Efficacy and Safety of New B Cell-Targeted Biologic Agent for the Treatment of Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis

Background: B cells are central to the pathogenesis of systemic lupus erythematosus (SLE). We aimed to analyze the efficacy and safety of new B cell-targeted drug therapies for SLE. Methods: A systematic review of randomized controlled trials (RCTs) and reference lists of relevant articles published from inception to 2022 were selected from PubMed, Scopus andWeb of Science databases. Random effects meta-analyses were performed to estimate an overall effect size for the risk of adverse events (AEs) and serious adverse events (SAEs) with belimumab and tabalumab treatment. Heterogeneity was assessed using the I2 statistic and meta-regression. Funnel asymmetry was evaluated using Egger’s test. Results: This study included 13 RCTs, of which three showed high risk of bias. Egger’s test showed no asymmetry. The risk of SAEs and AEs was lower in the treatment group with belimumab treatment. The risk of AEs for tabalumab treatment was lower in the treatment group and lower for SAEs. Conclusion: Belimumab and tabalumab therapies are effective and safe in the treatment of SLE, although tabalumab does not show sufficient statistical power. Advances in understanding the underlying mechanisms of SLE will be directed towards correlating clinical manifestations with specific pathogenic pathways and the development of precision medicine

Post-fire Management Effects on Sediment (Dis)Connectivity in Mediterranean Forest Ecosystems: Channel and Catchment Response

[Abstract] Forest fires and post-fire practices influence sediment connectivity (SC). In this study, we use the ‘aggregated index of connectivity’ (AIC) to assess SC in five Mediterranean catchments (198–1090 ha) affected by a wildfire in 2012 in south-eastern Spain. Two temporal scenarios were considered, immediately after the fire and before post-fire management, and 2 years after the fire including all practices (hillslope barriers, check-dams, afforestation, salvage logging and skid trails). One LiDAR (light detection and ranging)-derived digital elevation model (DEM, 2 m × 2 m resolution) was generated, per scenario. The five catchment outlets were established as the computation target (AICоᴜᴛ), and structural and functional SC were calculated. Index outputs were normalized to make the results of the non-nested catchments comparable (AICɴ₋оᴜᴛ). The output analysis includes the SC distribution along the catchments and at local scale (929 sub-catchments, 677 in the burned area), the hillslope and channel measures' effect on SC, and a sedimentological analysis using observed area-specific sediment yield (SSY) at 10 new (built after post-fire practices) concrete check-dams located in the catchments (SSY = 1.94 Mg ha⁻¹ yr⁻¹; σ = 1.22). The catchments with more circular shapes and steeper slopes were those with higher AICɴ₋оᴜᴛ. The structural SC maps – removing the rainfall erosivity influence – allowed evaluating the actual role played by the post-fire practices that reduced SC (x̅ = − 1.19%; σ = 0.41); while functional SC was linked to the actual change of SC (x̅ = + 5.32%; σ = 0.62). Hillslope treatments resulted in significant changes on AICɴ₋оᴜᴛ at sub-catchment scale with certain disconnectivity. A good and positive correlation was found between the SSY and the changes of AICɴ₋оᴜᴛ. However, the coarse DEM resolution explained the lack of effect of the rock check-dams – located on the secondary channels – on AICɴ₋оᴜᴛ. AICɴ₋оᴜᴛ proved to be a useful tool for decision making in post-fire restoration, but an optimal input data is still necessary to refine calculations.European Cooperation in Science and Technology; CA18135Gobierno de Castilla-la Mancha; Sbply/16/180501/ 000109This study was supported by funds provided to the VIS4FIRE Spanish R&D project (RTA2017-00042-C05-00) co-funded by the “Instituto Nacional de Investigación y Tecnología Agraria” (INIA) and FEDER programme. This study was done in the frame of the European Cooperation in Science and Technology (COST) action CA18135 ‘FIRElinks’ (Fire in the Earth System:Science & Society). J. González-Romero holds a scholarship (Sbply/16/180501/000109) from the Regional Government of Castilla-La Mancha/European Social Fund (ESF, EU)

Post-fire Management Effects on Hillslope-Stream Sediment Connectivity in a Mediterranean Forest Ecosystem

