A transformer model for cause-specific hazard prediction.

BACKGROUD: Modelling discrete-time cause-specific hazards in the presence of competing events and non-proportional hazards is a challenging task in many domains. Survival analysis in longitudinal cohorts often requires such models; notably when the data is gathered at discrete points in time and the predicted events display complex dynamics. Current models often rely on strong assumptions of proportional hazards, that is rarely verified in practice; or do not handle sequential data in a meaningful way. This study proposes a Transformer architecture for the prediction of cause-specific hazards in discrete-time competing risks. Contrary to Multilayer perceptrons that were already used for this task (DeepHit), the Transformer architecture is especially suited for handling complex relationships in sequential data, having displayed state-of-the-art performance in numerous tasks with few underlying assumptions on the task at hand. RESULTS: Using synthetic datasets of 2000-50,000 patients, we showed that our Transformer model surpassed the CoxPH, PyDTS, and DeepHit models for the prediction of cause-specific hazard, especially when the proportional assumption did not hold. The error along simulated time outlined the ability of our model to anticipate the evolution of cause-specific hazards at later time steps where few events are observed. It was also superior to current models for prediction of dementia and other psychiatric conditions in the English longitudinal study of ageing cohort using the integrated brier score and the time-dependent concordance index. We also displayed the explainability of our model's prediction using the integrated gradients method. CONCLUSIONS: Our model provided state-of-the-art prediction of cause-specific hazards, without adopting prior parametric assumptions on the hazard rates. It outperformed other models in non-proportional hazards settings for both the synthetic dataset and the longitudinal cohort study. We also observed that basic models such as CoxPH were more suited to extremely simple settings than deep learning models. Our model is therefore especially suited for survival analysis on longitudinal cohorts with complex dynamics of the covariate-to-outcome relationship, which are common in clinical practice. The integrated gradients provided the importance scores of input variables, which indicated variables guiding the model in its prediction. This model is ready to be utilized for time-to-event prediction in longitudinal cohorts.

The IMPACT Score: A New Score to Predict the Risk of Early Mortality in Cardiogenic Shock Patients Treated With Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) requires considerable human and financial resources. Few studies have focused on early mortality (ie, occurring within 72 hours after VA-ECMO implantation). The objective of this study was to establish a prognosis score-the IMPACT score (prediction of early mortality associated with VA-ECMO using preimplantation characteristics)-by determining the risk factors associated with early mortality. DESIGN: This was a retrospective and observational study. SETTING: The study was conducted at a University hospital. PARTICIPANTS: This single-center retrospective study included 147 patients treated with VA-ECMO for cardiogenic shock between 2014 and 2021. METHODS: The primary outcome was early mortality (ie, occurring within 72 hours after VA-ECMO implantation). Multivariate logistic regression was performed using a bootstrapping methodology to identify factors independently associated with early mortality. To construct the score, identified variables had points (pts) assigned corresponding to their odds ratio. RESULTS: A total of 147 patients were included in the study. Early mortality (<72 hours) was 26% (38 patients). Four variables were established: cardiac arrest (2 pts), lactate levels (3 pts), platelet count <100 g/L (4 pts), and renal-replacement therapy (5 pts). The IMPACT score had an area under the receiver operating characteristic curve of 0.78 (95% CI 0.86-0.70) to predict early mortality. CONCLUSIONS: In the authors' experience, 26% of patients treated with VA-ECMO presented early mortality. The IMPACT score is a reliable predictor of early mortality and may assist with VA-ECMO initiation decision-making.

Image augmentation and automated measurement of endotracheal-tube-to-carina distance on chest radiographs in intensive care unit using a deep learning model with external validation.

BACKGROUND: Chest radiographs are routinely performed in intensive care unit (ICU) to confirm the correct position of an endotracheal tube (ETT) relative to the carina. However, their interpretation is often challenging and requires substantial time and expertise. The aim of this study was to propose an externally validated deep learning model with uncertainty quantification and image segmentation for the automated assessment of ETT placement on ICU chest radiographs. METHODS: The CarinaNet model was constructed by applying transfer learning to the RetinaNet model using an internal dataset of ICU chest radiographs. The accuracy of the model in predicting the position of the ETT tip and carina was externally validated using a dataset of 200 images extracted from the MIMIC-CXR database. Uncertainty quantification was performed using the level of confidence in the ETT-carina distance prediction. Segmentation of the ETT was carried out using edge detection and pixel clustering. RESULTS: The interrater agreement was 0.18 cm for the ETT tip position, 0.58 cm for the carina position, and 0.60 cm for the ETT-carina distance. The mean absolute error of the model on the external test set was 0.51 cm for the ETT tip position prediction, 0.61 cm for the carina position prediction, and 0.89 cm for the ETT-carina distance prediction. The assessment of ETT placement was improved by complementing the human interpretation of chest radiographs with the CarinaNet model. CONCLUSIONS: The CarinaNet model is an efficient and generalizable deep learning algorithm for the automated assessment of ETT placement on ICU chest radiographs. Uncertainty quantification can bring the attention of intensivists to chest radiographs that require an experienced human interpretation. Image segmentation provides intensivists with chest radiographs that are quickly interpretable and allows them to immediately assess the validity of model predictions. The CarinaNet model is ready to be evaluated in clinical studies.

