48 research outputs found

    New tools for optimizing fluid resuscitation in acute pancreatitis

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    International audienceAcute pancreatitis (AP) is a frequent disease with degrees of increasing severity responsible for high morbidity. Despite continuous improvement in care, mortality remains significant. Because hypovolemia, together with microcirculatory dysfunction lead to poor outcome, fluid therapy remains a cornerstone of the supportive treatment. However, poor clinical evidence actually support the aggressive fluid therapy recommended in recent guidelines since available data are controversial. Fluid management remains unclear and leads to current heterogeneous practice. Different strategies may help to improve fluid resuscitation in AP. On one hand, integration of fluid therapy in a global hemodynamic resuscitation has been demonstrated to improve outcome in surgical or septic patients. Tailored fluid administration after early identification of patients with high-risk of poor outcome presenting inadequate tissue oxy-genation is a major part of this strategy. On the other hand, new decision parameters have been developed recently to improve safety and efficiency of fluid therapy in critically ill patients. In this review, we propose a personalized strategy integrating these new concepts in the early fluid management of AP. This new approach paves the way to a wide range of clinical studies in the field of AP

    Involvement of Mitochondrial Disorders in Septic Cardiomyopathy

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    Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. It remains a leading cause of death worldwide, despite the development of various therapeutic strategies. Cardiac dysfunction, also referred to as septic cardiomyopathy, is a frequent and well-described complication of sepsis and associated with worse clinical outcomes. Recent research has increased our understanding of the role of mitochondrial dysfunction in the pathophysiology of septic cardiomyopathy. The purpose of this review is to present this evidence as a coherent whole and to highlight future research directions.</jats:p

    Abnormal Mitochondrial cAMP/PKA Signaling Is Involved in Sepsis-Induced Mitochondrial and Myocardial Dysfunction

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    Adrenergic receptors couple to Gs-proteins leading to transmembrane adenylyl cyclase activation and cytosolic cyclic adenosine monophosphate (cAMP) production. Cyclic AMP is also produced in the mitochondrial matrix, where it regulates respiration through protein kinase A (PKA)-dependent phosphorylation of respiratory chain complexes. We hypothesized that a blunted mitochondrial cAMP-PKA pathway would participate in sepsis-induced heart dysfunction. Adult male mice were subjected to intra-abdominal sepsis. Mitochondrial respiration of cardiac fibers and myocardial contractile performance were evaluated in response to 8Br-cAMP, PKA inhibition (H89), soluble adenylyl cyclase inhibition (KH7), and phosphodiesterase inhibition (IBMX; BAY60-7550). Adenosine diphosphate (ADP)-stimulated respiratory rates of cardiac fibers were reduced in septic mice. Compared with controls, stimulatory effects of 8Br-cAMP on respiration rates were enhanced in septic fibers, whereas inhibitory effects of H89 were reduced. Ser-58 phosphorylation of cytochrome c oxidase subunit IV-1 was reduced in septic hearts. In vitro, incubation of septic cardiac fibers with BAY60-7550 increased respiratory control ratio and improved cardiac MVO2 efficiency in isolated septic heart. In vivo, BAY60-7550 pre-treatment of septic mice have limited impact on myocardial function. Mitochondrial cAMP-PKA signaling is impaired in the septic myocardium. PDE2 phosphodiesterase inhibition by BAY60-7550 improves mitochondrial respiration and cardiac MVO2 efficiency in septic mice

    Vibration Response Imaging: evaluation of rater agreement in healthy subjects and subjects with pneumonia