[Abstract] Forest fires intensify sediment transport and aggravate local and off-site consequences of soil erosion. This study evaluates the influence of post-fire measures on structural and functional sediment connectivity (SC) in five fire-affected Mediterranean catchments, which include 929 sub-catchments, by using the “aggregated index of connectivity” (AIC) at two temporal scenarios: I) immediately after the fire and before implementing post-fire practices (‘Pre-man’), and II) two years after the fire (‘Post-man’). The latter includes all the emergency stabilization practices, that are hillslope barriers, check-dams and afforestation. The stream system was set as the target of the computation (STR), to be representative of intense rainfall-runoff events with effective sediment delivery outside the catchments. Output normalization (AICN) allows comparing the results of the five basins between them. The sedimentological analysis is based on specific sediment yield (SSY) –measured at the check-dams installed after the fire –, and this data is used for output evaluation. Stream density and slope variables were the most influential factors on AICN-STR results at the sub-catchment scale. Post-fire hillslope treatments (barriers when built in high densities and afforestation) significantly reduced AICN-STR in comparison with untreated areas in both structural and functional approaches. Despite the presence of hillslope treatments, the higher erosive rainfall conditions resulted in higher AICN-STR values in the Post-man scenario (functional approach). A positive and good correlation was found between the measured SSY and the AICN-STR changes due to the post-fire practices and vegetation recovery, showing the good correspondence of the computation results and the real sediment dynamics of the studied catchments. Overall, AICN demonstrated to be a useful and versatile tool for post-fire management, which needs further research to optimize its applicability.The authors thank the Regional Government of Castilla-La Mancha (Junta de Comunidades de Castilla-La Mancha) for supporting the study and providing information about the undertaken measures in the burned area. This study was supported by funds provided to the VIS4FIRE Spanish R&D project (RTA 2017-00042-C05-00) co-funded by the “Instituto Nacional de Investigación y Tecnología Agraria” (INIA) and FEDER programme. This study was done in the frame of the European Cooperation in Science and Technology (COST) action CA18135 ‘FIRElinks’ (Fire in the Earth System: Science & Society). J. González-Romero holds a postdoctoral contract supported by the European Social Fund (ESF, EU). The authors declare no conflict of interest. E. Peña holds a scholarship (2020-PREUCLM-16032) from the UCLM and the European Social Fund (FSE). Pedro Antonio Plaza Álvarez holds a predoctoral fellowship from the Spanish Ministry of Education, Culture and Sport (FPU16/03296)Universidad de Castilla-La Mancha; 2020-PREUCLM-1603

Kinetics of immune responses elicited after three mRNA COVID-19 vaccine doses in predominantly antibody-deficient individuals

Mass vaccination campaigns reduced COVID-19 incidence and severity. Here, we evaluated the immune responses developed in SARS-CoV-2-uninfected patients with predominantly antibody-deficiencies (PAD) after three mRNA-1273 vaccine doses. PAD patients were classified based on their immunodeficiency: unclassified primary antibody-deficiency (unPAD, n = 9), common variable immunodeficiency (CVID, n = 12), combined immunodeficiency (CID, n = 1), and thymoma with immunodeficiency (TID, n = 1). unPAD patients and healthy controls (HCs, n = 10) developed similar vaccine-induced humoral responses after two doses. However, CVID patients showed reduced binding and neutralizing titers compared to HCs. Of interest, these PAD groups showed lower levels of Spike-specific IFN-γ-producing cells. CVID individuals also presented diminished CD8+T cells. CID and TID patients developed cellular but not humoral responses. Although the third vaccine dose boosted humoral responses in most PAD patients, it had limited effect on expanding cellular immunity. Vaccine-induced immune responses in PAD individuals are heterogeneous, and should be immunomonitored to define a personalized therapeutic strategies.info:eu-repo/semantics/publishedVersio

