diabetic Foot: Results of a Prompt Identification, Surgery and Antibiotic Therapy (P.I.S.A.) Protocol.

Necrotizing fasciitis (NF) is a rapidly progressive, life-threatening infection, involving the skin, soft tissue and fascia. We evaluated outcomes of its surgical management in diabetic foot (DF) patients in a tertiary referral centre. We retrospectively searched for NF in the database of our DF Section from 2016 to 2018. All cases were treated according to a multiprofessional integrated protocol, with Prompt Identification, Surgical debridement and systemic Antibiotic therapy (P.I.S.A. Protocol). We analysed short-term evolution (surgical procedures and major amputations), and long-term outcomes (survival and healing rates). Sixty-eight patients were referred to our DF clinic for suspicion of NF. The diagnosis was confirmed in 54 (79.4%; male/female 40/14; type 1/2 diabetes 6/48; age 62.8 ± 8.1 years; duration of diabetes 13.6 ± 10.1 years). According to the microbiological results, cases were classified as Type 1 (33-61.2%), 2 (7-12.9%) and 3 (14-25.9%). No significant differences were observed. All patients underwent a decompressive fasciotomy. Six patients (11.1%) required also a forefoot amputation and 12 (22.2%) a toe or ray amputation. No major amputation was performed in the short-term period. During the follow-up (26 ± 12 months) 46 patients (85%) healed in 94 ± 11 days. Of the remaining 8: 5 (9.2%) died for other reasons before healing, 2 (3.7%) recurred and one (1.9%) required a major amputation. Our experience reveals a relatively high prevalence of NF in DF; despite this, we observed how, when promptly and aggressively treated, NF has a good prognosis and it is not associated with an excess of limb loss and deaths.

["Open" Covid-19 ICU and the emotional impact on nurses: a qualitative study]. / La Rianimazione Covid-19 'aperta' e l'impatto emotivo sul personale infermieristico: uno studio qualitativo.

. "Open" Covid-19 ICU and the emotional impact on nurses: a qualitative study. INTRODUCTION: The Covid-19 pandemic has led hospitals to introduce restrictions on family visits at all levels of care. Intensive care units have suffered an increase in bed space and workload, closing to family visits. Health care personal, especially nurses, have experienced significant psycho-physical stress during the Covid-19 pandemic waves. AIM: To describe and investigate the experiences and the emotional impact of nurses who have experienced the Covid-19 ICU open to family visits. METHODS: Phenomenological qualitative study through the use of semi-structured interviews. RESULTS: From the interviews made to ten nurses, five themes emerged: reactions to the admission of family members, the active role of the family member, the effect of the visits on hospitalized patients, the return to normality, and the admission of family members as a therapeutic act. After an initial concern about the spread of infection, the nurses have welcomed with satisfaction the opening of ICU Covid-19 to visits. The entry of family members into the Covid-19 ICU was perceived as a facilitating factor for the patient's course and care. CONCLUSIONS: The humanization of care is a delicate process: in our study a strong emotional impact has emerged on the nursing staff, which produced joy, satisfaction and contentment, and even more on the impulse and the strength to continue doing their work. This organizational model has restored a kind of normality to patients, their families and health workers, despite the ongoing pandemic.

Gender and occupational role differences in work-related post-traumatic stress symptoms, burnout and global functioning in emergency healthcare workers.