Introducing the BlendedICU dataset, the first harmonized, international intensive care dataset.

OBJECTIVE: This study introduces the BlendedICU dataset, a massive dataset of international intensive care data. This dataset aims to facilitate generalizability studies of machine learning models, as well as statistical studies of clinical practices in the intensive care units. METHODS: Four publicly available and patient-level intensive care databases were used as source databases. A unique and customizable preprocessing pipeline extracted clinically relevant patient-related variables from each source database. The variables were then harmonized and standardized to the Observational Medical Outcomes Partnership (OMOP) Common Data Format. Finally, a brief comparison was carried out to explore differences in the source databases. RESULTS: The BlendedICU dataset features 41 timeseries variables as well as the exposure times to 113 active ingredients extracted from the AmsterdamUMCdb, eICU, HiRID, and MIMIC-IV databases. This resulted in a database of more than 309000 intensive care admissions, spanning over 13 years and three countries. We found that data collection, drug exposure, and patient outcomes varied strongly between source databases. CONCLUSION: The variability in data collection, drug exposure, and patient outcomes between the source databases indicated some dissimilarity in patient phenotypes and clinical practices between different intensive care units. This demonstrated the need for generalizability studies of machine learning models. This study provides the clinical data research community with essential data to build efficient and generalizable machine learning models, as well as to explore clinical practices in intensive care units around the world.

Extracorporeal Membrane Oxygenation for Respiratory Failure Related to COVID-19: A Nationwide Cohort Study.

BACKGROUND: Despite expanding use, knowledge on extracorporeal membrane oxygenation support during the COVID-19 pandemic remains limited. The objective was to report characteristics, management, and outcomes of patients receiving extracorporeal membrane oxygenation with a diagnosis of COVID-19 in France and to identify pre-extracorporeal membrane oxygenation factors associated with in-hospital mortality. A hypothesis of similar mortality rates and risk factors for COVID-19 and non-COVID-19 patients on venovenous extracorporeal membrane oxygenation was made. METHODS: The Extracorporeal Membrane Oxygenation for Respiratory Failure and/or Heart failure related to Severe Acute Respiratory Syndrome-Coronavirus 2 (ECMOSARS) registry included COVID-19 patients supported by extracorporeal membrane oxygenation in France. This study analyzed patients included in this registry up to October 25, 2020, and supported by venovenous extracorporeal membrane oxygenation for respiratory failure with a minimum follow-up of 28 days after cannulation. The primary outcome was in-hospital mortality. Risk factors for in-hospital mortality were analyzed. RESULTS: Among 494 extracorporeal membrane oxygenation patients included in the registry, 429 were initially supported by venovenous extracorporeal membrane oxygenation and followed for at least 28 days. The median (interquartile range) age was 54 yr (46 to 60 yr), and 338 of 429 (79%) were men. Management before extracorporeal membrane oxygenation cannulation included prone positioning for 411 of 429 (96%), neuromuscular blockage for 419 of 427 (98%), and NO for 161 of 401 (40%). A total of 192 of 429 (45%) patients were cannulated by a mobile extracorporeal membrane oxygenation unit. In-hospital mortality was 219 of 429 (51%), with a median follow-up of 49 days (33 to 70 days). Among pre-extracorporeal membrane oxygenation modifiable exposure variables, neuromuscular blockage use (hazard ratio, 0.286; 95% CI, 0.101 to 0.81) and duration of ventilation (more than 7 days compared to less than 2 days; hazard ratio, 1.74; 95% CI, 1.07 to 2.83) were independently associated with in-hospital mortality. Both age (per 10-yr increase; hazard ratio, 1.27; 95% CI, 1.07 to 1.50) and total bilirubin at cannulation (6.0 mg/dl or more compared to less than 1.2 mg/dl; hazard ratio, 2.65; 95% CI, 1.09 to 6.5) were confounders significantly associated with in-hospital mortality. CONCLUSIONS: In-hospital mortality was higher than recently reported, but nearly half of the patients survived. A high proportion of patients were cannulated by a mobile extracorporeal membrane oxygenation unit. Several factors associated with mortality were identified. Venovenous extracorporeal membrane oxygenation support should be considered early within the first week of mechanical ventilation initiation.