Penetrance of Dilated Cardiomyopathy in Genotype-Positive Relatives

BACKGROUND Disease penetrance in genotype -positive (G+) relatives of families with dilated cardiomyopathy (DCM) and the characteristics associated with DCM onset in these individuals are unknown. OBJECTIVES This study sought to determine the penetrance of new DCM diagnosis in G+ relatives and to identify factors associated with DCM development. METHODS The authors evaluated 779 G+ patients (age 35.8 +/- 17.3 years; 459 [59%] females; 367 [47%] with variants in TTN ) without DCM followed at 25 Spanish centers. RESULTS After a median follow-up of 37.1 months (Q1 -Q3: 16.3-63.8 months), 85 individuals (10.9%) developed DCM (incidence rate of 2.9 per 100 person -years; 95% CI: 2.3-3.5 per 100 person -years). DCM penetrance and age at DCM onset was different according to underlying gene group (log -rank P = 0.015 and P <0.01, respectively). In a multivariable model excluding CMR parameters, independent predictors of DCM development were: older age (HR per 1 -year increase: 1.02; 95% CI: 1.0-1.04), an abnormal electrocardiogram (HR: 2.13; 95% CI: 1.38-3.29); presence of variants in motor sarcomeric genes (HR: 1.92; 95% CI: 1.05-3.50); lower left ventricular ejection fraction (HR per 1% increase: 0.86; 95% CI: 0.82-0.90) and larger left ventricular end -diastolic diameter (HR per 1 -mm increase: 1.10; 95% CI: 1.06-1.13). Multivariable analysis in individuals with cardiac magnetic resonance and late gadolinium enhancement assessment (n = 360, 45%) identi fied late gadolinium enhancement as an additional independent predictor of DCM development (HR: 2.52; 95% CI: 1.43-4.45). CONCLUSIONS Following a first negative screening, approximately 11% of G+ relatives developed DCM during a median follow-up of 3 years. Older age, an abnormal electrocardiogram, lower left ventricular ejection fraction, increased left ventricular end -diastolic diameter, motor sarcomeric genetic variants, and late gadolinium enhancement are associated with a higher risk of developing DCM. (J Am Coll Cardiol 2024;83:1640 -1651) (c) 2024 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies

BACKGROUND: Filamin C (encoded by the FLNC gene) is essential for sarcomere attachment to the plasmatic membrane. FLNC mutations have been associated with myofibrillar myopathies, and cardiac involvement has been reported in some carriers. Accordingly, since 2012, the authors have included FLNC in the genetic screening of patients with inherited cardiomyopathies and sudden death. OBJECTIVES: The aim of this study was to demonstrate the association between truncating mutations in FLNC and the development of high-risk dilated and arrhythmogenic cardiomyopathies. METHODS: FLNC was studied using next-generation sequencing in 2,877 patients with inherited cardiovascular diseases. A characteristic phenotype was identified in probands with truncating mutations in FLNC. Clinical and genetic evaluation of 28 affected families was performed. Localization of filamin C in cardiac tissue was analyzed in patients with truncating FLNC mutations using immunohistochemistry. RESULTS: Twenty-three truncating mutations were identified in 28 probands previously diagnosed with dilated, arrhythmogenic, or restrictive cardiomyopathies. Truncating FLNC mutations were absent in patients with other phenotypes, including 1,078 patients with hypertrophic cardiomyopathy. Fifty-four mutation carriers were identified among 121 screened relatives. The phenotype consisted of left ventricular dilation (68%), systolic dysfunction (46%), and myocardial fibrosis (67%); inferolateral negative T waves and low QRS voltages on electrocardiography (33%); ventricular arrhythmias (82%); and frequent sudden cardiac death (40 cases in 21 of 28 families). Clinical skeletal myopathy was not observed. Penetrance was >97% in carriers older than 40 years. Truncating mutations in FLNC cosegregated with this phenotype with a dominant inheritance pattern (combined logarithm of the odds score: 9.5). Immunohistochemical staining of myocardial tissue showed no abnormal filamin C aggregates in patients with truncating FLNC mutations. CONCLUSIONS: Truncating mutations in FLNC caused an overlapping phenotype of dilated and left-dominant arrhythmogenic cardiomyopathies complicated by frequent premature sudden death. Prompt implantation of a cardiac defibrillator should be considered in affected patients harboring truncating mutations in FLNC.Instituto de Salud Carlos III [PI11/0699, PI14/0967, PI14/01477, RD012/0042/0029, RD012/0042/0049, RD012/0042/0066, RD12/0042/0069]; Spanish Ministry of Economy and Competitiveness [SAF2015-71863-REDT]; Plan Nacional de I+D+I; Plan Estatalde I+D+I, European Regional Development Fund; Health in Code SLS

Excavaciones arqueológicas en la Cañada Honda de Itálica (Santiponce, Sevilla). Primeros resultados.

