68 research outputs found
Etude des dysfonctions immunologiques induites par la circulation extracorporelle
No full textNosocomial infections can occur among patients under cardiopulmonary bypass (CPB) used during cardiac surgery or suffering from a cardiogenic schock (ECMO). These infections darken the patients’ prognosis and they are the translation of immune dysfunctions induced by CPB. The first aim of our work was to assess the phenotypic modifications induced by ECMO. We concluded that this device induces a recruitment of immatures neutrophils, increases lymphocytes apoptosis and diminishes their ability to proliferate. Therefore, we comprehensively examine the impact of CPB on every neutrophil’s functions. We observed that CPB does not impact neutrophils bactericidal functions and induces a recruitment of matures neutrophils. These cells are not responsible for the development of nosocomial infections. Finally, CPB, as ECMO, induces lymphocyte’s apoptosis and inhibit their proliferation ability. Moreover, we observed the recruitment of immunosuppressive cells: Myeloïd Derived Suppressor Cells. These cells catabolize the arginine (via an arginase pathway) which is an essential amino-acid for the lymphocyte. Our knowledge of the arginine metabolism during severe inflammatory conditions helped us to show that citrulline is more suitable to correct hypoargininemia. The citrulline supplementation could be propose to patients having cardiac surgery with CPB in order to prevent nosocomial infections.La circulation extracorporelle (CEC) utilisé en chirurgie cardiaque ou en réanimation pour la prise en charge d’un choc cardiogénique (ECMO) est associé à la survenue d’infections nosocomiales assombrissant le pronostic des patients. Ces infections sont l’expression de dysfonctions immunitaires induites par la CEC. La première partie de notre travail s’est attaché à décrire les modifications phénotypiques des différentes populations immunitaires induites par l’ECMO. Nous avons pu mettre en évidence que cette CEC induisait un recrutement de polynucléaires neutrophiles (PMN) immatures et une anergie lymphocytaire caractérisée par une apoptose marquée ainsi qu’une diminution des capacités de prolifération. Nous avons poursuivi notre travail par l’étude exhaustive des PMN au cours de la chirurgie cardiaque avec CEC. Cette technique induit le recrutement de PMN matures aux fonctions de bactéricidie intactes n’expliquant donc pas la susceptibilité des patients aux infections post-opératoires. Finalement, comme l’ECMO, la CEC de chirurgie cardiaque induit une augmentation de l’apoptose lymphocytaire ainsi qu’une diminution des capacités de prolifération. Ces anomalies sont associées au recrutement de cellules immunosuppressives, les Myeloïd Derived Supressor Cells qui, via leur activité arginase, entraine une diminution de la disponibilité en arginine. Cet acide aminé est indispensable aux fonctions lymphocytaires et notre connaissance du métabolisme de l’arginine au décours des état inflammatoires sévères nous a permis de montrer que la supplémentation en citrulline permet de corriger plus efficacement l’hypoargininémie. La supplémentation en citrulline laisse entrevoir de nouvelles perspectives thérapeutiques afin de limiter les conséquences des phénomènes immunosuppresseurs induits par la CEC
Immune dysfunctions induced by cardiopulmonary bypass
