Relationship Between Glucocerebrosidase Activity and Clinical Response to Enzyme Replacement Therapy in Patients With Gaucher Disease Type I

The quantification of enzyme activity in the patient treated with enzyme replacement therapy (ERT) has been suggested as a tool for dosage individualization, so we conducted a study to evaluate the relationship between glucocerebrosidase activity and clinical response in patients with Gaucher disease type I (GD1) to ERT. The study included patients diagnosed with GD1, who were being treated with ERT, and healthy individuals. Markers based on glucocerebrosidase activity measurement in patients’ leucocytes were studied: enzyme activity at 15 min. post-infusion (Act75) reflects the amount of enzyme that is distributed in the body post-ERT infusion, and accumulated glucocerebrosidase activity during ERT infusion (Act75-0) indicates the total drug exposure during infusion. The clinical response was evaluated based on criteria established by Pastores et al. and Gaucher Severity Score Index. Statistical analysis included ROC analysis and area under the curve test. Act75 and Act75-0 were found to be moderate predictive markers of an optimal clinical response (area under the ROC of Act75 was 0.733 and Act75-0 was 0.817). Act75-0 showed statistical significance in its discriminative capacity (p < 0.05) for obtaining an optimal response to ERT. The cut-off point was 58% (RR = 1.800; 95% CI: 1.003–3.229; p < 0.05). Moreover, Act75 showed a significant and inverse correlation with the Gaucher Severity Score Index, and Act75 and Act75-0 presented a significant correlation with residual enzyme activity at diagnosis. Markers based on glucocerebrosidase activity have a good correlation with clinical response to ERT. Therefore, it could provide supporting clinical data for dose management in GD1 patients

Estimation of Admission D-dimer Cut-off Value to Predict Venous Thrombotic Events in Hospitalized COVID-19 Patients: Analysis of the SEMI-COVID-19 Registry

Background: Venous thrombotic events (VTE) are frequent in COVID-19, and elevated plasma D-dimer (pDd) and dyspnea are common in both entities. Objective: To determine the admission pDd cut-off value associated with in-hospital VTE in patients with COVID-19. Methods: Multicenter, retrospective study analyzing the at-admission pDd cut-off value to predict VTE and anticoagulation intensity along hospitalization due to COVID-19. Results: Among 9386 patients, 2.2% had VTE: 1.6% pulmonary embolism (PE), 0.4% deep vein thrombosis (DVT), and 0.2% both. Those with VTE had a higher prevalence of tachypnea (42.9% vs. 31.1%; p = 0.0005), basal O2 saturation <93% (45.4% vs. 33.1%; p = 0.0003), higher at admission pDd (median [IQR]: 1.4 [0.6–5.5] vs. 0.6 [0.4–1.2] µg/ml; p < 0.0001) and platelet count (median [IQR]: 208 [158–289] vs. 189 [148–245] platelets × 109/L; p = 0.0013). A pDd cut-off of 1.1 µg/ml showed specificity 72%, sensitivity 49%, positive predictive value (PPV) 4%, and negative predictive value (NPV) 99% for in-hospital VTE. A cut-off value of 4.7 µg/ml showed specificity of 95%, sensitivity of 27%, PPV of 9%, and NPV of 98%. Overall mortality was proportional to pDd value, with the lowest incidence for each pDd category depending on anticoagulation intensity: 26.3% for those with pDd >1.0 µg/ml treated with prophylactic dose (p < 0.0001), 28.8% for pDd for patients with pDd >2.0 µg/ml treated with intermediate dose (p = 0.0001), and 31.3% for those with pDd >3.0 µg/ml and full anticoagulation (p = 0.0183). Conclusions: In hospitalized patients with COVID-19, a pDd value greater than 3.0 µg/ml can be considered to screen VTE and to consider full-dose anticoagulation. © 2021, Society of General Internal Medicine

Overview of guidelines for the management of dyslipidemia: EU perspectives

Vicente Giner-Galvañ,1 María José Esteban-Giner,1 Vicente Pallarés-Carratalá2,3 1Department of General Internal Medicine, Unit of Hypertension and Cardiometabolic Risk, Hospital Mare de Déu dels Lliris, Alcoy, Alicante, 2Department of Health Surveillance, Unión de Mutuas, Castellón de la Plana, 3Department of Medicine, Universitat Jaume I, Castellón, Spain Abstract: Modern medicine is characterized by a continuous genesis of evidence making it very difficult to translate the latest findings into a better clinical practice. Clinical practice guidelines (CPG) emerge to provide clinicians evidence-based recommendations for their daily clinical practice. However, the high number of existing CPG as well as the usual differences in the given recommendations usually increases the clinician’s confusion and doubts. It has apparently been the case for the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Guideline on the Treatment of Blood Cholesterol. These CPG proposed new and controversial concepts that have usually been considered an antagonist shift respective to European CPG. The most controversial published proposals are: 1) to consider evidence just from randomized clinical trials, 2) creation of a new cardiovascular (CV) risk calculator, 3) to consider reducing CV risk instead of reducing low-density lipoprotein cholesterol (LDLc) as the target of the treatment, and 4) consideration of statins as the only drugs for treatment. A deep analysis of the 2013 American College of Cardiology/American Heart Association CPG and comparison with the European ones show that from a practical and clinical point of view, there are more similarities than differences. To further help clinicians in their daily work, in the present globalized world, it is time to discuss and adopt a mutually agreed upon document created by both sides of the Atlantic. Probably it is not a short-term solution. Meanwhile, taking advantage of the similarities, the recommended practical attitude for the daily clinical practice should be based on 1) early detection of people with increased CV risk promoting the use of validated local scales, 2) reinforce the mainstream importance of nonpharmacological treatment, and 3) need for periodically monitoring response with analytical parameters (LDL or non-high-density lipoprotein cholesterol) and global CV risk estimation. Technological solutions such as the big data technology could help to obtain high-quality evidence in an intermediate term. Keywords: dyslipidemia, statins, cardiovascular risk, clinical practice guideline