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Purpose We hypothesized that a protocol of standardized fixed dose using prolonged infusion during the early phase of sepsis may avoid insufficient β-lactam concentrations. Methods In this single center prospective study, patients with sepsis and vasopressors were enrolled if they were treated by either piperacillin-tazobactam, meropenem or cefepime. Βeta-lactams were administered at fixed dose by prolonged infusion. Targeted plasma concentrations for piperacillin, meropenem and cefepime were above 80 mg/L, 8 mg/L and 38 mg/L respectively. Three blood samples were collected per patient over the first 48 h of treatment. Primary endpoint was target concentration achievement during the 48 first hours, defined as all plasma concentrations above the targeted threshold. Results Among the 89 patients completing the three samples, target concentrations were achieved for 61 (69%). Target concentrations were achieved in 20 (53%), 32 (89%), and 9 (60%) of the patients treated with piperacillin, meropenem and cefepime, respectively. By multivariate analysis, lower APACHE 2 score, higher baseline MDRD creatinine clearance, and piperacillin use were independently associated with insufficient β-lactam concentrations. Conclusion Despite a fixed dose antibiotic administration protocol with prolonged infusion insufficient β-lactam concentration was frequent at the early phase of sepsis, especially in less severe patients, without renal failure, and treated with piperacillin. In septic patients with vasopressors, piperacillin dosing higher than 16 g may be needed to achieve the recommended target concentration. Trial registration: NCT02820987

Background In comatose patients receiving oro-tracheal intubation for mechanical ventilation (MV), the risk of aspiration is increased. Aspiration can lead to chemical pneumonitis (inflammatory reaction to the gastric contents), or aspiration pneumonia (infection caused by inhalation of microorganisms). Distinguishing between the two types is challenging. We tested the interest of using a decisional algorithm based on procalcitonin (PCT) values to guide initiation and discontinuation of antibiotic therapies in intubated patients. Methods The PROPASPI (PROcalcitonin Pneumonia/pneumonitis Associated with ASPIration) trial is a multicenter, prospective, randomized, controlled, single-blind, superiority study comparing two strategies: (1) an intervention group where threshold PCT values were used to guide initiation and discontinuation of antibiotics (PCT group); and (2) a control group, where antibiotic therapy was managed at the physician’s discretion. Patients aged 18 years or over, intubated for coma (Glasgow score ≤ 8), with MV initiated within 48 h after admission, were eligible. The primary endpoint was the duration of antibiotic treatment during the first 15 days after admission to the ICU. Results From 24/2/2015 to 28/8/2019, 1712 patients were intubated for coma in the 5 participating centers, of whom 166 were included in the study. Data from 159 were available for intention-to-treat analysis: 81 in the PCT group, and 78 in the control group. Overall, 67 patients (43%) received antibiotics in the intensive care unit (ICU); there was no significant difference between groups (37 (46%) vs 30 (40%) for PCT vs control, p = 0.432). The mean duration of antibiotic treatment during the first 15 days in the ICU was 2.7 ± 3.8 days; there was no significant difference between groups (3.0 ± 4.1 days vs 2.3 ± 3.4 days for PCT vs control, p = 0.311). The mean number of days under MV was significantly higher in the PCT group (3.7 ± 3.6 days) than in controls (2.7 ± 2.5 days, p = 0.033). The duration of ICU stay was also significantly longer in the PCT group: 6.4 ± 6.5 days vs 4.6 ± 3.5 days in the control group (p = 0.043). After adjustment for SAPS II score, the difference in length of stay and duration of mechanical ventilation between groups was no longer significant. Conclusion The use of PCT values to guide therapy, in comparison to the use of clinical, biological (apart from PCT) and radiological criteria, does not modify exposure to antibiotics in patients intubated for coma. Trial registration Clinicaltrials.gov Identifier NCT02862314.

Background The prevalence of pressure injuries (PIs) in critically ill patients has been extensively studied, but there is uncertainty regarding the risk factors. The main objective of this study was to describe the prevalence of PIs in critically ill patients. Secondary objectives were to describe PI, use of preventive measures for PI, and factors associated with occurrence of PI in the intensive care unit (ICU). Material and methods This was a 1-day point-prevalence study performed on a weekday in June 2017 in ICUs in France. On the same day, we noted the presence or absence of PI in all hospitalised patients of the participating ICUs, data on the ICUs, and the characteristics of patients and of PI. Results Eighty-six participating ICUs allowed the inclusion of 1228 patients. The prevalence of PI on the study day was 18.7% (95% confidence interval: 16.6–21.0). PIs acquired in the ICU were observed in 12.5% (95% confidence interval: 10.6–14.3) of critically ill patients on the study day. The most frequent locations of PI were the sacrum (57.4%), heel (35.2%), and face (8.7%). Severe forms of PI accounted for 40.8% of all PIs. Antiulcer mattresses were used in 91.5% of the patients, and active and/or passive mobilisation was performed for all the patients. Multiple logistic regression analysis identified longer length of stay in the ICU, a higher Simplified Acute Physiology Score, higher body weight, motor neurological disorder, high-dose steroids, and absence of oral nutrition on the study day as factors independently associated with occurrence of PI in the ICU. Conclusion This large point-prevalence study shows that PIs are found in about one of five critically ill patients despite extensive use of devices for preventing PI. Acquisition of PI in the ICU is strongly related to the patient's severity of illness on admission to the ICU and length of stay in the ICU.

Background Patients with obesity are at higher risk for community-acquired and nosocomial infections. However, no study has specifically evaluated the relationship between obesity and ventilator-associated pneumonia (VAP). Research Question Is obesity associated with an increased incidence of VAP? Study Design and Methods This study was a post hoc analysis of the Impact of Early Enteral vs Parenteral Nutrition on Mortality in Patients Requiring Mechanical Ventilation and Catecholamines (NUTRIREA2) open-label, randomized controlled trial performed in 44 French ICUs. Adults receiving invasive mechanical ventilation and vasopressor support for shock and parenteral nutrition or enteral nutrition were included. Obesity was defined as BMI ≥ 30 kg/m2 at ICU admission. VAP diagnosis was adjudicated by an independent blinded committee, based on all available clinical, radiologic, and microbiologic data. Only first VAP episodes were taken into account. Incidence of VAP was analyzed by using the Fine and Gray model, with extubation and death as competing risks. Results A total of 699 (30%) of the 2,325 included patients had obesity; 224 first VAP episodes were diagnosed (60 and 164 in obese and nonobese groups, respectively). The incidence of VAP at day 28 was 8.6% vs 10.1% in the two groups (hazard ratio, 0.85; 95% CI 0.63-1.14; P = .26). After adjustment on sex, McCabe score, age, antiulcer treatment, and Sequential Organ Failure Assessment at randomization, the incidence of VAP remained nonsignificant between obese and nonobese patients (hazard ratio, 0.893; 95% CI, 0.66-1.2; P = .46). Although no significant difference was found in duration of mechanical ventilation and ICU length of stay, 90-day mortality was significantly lower in obese than in nonobese patients (272 of 692 [39.3%] patients vs 718 of 1,605 [44.7%]; P = .02). In a subgroup of patients (n = 123) with available pepsin and alpha-amylase measurements, no significant difference was found in rate of abundant microaspiration of gastric contents, or oropharyngeal secretions between obese and nonobese patients. Interpretation Our results suggest that obesity has no significant impact on the incidence of VAP.