OBJECTIVES: To explore gender and occupational role impact on work-related Post-Traumatic Stress Symptoms, Post-Traumatic Stress Disorder, burnout and global functioning in a sample of emergency healthcare workers. DESIGN: A cross-sectional study. PARTICIPANTS/SETTING: 126 healthcare workers of the Emergency Department, including Intensive Care Unit, Emergency Room and Emergency Medicine, of a major University Hospital in central Italy were recruited. MAIN OUTCOME MEASURES: Participants were assessed by means of the: Trauma and Loss Spectrum-Self Report (TALS-SR) to explore Post-Traumatic Stress Spectrum Symptoms, Professional Quality of Life (ProQOL) Scale to assess Compassion Satisfaction, Burnout and Compassion Fatigue and Work and Social Adjustment Scale (WSAS) to measure global functioning. RESULTS: The present findings showed females were more prone to develop Post-Traumatic Stress Symptoms, particularly re-experiencing (p = .010) and hyperarousal (p = .026) symptoms and medical doctors reporting higher Burnout (p < .001) and lower Compassion Satisfaction (p = .009) mean scores than nurses. Higher levels of functioning impairment emerged amongst medical doctors rather than nurses, in both social (p = .029) and private (p = .020) leisure activities. Linear correlations highlighted relationships between the TALS-SR, ProQOL and WSAS scores. Finally, medical doctor status was significantly associated with lower Compassion Satisfaction (p = .029) and higher Burnout (p = .015). CONCLUSION: Our results highlight high post-traumatic stress symptoms and burnout levels in emergency healthcare workers with a relevant impact of female gender and occupational role, supporting the need for preventive strategies, also in light of the current COVID-19 pandemic.

The interplay between acute post-traumatic stress, depressive and anxiety symptoms on healthcare workers functioning during the COVID-19 emergency: A multicenter study comparing regions with increasing pandemic incidence.

BACKGROUND: Healthcare workers (HCWs) deployed to the frontline during the COVID-19 pandemic are at risk for developing mental disorders, with a possible impact on their wellbeing and functioning. The present study aimed at investigating post-traumatic stress symptoms (PTSS), anxiety and depressive symptoms and their relationships with impairment in the functioning impairment among frontline HCWs from three Italian regions differently exposed to the first wave of the COVID-19 emergency: Tuscany (low), Emilia-Romagna (medium) and Lombardy (high). METHODS: 514 frontline HCWs were consecutively enrolled in hospital units devoted to the treatment of COVID-19 patients. They completed the IES-R, PHQ-9 and GAD-7 to assess PTSS, depressive and anxiety symptoms respectively, and the WSAS to investigate functioning impairment. RESULTS: A total of 23.5% of HCWs reported severe PTSS, 22.4% moderate-severe anxiety symptoms, 19.3% moderate-severe depressive symptoms and 22.8% impairment in global functioning. HCWs from the higher-exposure regions reported significantly higher scores in all instruments than those from lower-exposure regions. In a multiple linear regression model, PTSS, depressive and anxiety symptoms presented a significant positive association with the functioning impairment. Both PTSS and depression resulted to be independently related to functioning impairment. LIMITATIONS: The cross-sectional design and the use of self-report instruments. CONCLUSIONS: Depressive and PTSS appear to be the greatest contributors to functioning impairment in HCWs exposed to a massive stressful sanitary event as the COVID-19 pandemic. A more accurate assessment of work-related mental health outcomes in such population could help planning effective prevention strategies and therapeutic interventions.

Linezolid in the central nervous system: comparison between cerebrospinal fluid and plasma pharmacokinetics.

BACKGROUND: Linezolid is effective against methicillin-resistant Staphylococcus aureus, which may cause central nervous system (CNS) infections, but drug concentrations in plasma are characterized by a large inter-patient variability. Therefore, the present study was aimed at evaluating linezolid pharmacokinetics in plasma and cerebrospinal fluid (CSF) in 7 patients with external ventricular drainage, who received linezolid 600 mg twice daily as 1-h intravenous infusion to prevent CNS infections. METHODS: Plasma and CSF linezolid concentrations were measured by high-performance liquid chromatography (HPLC) after the 1(st) and 5(th) dose, and pharmacokinetics were evaluated by non-compartmental analysis. RESULTS: Values of the CSF area under the time/concentration curve (AUC) (range 18.2-85.5 and 19.6-160.5 h × mg/l at the 1st and 5th dose, respectively) were lower than those calculated in plasma (range 27.6-224.0 and 27.5-166.1 h × mg/l, respectively). For minimum inhibitory concentration (MIC) = 1 mg/l, CSF AUC/MIC values were nearly equal to or greater than 100 only in 2 subjects after the 1st and 5th dose, whereas mean time above the MIC (T > MIC) values were higher than 75% in only 3 patients. Similar results were obtained when pharmacokinetic/pharmacodynamic parameters were evaluated in plasma. CONCLUSION: The present results suggest that changes in linezolid doses and measurement of drug concentrations should be considered as useful strategies to optimize treatment in some patients.