Effect of Body Mass Index on the Clinical Outcomes of Adult Patients Treated With Venoarterial ECMO for Cardiogenic Shock.

OBJECTIVE: Current guidelines consider obesity to be a relative contraindication to venoarterial extracorporeal membrane oxygenation (VA-ECMO) for refractory cardiogenic shock. The authors investigated the effect of body mass index (BMI) on clinical outcomes in patients treated with VA-ECMO for cardiogenic shock. DESIGN: This was a retrospective and observational study. SETTING: University hospital. PARTICIPANTS: The study comprised 150 adult patients who underwent VA-ECMO for cardiogenic shock. MEASUREMENTS AND MAIN RESULTS: The primary outcome was intensive care unit (ICU) mortality. Of the 150 included patients, 10 were underweight (BMI < 18.5 kg/m²), 62 were normal weight (BMI = 18.5-24.9 kg/m²), 34 were overweight (BMI = 25.0-29.9 kg/m²), 34 were obese class I (BMI = 30.0-34.9 kg/m²), and 10 were obese class II (BMI = 35.0-39.9 kg/m²). All-cause ICU mortality was 62% (underweight, 70%; normal weight, 53%; overweight, 65%; class I obese, 71%; class II obese, 70%). After multivariate logistic regression, BMI was not associated with ICU mortality (adjusted odds ratio [aOR] 0.99 [0.92-1.07], p = 0.8). Analysis by BMI category showed unfavorable mortality trends in underweight patients (aOR 3.58 [0.82-19.6], p = 0.11) and class I obese patients (aOR 2.39 [0.95-6.38], p = 0.07). No statistically significant differences were found among BMI categories in the incidences of complications. CONCLUSION: The results suggested that BMI alone should not be considered an exclusion criterion for VA-ECMO. The unfavorable trend observed in underweight patients could be the result of malnutrition.

Differential diagnoses of severe COVID-19 in tropical areas: the experience of Reunion Island.

OBJECTIVE: To identify the differential diagnoses of severe COVID-19 and the distinguishing characteristics of critically ill COVID-19 patients in Reunion Island to help improve the triage and management of patients in this tropical setting. METHODS: This retrospective observational study was conducted from 11 March to 4 May 2020 in the only intensive care unit (ICU) authorised to manage COVID-19 patients in Reunion Island, a French overseas department located in the Indian Ocean region. All patients with unknown COVID-19 status were tested by polymerase chain reaction (PCR) on ICU admission; those who tested negative were transferred to the COVID-19-free area of the ICU. RESULTS: Over the study period, 99 patients were admitted to our ICU. A total of 33 patients were hospitalised in the COVID-19 isolation ward, of whom 11 were positive for COVID-19. The main differential diagnoses of severe COVID-19 were as follows: community-acquired pneumonia, dengue, leptospirosis causing intra-alveolar haemorrhage and cardiogenic pulmonary oedema. The median age of COVID-19-positive patients was higher than that of COVID-19-negative patients (71 [58-74] vs. 54 [46-63.5] years, P = 0.045). No distinguishing clinical, biological or radiological characteristics were found between the two groups of patients. All COVID-19-positive patients had recently travelled or been in contact with a recent traveller. CONCLUSIONS: In Reunion Island, dengue and leptospirosis are key differential diagnoses of severe COVID-19, and travel is the only distinguishing characteristic of COVID-19-positive patients. Our findings apply only to the particular context of Reunion Island at this time of the epidemic.

Severe bilateral pleuropneumonia caused by Legionella sainthelensi: a case report.

