Alterations of the Erythrocyte Membrane during Sepsis

Erythrocytes have been long considered as “dead” cells with transport of oxygen (O2) as their only function. However, the ability of red blood cells (RBCs) to modulate the microcirculation is now recognized as an important additional function. This capacity is regulated by a key element in the rheologic process: the RBC membrane. This membrane is a complex unit with multiple interactions between the extracellular and intracellular compartments: blood stream, endothelium, and other blood cells on the one hand, and the intracytoplasmic compartment with possible rapid adaptation of erythrocyte metabolism on the other. In this paper, we review the alterations in the erythrocyte membrane observed in critically ill patients and the influence of these alterations on the microcirculatory abnormalities observed in such patients. An understanding of the mechanisms of RBC rheologic alterations in sepsis and their effects on blood flow and on oxygen transport may be important to help reduce morbidity and mortality from severe sepsis

Contribution à l’étude de l’expression des phosphodiestérases et des apolipoprotéines L leucocytaires au cours du sepsis chez l’homme.

Le sepsis constitue une pathologie fréquente, grevée d’une morbi-mortalité encore élevée. Sa physiopathologie fait notamment intervenir des dysrégulations du système immunitaire inné et adaptatif et des voies de l’apoptose. Ce travail aborde l’expression leucocytaire de deux familles de protéines potentiellement impliquées dans sa physiopathologie :les phosphodiestérases (PDE) et les apolipoprotéines L (apoL). L’étude de l’expression des PDE sous-tend le fait que ces enzymes, qui dégradent les nucléotides cycliques (AMPc et GMPc), sont impliquées dans la modulation de nombreux processus inflammatoires, tant d’origine infectieuse que non-infectieuse. L’expression des PDE après administration de LPS chez l’Homme est cependant mal caractérisée, de même qu’au cours du sepsis. Le présent travail teste l’hypothèse selon laquelle le sepsis, caractérisé par un état de dysrégulation immune complexe, s’accompagne d’une répression de l’expression des PDE au sein des leucocytes circulants, contrairement à ce qui est observé dans des modèles standardisés d’inflammation aiguë (LPS) ;il met également en perspective, dans une démarche observationnelle, l’expression des PDE avec l’expression du complexe HLA-DR, un ensemble protéique permettant la présentation de l’antigène et dont l’expression est partiellement dépendante de l’AMPc. Trois études ont ainsi été menées :étude de l’expression des PDE au cours d’une endotoxinémie chez le volontaire sain (1), et au cours du sepsis au sein de leucocytes totaux circulants (2) ou de sous-populations leucocytaires de l’immunité innée (monocytes CD14+ou granulocytes CD15+) (3). Alors que l’administration intraveineuse de LPS chez le volontaire sain mène à l’induction précoce et transitoire de certaines PDE, de façon similaire aux observations in vitro, les patients septiques présentent au contraire dès leur admission, et jusqu’au 5ème jour, une réduction de l’expression de plusieurs PDE en comparaison aux volontaires sains, tant dans les leucocytes totaux que dans les populations CD14+ et CD15+. L’expression de plusieurs de ces PDE est corrélée aux ratios TNF-α/IL-10 qui sont suggestifs d’un état d’immunodépression, attesté par une réduction significative de l’expression du complexe HLA-DR. L’étude des apoL au cours du sepsis sous-tend quant à elle le fait que cette famille de protéines, qui partage des homologies avec des membres du groupe Bcl-2 impliqué dans l’apoptose, a été associée notamment à l’induction de phénomènes pro-apoptotiques ;or, le sepsis est associé à une apoptose retardée des polynucléaires neutrophiles, un phénomène potentiellement délétère au niveau tissulaire. L’hypothèse d’une répression de l’expression des apoL leucocytaires au cours du sepsis est ainsi posée. Dans le présent travail, une diminution de l’expression des apoL-1, 2, 3 et -6 est observée chez les patients de soins intensifs présentant ou non un sepsis en comparaison à des volontaires sains ;cette réduction, corrélée aux taux de protéine C-réactive, concerne tant les populations leucocytaires totales que les granulocytes CD15+, et intéresse tant les ARNm que l’expression protéique (apoL-6 excepté). Le pourcentage de cellules CD15+ apoptotiques est par ailleurs fortement corrélé aux taux d’ARNm des apoL-1 et -2. Ces observations sont reproduites in vitro en incubant des granulocytes CD15+ de volontaire sain avec du sérum de patients septiques ou non septiques. Ces résultats préliminaires suggèrent ainsi une implication des apoL dans la régulation de l’apoptose des neutrophiles au cours du sepsis.Doctorat en Sciences médicales (Médecine)info:eu-repo/semantics/nonPublishe

Transfusion strategies in patients with traumatic brain injury: Which is the optimal hemoglobin target?

