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Background and Methods: Cardiogenic shock remains one of the leading causes of death in patients with myocardial infarction. The Intra-aortic balloon pump (IABP) has been widely used as a treatment for acute myocardial infarction (AMI), despite recommendations against its routine use. In this paper, our aim is to analyze and share our own experience with IABP in the setting of AMI. We retrospectively reviewed the files of patients admitted with AMI and cardiogenic shock and for whom IABP was inserted between June 2016 and December 2022., Results: 300 patients with AMI and cardiogenic shock were admitted and benefited from IABP insertion and primary coronary revascularization. The overall mortality rate was 62.3%, the site related complication rate was 0.6%, and the overall complications rate (including site related and major bleeding) was 10.6%. There was a significantly higher mortality in the group of patients where the Left Anterior Descending artery (LAD) was the culprit lesion, in the group of patients who required dialysis, the group who had creatinine levels greater than 200 um/L compared to the group who had creatinine lower than 200 um/L, and in patients older than 70 years. Interestingly, no difference in mortality was observed between men and women, single versus multiple vessel disease, and between STEMI and non-STEMI patients., Conclusion: Mortality of AMI complicated by cardiogenic shock and treated by IABP remains high. However, IABP usage is associated with a low complication rate. Better selection criteria for IABP usage versus other more powerful mechanical circulatory support devices in such patients might improve the outcome for the patient., Competing Interests: Conflicts of Interest The authors report no financial relationships or conflicts of interest regarding the content herein., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Peripartum cardiomyopathy is a life-threatening condition that requires urgent diagnosis and management. Bromocriptine was established as disease specific therapy; less data is known about Cabergolin which is another prolactin secretion inhibitor. In this paper we report 4 peripartum cardiomyopathy cases treated successfully with Cabergoline, including a cardiogenic shock case requiring mechanical circulatory support., Competing Interests: Declaration of competing interest The Authors declares no conflict of interest., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

A 45 years old female patient was admitted to our facility for COVID -19 infection complicated by fulminant cardiac injury and refractory cardiogemic shock. She had echographic findings of reverse takotsubo cardiomyopathy. She was successfully treated by VA-ECMO allowing complete revocery of the left ventricule function and weaning from support., Competing Interests: Conflict of interest None., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Acute erythroleukemia (AEL or acute myeloid leukemia [AML]-M6) is a rare but aggressive hematologic malignancy. Previous studies showed that AEL leukemic cells often carry complex karyotypes and mutations in known AML-associated oncogenes. To better define the underlying molecular mechanisms driving the erythroid phenotype, we studied a series of 33 AEL samples representing 3 genetic AEL subgroups including TP53-mutated, epigenetic regulator-mutated (eg, DNMT3A, TET2, or IDH2), and undefined cases with low mutational burden. We established an erythroid vs myeloid transcriptome-based space in which, independently of the molecular subgroup, the majority of the AEL samples exhibited a unique mapping different from both non-M6 AML and myelodysplastic syndrome samples. Notably, >25% of AEL patients, including in the genetically undefined subgroup, showed aberrant expression of key transcriptional regulators, including SKI, ERG, and ETO2. Ectopic expression of these factors in murine erythroid progenitors blocked in vitro erythroid differentiation and led to immortalization associated with decreased chromatin accessibility at GATA1-binding sites and functional interference with GATA1 activity. In vivo models showed development of lethal erythroid, mixed erythroid/myeloid, or other malignancies depending on the cell population in which AEL-associated alterations were expressed. Collectively, our data indicate that AEL is a molecularly heterogeneous disease with an erythroid identity that results in part from the aberrant activity of key erythroid transcription factors in hematopoietic stem or progenitor cells., (© 2020 by The American Society of Hematology.)

This review article aim to highlight the right ventricular function peri left ventricular assist device implantation, and to assess the incidence, physiopathology, predictors, management and prognosis, of right ventricular failure post-implant., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

The bromodomain and extraterminal (BET) domain family proteins are epigenetic modulators involved in the reading of acetylated lysine residues. The first BET protein inhibitor to be identified, (+)-JQ1, a thienotriazolo-1, 4-diazapine, binds selectively to the acetyl lysine-binding pocket of BET proteins. We evaluated the impact on adipogenesis of this druggable targeting of chromatin epigenetic readers, by investigating the physiological consequences of epigenetic modifications through targeting proteins binding to chromatin. JQ1 significantly inhibited the differentiation of 3T3-L1 preadipocytes into white and brown adipocytes by down-regulating the expression of genes involved in adipogenesis, particularly those encoding the peroxisome proliferator-activated receptor (PPAR-γ), the CCAAT/enhancer-binding protein (C/EBPα) and, STAT5A and B. The expression of a constitutively activated STAT5B mutant did not prevent inhibition by JQ1. Thus, the association of BET/STAT5 is required for adipogenesis but STAT5 transcription activity is not the only target of JQ1. Treatment with JQ1 did not lead to the conversion of white adipose tissue into brown adipose tissue (BAT). BET protein inhibition thus interferes with generation of adipose tissue from progenitors, confirming the importance of the connections between epigenetic mechanisms and specific adipogenic transcription factors., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Malignant transformation is a multistep process requiring oncogenic activation, promoting cellular proliferation, frequently coupled to inhibition of terminal differentiation. Consequently, forcing the reengagement of terminal differentiation of transformed cells coupled or not with an inhibition of their proliferation is a putative therapeutic approach to counteracting tumorigenicity. UT7 is a human leukemic cell line able to grow in the presence of IL3, GM-CSF and Epo. This cell line has been widely used to study Epo-R/Epo signaling pathways but is a poor model for erythroid differentiation. We used the BET bromodomain inhibition drug JQ1 to target gene expression, including that of c-Myc. We have shown that only 2 days of JQ1 treatment was required to transitory inhibit Epo-induced UT7 proliferation and to restore terminal erythroid differentiation. This study highlights the importance of a cellular erythroid cycle break mediated by c-Myc inhibition before initiation of the erythropoiesis program and describes a new model for BET bromodomain inhibitor drug application., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Cerebral hemorrhage is usually associated to many cardiac disorders, mimicking acute coronary syndrome. We relate a case of a postmenopausal woman presenting at emergency room for acute coronary syndrome and whose evaluation revealed a subarachnoidal hemorrhage, normal coronary arteries, and a typical Tako Tsubo aspect on echocardiography with apical ballooning and hyperkinesis with basal hypokinesis., (Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.)