BACKGROUND: Legionella spp. are ubiquitous freshwater bacteria responsible for rare but potentially severe cases of Legionnaires' disease (LD). Legionella sainthelensi is a non-pneumophila Legionella species that was first isolated in 1980 from water near Mt. St-Helens (USA). Although rare cases of LD caused by L. sainthelensi have been reported, very little data is available on this pathogen. CASE PRESENTATION: We describe the first documented case of severe bilateral pleuropneumonia caused by L. sainthelensi. The patient was a 35-year-old woman with Sharp's syndrome treated with long-term hydroxychloroquine and corticosteroids who was hospitalized for an infectious illness in a university hospital in Reunion Island (France). The patient's clinical presentation was complicated at first (bilateral pneumonia, multiloculated pleural effusion, then bronchopleural fistula) but her clinical condition eventually improved with the reintroduction of macrolides (spiramycin) in intensive care unit. Etiological diagnosis was confirmed by PCR syndromic assay and culture on bronchoalveolar lavage. CONCLUSIONS: To date, only 14 documented cases of L. sainthelensi infection have been described worldwide. This pathogen is difficult to identify because it is not or poorly detected by urinary antigen and molecular methods (like PCR syndromic assays that primarily target L. pneumophila and that have only recently been deployed in microbiology laboratories). Pneumonia caused by L. sainthelensi is likely underdiagnosed as a result. Clinicians should consider the possibility of non-pneumophila Legionella infection in patients with a compatible clinical presentation when microbiological diagnostic tools targeted L. pneumophila tested negative.

Postpandemic Influenza Mortality of Venovenous Extracorporeal Membrane Oxygenation-Treated Patients in Reunion Island: A Retrospective Single Center Study.

OBJECTIVES: The aim of the present study was to assess the post-pandemic mortality of influenza in patients receiving venovenous extracorporeal membrane oxygenation (VV-ECMO) in Reunion Island, France, by comparing the incidence with other patients undergoing VV-ECMO. DESIGN: Retrospective, descriptive, and single-center cohort study. The primary outcome was the standardized mortality ratio for influenza based on the quartiles of the Respiratory Extracorporeal Membrane Oxygenation Survival Prediction score (RESP Score) in the reference population of patients undergoing VV-ECMO. SETTING: Intensive care unit (ICU), Felix Guyon Hospital, University Teaching Hospital of La Réunion, La Réunion, France. PARTICIPANTS: Consecutive patients on ECMO with positive polymerase chain reaction for influenza. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred twenty-seven consecutive patients were hospitalized in the ICU with a positive influenza polymerase chain reaction from January 2013 to December 2017. Twenty-four influenza patients underwent ECMO including 18 patients with VV-ECMO. During this period, 72 patients requiring VV-ECMO were hospitalized in the ICU. The overall mortality rate of influenza patients on VV-ECMO was 61% versus 46% for non-influenza patients. The standardized mortality ratio per quartile of RESP Score was 1.28 (95% confidence interval 0.61-2.35). CONCLUSIONS: In Reunion, the mortality of patients undergoing VV-ECMO for severe influenza is not lower than the expected mortality of all patients undergoing VV-ECMO.

Leptospirosis in ICU: A Retrospective Study of 134 Consecutive Admissions.

OBJECTIVES: Leptospirosis causes reversible multiple organ failure, and its mortality remains high. The aim of this study was to determine the mortality rate of leptospirosis in an ICU offering all types of organ support available nowadays and to compare it with mortality in bacterial sepsis. DESIGN: Retrospective, descriptive, and single-center cohort study. SETTINGS: The largest ICU of Reunion Island (Indian Ocean) in a teaching hospital. PATIENTS: Consecutive patients hospitalized in ICU for leptospirosis from January 2004 to January 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We report 134 cases of patients with leptospirosis hospitalized in ICU. The median age was 40 years (interquartile range, 30-52 yr), with a Simplified Acute Physiology Score II of 38 (27-50) and a Sequential Organ Failure Assessment score of 10 (8-12). Forty-one patients (31%) required mechanical ventilation and 76 (56%) required renal replacement therapy. The door-to-renal replacement therapy time was 0 (0-1) day after admission with a median urea of 25 mmol/L (17-32 mmol/L). Five patients required extracorporeal membrane oxygenation. The mortality rate was 6.0% (95% CI, 2.6-11.4). Among patients hospitalized for sepsis, the standardized mortality ratio of patients with leptospirosis with regards to Simplified Acute Physiology Score II was dramatically low: 0.40 (95% CI, 0.17 - 0.79). CONCLUSIONS: The mortality of severe leptospirosis is lower than for other bacterial infection, provided modern resuscitation techniques are available. Prompt organ support ensures very low mortality rates despite high severity scores.

Evaluation of Cardiac Index and Extravascular Lung Water After Single-Lung Transplantation Using the Transpulmonary Thermodilution Technique by the PiCCO2 Device.

