Thromboses et thrombopathies dans les syndromes myéloprolifératifs

Myeloproliferative neoplasms are acquired hematological malignancies, mainly affecting the adult and whose morbidity and mortality stems from haemostasis disorders. The most frequently encountered complications include thrombosis, affecting preferentially the arterial territory, but also atypical locations such as splanchnic vein thrombosis. The pathophysiology of these thromboses is complex and involves different actors: blood cells, endothelium and flow conditions. Numerous studies have been conducted to identify risk factors for thrombosis. To date, only two risk factors have been validated through prospective studies (age over 60 years old, history of thrombotic events) and allow classification of patients as “low risk” and “high risk” as the basis for current treatment recommendations. Haemorrhagic manifestations, less frequent than thrombosis, are mainly related to an alteration of primary haemostasis and are therefore manifested by mucocutaneous bleeding. In these patients, platelet dysfunctions and/or acquired Willebrand syndromes can be found. The pathophysiology of thrombosis and platelet dysfunction during myeloproliferative neoplasms remains to date partially unknown. In this review, we offer to focus on physiopathological mechanisms as well as the latest advances in their understanding.     

Polyglobulie rare par mutation du gène EGLN1 : à propos d’un cas et revue de la littérature

IntroductionThe origin of polycythemia is often simple to detect. Sometimes it is necessary to look for hereditary forms, the decisive parameters being the dosage of erythropoietin and the measurement of the oxygen dissociation curve (P50). These rare diseases are related to high oxygen-affinity haemoglobins, abnormalities of the erythropoietin receptor or dysfunction of the HIF (hypoxia-inducible factor) pathway.Case reportWe report the case of a 56-year-old patient with unexplained polycythemia associated with normal serum erythropoietin and normal P50, in whom the never previously described mutation c.400C>T (p.Gln134*) on exon 1 in the EGLN1 gene (encoding PHD2) was found.ConclusionIn the face of an unexplained polycythemia a good cooperation between clinicians and biologists is necessary to be able to characterize rare hereditary pathologies.     

老年糖尿病患者维生素D与握力和肌肉质量相关性研究

目的研究老年2型糖尿病(type 2 diabetes mellitus,T2DM)患者维生素D水平与肌肉质量和握力的相关性。方法选取2016年5月至2018年1月入住宣武医院内分泌科年龄≥60岁的2型糖尿病患者201例进行前瞻性研究,根据25羟维生素D[25-hydroxyvitamin D,25(OH)D]水平分为维生素D缺乏组[25(OH)D<20μg/L]140例和非缺乏组[20μg/L≤25)(OH)D<70μg/L]61例,测定患者握力、步速及上下肢肌肉质量。并进行体格检查和实验室检查。结果两组患者实验室各项指标比较差异均无统计学意义(P均>0.05)。维生素D非缺乏组患者的握力、上肢及下肢肌肉含量显著高于缺乏组[(33.49±9.43)kg与(29.59±10.30)kg、(4.99±1.09)kg与(4.57±1.11)kg、(15.69±3.10)kg与(14.54±3.03)kg,P值分别为0.010、0.015、0.017]。多因素Logistic回归分析显示维生素D缺乏与握力减低及下肢肌肉质量下降独立相关(OR=1.286,95%CI:1.197~1.346,P<0.01;OR=1.231,95%CI:1.102~1.283,P<0.05)。结论维生素D缺乏是老年2型糖尿病患者握力减低及下肢肌肉质量下降的危险因素。     

Simultaneous Endocardial and Epicardial Delineation of 3D Reentrant Ventricular Tachycardia

