Continuous Monitoring of Cerebral Autoregulation in Children Supported by Extracorporeal Membrane Oxygenation: A Pilot Study.

OBJECTIVE: Cerebral autoregulation (CA) impairment may pose a risk factor for neurological complications among children supported by extracorporeal membrane oxygenation (ECMO). Our first objective was to investigate the feasibility of CA continuous monitoring during ECMO treatment and to describe its evolution over time. The second objective was to analyze the association between CA impairment and neurological outcome. DESIGN: Observational prospective study. PATIENTS AND SETTING: Twenty-nine children treated with veno-arterial or veno-venous ECMO in the PICU of Nantes University Hospital, France, and the PICU of the IRCCS Giannina Gaslini Institute in Genoa, Italy. MEASUREMENTS: A correlation coefficient between the variations of regional cerebral oxygen saturation and the variations of mean arterial blood pressure (MAP) was calculated as an index of CA (cerebral oxygenation reactivity index, COx). A COx > 0.3 was considered as indicative of autoregulation impairment. COx-MAP plots were investigated allowing determining optimal MAP (MAPopt) and limits of autoregulation: lower (LLA) and upper (ULA). Neurological outcome was assessed by the onset of an acute neurological event (ANE) after ECMO start. RESULTS: We included 29 children (median age 84 days, weight 4.8 kg). MAPopt, LLA, and ULA were detected in 90.8% (84.3-93.3) of monitoring time. Mean COx was significantly higher during day 1 of ECMO compared to day 2 [0.1 (0.02-0.15) vs. 0.01 (- 0.05 to 0.1), p = 0.002]. Twelve children experienced ANE (34.5%). The mean COx and the percentage of time spent with a COx > 0.3 were significantly higher among ANE+ compared to ANE- patients [0.09 (0.01-0.23) vs. 0.04 (- 0.02 to 0.06), p = 0.04 and 33.3% (24.8-62.1) vs. 20.8% (17.3-23.7) p = 0.001]. ANE+ patients spent significantly more time with MAP below LLA [17.2% (6.5-32.9) vs. 5.6% (3.6-9.9), p = 0.02] and above ULA [13% (5.3-38.4) vs. 4.2% (2.7-7.4), p = 0.004], respectively. CONCLUSION: CA assessment is feasible in pediatric ECMO. The first 24 h following ECMO represents the most critical period regarding CA. Impaired autoregulation is significantly more severe among patients who experience ANE

Analysis of blood T follicular helper cells in renal operationally tolerant patients

Même si les traitements immunosuppresseurs ont grandement contribué à améliorer la survie du greffon en transplantation, ils comportent des effets secondaires potentiellement graves (cancer, néphrotoxicité, infections…). Certaines équipes de recherche se sont donc intéressées spécifiquement à de très rares patients transplantés rénaux, appelés patients tolérants, qui conservaient une bonne fonction de leur greffon durant des années et ce, en l’absence d’immunosuppresseurs. Plusieurs travaux ont permis de mettre en évidence le rôle primordial des lymphocytes B (LB), avec notamment un défaut de différenciation in vitro des LB en plasmocytes rapporté chez ces patients tolérants. C’est à partir de ce résultat que nous nous sommes intéressés aux lymphocytes T folliculaires helper (TFH), connus comme étant des cellules indispensables à la différenciation des LB. Dans un premier temps, nous avons mis en évidence un défaut quantitatif et qualitatif des TFH chez les patients tolérants comparé à des patients transplantés ayant une fonction stable sous immunosuppresseurs. Aussi, nous avons suggéré une implication des TFH dans l’apparition des anticorps anti-donneur (DSA), ce qui pourrait expliquer la faible proportion d’immunisation anti-donneur reportée chez les patients tolérants. Dans un deuxième temps, nous avons exploré les mécanismes moléculaires mis en jeu en réalisant une analyse transcriptomique haut débit par RNA Sequencing à partir de TFH purifiés. A partir de cette analyse, nous avons pu mettre en évidence plusieurs gènes potentiellement intéressants dans la régulation des TFH et dans l’interaction avec les LB chez les patients tolérants.Immunosuppressive drugs largely contributed to a better graft survival over time in transplantation, but induced serious side effects (cancer, nephrotoxicity, infections…). In this context, some researchers focused on rare renal transplanted recipients, who maintain a good graft function without any immunosuppressive drugs during several years. These patients are named operationally tolerant patients and are of considerable interest to immunologists. Studies on these patients reveal a critical role of B cells, with particularly an in vitro B cell differentiation defect reported in tolerant patients. Based on this report, we focused on blood T follicular helper cells (TFH) which are known to be crucial for supporting B cell differentiation. At first, we reported a qualitative and quantitative TFH defect in tolerant patients compared to transplanted patients with stable graft function under immunosuppression. Moreover, we suggest a potential role of TFH in post graft immunization with donor-specific antibodies (DSA), which could explain the low incidence of post-graft DSA immunization reported in tolerant patients. Secondly, based on a transcriptomic analysis of purified TFH by RNA Sequencing, we have highlighted several TFH genes potentially interesting in tolerant patients, concerning the TFH regulation and the cooperation between TFH and B cells

Évaluation de la prise en charge des enfants en insuffisance rénale aigüe traités par hémodiafiltration en réanimation pédiatrique au CHU de Nantes