Robertson et al. (JAMA 2014; 312:36-47) investigated the effects of two different thresholds of hemoglobin (Hb) to guide red blood cells transfusions (RBCT; 7 g/dL vs. 10 g/dL) in patients suffering from traumatic brain injury (TBI). In a two-center, controlled, open-label trial (from May 2006 and August 2012), comatose patients with a closed TBI were randomized within 6 hours since initial resuscitation to one of the two RBCT strategies and, in a factorial design (2x2), to receive erythropoietin (EPO) or placebo. Patients were excluded if they had a Glasgow Coma Scale (GCS) score of 3 with fixed and dilated pupils, penetrating trauma, pregnancy, life-threatening systemic injuries and severe preexisting diseases. A total of 200 patients (7 g/dL with [N.=49] or without EPO [N. =50]; 10 g/dL with [N.=53] or without EPO [N.=48]) were enrolled among 598 who were screened. There was no interaction between EPO and Hb thresholds on the primary outcome, which was the occurrence of favorable neurological outcome, assessed using the Glasgow Outcome Scale (GOS) at 6 months after the injury (favorable=GOS 4-5). Favorable outcome was similar between patients included in the 7 g/dL (37/87-43%) and the 10 g/dL group (31/94-33%) as if receiving EPO or placebo, even after adjustment for several covariates. Thromboembolic events were significantly more frequent in the group transfused at 10 g/dL (22/101 [22%] vs. 8/99 [8%]; P=0.009). We discussed how theses results might influence the management of such patients as well as the methodological limitations that underline the need for further investigations.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Epigastric pain as presentation of an addisonian crisis in a patient with Schmidt syndrome.

A 39-year-old woman presented with a 10-day history of epigastric pain accompanied by persistent fatigue and loss of appetite for 3 months. She had presented several weeks earlier with adhesive capsulitis, treated by local infiltration of corticosteroids. She was not taking any other medications. Results of heart, lung, and abdominal examinations were unremarkable, except for mild epigastric tenderness. Purple stretch marks were observed on examination of the skin. The only blood chemistry abnormalities were hyponatremia (125 mEq/L) and hyperkalemia (6.8 mEq/L). Based on the clinical and biologic picture, adrenal insufficiency was suspected. The patient was transferred to the intensive care unit and received hydrocortisone intravenously for 3 days. She was then given oral hydrocortisone and fludrocortisone. Biologic abnormalities reversed entirely; the final diagnosis was primary autoimmune adrenal insufficiency (Addison's disease) associated with autoimmune hypothyroidism (Schmidt syndrome). Adrenal insufficiency should be considered in patients with abdominal pain, especially when associated with electrolyte abnormalities.Case ReportsJournal Articleinfo:eu-repo/semantics/publishe

Relations entre la pensée scientifique et la médecine: les apports de Platon et d'Aristote.

Since the advent of philosophy and rational thought, a question has been raised: Is medicine an art, a science, a technique, or the three of them? In this paper we discuss two monuments of Western thought that have approached this topic: Plato and Aristotle. For Plato, medicine is focused on what is transient and changing and therefore it is a subordinate science. However, he has a positive view because it presupposes knowledge of all and he takes medicine as a dialectical model. Aristotle places medicine in his classification of sciences. He emphasizes the idea that the purpose of medicine is based on what "happens most often" and insists on essential role of experimentation. It is remarkable to notice that these ideas developed 2.500 years ago are still relevant and remain the core of the epistemological conceptions of modern medicine.info:eu-repo/semantics/publishe

Red blood cell transfusion in the critically ill patient.

Red blood cell (RBC) transfusion is a common intervention in intensive care unit (ICU) patients. Anemia is frequent in this population and is associated with poor outcomes, especially in patients with ischemic heart disease. Although blood transfusions are generally given to improve tissue oxygenation, they do not systematically increase oxygen consumption and effects on oxygen delivery are not always very impressive. Blood transfusion may be lifesaving in some circumstances, but many studies have reported increased morbidity and mortality in transfused patients. This review focuses on some important aspects of RBC transfusion in the ICU, including physiologic considerations, a brief description of serious infectious and noninfectious hazards of transfusion, and the effects of RBC storage lesions. Emphasis is placed on the importance of personalizing blood transfusion according to physiological endpoints rather than arbitrary thresholds.info:eu-repo/semantics/publishe

The sicker the patient, the more likely that transfusion will be beneficial

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Preoperative Transfusions to Limit the Deleterious Effects of Blood Transfusions

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Relationship between red cell storage duration and outcomes in adults receiving red cell transfusions: a systematic review.

INTRODUCTION: The duration of red blood cell (RBC) storage before transfusion may alter RBC function and supernatant and, therefore, influence the incidence of complications or even mortality. METHODS: A MEDLINE search from 1983 to December 2012 was performed to identify studies reporting age of transfused RBCs and mortality or morbidity in adult patients. RESULTS: Fifty-five studies were identified; most were single-center (93%) and retrospective (64%), with only a few, small randomized studies (eight studies, 14.5%). The numbers of subjects included ranged from eight to 364,037. Morbidity outcomes included hospital and intensive care unit (ICU) length of stay (LOS), infections, multiple organ failure, microcirculatory alterations, cancer recurrence, thrombosis, bleeding, vasospasm after subarachnoid hemorrhage, and cognitive dysfunction. Overall, half of the studies showed no deleterious effects of aged compared to fresh blood on any endpoint. Eleven of twenty-two (50%) studies reported no increased mortality, three of nine (33%) showed no increased LOS with older RBCs and eight of twelve (66%) studies showed no increased risks of organ failure. Ten of eighteen (55%) studies showed increased infections with transfusion of older RBCs. The considerable heterogeneity among studies and numerous methodological flaws precluded a formal meta-analysis. CONCLUSIONS: In this systematic review, we could find no definitive argument to support the superiority of fresh over older RBCs for transfusion.JOURNAL ARTICLESCOPUS: ar.jinfo:eu-repo/semantics/publishe

Transfusion de concentrés érythrocytaires – actualités 2012

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