Background and Aims Routine laboratory tests can be useful predictors in the early assessment of the severity and mortality of acute pancreatitis (AP). The aim of this study was to evaluate the accuracy of clinical and laboratory parameters for the prediction of mortality among patients admitted to the intensive care unit (ICU) for AP. Methods We conducted a retrospective analysis of prospectively collected data from Beth Israel Deaconess Hospital made publicly available to examine the relationship between routine clinical and laboratory parameters with respect to mortality for AP. Cox proportional hazard ratio was used to evaluate the impact of several routine laboratory markers on mortality. Receiver operation characteristic (ROC) curve was performed to determine the accuracy of diagnosis of laboratory tests by using area under curve (AUC) for the respective analysis. Results In total, 499 patients were admitted to the ICU for AP. Several factors for predicting mortality in AP at admission were identified in the multivariate analysis: alkaline phosphatase hazard ratio (HR) = 1.00 (1.00–1.00, p = 0.024), anion gap HR = 1.09 (1.00–1.20, p = 0.047), bilirubin total HR = 1.11 (1.06–1.17, p, Key Points This is the first study that evaluates the role of serum phosphate at baseline for predicting the mortality of acute pancreatitis (AP) in intensive care unit (ICU).This study found that serum phosphate is a useful laboratory marker for predicting the mortality of AP independently of other known factors.This study found that serum phosphate value greater than 3.78 mg/dl within the first 24 h after admission in the ICU could predict mortality (area under curve = 0.7, p

To evaluate the diagnostic performance of CT for transmural necrosis (TN) in non-occlusive mesenteric ischemia (NOMI) according to the bowel segment involved. From January 2009 to December 2019, all patients admitted to the intensive care unit (ICU) and requiring laparotomy for NOMI were retrospectively studied. CT had to have been performed within 24 h prior to laparotomy and were reviewed by two abdominal radiologists, with a consensus reading in case of disagreement. A set of CT features of mesenteric ischemia were assessed, separating the stomach, jejunum, ileum, and right (RC) and left colon (LC). Univariate and multivariate analyses were performed to identify features associated with TN. Its influence on overall survival (OS) was assessed. Among 145 patients, 95 (66%) had ≥ 1 bowel segment with TN, including 7 (5%), 31 (21%), 43 (29%), 45 (31%), and 52 (35%) in the stomach, jejunum, ileum, RC, and LC, respectively. Overall inter-reader agreement of CT features was significantly lower in the colon than in the small bowel (0.59 [0.52–0.65] vs 0.74 [0.70–0.77] respectively). The absence of bowel wall enhancement was the only CT feature associated with TN by multivariate analysis, whatever the bowel segment involved. Proximal TN was associated with poorer OS (p < 0.001). The absence of bowel wall enhancement remains the most consistent CT feature of transmural necrosis, whatever the bowel segment involved in NOMI. Inter-reader agreement of CT features is lower in the colon than in the small bowel. Proximal TN seems to be associated with poorer OS. • The absence of bowel wall enhancement is the most consistent CT feature associated with transmural necrosis in NOMI, whatever is the bowel segment involved. • Inter-reader agreement is lower in the colon than in the small bowel in NOMI. • In NOMI, the more proximal the bowel necrosis, the worse the prognosis.

Background The aim of this study is to determine whether severe COVID-19 patients harbour a higher risk of ICU-acquired pneumonia. Methods This retrospective multicentre cohort study comprised all consecutive patients admitted to seven ICUs for severe COVID-19 pneumonia during the first COVID-19 surge in France. Inclusion criteria were laboratory-confirmed SARS-CoV-2 infection and requirement for invasive mechanical ventilation for 48 h or more. Control groups were two historical cohorts of mechanically ventilated patients admitted to the ICU for bacterial or non-SARS-CoV-2 viral pneumonia. The outcome of interest was the development of ICU-acquired pneumonia. The determinants of ICU-acquired pneumonia were investigated in a multivariate competing risk analysis. Result One hundred and seventy-six patients with severe SARS-CoV-2 pneumonia admitted to the ICU between March 1st and 30th June of 2020 were included into the study. Historical control groups comprised 435 patients with bacterial pneumonia and 48 ones with viral pneumonia. ICU-acquired pneumonia occurred in 52% of COVID-19 patients, whereas in 26% and 23% of patients with bacterial or viral pneumonia, respectively (p p = 0.011). Conclusion COVID-19 appears an independent risk factor of ICU-acquired pneumonia in mechanically ventilated patients with pneumonia. Whether this is driven by immunomodulatory properties by the SARS-CoV-2 or this is related to particular processes of care remains to be investigated.

OBJECTIVE. The purpose of this study was to assess whether transmural bowel necrosis has distinct CT features based on the three main causes: occlusive acute mesenteric ischemia (AMI), nonocclusive AMI, and strangulated small-bowel obstruction (SBO). MATERIALS AND METHODS. From January 2010 to December 2017, the records of all patients with a pathologic diagnosis of transmural bowel necrosis were extracted from the pathology department database of a university hospital. The inclusion criteria for the study were presence of transmural bowel necrosis at pathologic examination and available contrast-enhanced CT images obtained within the 24 hours before surgery. Seventy-seven patients were finally included. The CT scans were retrospectively independently reviewed by two abdominal radiologists to identify the classic CT findings of transmural bowel necrosis. Statistical analyses were performed. RESULTS. Pneumatosis intestinalis was statistically more frequent in nonocclusive AMI (59%) than in occlusive AMI (29%) and strangulated SBO (7%) (p < 0.01), as were superior mesenteric venous gas (55%, 29%, and 0%; p < 0.01) and portal venous gas (48%, 10%, and 0%; p < 0.01). Decreased or absent bowel wall enhancement was more frequent in AMI than in SBO (nonocclusive AMI, 83%; occlusive AMI, 81%; SBO, 56%; p = 0.02), as was thinned bowel wall (nonocclusive AMI, 52%; occlusive AMI, 48%; SBO, 18%; p = 0.02). Spontaneous hyperattenuation of the bowel wall was more frequent in strangulated SBO (41%) than in nonocclusive AMI (10%) and occlusive AMI (14%) (p < 0.01). CONCLUSION. Transmural bowel necrosis has distinct CT findings according to its three main causes. Occlusive AMI is characterized by an absence of bowel wall enhancement and less mesenteric fat stranding, nonocclusive AMI by a high prevalence of pneumatosis intestinalis and portal venous gas, and strangulated SBO by spontaneous hyperattenuation of the bowel wall and an absence of pneumatosis intestinalis and portal venous gas.

Background Non-tunneled hemodialysis catheters are currently used for critically ill patients with acute kidney injury requiring extracorporeal renal replacement therapy. Strategies to prevent catheter dysfunction and infection with catheter locks remain controversial. Methods In a multicenter, randomized, controlled, double-blind trial, we compared two strategies for catheter locking of non-tunneled hemodialysis catheters, namely trisodium citrate at 4% (intervention group) versus unfractionated heparin (control group), in patients aged 18 years or older admitted to the intensive care unit and in whom a first non-tunneled hemodialysis catheter was to be inserted by the jugular or femoral vein. The primary endpoint was length of event-free survival of the first non-tunneled hemodialysis catheter. Secondary endpoints were: rate of fibrinolysis, incidence of catheter dysfunction and incidence of catheter-related bloodstream infection (CRBSI), all per 1000 catheter-days; number of hemorrhagic events requiring transfusion, length of stay in intensive care and in hospital; 28-day mortality. Results Overall, 396 randomized patients completed the trial: 199 in the citrate group and 197 in the heparin group. There was no significant difference in baseline characteristics between groups. The duration of event-free survival of the first non-tunneled hemodialysis catheter was not significantly different between groups: 7 days (IQR 3–10) in the citrate group and 5 days (IQR 3–11) in the heparin group (p = 0.51). Rates of catheter thrombosis, CRBSI, and adverse events were not statistically different between groups. Conclusions In critically ill patients, there was no significant difference in the duration of event-free survival of the first non-tunneled hemodialysis catheter between trisodium citrate 4% and heparin as a locking solution. Catheter thrombosis, catheter-related infection, and adverse events were not statistically different between the two groups. Trial registration Registered with Clinicaltrials.gov under the number NCT01962116. Registered 14 October 2013.