OBJECTIVES: First evaluation of the transpulmonary thermodilution technique by the PiCCO2 device to assess cardiac index and pulmonary edema during the postoperative course after single-lung transplantation. DESIGN: Prospective observational study. SETTINGS: Intensive care unit, university hospital (single center). PARTICIPANTS: Single-lung transplant patients. INTERVENTIONS: The authors compared cardiac index measured by PiCCO2 and pulmonary artery catheter and assessed pulmonary edema using extravascular lung water index and pulmonary vascular permeability index measured by PiCCO2. MEASUREMENTS AND MAIN RESULTS: A Bland-Altman method was used to compare cardiac index measured by PiCCO2 and pulmonary artery catheter. Extravascular lung water index and pulmonary vascular permeability index were compared according to the PaO2/FiO2 ratio with a threshold value of 150 mmHg. Ten single-lung transplant patients were included. Cardiac index measured by PiCCO2 and pulmonary artery catheter were 3.3 L/min/m2 (2.9-3.6) and 2.5 L/min/m2 (2.2-3.0). Bias for cardiac index was 0.71 L/min/m2 (-0.03; 1.44) and limit of agreements were -0.03 and 1.44 L/min/m2. Extravascular lung water index was 12 mL/kg (11-16) and pulmonary vascular permeability index was 2.3 (2.0-3.1), consistent with pulmonary edema. Extravascular lung water index was higher in the group of PaO2/FiO2 ratio ≤150 mmHg compared with the group of PaO2/FiO2 ratio >150 mmHg (17 v 12 mL/kg, p = 0.04), whereas pulmonary vascular permeability index only tended to be higher (3.1 v 2.1, p = 0.06). CONCLUSION: PiCCO2 device systematically overestimated cardiac index compared with pulmonary artery catheter. However, it might be useful to assess pulmonary edema in acute respiratory failure after single-lung transplantation.

Iatrogenic Tracheal Rupture Caused by Emergency Intubation: A Case Report.

BACKGROUND: Iatrogenic tracheal rupture is a rare but life-threatening complication. If suspected by clinical examination or chest radiograph, a computed tomography scan can confirm the diagnosis, but the criterion standard is a bronchoscopy. There is no consensus on its management. CASE REPORT: A 52-year-old woman was intubated in a prehospital setting after cardiac arrest. A gradual appearance of subcutaneous emphysema was observed after intubation. A computed tomography scan revealed a complicated tracheal rupture, pneumomediastinum, and pneumothorax. The management was surgical. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Intubation in emergency conditions increases the risk of tracheal rupture and a delay in management is an important prognostic factor.

First case of pleural empyema and pulmonary abscess caused by Eggerthia catenaformis.

Few data are available on the anaerobic bacterium Eggerthia catenaformis. Here we report the first clinical case of a patient with sepsis caused by pulmonary infection with E. catenaformis, and present the minimal inhibitory concentrations of different antimicrobial agents.

Skin antisepsis with chlorhexidine-alcohol versus povidone iodine-alcohol, with and without skin scrubbing, for prevention of intravascular-catheter-related infection (CLEAN): an open-label, multicentre, randomised, controlled, two-by-two factorial trial.

BACKGROUND: Intravascular-catheter-related infections are frequent life-threatening events in health care, but incidence can be decreased by improvements in the quality of care. Optimisation of skin antisepsis is essential to prevent short-term catheter-related infections. We hypothesised that chlorhexidine-alcohol would be more effective than povidone iodine-alcohol as a skin antiseptic to prevent intravascular-catheter-related infections. METHODS: In this open-label, randomised controlled trial with a two-by-two factorial design, we enrolled consecutive adults (age ≥18 years) admitted to one of 11 French intensive-care units and requiring at least one of central-venous, haemodialysis, or arterial catheters. Before catheter insertion, we randomly assigned (1:1:1:1) patients via a secure web-based random-number generator (permuted blocks of eight, stratified by centre) to have all intravascular catheters prepared with 2% chlorhexidine-70% isopropyl alcohol (chlorhexidine-alcohol) or 5% povidone iodine-69% ethanol (povidone iodine-alcohol), with or without scrubbing of the skin with detergent before antiseptic application. Physicians and nurses were not masked to group assignment but microbiologists and outcome assessors were. The primary outcome was the incidence of catheter-related infections with chlorhexidine-alcohol versus povidone iodine-alcohol in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01629550 and is closed to new participants. FINDINGS: Between Oct 26, 2012, and Feb 12, 2014, 2546 patients were eligible to participate in the study. We randomly assigned 1181 patients (2547 catheters) to chlorhexidine-alcohol (594 patients with scrubbing, 587 without) and 1168 (2612 catheters) to povidone iodine-alcohol (580 patients with scrubbing, 588 without). Chlorhexidine-alcohol was associated with lower incidence of catheter-related infections (0·28 vs 1·77 per 1000 catheter-days with povidone iodine-alcohol; hazard ratio 0·15, 95% CI 0·05-0·41; p=0·0002). Scrubbing was not associated with a significant difference in catheter colonisation (p=0·3877). No systemic adverse events were reported, but severe skin reactions occurred more frequently in those assigned to chlorhexidine-alcohol (27 [3%] patients vs seven [1%] with povidone iodine-alcohol; p=0·0017) and led to chlorhexidine discontinuation in two patients. INTERPRETATION: For skin antisepsis, chlorhexidine-alcohol provides greater protection against short-term catheter-related infections than does povidone iodine-alcohol and should be included in all bundles for prevention of intravascular catheter-related infections. FUNDING: University Hospital of Poitiers, CareFusion.