BackgroundMechanisms of scar-related ventricular tachycardia (VT) are largely based on computational and animal models that portray a 2-dimensional view.ObjectivesThe authors sought to delineate the human VT circuit with a 3-dimensional perspective from recordings obtained by simultaneous endocardial and epicardial mapping.MethodsHigh-resolution mapping was performed during 97 procedures in 89 patients with structural heart disease. Circuits were characterized by systematic isochronal analysis to estimate the dimensions of the isthmus and extent of the exit region recorded on both myocardial surfaces.ResultsA total of 151 VT morphologies were mapped, of which 83 underwent simultaneous endocardial and epicardial mapping; 17% of circuits activated in a 2-dimensional plane, restricted to 1 myocardial surface. Three-dimensional activation patterns with nonuniform transmural propagation were observed in 61% of circuits with only 4% showing transmurally uniform activation, and 18% exhibiting focal activation patterns consistent with mid-myocardial reentry. The dimensions of the central isthmus were 17 mm (12 to 28 mm) × 10 mm (9 to 19 mm) with 55% exhibiting a minimal dimension of <1.5 cm. QRS activation was transmural in 63% and located 43 mm (34 to 52 mm) from the central isthmus. On the basis of 6 proposed definitions for epicardial VT, the prevalence of an epicardial circuit ranged from 21% to 80% in ischemic cardiomyopathy and 28% to 77% in nonischemic cardiomyopathy.ConclusionsA 2D perspective oversimplifies the electrophysiological circuit responsible for reentrant human VT and simultaneous endocardial and epicardial mapping facilitates inferences about mid-myocardial activation. Intricate activation patterns are frequently observed on both myocardial surfaces, and the epicardium is functionally involved in the majority of circuits. Human reentry may exist within isthmus dimensions smaller than 1 cm, whereas QRS activation is often transmural and remote from the critical isthmus target. A 3-dimensional perspective of the VT circuit may enhance the precision of ablative therapy and may support a greater role for adjunctive strategies and technology to address arrhythmogenic tissue harbored in the mid-myocardium and subepicardium.     

The three faces of takotsubo cardiomyopathy in a single patient

While the classical apical ballooning takotsubo cardiomyopathy (TC) was first reported in the 1990s, the rarer mid-ventricular and basal variants were not formally recognized until recently and they remain poorly understood. In this case report, we describe a 67-year-old woman who, during her hospitalization for a subarachnoid hemorrhage and subsequent readmission, experienced multiple complications, each of which resulted in a different variant of TC. To our knowledge, this is the first report of a single patient developing all three variants of TC.     

Melatonin recovers sleep phase delayed by MK-801 through the melatonin MT2 receptor- Ca2+-CaMKII-CREB pathway in the ventrolateral preoptic nucleus

Melatonin (MLT) is widely used to treat sleep disorders although the underlying mechanism is still elusive. In mice, using wheel-running detection, we found that exogenous MLT could completely recover the period length prolonged by N-methyl-D-aspartate receptor (NMDAR) impairment due to the injection of the NMDAR antagonist MK-801, a preclinical model of psychosis. The analysis of the possible underlying mechanisms indicated that MLT could regulate the homeostatic state in the ventrolateral preoptic nucleus (VLPO) instead of the circadian process in the suprachiasmatic nucleus (SCN). In addition, our data showed that MK-801 decreased Ca²⁺-related CaMKII expression and CREB phosphorylation levels in the VLPO, and MLT could rescue these intracellular impairments but not NMDAR expression levels. Accordingly, Gcamp6 AAV virus was injected in-vivo to further monitor intracellular Ca²⁺ levels in the VLPO, and MLT demonstrated a unique ability to increase Ca²⁺ fluorescence compared with MK-801-injected mice. Additionally, using the selective melatonin MT₂ receptor antagonist 4-phenyl-2-propionamidotetralin (4P-PDOT), we discovered that the pharmacological effects of MLT upon NMDAR impairments were mediated by melatonin MT₂ receptors. Using electroencephalography/electromyography (EEG/EMG) recordings, we observed that the latency to the first nonrapid eye movement (NREM) sleep episode was delayed by MK-801, and MLT was able to recover this delay. In conclusion, exogenous MLT by acting upon melatonin MT₂ receptors rescues sleep phase delayed by NMDAR impairment via increasing intracellular Ca²⁺ signaling in the VLPO, suggesting a regulatory role of the neurohormone on the homeostatic system.