Background The classification of invasive pulmonary aspergillosis (IPA) issued by the European Organization for the Research and Treatment of Cancer/Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) is used for immunocompromised patients. An alternative algorithm adapted to the intensive care unit (ICU) population has been proposed (AspICU), but this algorithm did not include microbial biomarkers such as the galactomannan antigen and the Aspergillus quantitative PCR. The objective of the present pilot study was to evaluate a new algorithm that includes fungal biomarkers (BM-AspICU) for the diagnosis of probable IPA in an ICU population. Patients and methods Data from 35 patients with pathology-proven IPA according to European Organization for the Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSGERC)-2008 criteria were extracted from the French multicenter database of the Invasive Fungal Infections Surveillance Network (RESSIF). The patients were investigated according to the AspICU algorithm, and the BM-AspICU algorithm in analyzing the clinical, imaging, and biomarker data available in the records, without taking into account the pathology findings. Results Eight patients had to be excluded because no imaging data were recorded in the database. Among the 27 proven IPAs with complete data, 16 would have been considered as putative IPA with the AspICU algorithm and 24 would have been considered as probable IPA using the new algorithm BM-AspICU. Seven out of the 8 patients with probable BM-AspICU IPA (and not classified with the AspICU algorithm) had no host factors and no Aspergillus-positive broncho-alveolar lavage fluid (BALF) culture. Three patients were non-classifiable with any of the two algorithms, because they did not have any microbial criteria during the course of the infection, and diagnosis of proven aspergillosis was done using autopsy samples. Conclusion Inclusion of biomarkers could be effective to identify probable IPA in the ICU population. A prospective study is needed to validate the routine application of the BM-AspICU algorithm in the ICU population.

Background Little is known on the outcome and risk factors for mortality of patients admitted in Intensive Care units (ICUs) for Acute cholangitis (AC). Methods Retrospective multicenter study included adults admitted in eleven intensive care units for a proven AC from 2005 to 2018. Risk factors for in-hospital mortality were identified using multivariate analysis. Results Overall, 382 patients were included, in-hospital mortality was 29%. SOFA score at admission was 8 [5–11]. Biliary obstruction was mainly related to gallstone (53%) and cancer (22%). Median total bilirubin and PCT were respectively 83 µmol/L [50–147] and 19.1 µg/L [5.3–54.8]. Sixty-three percent of patients (n = 252) had positive blood culture, mainly Gram-negative bacilli (86%) and 14% produced extended spectrum beta lactamase bacteria. At ICU admission, persisting obstruction was frequent (79%) and biliary decompression was performed using therapeutic endoscopic retrograde cholangiopancreatography (76%) and percutaneous transhepatic biliary drainage (21%). Adjusted mortality significantly decreased overtime, adjusted OR for mortality per year was 0.72 [0.54–0.96] (p = 0.02). In a multivariate analysis, factors at admission associated with in-hospital mortality were: SOFA score (OR 1.14 [95% CI 1.05–1.24] by point, p = 0.001), lactate (OR 1.21 [95% CI 1.08–1.36], by 1 mmol/L, p p p p = 0.002). Time between ICU admission and biliary decompression > 48 h was associated with in-hospital mortality (adjusted OR 2.73 [95% CI 1.30–6.22], p = 0.02). Conclusions In this large retrospective multicenter study, we found that AC-associated mortality significantly decreased overtime. Severity of organ failure, cause of obstruction and local complications of AC are risk factors for mortality, as well as delayed biliary drainage > 48 h.

Background Previous studies reporting the causes of death in patients with severe COVID-19 have provided conflicting results. The objective of this study was to describe the causes and timing of death in patients with severe COVID-19 admitted to the intensive care unit (ICU). Methods We performed a retrospective study in eight ICUs across seven French hospitals. All consecutive adult patients (aged ≥ 18 years) admitted to the ICU with PCR-confirmed SARS-CoV-2 infection and acute respiratory failure were included in the analysis. The causes and timing of ICU deaths were reported based on medical records. Results From March 1, 2020, to April 28, 287 patients were admitted to the ICU for SARS-CoV-2 related acute respiratory failure. Among them, 93 patients died in the ICU (32%). COVID-19-related multiple organ dysfunction syndrome (MODS) was the leading cause of death (37%). Secondary infection-related MODS accounted for 26% of ICU deaths, with a majority of ventilator-associated pneumonia. Refractory hypoxemia/pulmonary fibrosis was responsible for death in 19% of the cases. Fatal ischemic events (venous or arterial) occurred in 13% of the cases. The median time from ICU admission to death was 15 days (25th–75th IQR, 7–27 days). COVID-19-related MODS had a median time from ICU admission to death of 14 days (25th–75th IQR: 7–19 days), while only one death had occurred during the first 3 days since ICU admission. Conclusions In our multicenter observational study, COVID-19-related MODS and secondary infections were the two leading causes of death, among severe COVID-19 patients admitted to the ICU.

Purpose To evaluate whether abdominal atherosclerosis was associated with poorer outcome in a single-centre cohort of patients suffering from nonocclusive mesenteric ischemia (NOMI). Methods From January 2009 to December 2019, 121 consecutive patients from the critical care unit who underwent laparotomy for suspected NOMI and with available unenhanced and contrast-enhanced CT were included. Clinical and biological data at the time of the CT scan were retrospectively extracted from medical charts and reviewed by a single radiologist. Unenhanced CT acquisitions were used to calculate calcium scores of the abdominal aorta, celiac trunk, superior mesenteric artery (SMA) and common iliac arteries according to the Agatston method. Univariate and multivariate analysis were performed. Results Among the 121 patients with NOMI and calcium score calculation, only 4 patients had no aortic calcifications (3 %) and 32 had no superior mesenteric artery calcification (26 %). 35 patients (29 %) died within 24 h after the abdominal CT scan. Univariate analysis showed that a total abdominal calcium score greater than 15 000 (last quartile) was significantly associated with death within 24 h (14 (40 %) vs 17 (20 %) patients, p = 0.035). By multivariate analysis, a total abdominal calcium score greater than 15 000 was an independent risk factor for death (HR = 1.94, 95 %CI [1.02–3.73], p = 0.044). Regarding separate calcium scores, only a SMA calcium score greater than 50 was a risk factor for death (HR 2.46, 95 %CI [1.14–3.93], p = 0.019). Conclusion Our results show that abdominal atherosclerosis, especially in the SMA, is associated with poorer outcome in NOMI.