Characteristics and outcomes of anti-infective de-escalation during health care-associated intra-abdominal infections.

BACKGROUND: De-escalation is strongly recommended for antibiotic stewardship. No studies have addressed this issue in the context of health care-associated intra-abdominal infections (HCIAI). We analyzed the factors that could interfere with this process and their clinical consequences in intensive care unit (ICU) patients with HCIAI. METHODS: All consecutive patients admitted for the management of HCIAI who survived more than 3 days following their diagnosis, who remained in the ICU for more than 3 days, and who did not undergo early reoperation during the first 3 days were analyzed prospectively in an observational, single-center study in a tertiary care university hospital. RESULTS: Overall, 311 patients with HCIAI were admitted to the ICU. De-escalation was applied in 110 patients (53%), and no de-escalation was reported in 96 patients (47%) (escalation in 65 [32%] and unchanged regimen in 31 [15%]). Lower proportions of Enterococcus faecium, nonfermenting Gram-negative bacilli (NFGNB), and multidrug-resistant (MDR) strains were cultured in the de-escalation group. No clinical difference was observed at day 7 between patients who were de-escalated and those who were not. Determinants of de-escalation in multivariate analysis were adequate empiric therapy (OR 9.60, 95% CI 4.02-22.97) and empiric use of vancomycin (OR 3.39, 95% CI 1.46-7.87), carbapenems (OR 2.64, 95% CI 1.01-6.91), and aminoglycosides (OR 2.31 95% CI 1.08-4.94). The presence of NFGNB (OR 0.28, 95% CI 0.09-0.89) and the presence of MDR bacteria (OR 0.21, 95% CI 0.09-0.52) were risk factors for non-de-escalation. De-escalation did not change the overall duration of therapy. The risk factors for death at day 28 were presence of fungi (HR 2.64, 95% CI 1.34-5.17), Sequential Organ Failure Assessment score on admission (HR 1.29, 95% CI 1.16-1.42), and age (HR 1.03, 95% CI 1.01-1.05). The survival rate expressed by a Kaplan-Meier curve was similar between groups (log-rank test p value 0.176). CONCLUSIONS: De-escalation is a feasible option in patients with polymicrobial infections such as HCIAI, but MDR organisms and NFGNB limit its implementation.

Prognosis of Prolonged Intensive Care Unit Stay After Aortic Valve Replacement for Severe Aortic Stenosis in Octogenarians.

OBJECTIVES: Octogenarians considered for cardiac surgery encounter more complications than other patients. Postoperative complications raise the question of continuation of high-cost care for patients with limited life expectancy. Duration of hospitalization in intensive care after cardiac surgery may differ between octogenarians and other patients. The objectives were evaluating the mortality rate of octogenarians experiencing prolonged hospitalization in intensive care and defining the best cut-off for prolonged intensive care unit length of stay. DESIGN: A single-center observational study. SETTING: A postoperative surgical intensive care unit in a tertiary teaching hospital in Paris, France. PARTICIPANTS: All consecutive patients older than 80 years considered for aortic valve replacement for aortic stenosis were included. MEASUREMENTS AND MAIN RESULTS: Mortality rate was determined among patients experiencing prolonged stay in intensive care with organ failure and without organ failure. An ROC curve determined the optimal cut-off defining prolonged hospitalization in intensive care according to the occurrence of postoperative complications. Multivariate analysis determined risk factors for early death or prolonged intensive care stay. The optimal cut-off defining prolonged intensive care unit length of stay was 4 days. Low ventricular ejection fraction (odds ratio [OR] = 0.95; 95% confidence interval [CI] 0.96-0.83; p = 0.0016), coronary disease (OR = 2.34; 95% CI 1.19-4.85; p = 0.014), and need for catecholamine (OR = 2.79; 95% CI 1.33-5.88; p = 0.0068) were associated with eventful postoperative course. There was not a hospitalization duration beyond which the prognosis significantly worsened. CONCLUSIONS: Prolonged length of stay in ICU without organ failure is not associated with increased mortality. No specific duration of hospitalization in intensive care was associated with increased mortality. Continuation of care should be discussed on an individual basis.

