Novel Agents as Main Drivers for Continued Improvement in Survival in Multiple Myeloma

[Background]: New therapeutic strategies have improved the prognosis of multiple myeloma (MM), changing the accepted view of this disease from being incurable to treatable. [Methods]: We studied 1001 patients with MM between 1980 and 2020, grouping patients into ten-year periods by diagnosis 1980–1990, 1991–2000, 2001–2010 and 2011–2020. [Results]: After 65.1 months of follow-up, the median OS of the cohort was 60.3 months, and OS increased significantly over time: 22.4 months in 1980–1990, 37.4 months in 1991–2000, 61.8 months in 2001–2010 and 103.6 months in 2011–2020 (p 10 years of survival. [Conclusions]: The combination of novel agents appears to be the main factor for the improvement in survival in MM, which is becoming a chronic and even curable disease in a subtype of patients without high-risk features.Peer reviewe

Brain and immune system-derived extracellular vesicles mediate regulation of complement system, extracellular matrix remodeling, brain repair and antigen tolerance in Multiple sclerosis

Background: Multiple sclerosis (MS) is an immune-mediated central nervous system disease whose course is unpredictable. Finding biomarkers that help to better comprehend the disease's pathogenesis is crucial for supporting clinical decision-making. Blood extracellular vesicles (EVs) are membrane-bound particles secreted by all cell types that contain information on the disease's pathological processes. Purpose: To identify the immune and nervous system-derived EV profile from blood that could have a specific role as biomarker in MS and assess its possible correlation with disease state. Results: Higher levels of T cell-derived EVs and smaller size of neuron-derived EVs were associated with clinical relapse. The smaller size of the oligodendrocyte-derived EVs was related with motor and cognitive impairment. The proteomic analysis identified mannose-binding lectin serine protease 1 and complement factor H from immune system cell-derived EVs as autoimmune disease-associated proteins. We observed hepatocyte growth factor-like protein in EVs from T cells and inter-alpha-trypsin inhibitor heavy chain 2 from neurons as white matter injury-related proteins. In patients with MS, a specific protein profile was found in the EVs, higher levels of alpha-1-microglobulin and fibrinogen β chain, lower levels of C1S and gelsolin in the immune system-released vesicles, and Talin-1 overexpression in oligodendrocyte EVs. These specific MS-associated proteins, as well as myelin basic protein in oligodendrocyte EVs, correlated with disease activity in the patients with MS. Conclusion: Neural-derived and immune-derived EVs found in blood appear to be good specific biomarkers in MS for reflecting the disease state.This work was sponsored by a grant from Miguel Servet (CP20/00024 to Laura Otero-Ortega), Miguel Servet (CPII20/00002 to María Gutiérrez-Fernández), a predoctoral fellowship (FI18/00026 to Fernando Laso-García), a Río-Hortega grant (CM22/00065 to Gabriel Torres Iglesias and CM20/00047 to Elisa Alonso-López) and by Research Project (PI21/00918) from the Instituto de Salud Carlos III and co-funded by the European Union and by a grant CA1/RSUE/2021-00753 to Dolores Piniella funded by Ministerio de Universidades, Plan de Recuperación, Transformación y Resiliencia y la Universidad Autónoma de Madrid.S

Phage-Derived and Aberrant HaloTag Peptides Immobilized on Magnetic Microbeads for Amperometric Biosensing of Serum Autoantibodies and Alzheimer's Disease Diagnosis

An electrochemical biosensing platform for serum autoantibodies (AAbs) detection is reported in this work, exploiting for the first time six Alzheimer's disease (AD)-specific phage-derived and frameshift aberrant HaloTag peptides as receptors, immobilized on magnetic microbeads (MBs) surface and captured on disposable electrodes to perform amperometric detection. Operational analytical characteristics and clinical diagnostic ability of the bioplatform were probed in optimized key experimental conditions by analysing serum AAbs of AD patients and healthy subjects. The value of 100% obtained for AUC, sensitivity, and selectivity from the all peptides combined ROC curve, indicate full AD-diagnostic capability of the methodology, which was further implemented, as proof of concept, in a POC multiplexing platform to detect the signature in a single test over clinically actionable times (1 h 15 min), opening great promise for the type of diagnosis and AD patients’ monitoring follow-up currently pursued

Accesibilidad en los espacios públicos urbanizados

El libro, coordinado por el Director de ACCEPLAN, Fernando Alonso López, viene a ser un reflejo de los avances entorno a la búsqueda de accessibilidad universal en los espacios públicos urbanizados. Para aproximarse a la realidad normativa y técnica de la Orden Ministerial el libro se estructura en artículos referentes al contexto normativo, a los contenidos de la Orden, y a reflexiones y criterios en torno a la accesibilidad en la ciudad. Del conjunto de artículos, por su variedad y por su carácter multidiciplinar, se extrae un libro de referencia que ofrece la variedad de enfoques del tema y que ayuda a interpretar mejor la Orden Ministerial, su contribución a los objetivos de la Ley 51/2003 de Igualdad de Oportunidades No Discriminación y Accesibilidad Universal, LIONDAU, y su utilidad en la comformación de unas ciudades cada vez más abiertas a la diversidad funcional y a la convivencia.El llibre, coordinat pel director de ACCEPLAN, Fernando Alonso López, ve a ser un reflex dels avenços entorn de la recerca d'accessibilitat universal en els espais públics urbanitzats. Per conèixer un realitat normativa i tècnica de l'Ordre Ministerial el llibre s'estructura en articles referents al context normatiu, als continguts de l'Ordre, ja reflexions i criteris al voltant de l'accessibilitat a la ciutat. Del conjunt d'articles, per la seva varietat i pel seu caràcter multidiciplinar, s'extreu un llibre de referència que ofereix la varietat d'enfocaments del tema i que ajuda a interpretar millor l'Ordre Ministerial, la seva contribució als objectius de la Llei 51/2003 de Igualtat d'Oportunitats No Discriminació i Accessibilitat Universal, LIONDAU, i la seva utilitat en la comformación d'unes ciutats cada vegada més obertes a la diversitat funcional ia la convivència