Background The properties of semi-elemental enteral nutrition might theoretically improve gastrointestinal tolerance in brain-injured patients, known to suffer gastroparesis. The purpose of this study was to compare the efficacy and tolerance of a semi-elemental versus a polymeric formula for enteral nutrition (EN) in brain-injured critically ill patients. Methods Prospective, randomized study including brain-injured adult patients [Glasgow Coma Scale (GCS) ≤ 8] with an expected duration of mechanical ventilation > 48 h. Intervention: an enteral semi-elemental (SE group) or polymeric (P group) formula. EN was started within 36 h after admission to the intensive care unit and was delivered according to a standardized nurse-driven protocol. The primary endpoint was the percentage of patients who received both 60% of the daily energy goal at 3 days and 100% of the daily energy goal at 5 days after inclusion. Tolerance of EN was assessed by the rate of gastroparesis, vomiting and diarrhea. Results Respectively, 100 and 95 patients were analyzed in the SE and P groups: Age (57[44–65] versus 55[40–65] years) and GCS (6[3–7] versus 5[3–7]) did not differ between groups. The percentage of patients achieving the primary endpoint was similar (46% and 48%, respectively; relative risk (RR) [95% confidence interval (CI)] = 1.05 (0.78–1.42); p = 0.73). The mean daily energy intake was, respectively, 20.2 ± 6.3 versus 21.0 ± 6.5 kcal/kg/day (p = 0.42). Protein intakes were 1.3 ± 0.4 versus 1.1 ± 0.3 g/kg/day (p p = 0.21), and 16% versus 8% patients suffered from diarrhea (p = 0.11). No patient presented vomiting in either group. Conclusion Semi-elemental compared to polymeric formula did not improve daily energy intake or gastrointestinal tolerance of enteral nutrition. Trial registration EudraCT/ID-RCB 2012-A00078-35 (registered January 17, 2012).

A 22-year-old man with no relevant medical history except hashish use (10 joints a day) was admitted to the intensive care unit in December 2018 for refractory acute respiratory distress syndrome (ARDS). He presented dry cough and dyspnoea for 1 week. After intubation, veno-venous extracorporeal membrane oxygenation (VV-ECMO) was required because of severe hypoxemia and very low respiratory compliance (15 mL/cmH2O). Given the possibility of severe community-acquired pneumonia and influenza, urgent antibiotic therapy associating cephalosporin plus macrolid and …

Risk factors associated with pulmonary embolism in coronavirus disease 2019 acute respiratory distress syndrome patients deserve to be better known. We therefore performed a post hoc analysis from the COronaVirus-Associated DIsease Study (COVADIS) project, a multicenter observational study gathering 21 ICUs from France (n = 12) and Belgium (n = 9). Three-hundred seventy-five consecutive patients with moderate-to-severe acute respiratory distress syndrome and positive coronavirus disease 2019 were included in the study. At day 28, 15% were diagnosed with pulmonary embolism. Known risk factors for pulmonary embolism including cancer, obesity, diabetes, hypertension, and coronary artery disease were not associated with pulmonary embolism. In the multivariate analysis, younger age (< 65 yr) (odds ratio, 2.14; 1.17-4.03), time between onset of symptoms and antiviral administration greater than or equal to 7 days (odds ratio, 2.39; 1.27-4.73), and use of neuromuscular blockers greater than or equal to 7 days (odds ratio, 1.89; 1.05-3.43) were independently associated with pulmonary embolism. These new findings reinforce the need for prospective studies that will determine the predictors of pulmonary embolism among patients with severe coronavirus disease 2019.

Summary Background Altered body composition may impact on the clinical course of Crohn's disease (CD) but is not detected by the simple body mass index (BMI) assessment. Aim To assess the prevalence of sarcopenia and visceral obesity by a single computed tomography (CT) slice, and its association with adverse events in an adult hospitalized CD cohort. Methods 88 CD patients who had abdominal CT scans during hospitalization were retrospectively enrolled. The skeletal muscle index (SMI) at the third lumbar vertebra level was used to assess sarcopenia. Sarcopenia was defined as a SMI Results The prevalence of sarcopenia was 58%, malnutrition 21.6%, and visceral obesity 19.3%. Among sarcopenic patients, 49% had a normal BMI, 13.7% were overweight, and 1(2%) was obese. Sarcopenic CD patients had significantly more abscesses (51% vs 16.7%, p = 0.001), hospitalizations (61.2% vs 36.1%, p = 0.022) and digestive surgery (63.3% vs 27.8%, p = 0.001) than non-sarcopenic patients during the follow-up, whereas usual malnutrition assessment was not correlated with disease outcomes. In multivariate analysis, both sarcopenia and visceral obesity were associated with further occurrence of digestive surgery. Conclusion Both sarcopenia and visceral obesity were associated with adverse outcomes in severe CD patients whereas usual nutritional assessment was not.

International audience; Purpose: To report the incidence, risk factors, clinical presentation, and outcome predictors of severe leptospirosis requiring intensive care unit (ICU) admission in a temperate zone.Methods: LEPTOREA was a retrospective multicentre study conducted in 79 ICUs in metropolitan France. Consecutive adults admitted to the ICU for proven severe leptospirosis from January 2012 to September 2016 were included. Multiple correspondence analysis (MCA) and hierarchical classification on principal components (HCPC) were performed to distinguish different clinical phenotypes.Results: The 160 included patients (0.04% of all ICU admissions) had median values of 54 years [38-65] for age, 40 [28-58] for the SAPSII, and 11 [8-14] for the SOFA score. Hospital mortality was 9% and was associated with older age; worse SOFA score and early need for endotracheal ventilation and/or renal replacement therapy; chronic alcohol abuse and worse hepatic dysfunction; confusion; and higher leucocyte count. Four phenotypes were identified: moderately severe leptospirosis (n = 34, 21%) with less organ failure and better outcomes; hepato-renal leptospirosis (n = 101, 63%) with prominent liver and kidney dysfunction; neurological leptospirosis (n = 8, 5%) with the most severe organ failures and highest mortality; and respiratory leptospirosis (n = 17, 11%) with pulmonary haemorrhage. The main risk factors for leptospirosis contamination were contact with animals, contact with river or lake water, and specific occupations.Conclusions: Severe leptospirosis was an uncommon reason for ICU admission in metropolitan France and carried a lower mortality rate than expected based on the high severity and organ-failure scores. The identification in our population of several clinical presentations may help clinicians establish an appropriate index of suspicion for severe leptospirosis.

Background Microaspiration of gastric and oropharyngeal secretions is the main mechanism of entry of bacteria into the lower respiratory tract in intubated critically ill patients. The aim of this study is to determine the impact of enteral nutrition, as compared with parenteral nutrition, on abundant microaspiration of gastric contents and oropharyngeal secretions. Methods Planned ancillary study of the randomized controlled multicenter NUTRIREA2 trial. Patients with shock receiving invasive mechanical ventilation were randomized to receive early enteral or parenteral nutrition. All tracheal aspirates were collected during the 48 h following randomization. Abundant microaspiration of gastric contents and oropharyngeal secretions was defined as the presence of significant levels of pepsin (> 200 ng/ml) and salivary amylase (> 1685 UI/ml) in > 30% of tracheal aspirates. Results A total of 151 patients were included (78 and 73 patients in enteral and parenteral nutrition groups, respectively), and 1074 tracheal aspirates were quantitatively analyzed for pepsin and amylase. Although vomiting rate was significantly higher (31% vs 15%, p = 0.016), constipation rate was significantly lower (6% vs 21%, p = 0.010) in patients with enteral than in patients with parenteral nutrition. No significant difference was found regarding other patient characteristics. The percentage of patients with abundant microaspiration of gastric contents was significantly lower in enteral than in parenteral nutrition groups (14% vs 36%, p = 0.004; unadjusted OR 0.80 (95% CI 0.69, 0.93), adjusted OR 0.79 (0.76, 0.94)). The percentage of patients with abundant microaspiration of oropharyngeal secretions was significantly higher in enteral than in parenteral nutrition groups (74% vs 54%, p = 0.026; unadjusted OR 1.21 (95% CI 1.03, 1.44), adjusted OR 1.23 (1.01, 1.48)). No significant difference was found in percentage of patients with ventilator-associated pneumonia between enteral (8%) and parenteral (10%) nutrition groups (HR 0.78 (0.26, 2.28)). Conclusions Our results suggest that enteral and parenteral nutrition are associated with high rates of microaspiration, although oropharyngeal microaspiration was more common with enteral nutrition and gastric microaspiration was more common with parenteral nutrition. Trial registration ClinicalTrials.gov, NCT03411447. Registered 18 July 2017. Retrospectively registered.