Dynamic changes of microbial flora and therapeutic consequences in persistent peritonitis.

INTRODUCTION: Persistent peritonitis is a frequent complication of secondary peritonitis requiring additional reoperations and antibiotic therapy. This situation raises specific concerns due to microbiological changes in peritoneal samples, especially the emergence of multidrug-resistant (MDR) strains. Although this complication has been extensively studied, the rate and dynamics of MDR strains have rarely been analysed. METHODS: We compared the clinical, microbiological and therapeutic data of consecutive ICU patients admitted for postoperative peritonitis either without subsequent reoperation (n = 122) or who underwent repeated surgery for persistent peritonitis with positive peritoneal fluid cultures (n = 98). Data collected on index surgery for the treatment of postoperative peritonitis were compared between these two groups. In the patients with persistent peritonitis, the data obtained at the first, second and third reoperations were compared with those of index surgery. Risk factors for emergence of MDR strains were assessed. RESULTS: At the time of index surgery, no parameters were able to differentiate patients with or without persistent peritonitis except for increased severity and high proportions of fungal isolates in the persistent peritonitis group. The mean time to reoperation was similar from the first to the third reoperation (range: 5 to 6 days). Septic shock was the main clinical expression of persistent peritonitis. A progressive shift of peritoneal flora was observed with the number of reoperations, comprising extinction of susceptible strains and emergence of 85 MDR strains. The proportion of patients harbouring MDR strains increased from 41% at index surgery, to 49% at the first, 54% at the second (P = 0.037) and 76% at the third reoperation (P = 0.003 versus index surgery). In multivariate analysis, the only risk factor for emergence of MDR strains was time to reoperation (OR 1.19 per day, 95%CI (1.08 to 1.33), P = 0.0006). CONCLUSIONS: Initial severity, presence of Candida in surgical samples and inadequate source control are the major risk factors for persistent peritonitis. Emergence of MDR bacteria is frequent and increases progressively with the number of reoperations. No link was demonstrated between emergence of MDR strains and antibiotic regimens, while source control and its timing appeared to be major determinants of emergence of MDR strains.

Postoperative pneumonia following cardiac surgery in non-ventilated patients versus mechanically ventilated patients: is there any difference?

INTRODUCTION: No studies have compared ventilator-associated pneumonia (VAP) and non-VAP following cardiac surgery (CS). The aim of this study was to assess the incidence, clinical and microbiologic features, treatment characteristics and prognosis of postoperative pneumonia following CS with a special focus on non-VAP. METHODS: This was a retrospective cohort study based on a prospectively collected database. We compared cases of non-VAP and VAP following CS observed between January 2005 and December 2012. Statistical analysis consisted of bivariate and multivariate analysis. RESULTS: A total of 257 (3.5%) of 7,439 consecutive CS patients developed postoperative pneumonia, including 120 (47%) cases of non-VAP. Patients with VAP had more frequent history of congestive heart failure (31% vs. 17%, P = 0.006) and longer duration of cardiopulmonary bypass (105 vs 76 min, P < 0.0001), than patients with non-VAP. No significant differences were observed between the 2 groups in terms of the types of microorganisms isolated with high proportions of Enterobacteriaceae (35%), Pseudomonas aeruginosa (20.2%) and Haemophilus spp (20.2%), except for a lower proportion of Methicillin-susceptible S. aureus in the non-VAP group (3.2% vs 7.9%, P = 0.03). In the intensive care unit, patients with non-VAP had lower sequential organ failure assessment scores than patients with VAP (8 ± 3 versus 9 ± 3, P = 0.004). On multivariate analysis, in-hospital mortality was similar in both groups (32% in the non-VAP group and 42% in the VAP group, adjusted Odds Ratio (aOR): 1.4; 95% confidence intervals (CI): 0.7-2.5; P = 0.34) and appropriate empiric antibiotic therapy was associated with a reduction of in-hospital mortality (aOR: 0.4; 95% CI: 0.2-1; P = 0.05). Piperacillin/tazobactam or imipenem monotherapy constituted appropriate empiric therapy in the two groups, with values reaching 93% and 95% with no differences between VAP and non-VAP cases. CONCLUSIONS: Intensive care patients with VAP are more severely ill than non-VAP patients following CS. Nevertheless, patients with non-VAP and VAP following CS have similar outcomes. This study suggests that the empiric antibiotic regimen in patients with pneumonia following CS should include at least a broad-spectrum antibiotic targeting non-fermenting Gram-negative bacilli, regardless of the type of pneumonia, and targeting S. aureus in VAP patients.