Background and Aim: Decrease in heart rate variability (HRV) is a known risk factor for cardiovascular morbidity and mortality. The aim of our study is to evaluate HRV in chronic hemodialysis patients and to determine factors that might decrease or increase it., Methods: This is a retrospective study including 51 patients, 23 males and 28 females, with a mean of age of 64.5 years (23-84 years) on chronic hemodialysis for end stage renal disease due to various causes. Twenty-four-hour heart rate monitoring was recorded in all patients to evaluate HRV. HRV of hemodialysis patients was compared to normal patients (control). We also looked for correlation between HRV and a number of clinical and biological factors., Results: All HRV parameters were decreased in chronic hemodialysis patients compared to normal controls with a significant difference (p<0.0005). HRV decreases with age (p=0.012), and is lower in diabetic patients (p=0.026). Interestingly, we found that chronic hemodialysis patients on beta-blockers had higher HRV with p=0.011., Conclusion: HRV is reduced in chronic hemodialysis patients mainly in old and diabetic patients, but this decrease is less important in those receiving beta-blockers.

Objective: Tilt Table testing is widely used for the diagnosis and evaluation of vasovagal syncope. By evaluating the fluctuations of the autonomic nervous system that play an important role in syncope genesis, heart rate variability (HRV) can be considered as a tool of added value., Methods: We evaluated prospectively 123 patients admitted for recurrent syncope with a positive tilt Table testing. A time domain analysis of a 24 hours ambulatory electrocardiography was used in all patients to asses the particularities of their autonomic function. We compared their results with those obtained from a group of 82 healthy volunteers., Results: Statistical analysis of the results showed a significant increase of all HRV parameters in the group of vasovagal syncope compared to the healthy volunteers. SDNNidx (58 vs 42; p < 0.001), rMSSD (40 vs 27; p < 0.001), SDNN (102 vs 83; p < 0.001), SDANN (79 vs 67; p< 0.001), pNN50 (11 vs 4.9; p <0.001)., Conclusion: Time domain analysis of heart rate variability reveals increased values in patients with vasovagal syncope. It seems to be an interesting, easy and complementary test in the evaluation of syncope of unknown etiology.

This paper reviews current evidence on the role of admission and fasting glycaemia as prognostic markers in patients with acute coronary syndromes. Though both parameters are correlated, they give different prognostic information and are related to both in-hospital complications, including death, and long-term outcomes. As hyperglycemia at the acute stage of myocardial infarction is an independent predictor of untoward cardiovascular events, blood glucose measurements should become routine in all patients presenting with acute coronary syndromes.

Activation of the erythropoietin receptor (EpoR) after Epo binding is very transient because of the rapid activation of strong down-regulation mechanisms that quickly decrease Epo sensitivity of the cells. Among these down-regulation mechanisms, receptor internalization and degradation are probably the most efficient. Here, we show that the Epo receptor was rapidly ubiquitinated after ligand stimulation and that the C-terminal part of the Epo receptor was degraded by the proteasomes. Both ubiquitination and receptor degradation by the proteasomes occurred at the cell surface and required Janus kinase 2 (Jak2) activation. Moreover, Epo-EpoR complexes were rapidly internalized and targeted to the lysosomes for degradation. Neither Jak2 nor proteasome activities were required for internalization. In contrast, Jak2 activation was necessary for lysosome targeting of the Epo-EpoR complexes. Blocking Jak2 with the tyrphostin AG490 led to some recycling of internalized Epo-Epo receptor complexes to the cell surface. Thus, activated Epo receptors appear to be quickly degraded after ubiquitination by 2 proteolytic systems that proceed successively: the proteasomes remove part of the intracellular domain at the cell surface, and the lysosomes degrade the remaining part of the receptor-hormone complex. The efficiency of these processes probably explains the short duration of intracellular signaling activated by Epo.

We examined the role of the Src kinase Lyn in phospholipase C-gamma 2 (PLC-gamma 2) and phosphatidylinositol (PI) 3-kinase activation in erythropoietin (Epo)-stimulated FDC-P1 cells transfected with a wild type (WT) Epo-receptor (Epo-R). We showed that two inhibitors of Src kinases, PP1 and PP2, abolish both PLC-gamma 2 tyrosine phosphorylation and PI 3-kinase activity in WT Epo-R FDC-P1 cells. We also demonstrated that Epo-phosphorylated Lyn is associated with tyrosine phosphorylated PLC-gamma 2 and PI 3-kinase in WT Epo-R FDC-P1-stimulated cells. Moreover Epo-activated Lyn phosphorylates in vitro PLC-gamma 2 immunoprecipitated from unstimulated cells. Our results suggest that the Src kinase Lyn is involved in PLC-gamma 2 phosphorylation and PI 3-kinase activation induced by Epo.