En este artículo presentamos el resumen de los resultados de la excavación arqueológica desarrollada en la Cañada Honda de Itálica entre los años 2017 y 2019. Gracias a esta actividad se ha podido excavar parte de la crujía que conforma la cabecera de la domus del mismo nombre, abordando también la documentación y análisis arqueológico de las estructuras que hasta ahora se encontraban a la vista, resultado de excavaciones previas a nuestra intervención. Como resultado de los trabajos efectuados se han identificado tres nuevos espacios de la vivienda, situados en la cabecera del edificio: el triclinium y dos patios adyacentes al mismo. Igualmente, los nuevos datos estratigráficos aportados por la excavación han permitido ajustar la datación del abandono de la casa, que situamos en la segunda mitad del s. III d.C., momento a partir del cual se produce el expolio y derrumbe del edificio. Por su parte, de las tabernae que se disponen en dos de los laterales de la casa, al memos una de ellas se mantienen en uso hasta el s. V d.C., experimentando distintas reformas.Este trabajo es resultado del Proyecto de Inves­tigación I+D «La creación y trasmisión de mode­los adrianeos en el Mediterráneo. Villa Adriana y la Bética» (FEDER UPO­1266148), concedido por la Consejería de Economía, Conocimiento, Empresas y Universidad de la Junta de Andalucía/Unión Eu­ropea (2020­2022)

Científicas españolas: un mundo por descubrir

Objetivos: La Unión Europea sugiere, entre otros puntos, que la formación universitaria sea complementada con los avances que se vayan produciendo en la investigación científica y, además, pone un especial énfasis en la digitalización de contenidos y en la difusión a través de internet en la Educación Superior. Por ello, el objetivo del proyecto llevado a cabo fue realizar una actividad en la que los alumnos entrevistaran a una mujer científica española que trabajara en alguno de los temas estudiados en clases e ir creando un blog, vinculado a Facebook, con las entrevistas realizadas. De esta forma, además de dar visibilidad a las científicas de nuestro país, ya que en muchos casos la mujer está infravalorada por la sociedad en el ámbito científico, se pretendía conseguir la participación activa del alumnado y favorecer y fomentar su aprendizaje activo, desarrollar la capacidad del alumno de profundizar en un tema de investigación y de plantearse y de que tomaran conciencia del relevante nivel científico que existe en nuestro país y, en concreto, de la importancia que tienen las mujeres. Metodología: Se propuso la actividad a alumnos de 5 Grados diferentes (Farmacia, Doble Grado de Nutrición y Dietética, Ciencia y Tecnología de los Alimentos, Terapia Ocupacional y Óptica y Optometría). Los alumnos interesados en participar formaron grupos de trabajo y eligieron el tema sobre el que querían trabajar del listado propuesto por los profesores. Buscaron una mujer científica española de reconocido prestigio que trabajara en el tema elegido y, después de comunicárselo al profesor, se pusieron en contacto con ella para solicitarles la realización de la entrevista. Una vez que esta accedía a su realización, los alumnos prepararon un dossier de preguntas basándose en los trabajos publicados de la misma, y, tras ser supervisado y corregido por el profesor, eran formuladas a la científica elegida. Una vez realizada la entrevista, los alumnos redactaron un artículo y tras su revisión por el profesor, se hacía público en el blog. Para dar mayor visibilidad al blog, se creó una cuenta abierta de Facebook en la que se iba vinculando el mismo. Al final de todo el proceso se realizó una valoración de la actividad global por parte de los alumnos mediante una encuesta de opinión tipo Likert. Resultados: Se ofertó la actividad a 581 alumnos y participaron 195 (33,6%). Con la actividad propuesta se ha conseguido la participación activa de un porcentaje considerable del alumnado, destacando en los Grados de CYTA (78,4%), Doble Grado de Farmacia y Nutrición (72,3%) y Farmacia (24,1%). Dentro de los que participaron en la actividad, el porcentaje de aprobados fue mayor que el de suspensos (78 vs. 22%; p<0,05, respectivamente). Por otra parte, la valoración otorgada a la actividad fue bastante buena (3,8 sobre 5 puntos), aunque muchos estudiantes manifestaron que les llevó bastante tiempo su realización. Por último, según los alumnos, la actividad les hizo tomar conciencia del alto nivel científico de muchas científicas españolas (4,5 puntos sobre 5)

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 +/- 19.2 years) recruited from 29 international centers. RESULTS At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% +/- 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of <= 35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe