Characterization of the plasma proteomic profile of Fabry disease: Potential sex- and clinical phenotype-specific biomarkers.

Fabry disease (FD) is a X-linked rare lysosomal storage disorder caused by deficient α-galactosidase A (α-GalA) activity. Early diagnosis and the prediction of disease course are complicated by the clinical heterogeneity of FD, as well as by the frequently inconclusive biochemical and genetic test results that do not correlate with clinical course. We sought to identify potential biomarkers of FD to better understand the underlying pathophysiology and clinical phenotypes. We compared the plasma proteomes of 50 FD patients and 50 matched healthy controls using DDA and SWATH-MS. The >30 proteins that were differentially expressed between the 2 groups included proteins implicated in processes such as inflammation, heme and haemoglobin metabolism, oxidative stress, coagulation, complement cascade, glucose and lipid metabolism, and glycocalyx formation. Stratification by sex revealed that certain proteins were differentially expressed in a sex-dependent manner. Apolipoprotein A-IV was upregulated in FD patients with complications, especially those with chronic kidney disease, and apolipoprotein C-III and fetuin-A were identified as possible markers of FD with left ventricular hypertrophy. All these proteins had a greater capacity to identify the presence of complications in FD patients than lyso-GB3, with apolipoprotein A-IV standing out as being more sensitive and effective in differentiating the presence and absence of chronic kidney disease in FD patients than renal markers such as creatinine, glomerular filtration rate and microalbuminuria. Identification of these potential biomarkers can help further our understanding of the pathophysiological processes that underlie the heterogeneous clinical manifestations associated with FD.

[Effectiveness of the EQ-5D and CRES-4 questionnaire for assessing the impact on the quality of life of patients and the level of satisfaction after exchanging dicumarinics for edoxabán: Real-life experience based on a multicentre study]. / Utilidad del cuestionario EQ-5D y CRES-4 para la valoración de la calidad de vida y grado de satisfacción tras el cambio de dicumarínicos por edoxabán: experiencia vida real de un estudio multicéntrico.

BACKGROUND AND OBJECTIVE: Atrial fibrillation and anticoagulation decrease the quality of life of patients. The aim of this study is to assess the quality of life and the degree of satisfaction after changing from VKA to edoxaban anticoagulants. MATERIAL AND METHODS: Prospective, multicentre study, including 105 patients in dicumarinic anticoagulant treatment replaced by edoxaban. Their quality of life was evaluated before and after using the EQ-5D questionnaire, and the degree of satisfaction with CRES-4 scale. RESULTS: Average 75 years, CHA2DS2VASC3,5 and HASBLED2,1; thromboembolic events and clinically relevant bleeding during follow-up <1%. EQ-5D showed a significant overall improvement in the mobility and anxiety parameters (P=.023, 95%CI: .0175-.23; P=.019, 95%CI:=.028-.31). The CRES-4 questionnaire showed satisfaction with the therapist of 95%, a positive impact on life of 73% and a negative impact of 3.8%. The emotional state attributed to the change in treatment improved (41% vs 69.5%, P=.0001). The final score of the CRES-4 weakly correlated with the emotional situation of the EQ-5D questionnaire. CONCLUSIONS: The change of anticoagulant for edoxaban improves the quality of life and the degree of patient satisfaction, and the EQ-5D and CRES-4 quality of life questionnaires can be used complementarily.

Severe thrombocytopenia induced by iodinated contrast after coronary angiography: The use of gadolinium contrast and intravascular ultrasound as an alternative to guide percutaneous coronary intervention.

Acute contrast-induced thrombocytopenia is a rare event with the use of modern low osmolarity iodinated contrast media. The pathophysiological mechanism that causes platelet counts to drop has not been identified, but an immunological mechanism is suspected due to cytotoxicity after previous exposure to contrast. We report the case of a 47-year-old male patient with acute severe thrombocytopenia due to iodinated contrast media exposure. His platelet count after the procedure with the highest amount of contrast was zero, which is the lowest reported platelet count to date. Percutaneous coronary revascularization under both intravascular ultrasound and gadolinium contrast guidance was performed without complications. The most feared complication after the use of gadolinium is nephrogenic systemic fibrosis, especially in patients on hemodialysis.

Idiopathic Paroxysmal Atrio-Ventricular Block. What is The Mechanism?

Idiopathic paroxysmal atrioventricular (AV) block poses a true diagnostic challenge. What is clear about this entity is the confusion about its definition and consequently about its etiology. According to certain sources, the diagnosis of this block requires the lack of a structural cardiac pathology that justifies the observed manifestations and an absence of electrocardiographic disorders prior to an episode. The clinical presentation of idiopathic paroxysmal AV block does not differ from that of another cardiogenic syncope or of a vasovagal syncope with a significant cardioinhibitory component. With respect to the mechanism that explains this block, it has been postulated that patients with low basal adenosine levels exhibit hyperaffinity of the A2 receptors of the AV node. Variations in plasma adenosine levels may favor episodes of paroxysmal AV block. The diagnosis of this block is complex and can require years to determine. Routine electrophysiological examination of these patients is not cost effective due to the low sensitivity and specificity of this approach. Numerous groups have supported the use of an implantable loop recorder to substantiate AV block paroxysms and assess their clinical correlations. Permanent stimulation devices are utilized to reduce syncopal recurrence.