International audience

IF 79.258 (2017); International audience; BackgroundAcute kidney injury is the most frequent complication in patients with septic shock and is an independent risk factor for death. Although renal-replacement therapy is the standard of care for severe acute kidney injury, the ideal time for initiation remains controversial.MethodsIn a multicenter, randomized, controlled trial, we assigned patients with early-stage septic shock who had severe acute kidney injury at the failure stage of the risk, injury, failure, loss, and end-stage kidney disease (RIFLE) classification system but without life-threatening complications related to acute kidney injury to receive renal-replacement therapy either within 12 hours after documentation of failure-stage acute kidney injury (early strategy) or after a delay of 48 hours if renal recovery had not occurred (delayed strategy). The failure stage of the RIFLE classification system is characterized by a serum creatinine level 3 times the baseline level (or ≥4 mg per deciliter with a rapid increase of ≥0.5 mg per deciliter), urine output less than 0.3 ml per kilogram of body weight per hour for 24 hours or longer, or anuria for at least 12 hours. The primary outcome was death at 90 days.ResultsThe trial was stopped early for futility after the second planned interim analysis. A total of 488 patients underwent randomization; there were no significant between-group differences in the characteristics at baseline. Among the 477 patients for whom follow-up data at 90 days were available, 58% of the patients in the early-strategy group (138 of 239 patients) and 54% in the delayed-strategy group (128 of 238 patients) had died (P=0.38). In the delayed-strategy group, 38% (93 patients) did not receive renal-replacement therapy. Criteria for emergency renal-replacement therapy were met in 17% of the patients in the delayed-strategy group (41 patients).ConclusionsAmong patients with septic shock who had severe acute kidney injury, there was no significant difference in overall mortality at 90 days between patients who were assigned to an early strategy for the initiation of renal-replacement therapy and those who were assigned to a delayed strategy. (Funded by the French Ministry of Health; IDEAL-ICU ClinicalTrials.gov number, NCT01682590.)

International audience; Background In this study, we primarily sought to assess the ability of flow cytometry to predict early clinical deterioration and overall survival in patients with sepsis admitted in the ED and ICU. Methods Patients admitted for community-acquired acute sepsis from 11 hospital centers were eligible. Early (day 7) and late (day 28) deaths were notified. Levels of CD64pos granulocytes, CD16pos monocytes, CD16dim immature granulocytes (IGs), and T and B lymphocytes were assessed by flow cytometry using an identical, cross-validated, robust, and simple consensus standardized protocol in each center. Results Among 1,062 patients screened, 781 patients with confirmed sepsis were studied (age, 67 ± 48 years; Simplified Acute Physiology Score II, 36 ± 17; Sequential Organ Failure Assessment, 5 ± 4). Patients were divided into three groups (sepsis, severe sepsis, and septic shock) on day 0 and on day 2. On day 0, patients with sepsis exhibited increased levels of CD64pos granulocytes, CD16pos monocytes, and IGs with T-cell lymphopenia. Clinical severity was associated with higher percentages of IGs and deeper T-cell lymphopenia. IG percentages tended to be higher in patients whose clinical status worsened on day 2 (35.1 ± 35.6 vs 43.5 ± 35.2, P =.07). Increased IG percentages were also related to occurrence of new organ failures on day 2. Increased IG percentages, especially when associated with T-cell lymphopenia, were independently associated with early (P andlt;.01) and late (P andlt;.01) death. Conclusions Increased circulating IGs at the acute phase of sepsis are linked to clinical worsening, especially when associated with T-cell lymphopenia. Early flow cytometry could help clinicians to target patients at high risk of clinical deterioration. Trial Registry ClinicalTrials.gov; No. NCT01995448; URL www.clinicaltrials.gov © 2018 American College of Chest Physicians

The aims of the present work were to reevaluate, prospectively, the diagnostic value of already-described computed tomography (CT) landmarks of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) and to study the diagnostic value of some undescribed CT signs for the diagnosis of IAH and ACS.Consecutive patients admitted to the intensive care unit (ICU) in shock for whom an abdominal CT was clinically indicated were included. CT examinations were reviewed and scored by two reviewers for the 12 proposed CT features of IAH and ACS. Intravesical pressure (IVP) was measured for each patient. Imaging features and clinical data of patients with IAH (IVP ≥ 12 mmHg) were compared to those of patients with normal intra-abdominal pressure (IVP 12 mmHg).Forty-one patients were included. Twenty-one patients (51%) presented IAH with an IVP value ≥ 12 mmHg. Four patients (10%) were considered to have ACS (10%). Only an increased peritoneal-to-abdominal height ratio (PAR) was associated with the presence of IAH (PAR = 0.45 [0.40-0.49] in patients with IVP 12 mmHg and PAR = 0.52 [0.48-0.53] in patients with IVP ≥ 12 mmHg; p 0.001). Increased PAR ≥ 0.52 had a specificity of 85% for IAH diagnosis.The present study suggests that a PAR ≥ 0.52 could help radiologists to identify IAH on abdominal CT scan and could lead to adequate identification and/or treatment, even at early stages of IAH.• CT is an efficient first-intention procedure to evaluate and follow up underlying conditions in critically ill patients at risk of IAH and ACS overcome. • Raising the possibility of an IAH on a CT examination is relevant information for the clinician. • The only factors associated with intra-abdominal hypertension were the peritoneal-to-abdominal height ratio (PAR) and the ratio of maximal anteroposterior to transverse abdominal diameter (which define the round belly sign when 0.8).

To report the utility of abdominal ultrasonography to identify portal venous gas in patients with shock, as an indicator of acute mesenteric ischemia, and to illustrate the aspect of portal venous gas on ultrasonography.Clinical observation of a patient, images of abdominal ultrasonography and abdominal computed tomography, and video of portal venous gas.Not applicable.Relevant information contained in the medical observation of the patient and selection of image and video of ultrasonography performed in the patient.We report a case of nonocclusive mesenteric ischemia in a 76-year-old patient following cardiac surgery. The diagnosis of acute mesenteric ischemia was proposed based on evidence of portal venous gas on abdominal ultrasonography and then confirmed by abdominal computed tomography showing transverse colonic ischemia, the presence of gas in the mesenteric veins but not in the portal vein. Urgent laparotomy confirmed extensive nonocclusive mesenteric ischemia, and the patient rapidly died of multiple organ failure.Intensive care physicians should be aware of the ultrasound characteristics of portal venous gas. In patients with shock, in addition to cardiac and thoracic echography, investigation of portal venous gas using bedside ultrasonography may help the clinician to identify patients in whom acute mesenteric ischemia develops.