Post-traumatic stress disorder, burnout and their impact on global functioning in Italian emergency healthcare workers.

BACKGROUND: Post-traumatic stress disorder (PTSD) and burnout are severe and frequent conditions among emergency healthcare workers exposed to repeated work-related traumatic experiences. The aim of the present study was to investigate PTSD, burnout and global functioning in a sample of emergency healthcare workers (HCWs) of a major university hospital in Italy, exploring possible correlations between the two constructs. METHODS: The study sample included 137 medical and nursing Emergency Room and Intensive Care Unit staff members of a major University Hospital in Italy (Pisa), all assessed by means of the Trauma and Loss Spectrum - Self Report (TALS-SR), for post-traumatic stress spectrum, the Professional Quality of Life Scale - Revision IV (ProQOL R-IV), for burnout related to work activities, and the Work and Social Adjustment Scale (WSAS), for global functioning. RESULTS: Forty-nine subjects reported a full (18, 14.3%) or partial (31, 24.6%) symptomatological DSM-5 PTSD. HCWs with PTSD reported significantly higher burnout scores and global functioning impairment compared to those without PTSD. Mean to good significant correlations emerged between the TALS-SR total and domains scores, the ProQOL subscales and the WSAS scores. CONCLUSIONS: This work, conducted before the COVID-19 pandemic, underlines a positive correlation between burnout and post-traumatic stress spectrum symptoms in emergency HCWs, showing the need for a deeper assessment of work-related post-traumatic stress symptoms in such population in order to improve the well-being and to prevent burnout.

High dose coupled plasma filtration and adsorption in septic shock patients. Results of the COMPACT-2: a multicentre, adaptive, randomised clinical trial.

PURPOSE: This study aimed at evaluating the efficacy and safety of high-dose (> 0.2 L/kg of treated plasma per day) coupled plasma filtration-adsorption (CPFA) in treating patients with septic shock. METHODS: Multicentre, randomised, adaptive trial, performed in 12 Italian intensive care units (ICUs). Patients aged 14 or more, admitted to the ICU with septic shock, or had developed it during the stay were eligible. The final outcome was mortality at discharge from the last hospital at which the patient received care. RESULTS: Between May 2015, and October 2017, 115 patients were randomised. The first interim analysis revealed a number of early deaths, prompting an unplanned analysis. Last hospital mortality was non-significantly higher in the CPFA (55.6%) than in the control group (46.2%, p = 0.35). The 90-day survival curves diverged in favour of the controls early after randomisation and remained separated afterwards (p = 0.100). An unplanned analysis showed higher mortality in CPFA compared to controls among patients without severe renal failure (p = 0.025); a dose-response relationship was observed between treated plasma volume and mortality (p = 0.010). CONCLUSION: The COMPACT-2 trial was stopped due to the possible harmful effect of CPFA in patients with septic shock. The harmful effect, if present, was particularly marked in the early phase of septic shock. Patients not requiring renal replacement therapy seemed most exposed to the possible harm, with evidence of a dose-response effect. Until the mechanisms behind these results are fully understood, the use of CPFA for the treatment of patients with septic shock is not recommended.

Work and social functioning in frontline healthcare workers during the covid-19 pandemic in Italy: role of acute post-traumatic stress, depressive and anxiety symptoms.

