The Warburg Effect as a Type B Lactic Acidosis in a Patient With Acute Myeloid Leukemia: A Diagnostic Challenge for Clinicians

IntroductionThe Warburg effect (WE) is an uncommon cause of type B lactic acidosis (LA) due to a deregulation of carbohydrate metabolism in neoplastic cells where lactic fermentation predominates over oxidative phosphorylation regardless of the oxygen level.Case presentationWe report the case of a 57-year-old man presenting with concomitant acute myeloid leukemia and type B LA with asymptomatic hypoglycemia. We did not find arguments for a septic state, liver dysfunction, or acute mesenteric ischemia. The WE was suspected, and chemotherapy was immediately undertaken. We observed a rapid and sustained decrease in lactate level and normalization of blood glucose. Unfortunately, we noted a relapse of acute leukemia associated with WE soon after treatment initiation and the patient died in the Intensive Care unit.DiscussionSome patients may present complications directly related to an underlying hematological malignancy. The WE is one of these complications and should be suspected in patients with both hypoglycemia and LA. We propose a checklist in order to help clinicians manage this life-threatening complication. Before considering WE, clinicians should eliminate diagnoses such as septic shock or mesenteric ischemia, which require urgent and specific management.ConclusionThe diagnosis of WE can be challenging for clinicians in the Hematology department and the Intensive Care unit. Prompt diagnosis and rapid, adapted chemotherapy initiation may benefit patient survival

Annexin-V positive extracellular vesicles level is increased in severe COVID-19 disease

ObjectivesTo evaluate extracellular vesicles levels in a cohort of SARS-CoV-2’s patients hospitalized in an intensive care unit with and without COVID-19 associated thromboembolic events.MethodsIn this study, we aim to assess endothelial and platelet membrane-derived extracellular vesicles levels in a cohort of SARS-CoV-2 patients with and without COVID-19-associated thromboembolic events who were hospitalized in an intensive care unit. Annexin-V positive extracellular vesicles levels were prospectively assessed by flow cytometry in one hundred twenty-three critically ill adults diagnosed with acute respiratory distress syndrome associated with a SARS-CoV-2 infection, ten adults diagnosed for moderate SARS-CoV-2 infection and 25 healthy volunteers.ResultsOn our critically ill patients, thirty-four patients (27.6%) had a thromboembolic event, Fifty-three (43%) died. Endothelial and platelet membrane-derived extracellular vesicles were drastically increased in SARS-CoV-2 patients hospitalized in the ICU compared to healthy volunteers. Moreover a slighty higher small/large ratio for platelets membrane-derived extracellular vesicles in patients was linked to thrombo-embolic events.ConclusionA comparison between total annexin-V positive extracellular vesicles levels in severe and moderate SARS-CoV-2 infection and healthy controls showed a significant increase in patients with severe infection and their sizes could be considered as biomarkers of SARS-CoV-2 associated thrombo-embolic events

Effect of oral calcium carbonate on aortic calcification in apolipoprotein E-deficient (apoE−/−) mice with chronic renal failure

Background. In chronic kidney disease (CKD) patients, the intake of calcium-based phosphate binders is associated with a marked progression of coronary artery and aortic calcification, in contrast to patients receiving calcium-free phosphate binders. The aim of this study was to reexamine the role of calcium carbonate in vascular calcification and to analyse its effect on aortic calcification-related gene expression in chronic renal failure (CRF). Methods. Mice deficient in apolipoprotein E underwent either sham operation or subtotal nephrectomy to create CRF. They were then randomly assigned to one of the three following groups: a control non-CRF group and a CRF group fed on standard diet, and a CRF group fed on calcium carbonate enriched diet, for a period of 8 weeks. Aortic atherosclerotic plaque and calcification were evaluated using quantitative morphologic image processing. Aortic gene and protein expression was examined using immunohistochemistry and Q-PCR methods. Results. Calcium carbonate supplementation was effective in decreasing serum phosphorus but was associated with a higher serum calcium concentration. Compared with standard diet, calcium carbonate enriched diet unexpectedly induced a significant decrease of both plaque (p < 0.05) and non-plaque-associated calcification surface (p < 0.05) in CRF mice. It also increased osteopontin (OPN) protein expression in atherosclerotic lesion areas of aortic root. There was also a numerical increase in OPN and osteoprotegerin gene expression in total thoracic aorta but the difference did not reach the level of significance. Finally, calcium carbonate did not change the severity of atherosclerotic lesions. Conclusion. In this experimental model of CRF, calcium carbonate supplementation did not accelerate but instead decreased vascular calcification. If our observation can be extrapolated to humans, it appears to question the contention that calcium carbonate supplementation, at least when given in moderate amounts, necessarily enhances vascular calcification. It is also compatible with the hypothesis of a preponderant role of phosphorus over that of calcium in promoting vascular calcification in CR

Insuffisance rénale chronique et sepsis (évaluation hémodynamique et de la réaction inflammatoire dans un modèle expérimental murin)