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    Abstract Background We evaluated pulmonologists variability in the interpretation of Vibration response imaging (VRI) obtained from healthy subjects and patients hospitalized for community acquired pneumonia. Methods The present is a prospective study conducted in a tertiary university hospital. Twenty healthy subjects and twenty three pneumonia cases were included in this study. Six pulmonologists blindly analyzed images of normal subjects and pneumonia cases and evaluated different aspects of VRI images related to the quality of data aquisition, synchronization of the progression of breath sound distribution and agreement between the maximal energy frame (MEF) of VRI (which is the maximal geographical area of lung vibrations produced at maximal inspiration) and chest radiography. For qualitative assessment of VRI images, the raters' evaluations were analyzed by degree of consistency and agreement. Results The average value for overall identical evaluations of twelve features of the VRI image evaluation, ranged from 87% to 95% per rater (94% to 97% in control cases and from 79% to 93% per rater in pneumonia cases). Inter-rater median (IQR) agreement was 91% (82-96). The level of agreement according to VRI feature evaluated was in most cases over 80%; intra-class correlation (ICC) obtained by using a model of subject/rater for the averaged features was overall 0.86 (0.92 in normal and 0.73 in pneumonia cases). Conclusions Our findings suggest good agreement in the interpretation of VRI data between different raters. In this respect, VRI might be helpful as a radiation free diagnostic tool for the management of pneumonia.</p

    Outcome and prognostic factors of patients with right-sided infective endocarditis requiring intensive care unit admission

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    Abstract Background Right-sided infective endocarditis (RSIE) is an uncommon diagnosis accounting for less than 10% of cases of infective endocarditis. Optimal management for severely ill patients with RSIE remains challenging because few studies reported on management and outcome. The goal of our study was to determine outcome and associated prognostic factors in a population of ICU patients with a diagnosis of definite, active and severe RSIE. Methods We performed a retrospective study in 10 French ICUs between January 2002 and December 2012. Main outcome was mortality at 30 days after ICU admission. Significant variables associated with 30-days mortality in the bivariate analysis were included in a logistic regression analysis. Results A total of 37 patients were studied. Mean age was 47.9 ± 18.4 years. Mean SAPS II, SOFA score and Charlson comorbidity index were 32.4 ± 17.4, 6.3 ± 4.4 and 3.1 ± 3.4, respectively. Causative pathogens, identified in 34 patients, were mainly staphylococci (n = 29). The source of endocarditis was a catheter related infection in 10 patients, intravenous drug abuse in 8 patients, cutaneous in 7 patients, urinary tract related in one patient and has an unknown origin in 7 patients. Vegetation size was higher than 20 mm for 14 patients. Valve tricuspid regurgitation was classified as severe in 11 patients. All patients received initial appropriate antimicrobial therapy. Aminoglycosides were delivered in combination with β-lactam antibiotics or vancomycin in 22 patients. Surgical procedure was performed in 14 patients. Eight patients (21.6%) died within 30 days following ICU admission. One independent prognostic factor was identified: use of aminoglycosides was associated with improved outcome (OR = 0.1; 95%CI = 0.0017–0.650; p = 0.007). Conclusion Mortality of patients with RSIE needing ICU admission is high. Aminoglycosides used in combination with β-lactam or vancomycin could reduce 30 days mortality

    Protein recycling and limb muscle recovery after critical illness in slow- and fast-twitch limb muscle

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    An impaired capacity of muscle to regenerate after critical illness results in long-term functional disability. We previously described in a long-term rat peritonitis model that gastrocnemius displays near-normal histology whereas soleus demonstrates a necrotizing phenotype. We thus investigated the link between the necrotizing phenotype of critical illness myopathy and proteasome activity in these two limb muscles. We studied male Wistar rats that underwent an intraperitoneal injection of the fungal cell wall constituent zymosan or n-saline as a sham-treated control. Rats (n = 74) were killed at 2, 7, and 14 days postintervention with gastrocnemius and soleus muscle removed and studied ex vivo. Zymosan-treated animals displayed an initial reduction of body weight but a persistent decrease in mass of both lower hindlimb muscles. Zymosan increased chymotrypsin- and trypsin-like proteasome activities in gastrocnemius at days 2 and 7 but in soleus at day 2 only. Activated caspases-3 and -9, polyubiquitin proteins, and 14-kDa fragments of myofibrillar actin (proteasome substrates) remained persistently increased from day 2 to day 14 in soleus but not in gastrocnemius. These results suggest that a relative proteasome deficiency in soleus is associated with a necrotizing phenotype during long-term critical illness. Rescuing proteasome clearance may offer a potential therapeutic option to prevent long-term functional disability in critically ill patients.</p
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