No full textLa circulation extracorporelle (CEC) utilisé en chirurgie cardiaque ou en réanimation pour la prise en charge d’un choc cardiogénique (ECMO) est associé à la survenue d’infections nosocomiales assombrissant le pronostic des patients. Ces infections sont l’expression de dysfonctions immunitaires induites par la CEC. La première partie de notre travail s’est attaché à décrire les modifications phénotypiques des différentes populations immunitaires induites par l’ECMO. Nous avons pu mettre en évidence que cette CEC induisait un recrutement de polynucléaires neutrophiles (PMN) immatures et une anergie lymphocytaire caractérisée par une apoptose marquée ainsi qu’une diminution des capacités de prolifération. Nous avons poursuivi notre travail par l’étude exhaustive des PMN au cours de la chirurgie cardiaque avec CEC. Cette technique induit le recrutement de PMN matures aux fonctions de bactéricidie intactes n’expliquant donc pas la susceptibilité des patients aux infections post-opératoires. Finalement, comme l’ECMO, la CEC de chirurgie cardiaque induit une augmentation de l’apoptose lymphocytaire ainsi qu’une diminution des capacités de prolifération. Ces anomalies sont associées au recrutement de cellules immunosuppressives, les Myeloïd Derived Supressor Cells qui, via leur activité arginase, entraine une diminution de la disponibilité en arginine. Cet acide aminé est indispensable aux fonctions lymphocytaires et notre connaissance du métabolisme de l’arginine au décours des état inflammatoires sévères nous a permis de montrer que la supplémentation en citrulline permet de corriger plus efficacement l’hypoargininémie. La supplémentation en citrulline laisse entrevoir de nouvelles perspectives thérapeutiques afin de limiter les conséquences des phénomènes immunosuppresseurs induits par la CEC.Nosocomial infections can occur among patients under cardiopulmonary bypass (CPB) used during cardiac surgery or suffering from a cardiogenic schock (ECMO). These infections darken the patients’ prognosis and they are the translation of immune dysfunctions induced by CPB. The first aim of our work was to assess the phenotypic modifications induced by ECMO. We concluded that this device induces a recruitment of immatures neutrophils, increases lymphocytes apoptosis and diminishes their ability to proliferate. Therefore, we comprehensively examine the impact of CPB on every neutrophil’s functions. We observed that CPB does not impact neutrophils bactericidal functions and induces a recruitment of matures neutrophils. These cells are not responsible for the development of nosocomial infections. Finally, CPB, as ECMO, induces lymphocyte’s apoptosis and inhibit their proliferation ability. Moreover, we observed the recruitment of immunosuppressive cells: Myeloïd Derived Suppressor Cells. These cells catabolize the arginine (via an arginase pathway) which is an essential amino-acid for the lymphocyte. Our knowledge of the arginine metabolism during severe inflammatory conditions helped us to show that citrulline is more suitable to correct hypoargininemia. The citrulline supplementation could be propose to patients having cardiac surgery with CPB in order to prevent nosocomial infections
Etude des dysfonctions immunologiques induites par la circulation extracorporelle
No full textNosocomial infections can occur among patients under cardiopulmonary bypass (CPB) used during cardiac surgery or suffering from a cardiogenic schock (ECMO). These infections darken the patients’ prognosis and they are the translation of immune dysfunctions induced by CPB. The first aim of our work was to assess the phenotypic modifications induced by ECMO. We concluded that this device induces a recruitment of immatures neutrophils, increases lymphocytes apoptosis and diminishes their ability to proliferate. Therefore, we comprehensively examine the impact of CPB on every neutrophil’s functions. We observed that CPB does not impact neutrophils bactericidal functions and induces a recruitment of matures neutrophils. These cells are not responsible for the development of nosocomial infections. Finally, CPB, as ECMO, induces lymphocyte’s apoptosis and inhibit their proliferation ability. Moreover, we observed the recruitment of immunosuppressive cells: Myeloïd Derived Suppressor Cells. These cells catabolize the arginine (via an arginase pathway) which is an essential amino-acid for the lymphocyte. Our knowledge of the arginine metabolism during severe inflammatory conditions helped us to show that citrulline is more