Au CHU de Nantes, une dizaine d'enfants par an sont traités en réanimation pédiatrique par hémodiafiltration veino-veineuse continue pour une insuffisance rénale aigue. L'objectif de ce travail était d'évaluer les pratiques du service selon une démarche d'évaluation des pratiques professionnelles définie par des sociétés savantes. Les résultats montrent que certains aspects sont maitrisés par l'équipe tels que l'anticoagulation, l'abandon des solutés à base d'acétate, le branchement isovolémique ou la manipulation de néphrotoxiques. D'autres peuvent faire l'objet d'amélioration, tels que l'évaluation optimale de l'état hémodynamique et les apports hydroélectrolytiques adaptés. En complément du protocole d'hémodiafiltration déjà existant, une fiche d'aide à la prescription pourrait être mise en place pour faciliter la prise en charge en urgence de ces patients.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

Virus or bacteria: Is It the only cause of sepsis-induced rhabdomyolysis?

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Phenotype and functions of B cells in patients with acute brain injuries

International audienceBackground: Brain injuries (BI) induce a state of systemic immunosuppression, leading to a high risk of pneumonia. In this pilot study, we investigated the status of B cell compartment in BI patients.Methods: A prospective observational study was performed in 2 intensive care units in a university hospital. Blood samples were collected in 14 patients at day 1 and day 7 after acute BI. The phenotype and the ability of B cells to secrete IL-10 were compared to 11 healthy volunteers (HV).Results: Among the circulating lymphocytes, the frequency of B cells was significantly higher in BI patients compared to HV (p < 0.001). B cells from BI patients displayed an activated profil on day 7 after BI, reflected by a significantly higher proportion of CD27 + memory (p = 0.01) and CD27 + IgD − switched memory B cells (p = 0.02), as well as a significantly higher blood level of IgA (p = 0.001) and IgM (p < 0.001) as compared to day 1. The frequency of IL-10 secreting B cells (IL-10 + B cells) on day 1 and day 7 was significantly lower in BI patients compared to HV (p < 0.05). Interestingly, we observed that all BI patients with high frequency of IL-10 + B cells on day 1 displayed an episode of pneumonia, and had a longer duration of mechanical ventilation and ICU stay compared to BI patients with low proportion of IL-10 + B cells.Conclusion: This study provides an extensive description of the phenotype and function of B cells in BI patients. Our results suggest that IL-10 + B cells could play a major role in immunosuppression after BI

HLA-DR expression in neonates after cardiac surgery under cardiopulmonary bypass: a pilot study

Abstract Monocyte HLA-DR expression has been reported as a marker of immunosuppression and a predictor of sepsis development. However, to date, there is no report on monocyte HLA-DR monitoring exclusively in neonates (< 28 days of life) who underwent cardiac surgery under cardiopulmonary bypass (CPB), which have a high risk of nosocomial infection. In this pilot study, we studied nine neonates with a diagnosis of congenital heart disease requiring surgery under CPB. There was a significant reduction in monocyte HLA-DR expression for the first two postoperative days, as compared to preoperatively (p = 0.004). Moreover, neonates who displayed an episode of NI had a dramatically lower HLA-DR expression at day 4, as compared to neonates without NI (4257 AB/c [2220–5895] vs 14,947 AB/c [9858–16,960]; p = 0.04). Our preliminary results could indicate that HLA-DR expression may be a useful biomarker of immunosuppression-induced secondary infection after CPB in neonates

Immunophenotype of a Rat Model of Duchenne's Disease and Demonstration of Improved Muscle Strength After Anti-CD45RC Antibody Treatment

International audienceCorticosteroids (CS) are standard therapy for the treatment of Duchenne's muscular dystrophy (DMD). Even though they decrease inflammation, they have limited efficacy and are associated with significant side effects. There is therefore the need for new protolerogenic treatments to replace CS. Dystrophin-deficient rats (Dmd mdx ) closely resemble the pathological phenotype of DMD patients. We performed the first Immunophenotyping of Dmd mdx rats and showed leukocyte infiltration in skeletal and cardiac muscles, which consisted mostly of macrophages and T cells including CD45RChigh T cells. Muscles of DMD patients also contain elevated CD45RChigh T cells. We treated Dmd mdx rats with an anti-CD45RC MAb used in previous studies to deplete CD45RChigh T cells and induce immune tolerance in models of organ transplantation. Treatment of young Dmd mdx rats with anti-CD45RC MAb corrected skeletal muscle strength and was associated with depletion of CD45RChigh T cells with no side effects. Treatment of young Dmd mdx rats with prednisolone resulted in increase in skeletal muscle strength but also severe growth retardation. In conclusion, anti-CD45RC MAb treatment has potential in the treatment of DMD and might eventually result in reduction or elimination of CS use

Impact of Arterial Carbon Dioxide and Oxygen Content on Cerebral Autoregulation Monitoring Among Children Supported by ECMO

Cerebral autoregulation (CA) impairment is associated with neurological complications among children supported by extracorporeal membrane oxygenation (ECMO). Severe variations of arterial CO2 (PaCO2) and O2 (PaO2) tension after ECMO onset are common and associate with mortality and poor neurological outcome. The impact of gas exchange on CA among critically ill patients is poorly studied

CXCR5+PD1+ICOS+ circulating T follicular helpers are associated with de novo donor-specific antibodies after renal transplantation

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