BACKGROUND: Evidence highlights healthcare workers (HCWs) facing outbreaks, particularly the ongoing covid-19 pandemic, are at increased risk of negative mental health outcomes, particularly post-traumatic stress symptoms (PTSS), anxiety and depression. Data from previous outbreaks highlighted the risk for a negative impact on HCWs' social and occupational functioning, but scant data have investigated this issue in the framework of the covid-19 pandemic. A number of effective interventions have been proposed to support mental health and well-being of HCWs in emerging infectious outbreaks, but it is important to acknowledge the differential impact of mental disorders on different dimensions of functioning. METHODS: The study explored the associations between work and social functioning and PTSS, depression and anxiety in a sample of 265 frontline HCWs employed at a major university hospital in Italy (Pisa), facing the first period of the covid-19 pandemic. Individuals were assessed by means of the Impact of Event Scale-Revised (IES-R) for PTSS, the Patient Health Questionnaire-9 (PHQ-9) for depressive symptoms, the General Anxiety Disorder-7 Item (GAD-7) for anxiety symptoms and the Work and Social Adjustment Scale (WSAS) to assess work and social functioning. RESULTS: Higher levels of functioning impairment were found among individuals with moderate to severe acute PTSS, depressive and anxiety symptoms with respect to those without. Acute PTSS and depressive symptoms were predictive factors of impairment in each domain of functioning analyzed. Anxiety symptoms were associated with impairment in both work and home management activities. Frontline activity was associated with impairment in both private and social leisure activities. CONCLUSIONS: Long-term perspective studies are warranted to better investigate the psychopathological burden on HCWs' work and social functioning and to promote adequate intervention strategies.

Low diaphragm muscle mass predicts adverse outcome in patients hospitalized for COVID-19 pneumonia: an exploratory pilot study.

BACKGROUND: The aim of this study was to evaluate whether measurement of diaphragm thickness (DT) by ultrasonography may be a clinically useful noninvasive method for identifying patients at risk of adverse outcomes defined as need of invasive mechanical ventilation or death. METHODS: We prospectively enrolled 77 patients with laboratory-confirmed COVID-19 infection admitted to our intermediate care unit in Pisa between March 5 and March 30, 2020, with follow-up until hospital discharge or death. Logistic regression was used identify variables potentially associated with adverse outcomes and those P<0.10 were entered into a multivariate logistic regression model. Cumulative probability for lack of adverse outcomes in patients with or without low baseline diaphragm muscle mass was calculated with the Kaplan-Meier product-limit estimator. RESULTS: The main findings of this study are that: 1) patients who developed adverse outcomes had thinner diaphragm than those who did not (2.0 vs. 2.2 mm, P=0.001); and 2) DT and lymphocyte count were independent significant predictors of adverse outcomes, with end-expiratory DT being the strongest (ß=-708; OR=0.492; P=0.018). CONCLUSIONS: Diaphragmatic ultrasound may be a valid tool to evaluate the risk of respiratory failure. Evaluating the need of mechanical ventilation treatment should be based not only on PaO2/FiO2, but on a more comprehensive assessment including DT because if the lungs become less compliant a thinner diaphragm, albeit free of intrinsic abnormality, may become exhausted, thus contributing to severe respiratory failure.

A pandemic recap: lessons we have learned.

On January 2020, the WHO Director General declared that the outbreak constitutes a Public Health Emergency of International Concern. The world has faced a worldwide spread crisis and is still dealing with it. The present paper represents a white paper concerning the tough lessons we have learned from the COVID-19 pandemic. Thus, an international and heterogenous multidisciplinary panel of very differentiated people would like to share global experiences and lessons with all interested and especially those responsible for future healthcare decision making. With the present paper, international and heterogenous multidisciplinary panel of very differentiated people would like to share global experiences and lessons with all interested and especially those responsible for future healthcare decision making.

A rapid high-performance liquid chromatography method to measure linezolid and daptomycin concentrations in human plasma.