Risk factors for postoperative pneumonia after cardiac surgery and development of a preoperative risk score*.

OBJECTIVES: The aims of this study were, first, to identify risk factors for microbiology-proven postoperative pneumonia after cardiac surgery and, second, to develop and validate a preoperative scoring system for the risk of postoperative pneumonia. DESIGN AND SETTING: A single-center cohort study. PATIENTS: All consecutive patients undergoing cardiac surgery between January 2006 and July 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Multivariate analysis of risk factors for postoperative pneumonia was performed on data from patients operated between January 2006 and December 2008 (training set). External temporal validation was performed on data from patients operated between January 2009 and July 2011 (validation set). Preoperative variables identified in multivariate analysis of the training set were then used to develop a preoperative scoring system that was validated on the validation set. Postoperative pneumonia occurred in 174 of the 5,582 patients (3.1%; 95% CI, 2.7-3.6). Multivariate analysis identified four risk factors for postoperative pneumonia: age (odds ratio, 1.02; 95% CI, 1.01-1.03), chronic obstructive pulmonary disease (odds ratio, 2.97; 95% CI, 1.8-4.71), preoperative left ventricular ejection fraction (odds ratio, 0.98; 95% CI, 0.96-0.99), and the interaction between RBC transfusion during surgery and duration of cardiopulmonary bypass (odds ratio, 2.98; 95% CI, 1.96-4.54). A 6-point score including the three preoperative variables then defined two risk groups corresponding to postoperative pneumonia rates of 1.8% (score < 3) and 6.5% (score ≥ 3). CONCLUSION: Assessing preoperative risk factors for postoperative pneumonia with the proposed scoring system could help to implement a preventive policy in high-risk patients with a risk of postoperative pneumonia greater than 4% (i.e., patients with a score ≥ 3).

Severe leptospirosis in tropical and non-tropical areas: A comparison of two french, multicentre, retrospective cohorts.

BACKGROUND: Leptospirosis is an anthropozoonosis that occurs worldwide but is more common in tropical regions. Severe forms may require intensive care unit (ICU) admission. Whether the clinical patterns and outcomes differ between tropical and non-tropical regions with similar healthcare systems is unclear. Our objective here was to address this issue by comparing two cohorts of ICU patients with leptospirosis managed in mainland France and in the overseas French department of Réunion, respectively. METHODOLOGY/PRINCIPAL FINDINGS: We compared two retrospective cohorts of patients admitted to intensive care for severe leptospirosis, one from Reunion Island in the Indian Ocean (tropical climate) and the other from metropolitan France (temperate climate). Chi-square and Student's t tests were used for comparisons. After grouping the two cohorts, we also performed multiple correspondence analysis and hierarchical clustering to search for distinct clinical phenotypes. The Réunion and Metropolitan France cohorts comprised 128 and 160 patients respectively. Compared with the Réunion cohort, the metropolitan cohort had a higher mean age (42.5±14.1 vs. 51.4±16.5 years, p<0.001). Severity scores, length of stay and mortality did not differ between the two cohorts. Three phenotypes were identified: hepato-renal leptospirosis (54.5%) characterized by significant hepatic, renal and coagulation failure, with a mortality of 8.3%; moderately severe leptospirosis (38.5%) with less severe organ failure and the lowest mortality rate (1.8%); and very severe leptospirosis (7%) manifested by neurological, respiratory and cardiovascular failure, with a mortality of 30%. CONCLUSIONS/SIGNIFICANCE: The outcomes of severe leptospirosis requiring ICU admission did not differ between tropical and temperate regions with similar healthcare access, practices, and resources, despite some differences in patient characteristics. The identification of three different clinical phenotypes may assist in the early diagnosis and management of severe leptospirosis.