suitable to correct hypoargininemia. The citrulline supplementation could be propose to patients having cardiac surgery with CPB in order to prevent nosocomial infections.La circulation extracorporelle (CEC) utilisé en chirurgie cardiaque ou en réanimation pour la prise en charge d’un choc cardiogénique (ECMO) est associé à la survenue d’infections nosocomiales assombrissant le pronostic des patients. Ces infections sont l’expression de dysfonctions immunitaires induites par la CEC. La première partie de notre travail s’est attaché à décrire les modifications phénotypiques des différentes populations immunitaires induites par l’ECMO. Nous avons pu mettre en évidence que cette CEC induisait un recrutement de polynucléaires neutrophiles (PMN) immatures et une anergie lymphocytaire caractérisée par une apoptose marquée ainsi qu’une diminution des capacités de prolifération. Nous avons poursuivi notre travail par l’étude exhaustive des PMN au cours de la chirurgie cardiaque avec CEC. Cette technique induit le recrutement de PMN matures aux fonctions de bactéricidie intactes n’expliquant donc pas la susceptibilité des patients aux infections post-opératoires. Finalement, comme l’ECMO, la CEC de chirurgie cardiaque induit une augmentation de l’apoptose lymphocytaire ainsi qu’une diminution des capacités de prolifération. Ces anomalies sont associées au recrutement de cellules immunosuppressives, les Myeloïd Derived Supressor Cells qui, via leur activité arginase, entraine une diminution de la disponibilité en arginine. Cet acide aminé est indispensable aux fonctions lymphocytaires et notre connaissance du métabolisme de l’arginine au décours des état inflammatoires sévères nous a permis de montrer que la supplémentation en citrulline permet de corriger plus efficacement l’hypoargininémie. La supplémentation en citrulline laisse entrevoir de nouvelles perspectives thérapeutiques afin de limiter les conséquences des phénomènes immunosuppresseurs induits par la CEC
Etude des dysfonctions immunologiques induites par la circulation extracorporelle
No full textNosocomial infections can occur among patients under cardiopulmonary bypass (CPB) used during cardiac surgery or suffering from a cardiogenic schock (ECMO). These infections darken the patients’ prognosis and they are the translation of immune dysfunctions induced by CPB. The first aim of our work was to assess the phenotypic modifications induced by ECMO. We concluded that this device induces a recruitment of immatures neutrophils, increases lymphocytes apoptosis and diminishes their ability to proliferate. Therefore, we comprehensively examine the impact of CPB on every neutrophil’s functions. We observed that CPB does not impact neutrophils bactericidal functions and induces a recruitment of matures neutrophils. These cells are not responsible for the development of nosocomial infections. Finally, CPB, as ECMO, induces lymphocyte’s apoptosis and inhibit their proliferation ability. Moreover, we observed the recruitment of immunosuppressive cells: Myeloïd Derived Suppressor Cells. These cells catabolize the arginine (via an arginase pathway) which is an essential amino-acid for the lymphocyte. Our knowledge of the arginine metabolism during severe inflammatory conditions helped us to show that citrulline is more suitable to correct hypoargininemia. The citrulline supplementation could be propose to patients having cardiac surgery with CPB in order to prevent nosocomial infections.La circulation extracorporelle (CEC) utilisé en chirurgie cardiaque ou en réanimation pour la prise en charge d’un choc cardiogénique (ECMO) est associé à la survenue d’infections nosocomiales assombrissant le pronostic des patients. Ces infections sont l’expression de dysfonctions immunitaires induites par la CEC. La première partie de notre travail s’est attaché à décrire les modifications phénotypiques des différentes populations immunitaires induites par l’ECMO. Nous avons pu mettre