Objectifs : Nos données cliniques suggèrent une surmortalité du patient insuffisant rénal chronique (IRC) hospitalisé pour choc septique, confirmée par une étude de survie après création d un sepsis par le lipopolysaccharide (LPS), sur des souris urémiques. Nous explorons le retentissement cardiaque, hémodynamique et inflammatoire du sepsis afin de trouver une explication mécanistique. Démarche : Cent quinze souris ont été réparties en 4 groupes : sham-placebo, sham-LPS, IRC-placebo et IRC-LPS. A H6 de l injection de LPS, une échographie cardiaque (ETT) évaluait la fonction systolique, diastolique du ventricule gauche (VG) et un cathétérisme carotidien mesurait la pression artérielle (PA) et la constante de temps de relaxation du VG Tau. L urémie et les cytokines IL-6 et TNFa étaient dosées dans le serum et dans le myocarde pour l IL-6. L expression de VCAM-1 et la transcription de SERCA2. Résultats : Le LPS provoquait une insuffisance rénale aiguë, une tachycardie mais la PA et Tau restaient inchangés. L ETT montrait la dysfonction diastolique et l hypertrophie ventriculaire gauche de l IRC et les dysfonctions systolique et diastolique du LPS. Après LPS, seul l index de Teï était différent entre les souris sham et les souris IRC (480+-120 vs 620+-150) sans qu on puisse affirmer la dysfonction diastolique majorée. SERCA2 s exprimait de façon identique dans les 4 groupes. Le dosage sérique des cytokines montrait une réaction inflammatoire majorée dans le groupe IRC-LPS comparé au groupe sham-LPS. Les taux d IL-6 et de VCAM-1 dans le myocarde montraient un effet du LPS mais non aggravé par l IRC préexistante. Conclusion : Nous montrons une réaction inflammatoire au LPS majorée en cas d IRC préexistante et que la surmortalité n est pas expliquée par une dysfonction cardiaque plus sévère, à ce stade du sepsis. Nous testons actuellement l hypothèse d une atteinte vasculaire majorée par l IRC même si on ne peut exclure une défaillance cardiaque retardée.Context and objectives : Our clinical data suggest that the rate of mortality of the patients with septic shock is increased when chronic kidney disease (CKD), confirmed by a survey experiment after sepsis induced by a lipopolysaccaharide (LPS) injection in uremic mice. We explored cardiac, hemodynamical and inflammatory sepsis consequences to find the mechanisms increasing the mortality of CKD mice. Approach : Sepsis was induced using an intraperitoneal injection of lipopolysaccharide (LPS). One hundred and fifteen mice were divided in 4 groups : sham-placebo, sham-LPS, CKD-placebo et CKD-LPS. Six hours after LPS injection an echocardiography explored systolic and diastolic function and a carotid catheterism was performed to measure arterial pressure and the time constant of left ventricle isovolumic relaxation Tau. Uremia and cytokines IL-6 and TNFa were measured in serum and in heart for IL-6 only. VCAM-1 myocardial expression and SERCA2 transcription were quantified. Results : LPS induced an acute kidney injury, mice heart frequency was higher but arterial pressure and Tau remained unchanged. Echocardiographic measurements showed diastolic dysfunction and left ventricle hypertrophy in CKD groups and LPS induced contractility and diastolic abnormalities. After LPS, Teï index was the only parameter to be different between sham mice and CKD mice (480+-120 vs 620+-150) but we could not assert diastolic dysfunction because the ejection time was shorter. SERCA2 expression was statistically the same in the 4 groups. Serum cytokines levels revealed an increased inflammatory reaction in the CKD-LPS group compared to the sham-LPS group. Myocardial IL-6 level and VAM-1 expression were increased by LPS but did not differ when CKD was considered. Conclusion : Our study demonstrates that inflammatory reaction induced by LPS is exacerbated by preexisting CKD and that the higher mortality rate when CKD comorbidity cannot be explained because of a more severe cardiac dysfunction, at this time of sepsis. More impaired septic vascular function and structure is a hypothesis that we are investigating, even we cannot definitely exclude a delayed myocardial dysfunction.AMIENS-BU Santé (800212102) / SudocSudocFranceF

Facteurs influençant la réussite à l'examen classant national chez les étudiants en médecine d'Amiens (promotion 2011)

Le but était de trouver des facteurs prédictifs socio-démographiques, liés à l environnement de travail, à la motivation ou au cursus, de réussite à l Examen Classant National (ECN) défini par un rang de classement inférieur à 2400. Méthodes : Un questionnaire a été remis aux étudiants de 4ème année du Deuxième Cycle des Etudes Médicales de la promotion 2011 à Amiens, les résultats ont été corrélés au rang de classement à l ECN avec analyse uni puis multivariée. Les résultats scolaires sur tout le cursus de médecine ont été étudiés. Résultats : Le taux de réponses était de 87.6% au questionnaire soit 128 étudiants. Ils étaient satisfaits de leur faculté (86%), mais 70% d entre eux déclarent se dispenser de presque tous les cours car jugeant leurs contenus inadaptés (75%). En analyse univariée les facteurs significatifs favorisant un classement 2400. In the multivariate analysis 2 parameters remained independently and significantly associated with a rank <2400: the age (odds ratio(OR) 0.4, 95% confidence interval (IC) 0.22-0.77 ; p=0.0055) and the participation in an association (OR : 7.7 [2,19-26,85] ; p=0.0014). Conclusion : Our study demonstarte that the age and the participation to an association seem to be independantly associated with a rank <2400 at the NRE. Further similar studies should be conducted in different French universities to confirm or infirm our results.AMIENS-BU Santé (800212102) / SudocSudocFranceF

From Upper Respiratory Symptoms to Hemophagocytic Lymphohistiocytosis: Case Report of a Human Adenovirus Infection in Haploidentical Hematopoietic Stem Cell Transplant Recipient

Human adenovirus infection is rare in adult population, except for in immunocompromised individuals. Recipients of allogenic haploidentical hematopoietic stem cell transplantation are reported at high risk for human adenovirus, which is often lethal when it evolves into the disseminated form. Despite existent guidelines, prevention, early diagnosis, and therapeutics remain challenging. Here, we report the case of a fatal evolution of human adenovirus respiratory infection and discuss the actual recommendations to prevent recurrence of this major issue