International audience; Aims The role of extracorporeal membrane oxygenation (ECMO) remains ill defined in pulmonary embolism (PE). We investigated outcomes in patients with high-risk PE undergoing ECMO according to initial therapeutic strategy. Methods and results From 01 January 2014 to 31 December 2015, 180 patients from 13 Departments in nine centres with high-risk PE were retrospectively included. Among those undergoing ECMO, we compared characteristics and outcomes according to adjunctive treatment strategy (systemic thrombolysis, surgical embolectomy, or no reperfusion therapy). Primary outcome was all-cause 30-day mortality. Secondary outcome was 90-day major bleeding. One hundred and twenty-eight patients were treated without ECMO; 52 (mean age 47.6 years) underwent ECMO. Overall 30-day mortality was 48.3% [95% confidence interval (CI) 41-56] (87/180); 43% (95% CI 34-52) (55/128) in those treated without ECMO vs. 61.5% (95% CI 52-78) (32/52) in those with ECMO (P = 0.008). In patients undergoing ECMO, 30-day mortality was 76.5% (95% CI 57-97) (13/17) for ECMO+fibrinolysis, 29.4% (95% CI 51-89) (5/17) for ECMO+surgical embolectomy, and 77.7% (95% CI 59-97) (14/18) for ECMO alone (P = 0.004). Among patients with ECMO, 20 (38.5%, 95% CI 25-52) had a major bleeding event in-hospital; without significant difference across groups. Conclusion In patients with high-risk PE, those with ECMO have a more severe presentation and worse prognosis. Extracorporeal membrane oxygenation in patients with failed fibrinolysis and in those with no reperfusion seems to be associated with particularly unfavourable prognosis compared with ECMO performed in addition to surgical embolectomy. Our findings suggest that ECMO does not appear justified as a stand-alone treatment strategy in PE patients, but shows promise as a complement to surgical embolectomy.

International audience; Clinical research remains a vital contributor to medical knowledge, and is an established and integral part of the practice of medicine worldwide. Respect for patient autonomy and ethical principles dictate that informed consent must be obtained from subjects before they can be enrolled into clinical research, yet these conditions may be difficult to apply in real practice in the intensive care unit (ICU). A number of factors serve to complexify the consent process in critically ill patients, notably decisional incapacity of the patient due to illness or sedation. Obtaining consent for research from a designated proxy or family member, commonly termed a "surrogate decision maker" (SDM) may be difficult, since SDMs dealing with the emotional, psychological and logistic impact of a sudden hospitalisation of their loved-one are not always receptive to the idea of research or emotionally equipped to reflect rationally on the opportunities being proposed to them. In addition, time constraints and workload pressures on the attending physician may render consent opportunities unfeasible, and the resulting loss of eligible patients could represent a bias in clinical trials, or limit the generalizability of their results. Alternative procedures such as deferred or waived consent have been used in the past and may be suitable alternatives in certain conditions, provided appropriate approval from institutional review boards (IRBs) can be obtained, in accordance with existing legislation. Some of the main questions inherent to the conduct of clinical research in critically ill patients are discussed in this review.

We report here the case of a 55-year-old man from Mali, who presented with abdominal pain. Radiological exploration revealed an ileo-colonic mass surrounding the appendix. A biopsy was taken and on histology, transmural granulomatous inflammation of numerous eosinophils, lymphocytes, plasmocytes and giant cells was seen. Tuberculosis was suspected clinically and an antibiotic treatment was initiated. Two months later, the patient died of septic complications. Basidiobolus ranarum was identified by PCR. Pathogens were retrospectively highlighted on biopsies. These elements were between 10 and 15 μm in diameter, occasionally pseudo-septated, and were surrounded by a thick eosinophilic cuff. The thick eosinophilic cuff was identified as the Splendore-Hoeppli phenomenon. Basidiobolomycosis is a well-known infection in the tropical areas. Basidiobolus sp., fungus of the order Entomophtorales are a known cause of chronic subcutaneous mycosis. Gastro-intestinal basidiobolomycosis is rare and presents considerable diagnostic difficulty. This infection needs to be diagnosed because surgical resection and prolonged antifungal treatment are curable in most cases.

Background The role of veno-arterial extracorporeal membrane oxygenation (ECMO) remains ill defined in patients with high-risk pulmonary embolism (PE). We investigated the outcomes in patients with high-risk PE undergoing ECMO according to the initial therapeutic strategy. Methods Patients from 9 centres with high-risk PE undergoing ECMO for cardiac arrest or persistent shock were included. We compared patients according to treatment strategy (systemic thrombolysis, surgical embolectomy, or no reperfusion therapy). The primary outcome was all-cause 30-day mortality. Secondary outcomes were successful weaning from ECMO and major bleeding. Results From January 2014 to December 2015, 52 patients (mean age 47.6 years) underwent ECMO for refractory cardiogenic shock (n = 13, 25%) and cardiac arrest (n = 39, 75%), of whom 18 (46%) had ECMO initiated during cardiopulmonary resuscitation. Overall 30-day mortality was 61.5% (32/52): 76.5% (13/17) in patients treated with fibrinolysis, 29.4% (5/17) in patients treated with surgical embolectomy, and 77.8% (14/18) in patients who received ECMO alone (P = 0.004). Nineteen (36.5%) patients were successfully weaned from ECMO (5/17 (29.4%) in patients with fibrinolysis; 11/17 (64.7%) in patients with surgical embolectomy, 3/18 (17.7%) in patients with ECMO alone, P = 0.009). Twenty patients (38.5%) had a major bleeding event in-hospital; without significant difference across groups. Conclusion Mortality is high in PE patients with ECMO, especially in those undergoing fibrinolysis and in those with no reperfusion. Life-support therapy with ECMO should not be considered as a stand-alone treatment strategy in high risk PE patients, but shows promise as a complement to surgical embolectomy.

Highlights • Ultrasonography is a useful tool for portal venous gas identification in critically ill patients. • Portal venous gas can be observed at the early phase of acute mesenteric ischemia. • Transient portal venous gas with rapid disappearance is indicative of the resolution of the ischemia., Objectives To report the utility of abdominal ultrasonography (US) to identify the presence of portal venous gas (PVG) during non-occlusive mesenteric ischemia (NOMI), and to follow the disappearance of portal venous gas after resolution of the NOMI. Data sources This was a clinical observation of a patient, with images of abdominal computed tomography (CT), and a video of portal venous gas identified by ultrasonography. Data synthesis We describe the case of an adult patient admitted to our ICU for NOMI developing 48 h after cardiac surgery. Medical intensive care associated with jejunal resection and vacuum-assisted closure led to rapid recovery. Three weeks later, the patient presented acute pulmonary edema, and developed a new episode of NOMI that was suspected by identification of PVG on US, and then confirmed on abdominal CT. The patient rapidly improved after orotracheal intubation and treatment of pulmonary edema. A second US performed 9 h later showed disappearance of PVG. The laparotomy performed 10 h after the first US did not find evidence of small bowel or colon ischemia. The postoperative period was uneventful. Conclusions US is a useful tool for the detection of PVG in critically ill patients, prompting suspicion of AMI. PVG can be observed at the early phase of AMI, even before irreversible transmural gut ischemia; transient PVG that disappears rapidly (within several hours) may suggest resolution of the NOMI.

Tramadol is a weak opioid analgesic indicated for the treatment of moderate to severe pain. Tramadol intoxication can be lethal, and this drug is frequently involved in voluntary overdose. Classically, tramadol intoxication is associated with neurological and respiratory side effects. In contrast, cardiac effects are poorly documented in the literature. We report a case of severe tramadol intoxication, with plasma concentration 20 times the toxic threshold, complicated by refractory cardiogenic shock, successfully treated by extra corporeal life support (ECLS) with a favorable cardiac outcome and ECLS weaning at day 10. Seizure, clonus, and nonreactive mydriasis were present during 4 days, and complete awakening was delayed to day 15. Poisoning caused by high doses of tramadol can lead to refractory cardiogenic shock, and ECLS can be considered as effective rescue therapy in this context.