Daptomycin and linezolid, recently introduced to treat severe Gram-positive infections, are effective against multidrug-resistant Gram-positive microorganisms such as methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, and vancomycin-resistant Enterococci bacteria that are less sensitive or frankly resistant, including methicillin-resistant S. aureus. However, alteration of their plasma profile has been described in some patients and this may be associated with toxicities or selection of resistant strains. The measurement of plasma concentrations of both drugs may allow the identification of those subjects at major risk of adverse events. Therefore, a rapid and sensitive high-performance liquid chromatography method for the analysis of daptomycin and linezolid was developed and applied in clinical settings. Drugs were extracted from plasma by adding methanol and, after centrifugation, clear supernatants were injected into the high-performance liquid chromatography system. Isocratic elution (1.5 mL/min) was performed using a mobile phase consisting of ammonium phosphate buffer 40 mM, pH 4.0, acetonitrile (70:30, vol/vol) through a BDS C8 Hypersil stationary phase (250 x 4.6 mm, 5 mum); ultraviolet detection was used at 214 nm. Linezolid and daptomycin eluted within 20 minutes from the injection, and mean recoveries ranged between 95.4% and 112.1%, respectively. The method was linear (coefficient of linearity, 0.998-0.999) over the full range of concentrations assayed, from 0.78125 mg/L (limit of quantitation) to 100 mg/L for both drugs. The Sy.x values were equal to 0.25 +/- 0.10 and 0.29 +/- 0.18 mg/L for daptomycin and linezolid, respectively. Precision values were lower than 20% over the entire range of calibration standard, and accuracy was within the range of 80% to 120% for all concentrations. The present method proved to be sensitive and specific to measure daptomycin and linezolid plasma concentrations in patients affected by severe Gram-positive infections, allowing therapeutic drug monitoring in those patients at major risk of severe adverse events.

Effect of a lung protective strategy for organ donors on eligibility and availability of lungs for transplantation: a randomized controlled trial.

CONTEXT: Many potential donor lungs deteriorate between the time of brain death and evaluation for transplantation suitability, possibly because of the ventilatory strategy used after brain death. OBJECTIVE: To test whether a lung protective strategy increases the number of lungs available for transplantation. DESIGN, SETTING, AND PATIENTS: Multicenter randomized controlled trial of patients with beating hearts who were potential organ donors conducted at 12 European intensive care units from September 2004 to May 2009 in the Protective Ventilatory Strategy in Potential Lung Donors Study. Interventions Potential donors were randomized to the conventional ventilatory strategy (with tidal volumes of 10-12 mL/kg of predicted body weight, positive end-expiratory pressure [PEEP] of 3-5 cm H(2)O, apnea tests performed by disconnecting the ventilator, and open circuit for airway suction) or the protective ventilatory strategy (with tidal volumes of 6-8 mL/kg of predicted body weight, PEEP of 8-10 cm H(2)O, apnea tests performed by using continuous positive airway pressure, and closed circuit for airway suction). MAIN OUTCOME MEASURES: The number of organ donors meeting eligibility criteria for harvesting, number of lungs harvested, and 6-month survival of lung transplant recipients. RESULTS: The trial was stopped after enrolling 118 patients (59 in the conventional ventilatory strategy and 59 in the protective ventilatory strategy) because of termination of funding. The number of patients who met lung donor eligibility criteria after the 6-hour observation period was 32 (54%) in the conventional strategy vs 56 (95%) in the protective strategy (difference of 41% [95% confidence interval {CI}, 26.5% to 54.8%]; P <.001). The number of patients in whom lungs were harvested was 16 (27%) in the conventional strategy vs 32 (54%) in the protective strategy (difference of 27% [95% CI, 10.0% to 44.5%]; P = .004). Six-month survival rates did not differ between recipients who received lungs from donors ventilated with the conventional strategy compared with the protective strategy (11/16 [69%] vs 24/32 [75%], respectively; difference of 6% [95% CI, -22% to 32%]). CONCLUSION: Use of a lung protective strategy in potential organ donors with brain death increased the number of eligible and harvested lungs compared with a conventional strategy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00260676.