Proof of concept of a new plasma complement Factor H from waste plasma fraction.

Introduction: Complement factor H (FH) is a major regulator of the complement alternative pathway, its mutations predispose to an uncontrolled activation in the kidney and on blood cells and to secondary C3 deficiency. Plasma exchange has been used to correct for FH deficiency and although the therapeutic potential of purified FH has been suggested by in vivo experiments in animal models, a clinical approved FH concentrate is not yet available. We aimed to develop a purification process of FH from a waste fraction rather than whole plasma allowing a more efficient and ethical use of blood and plasma donations. Methods: Waste fractions from industrial plasma fractionation (pooled human plasma) were analyzed for FH content by ELISA. FH was purified from unused fraction III and its decay acceleration, cofactor, and C3 binding capacity were characterized in vitro. Biodistribution was assessed by high-resolution dynamic PET imaging. Finally, the efficacy of the purified FH preparation was tested in the mouse model of C3 glomerulopathy (Cfh-/- mice). Results: Our purification method resulted in a high yield of highly purified (92,07%), pathogen-safe FH. FH concentrate is intact and fully functional as demonstrated by in vitro functional assays. The biodistribution revealed lower renal and liver clearance of human FH in Cfh-/- mice than in wt mice. Treatment of Cfh-/- mice documented its efficacy in limiting C3 activation and promoting the clearance of C3 glomerular deposits. Conclusion: We developed an efficient and economical system for purifying intact and functional FH, starting from waste material of industrial plasma fractionation. The FH concentrate could therefore constitute possible treatments options of patients with C3 glomerulopathy, particularly for those with FH deficiency, but also for patients with other diseases associated with alternative pathway activation.

Venous Thromboembolism Management throughout the COVID-19 Era: Addressing Acute and Long-Term Challenges.

Background: COVID-19 increases the risk of venous thromboembolism (VTE) through a complex interplay of mechanisms collectively referred to as immunothrombosis. Limited data exist on VTE challenges in the acute setting throughout a dynamic long-term follow-up of COVID-19 patients compared to non-COVID-19 patients. The aim of the study was to investigate acute and long-term management and complications in VTE patients with and without COVID-19. Methods: A prospective, observational, single-center cohort study on VTE patients followed from the acute care stage until 24 months post-diagnosis. Results: 157 patients, 30 with COVID-19-associated VTE and 127 unrelated to COVID-19, were enrolled. The mean follow-up was 10.8 (±8.9) months. COVID-19 patients had fewer comorbidities (1.3 ± 1.29 vs. 2.26 ± 1.68, p < 0.001), a higher proportion of pulmonary embolism at baseline (96.7% vs. 76.4%, p = 0.01), and had a lower probability of remaining on anticoagulant therapy after three months (p < 0.003). The most used initial therapy was low-molecular-weight heparin in 130/157 cases, followed by long-term treatment with direct oral anticoagulants in 123/157. Two (6.7%) COVID-19 vs. three (2.4%) non-COVID-19 patients (p = 0.243) had major hemorrhagic events, all of them within the first three months. Four (3.1%) non-COVID-19 patients had VTE recurrence after six months. Three (2.4%) non-COVID-19 patients developed chronic thromboembolic pulmonary hypertension. There were no fatalities among patients with COVID-19, compared to a mortality of 12/127 (9.4%) in the non-COVID-19 subgroup (p = 0.027). Discussion: Our study offers a comprehensive overview of the evolving nature of VTE management, emphasizing the importance of personalized risk-based approaches, including a limited course of anticoagulation for most COVID-19-associated VTE cases and reduced-dose extended therapy for high-risk subsets.

Fundamentos y métodos de las revisiones sistemáticas / Fundamentals and method of systematic reviews

Las revisiones sistemáticas (RS) son síntesis cualitativas y, a veces, cuantitativas sobre la evidencia disponible respecto de un tema puntual. Este trabajo contextualiza su origen en el movimiento de la medicina basada en la evidencia y las define como un tipo de investigación orientada a identificar, valorar críticamente y sintetizar conocimiento científico previo. El método de RS se presenta aquí en una serie de fases o pasos: planteo del objetivo, búsqueda y selección de estudios, evaluación de calidad, extracción y análisis de datos, metaanálisis e interpretación de resultados. Los criterios de evaluación de la evidencia científica, un pilar fundamental de este tipo de investigación, son la validez interna, la precisión y la validez externa de los resultados. La calidad de la evidencia científica, junto con la cantidad y la consistencia, son la base sobre las cuales se pueden establecer recomendaciones. El método de RS es útil en la práctica profesional, donde se requiere el manejo de evidencia científica actualizada sobre los asuntos en los que a diario se deciden diagnósticos o intervenciones, así como un tipo de investigación que puede implementarse en grado o posgrado, ya que podría llegar a resultados originales mediante la síntesis de sus antecedentes

Systematic reviews (SR) are qualitative and, sometimes, quantitative syntheses on the available evidence regarding a specific topic. This work contextualizes its origin in the evidence-based medicine movement and defines it as a type of health research aimed to identify, critically appraise and synthesize previous scientific knowledge. The SR method is presented here in a series of steps: objective, search and selection of studies, quality assessment, data extraction and analysis, meta-analysis and interpretation of results. The internal validity, precision and external validity of the results are explained as criteria to assess the quality of the evidence. The quality of the evidence, together with the quantity and consistency, are the basis on which recommendations can be made. The SR method is useful in professional practice, where the management of up-to-date scientific evidence is required to make decisions on diagnoses or interventions daily, as well as a type of research that can be implemented in undergraduate or graduate studies, since it could arrive at original results by synthesizing the previous knowledge.