International audience; BACKGROUND AND AIMS: It is well established that Crohn's disease (CD) is associated with an increased risk of small bowel adenocarcinoma (SBA). The data concerning SBA risk factors in CD are scanty. The aim of this study was to identify them. METHODS: In 11 French centers affiliated with the GETAID (Groupe d'Etude Thérapeutique des Affections Inflammatoires du Tube Digestif), we identified 29 patients with CD and SBA. Eighty-seven CD controls without SBA recruited in a single center were matched to the cases for sex, age, duration, and CD site. A conditional logistic regression, taking into account the matching between cases and controls, was performed. RESULTS: In univariate analysis, the cases had had significantly less small bowel resection and received prolonged treatment with salicylates (more than 2 yr), less often than the controls (odds ratio, OR [95% confidence interval, CI] 0.07 [0.01-0.32] and 0.29 [0.10-0.82], respectively). In multivariate analysis, both associations remained significant (OR 0.04 [0.01-0.28], P= 0.001; OR 0.16 [0.03-0.79], P= 0.02, respectively). CONCLUSION: This study suggests that small bowel resection and prolonged salicylates use may protect against SBA in CD patients.

Purpose of review Gut barrier failure is associated with bacterial translocation, systemic inflammation, and is presumed to be associated with the development of multiple organ dysfunction syndrome. As the gut barrier function is carried out by a monolayer of enterocytes, a minimum requirement is the integrity of the enterocytes, and controlled paracellular permeability between adjacent enterocytes. Many factors can cause critically ill patients to lose gut barrier function by a mechanism of enterocyte damage; for example, small bowel ischemia or hypoxia, sepsis, systemic inflammatory response syndrome, or absence of enteral feeding. Recent findings Two enterocyte biomarkers may help the intensivist to identify enterocyte damage and dysfunction, namely plasma citrulline, a biomarker of functional enterocyte mass, and plasma or urinary intestinal fatty acid-binding protein, a marker of enterocyte damage. This review focuses on results obtained with these biomarkers in the context of critical care, in particular: prevalence of enterocyte biomarker abnormalities; mechanisms associated with enterocyte damage and dysfunction; link with systemic inflammation, bacterial translocation, and clinical intestinal dysfunction; prognostic value of enterocyte biomarkers. Lastly, we also review the limits of these biomarkers. Summary Enterocyte biomarkers may help the intensivist to identify patients presenting with intestinal damage, and who are at risk of bacterial translocation and systemic inflammatory response syndrome, as well as those with decreased enterocyte function, at risk of malabsorption. Enterocyte biomarkers should be interpreted with caution in the critically ill and should be interpreted within the overall clinical context of the patient.

In a recent issue of Critical Care, Poole and colleagues found that plasma citrulline concentration and glucose absorption were reduced in 20 critically ill patients compared with 15 controls; however, the authors found no correlation between these two variables. This study highlights the question of the accuracy of plasma citrulline for assessing small bowel function in critically ill patients. Future studies should take into account the type of intestinal failure considered, the particular metabolism of citrulline, the time of plasma citrulline measurement, as well as the range of citrullinemia considered.

Cardiac arrest is considered to be a cause of small bowel ischemia, but the consequences of cardiac arrest on the human small bowel have been rarely studied. Plasma citrulline concentration is a marker of functional enterocyte mass, and plasma intestinal fatty acid-binding protein (I-FABP) concentration is a marker of enterocyte damage. We aimed to measure enterocyte biomarkers after cardiac arrest and to study the prognostic value of biomarker abnormalities. This is a prospective, observational, single-center study of patients admitted to the intensive care unit (ICU) for cardiac arrest, evaluating plasma citrulline and I-FABP concentrations at admission and after 24 h and variables according to the Utstein criteria. Variables according to 28-day Cerebral Performance Category score of 1 to 2 (good neurological outcome) versus 3 to 5 (poor neurological outcome) were compared. Sixty-nine patients with cardiac arrest of both cardiac and hypoxic origin were included. At ICU admission, plasma citrulline concentration was low in 65% and plasma I-FABP was elevated in 82% of the patients. After 24 h, plasma citrulline was low in 82% and I-FABP was normal in 60% of the patients. Patients with a poor neurological outcome had a lower plasma citrulline concentration and a higher I-FABP concentration at ICU admission. By multivariate analysis, plasma citrulline levels of 13.1 μmol L or less and I-FABP more than 260 pg mL were independently associated with a poor neurological outcome (odds ratio, 21.9 [2.2-215], and odds ratio, 13.6 [1.4-129], respectively). Cardiac arrest resuscitation is associated with evidence of small bowel mucosal damage in most patients, with a short and intense I-FABP elevation at admission and a decrease in citrulline concentration during the first day. In this study, low plasma citrulline and high I-FABP concentrations at ICU admission were predictive of a poor neurological outcome. This study confirms that cardiac arrest is a model of small bowel mucosal ischemia and suggests that enterocyte damage is a piece in the puzzle of post-cardiac arrest syndrome.

International audience; BACKGROUND:: Crohn's disease (CD) is associated with an increased risk of small bowel adenocarcinoma (SBA). However, there are no guidelines for the screening and early diagnosis of SBA. Colorectal cancer associated with chronic colitis arises from dysplasia. High-risk patients benefit from surveillance colonoscopies aimed to detect dysplasia. The dysplasia-carcinoma sequence remains poorly documented in CD-associated SBA. Moreover, molecular data about SBA complicating CD and associated dysplasia are very limited. We therefore assessed dysplasia and several key molecular markers of carcinogenesis in SBA and dysplasia developed in patients with CD. METHODS:: Forty-five SBA complicating CD and 4 specimens with dysplasia without SBA were screened. In SBA, we looked for dysplasia and determined their pathological characteristics (type, grade, distribution). We also stained for mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), p53, β-catenin, and p16 and looked for KRAS, BRAF and PIK3CA mutations. RESULTS:: All neoplastic lesions, except 1 lesion, were found in inflamed mucosal areas. Dysplasia was found in 20 of 41 patients with SBA (49%). Dysplasia was flat or raised, low grade or high grade, and adjacent or distant to concomitant SBA. Molecular markers of SBA carcinogenesis complicating CD were similar to those observed in chronic colitis-related colorectal cancer (KRAS, BRAF, p53, MSI), although differences were observed for β-catenin and p16. No PIK3CA mutations were observed. CONCLUSIONS:: These results suggest that there is an inflammation-dysplasia-adenocarcinoma sequence in at least half of CD-related SBA, similar to what is observed in chronic colitis-related colorectal cancer and may have implications for the prevention and treatment of this cancer.

International audience; PURPOSE: Multiple organ failure is a leading cause of death in critically ill patients and could be secondary to early gut ischemia. Plasma citrulline is a biomarker of enterocyte mass, and critically ill patients may have enterocyte mass reduction. The objectives of this study were to assess plasma citrulline kinetics and its prognostic value in critically ill patients. METHODS: This prospective observational study included adults without small bowel disease and without chronic renal failure consecutively admitted to a single intensive care unit. Prognostic variables as well as plasma citrulline concentrations were studied at admission, 12, 24, 48 h, and the 7th day after admission. Univariate and multivariate analyses including plasma citrulline (0-10, 11-20, and >20 micromol l(-1)) and other variables were performed. RESULTS: Sixty-seven patients were included, and the 28-day mortality was 34%. During the 1st day mean plasma citrulline decreased from 18.8 to 13.5 micromol l(-1). Low plasma citrulline at 24 h was associated with low plasma glutamine and arginine (p = 0.01 and 0.04), and high plasma CRP concentration, nosocomial infection rate, and 28-day mortality (p = 0.008, 0.03, and 0.02, respectively). In multivariate analysis plasma citrulline < or = 10 micromol l(-1) at 24 h and SOFA score > or =8 at 24 h were associated with 28-day mortality(odds ratios 8.70 and 15.08). CONCLUSIONS: In critically ill patients, low plasma citrulline at 24 h is an independent factor of mortality and could be a marker of acute intestinal failure.