en évidence que cette CEC induisait un recrutement de polynucléaires neutrophiles (PMN) immatures et une anergie lymphocytaire caractérisée par une apoptose marquée ainsi qu’une diminution des capacités de prolifération. Nous avons poursuivi notre travail par l’étude exhaustive des PMN au cours de la chirurgie cardiaque avec CEC. Cette technique induit le recrutement de PMN matures aux fonctions de bactéricidie intactes n’expliquant donc pas la susceptibilité des patients aux infections post-opératoires. Finalement, comme l’ECMO, la CEC de chirurgie cardiaque induit une augmentation de l’apoptose lymphocytaire ainsi qu’une diminution des capacités de prolifération. Ces anomalies sont associées au recrutement de cellules immunosuppressives, les Myeloïd Derived Supressor Cells qui, via leur activité arginase, entraine une diminution de la disponibilité en arginine. Cet acide aminé est indispensable aux fonctions lymphocytaires et notre connaissance du métabolisme de l’arginine au décours des état inflammatoires sévères nous a permis de montrer que la supplémentation en citrulline permet de corriger plus efficacement l’hypoargininémie. La supplémentation en citrulline laisse entrevoir de nouvelles perspectives thérapeutiques afin de limiter les conséquences des phénomènes immunosuppresseurs induits par la CEC
Cardiopulmonary bypass and VA-ECMO induced immune dysfunction: common features and differences, a narrative review
No full textInternational audienceCardiopulmonary bypass (CPB) and veno-arterial extracorporeal membrane oxygenation are critical tools in contemporary cardiac surgery and intensive care, respectively. While these techniques share similar components, their application contexts differ, leading to distinct immune dysfunctions which could explain the higher incidence of nosocomial infections among ECMO patients compared to those undergoing CPB. This review explores the immune modifications induced by these techniques, comparing their similarities and differences, and discussing potential treatments to restore immune function and prevent infections. The immune response to CPB and ECMO involves both humoral and cellular components. The kinin system, complement system, and coagulation cascade are rapidly activated upon blood contact with the circuit surfaces, leading to the release of pro-inflammatory mediators. Ischemia-reperfusion injury and the release of damage-associated molecular patterns further exacerbate the inflammatory response. Cellular responses involve platelets, neutrophils, monocytes, dendritic cells, B and T lymphocytes, and myeloid-derived suppressor cells, all of which undergo phenotypic and functional alterations, contributing to immunoparesis. Strategies to mitigate immune dysfunctions include reducing the inflammatory response during CPB/ECMO and enhancing immune functions. Approaches such as off-pump surgery, corticosteroids, complement inhibitors, leukocyte-depleting filters, and mechanical ventilation during CPB have shown varying degrees of success in clinical trials. Immunonutrition, particularly arginine supplementation, has also been explored with mixed results. These strategies aim to balance the inflammatory response and support immune function, potentially reducing infection rates and improving outcomes. In conclusion, both CPB and ECMO trigger significant immune alterations that increase susceptibility to nosocomial infections. Addressing these immune dysfunctions through targeted interventions is essential to improving patient outcomes in cardiac surgery and critical care settings. Future research should focus on refining these strategies and developing new approaches to better manage the immune response in patients undergoing CPB and ECMO
Characterization of pellicles formed by Acinetobacter baumannii at the air-liquid interface
No full textThe clinical importance of Acinetobacter baumannii is partly due to its natural ability to survive in the hospital environment.