Recovery of polyclonal immunoglobulins one year after autologous stem cell transplantation as a long-term predictor marker of progression and survival in multiple myeloma

Immunoparesis or suppression of polyclonal immunoglobulins is a very common condition in newly diagnosed myeloma patients. However, the recovery of polyclonal immunoglobulins in the setting of immune reconstitution after autologous stem cell transplantation and its effect on outcome has not yet been explored. We conducted this study in a cohort of 295 patients who had undergone autologous transplantation. In order to explore the potential role of immunoglubulin recovery as a dynamic predictor of progression or survival after transplantation, conditional probabilities of progression-free survival and overall survival were estimated according to immunoglobulin recovery at different time points using a landmark approach. One year after transplant, when B-cell reconstitution is expected to be completed, among 169 patients alive and progression free, 88 patients (52%) showed immunoglobulin recovery and 81 (48%) did not. Interestingly, the group with immunoglobulin recovery had a significantly longer median progression-free survival than the group with persistent immunoparesis (median 60.4 vs. 27.9 months, respectively; Hazard Ratio: 0.45, 95%Confidence Interval: 0.31–0.66;

Role of educational level in the relationship between Body Mass Index (BMI) and health-related quality of life (HRQL) among rural Spanish women

BACKGROUND: The impact of obesity on health-related quality of life (HRQL) has been little explored in rural areas. The goal of this study is to ascertain the association between obesity and HRQL among Spanish women living in a rural area, and the influence of their educational level. METHODS: Cross-sectional study with personal interview of 1298 women (aged 18 to 60) randomly selected from the electoral rolls of 14 towns in Galicia, a region in the north-west of Spain. HRQL was assessed using the SF-36 questionnaire. The association between body mass index (BMI) and suboptimal scores in the different HRQL dimensions was summarised using odds ratios (ORs), obtained from multivariate logistic regression models. Separate analyses were conducted for women who had finished their education younger than 16 years old and women with secondary education to assess differences in the relationship between BMI and HRQL according to educational level. RESULTS: Among women with primary or lower education, obesity was associated with a higher prevalence of suboptimal values in the following dimensions: Physical functioning (OR: 1.97; 95%CI: 1.22-3.18); Role-physical (OR: 1.81; 95%CI: 1.04-3.14); General health (OR: 1.76; 95%CI: 1.10-2.81); and Role-emotional (OR: 2.52; 95%CI: 1.27-5.03). In women with higher education, physical functioning was the only dimension associated with obesity (OR: 2.02: 95%CI 0.83-4.97). CONCLUSION: The impact of obesity on women's HRQL is greater among those with a lower educational level. This group registered higher prevalence of obesity and poorer self-perceived health.This study was funded by the Instituto de Salud Carlos III (grant 001/05).S

Risk Factors for COVID-19 in Inflammatory Bowel Disease: A National, ENEIDA-Based Case–Control Study (COVID-19-EII)

(1) Scant information is available concerning the characteristics that may favour the acquisition of COVID-19 in patients with inflammatory bowel disease (IBD). Therefore, the aim of this study was to assess these differences between infected and noninfected patients with IBD. (2) This nationwide case-control study evaluated patients with inflammatory bowel disease with COVID-19 (cases) and without COVID-19 (controls) during the period March-July 2020 included in the ENEIDA of GETECCU. (3) A total of 496 cases and 964 controls from 73 Spanish centres were included. No differences were found in the basal characteristics between cases and controls. Cases had higher comorbidity Charlson scores (24% vs. 19%; p = 0.02) and occupational risk (28% vs. 10.5%; p < 0.0001) more frequently than did controls. Lockdown was the only protective measure against COVID-19 (50% vs. 70%; p < 0.0001). No differences were found in the use of systemic steroids, immunosuppressants or biologics between cases and controls. Cases were more often treated with 5-aminosalicylates (42% vs. 34%; p = 0.003). Having a moderate Charlson score (OR: 2.7; 95%CI: 1.3-5.9), occupational risk (OR: 2.9; 95%CI: 1.8-4.4) and the use of 5-aminosalicylates (OR: 1.7; 95%CI: 1.2-2.5) were factors for COVID-19. The strict lockdown was the only protective factor (OR: 0.1; 95%CI: 0.09-0.2). (4) Comorbidities and occupational exposure are the most relevant factors for COVID-19 in patients with IBD. The risk of COVID-19 seems not to be increased by immunosuppressants or biologics, with a potential effect of 5-aminosalicylates, which should be investigated further and interpreted with caution

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

EducaFarma 11.0

Memoria ID2022-036. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2022-2023

EducaFarma 9.0

Memoria ID-020 Ayudas de la Universidad de Salamanca para la innovación docente, curso 2020-2021