International audience; Thrombotic thrombocytopenic purpura (TTP) is a severe multisystemic microvascular disease defined by the association of hemolytic anemia, thrombocytopenia, acute renal failure, fever, and neurological disorders. The pathophysiology has recently been elucidated by the discovery of a von Willebrand factor-cleaving protease (ADAMTS13) deficiency involved in platelet aggregation and ischemia. The association between TTP and acute pancreatitis (AP) has rarely been reported, described either as a cause or a consequence. The role of ADAMTS13 during AP is still unknown. We describe the case of a 41-year-old woman who developed a TTP, with decreased ADAMTS13 activity, associated with severe AP. Published cases of thrombotic microangiopathy associated with AP are reviewed. The pathophysiology, management, prognostic factors, and rationale for treatment are discussed. AP should be sought in patients with TTP presenting with abdominal pain. On the other hand, TTP should be considered in patients with AP and thrombocytopenia.

s of the 4th Congress of ECCO the European Crohn’s and Colitis Organisation S31 erosive pustular lesions on parietal sculp with remarkable progression to obvious PG during the next two days. The blood cultures were sterile and systemical steroids were introduced. Headache, neck pain and dysphagia gradually regressed and disappeared. Laboratory markers of inflammation returned to normal. Marked improvement of the skin ulcerations on right dorsum and the sculp and almost complete healing occurred after three months of treatment with corticosteroids. Conclusion: An unusual clinical appearance and course of PG in IBD patient was presented. An atypical variant like pyoderma of the neck and head is very rare presentation. It can be aggressive and often associated with neurologic symptoms. This case shows that atypical PG is sometimes difficult to confirm and establish the clinical value of 99mTc-HMPAO-LLS in differential diagnosis of extraintestinal manifestations and septic complications of IBD. P051 Prospective study of contrast-enhanced small bowel sonography (CES) in patients with Crohn’s disease (CD) operated of an ileal stenosis. Preliminary results L. Quencez1, M. De Billy1, G. Viennet1, G. Piton1, E. Delabrousse1, F. Carbonnel2 *. 1CHU Besancon, Besancon, France, 2CHU Bicetre, Le Kremlin Bicetre, France Introduction: contrast-enhanced sonography (CES) may assess vascular pattern of the bowel wall. The aim of this study was to compare CES to pathological examination of resected ileal specimens in CD. Patients and Methods: patients who required an ileal resection for an ileal stenosis due to CD underwent a CES and an abdominal CT scan before the operation. Semi quantitative evaluations of bowel wall enhancement on CES (adapted Limberg classification in 4 stages), of inflammation on the CT scan (Am J Gastroenterol 2007;102:2541), and of fibrosis and inflammation in the resected ileal specimen were performed (Am J Gastroenterol 2007;102:2541). Each of these evaluations was blinded of the results of the others. Preliminary results: 12/13 of resected ileal specimens had marked histological inflammation; 10 of these 12 patients had intense vascular enhancement of the bowel wall (Limberg 3 or 4) preoperatively. The only specimen without inflammation had a weak vascular enhancement on CES (Limberg 2). In specimens with mixed pattern (fibrosis and inflammation) CES showed an intense vascular enhancement (3/3). CES was inferior to CT scan for topography of lesions (including number and length of stenoses) and diagnosis of fistulas and abcesses. A bowel thickening 7mm in CES was found in 7 patients; 6 of them had inflammation-predominant lesions in resected bowel specimens. Conclusion: Most resected ileal specimens for CD have a marked inflammation, which appears to be well recognized by CES (Limberg classification 3 or 4 and bowel thickness 7mm). These preliminary results need to be confirmed. P052 Capsule endoscopy in suspected Crohn’s disease our initial experience A. Sadio*, A. Castanheira, P. Peixoto, E. Cancela, R. Araujo, P. Ministro, A. Silva. S. Teotonio Hospital, Viseu, Portugal Background: Capsule endoscopy (CE) allows for complete visualization of small bowel mucosa in a minimally invasive manner, representing a valuable diagnostic tool in patients with suspected Crohn’s disease (CD), whose initial endoscopic or radiological exams were negative or inconclusive. Aims and Methods: To evaluate the diagnostic yield of CE in patients with suspected CD. We rectrospectively analized medical records of patients submitted to CE and the following data were evaluated: age, sex, signs and symptoms and their duration, body mass index (BMI), previous diagnostic exams, CE findings, new medication started, clinical evolution. To establish the diagnosis of CD on CE we considered the following findings: 6 erosions or aphtoid ulcers

Background The triage nurse is involved in the early identification of the most severe patients at emergency department (ED) presentation. However, clinical criteria alone may be insufficient to identify them correctly. Measurement of capillary lactate concentration at ED presentation may help to discriminate these patients. The primary objective of this study was to identify the prognostic value of capillary lactate concentration measured by the triage nurse among patients presenting to the ED. Methods This was a prospective observational study, performed in the ED of a university hospital. At ED presentation, capillary lactate measurement was performed by the triage nurse among patients presenting with a clinical criteria of systemic inflammatory response syndrome (SIRS). Clinical variables usually used to determine severity were collected at presentation. Twenty-eight-day mortality and MEDS score were recorded. Results One hundred seventy-six patients with clinical SIRS presented to the ED. Median age was 72 years, and 28-day mortality was 16%. Capillary lactate at ED presentation was significantly higher among 28-day non-survivors than among survivors (5.7 mmol.L−1 [3.2 to 7.4] vs 2.9 mmol.L−1 [1.9 to 5.2], p = 0.003). A score based on mottling and capillary lactate concentration >3.6 mmol.L−1 was significantly associated with 28-day mortality (area under curve, AUC = 0.75), independently of the MEDS score (AUC = 0.79) for the prediction of 28-day mortality (AUC global model 0.87). Conclusions A high capillary lactate concentration measured by the triage nurse among patients presenting to the ED with clinical SIRS is associated with a high risk of death. A score calculated by the triage nurse, based on mottling and capillary lactate concentration, appears to be useful for identifying the most severe patients.

Background The best predictors of short- and medium-term mortality of cirrhotic patients receiving intensive care support are unknown. Methods We conducted meta-analyses from 13 studies (2523 cirrhotics) after selection of original articles and response to a standardized questionnaire by the corresponding authors. End-points were in-ICU, in-hospital, and 6-month mortality in ICU survivors. A total of 301 pooled analyses, including 95 analyses restricted to 6-month mortality among ICU survivors, were conducted considering 249 variables (including reason for admission, organ replacement therapy, and composite prognostic scores). Results In-ICU, in-hospital, and 6-month mortality was 42.7, 54.1, and 75.1%, respectively. Forty-eight patients (3.8%) underwent liver transplantation during follow-up. In-ICU mortality was lower in patients admitted for variceal bleeding (OR 0.46; 95% CI 0.36–0.59; p 19 at baseline (OR 8.54; 95% CI 2.09–34.91; p 26 (OR 3.97; 95% CI 1.92–8.22; p