This persistence may be explained by its capacity to form biofilms and, interestingly, A. baumannii can form pellicles at the
air-liquid interface more readily than other less pathogenic Acinetobacter species. Pellicles from twenty-six strains were
morphologically classified into three groups: I) egg-shaped (27%); II) ball-shaped (50%); and III) irregular pellicles (23%). One
strain representative of each group was further analysed by Brewster’s Angle Microscopy to follow pellicle development,
demonstrating that their formation did not require anchoring to a solid surface. Total carbohydrate analysis of the matrix
showed three main components: Glucose, GlcNAc and Kdo. Dispersin B, an enzyme that hydrolyzes poly-Nacetylglucosamine
(PNAG) polysaccharide, inhibited A. baumannii pellicle formation, suggesting that this exopolysaccharide
contributes to pellicle formation. Also associated with the pellicle matrix were three subunits of pili assembled by chaperonusher
systems: the major CsuA/B, A1S_1510 (presented 45% of identity with the main pilin F17-A from enterotoxigenic
Escherichia coli pili) and A1S_2091. The presence of both PNAG polysaccharide and pili systems in matrix of pellicles might
contribute to the virulence of this emerging pathogen
Impact of human communications molecules on respiratory tractus bacterial pathogen
No full textInternational audienc
Cerebral nocardiosis in a patient treated with pembrolizumab: a first case report
No full textInternational audienceackground: Checkpoints inhibitors (CPIs) are increasingly used for the treatment of several malignancies. The most common side effects are Immune Related Adverse Events, while infectious complications are rare, especially cerebral nocardiosis.Case presentation: Here, we report the first clinical case of a cerebral nocardiosis revealed after seizure in a patient treated by pembrolizumab for a metastatic lung cancer, in the absence of any additional immunosuppressive therapy or risk factors for cerebral nocardiosis. The extended evaluation including a brain CT-scan did not reveal any lesion before pembrolizumab. Nevertheless, the 3-month delay between the start of Pembrolizumab and the diagnosis of cerebral nocardiosis suggests that the infection occurred prior to the CPI. Unfortunately, the patient died during treatment for cerebral nocardiosis, while the lung cancer tumor mass had decreased by 80% after the sixth cycle of pembrolizumab.Conclusions: This case report emphasizes that clinicians should consider diagnoses other than metastasis in a patient with a brain mass and metastatic cancer treated with CPI, such as opportunistic infections or IRAE
Early discontinuation of combination antibiotic therapy in severe community-acquired pneumonia: a retrospective cohort study
No full textAbstract Background Severe community-acquired pneumonia (SCAP) is commonly treated with an empiric combination therapy, including a macrolide, or a quinolone and a β-lactam. However, the risk of Legionella pneumonia may lead to a prolonged combination therapy even after negative urinary antigen tests (UAT). Methods We conducted a retrospective cohort study in a French intensive care unit (ICU) over 6 years and included all the patients admitted with documented SCAP. All patients received an empirical combination therapy with a β-lactam plus a macrolide or quinolone, and a Legionella UAT was performed. Macrolide or quinolone were discontinued when the UAT was confirmed negative. We examined the clinical and epidemiological features of SCAP and analysed the independent factors associated with ICU mortality. Results Among the 856 patients with documented SCAP, 26 patients had atypical pneumonia: 18 Legionella pneumophila (LP) serogroup 1, 3 Mycoplasma pneumonia (MP), and 5 Chlamydia psittaci (CP). UAT diagnosed 16 (89%) Legionella pneumonia and PCR confirmed the diagnosis for the other atypical pneumonia. No atypical pneumonia was found by culture only. Type of pathogen was not associated with a higher ICU mortality in the multivariate analysis. Conclusion Legionella pneumophila UAT proved to be highly effective in detecting the majority of cases, with only a negligible percentage of patients being missed, but is not sufficient to diagnose atypical pneumonia, and culture did not provide any supplementary information. These results suggest that the discontinuation of macrolides or quinolones may be a safe option when Legionella UAT is negative in countries with a low incidence of Legionella pneumonia
Pseudomonas aeruginosa Biofilm Lifecycle: Involvement of Mechanical Constraints and Timeline of Matrix Production
No full textPseudomonas aeruginosa is an opportunistic pathogen causing acute and chronic infections, especially in immunocompromised patients. Its remarkable adaptability and resistance to various antimicrobial treatments make it difficult to eradicate. Its persistence is enabled by its ability to form a biofilm. Biofilm is a community of sessile micro-organisms in a self-produced extracellular matrix, which forms a scaffold facilitating cohesion, cell attachment, and micro- and macro-colony formation. This lifestyle provides protection against environmental stresses, the immune system, and antimicrobial treatments, and confers the capacity for colonization and long-term persistence, often characterizing chronic infections. In this review, we retrace the events of the life cycle of P. aeruginosa biofilm, from surface perception/contact to cell spreading. We focus on the importance of extracellular appendages, mechanical constraints, and the kinetics of matrix component production in each step of the biofilm life cycle
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