Efectividad del tratamiento anti-TNFa en pacientes con enfermedad de crohn que no han alcanzado la remisión con un primer anti-TNFa

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 6-07-2016Los fármacos anti-TNFα son efectivos para inducir y mantener la remisión clínica en los pacientes con enfermedad de Crohn. Desafortunadamente, un porcentaje importante de enfermos no logra alcanzar dicha remisión, por obtener sólo respuesta parcial al tratamiento o por no presentar ningún tipo de respuesta a éste. El uso consecutivo de diferentes fármacos anti-TNFα parece ser efectivo si el motivo de suspensión inicial fue la pérdida de respuesta o la intolerancia. Pero disponemos de pocos datos sobre la evolución de aquellos pacientes que reciben un anti-TNFα tras no haber alcanzado la remisión con el primero. Según diferentes estudios, el porcentaje de pacientes que no alcanzan la remisión clínica con un anti-TNFα podrían oscilar entre el 50 y el 80%. A pesar de ser un porcentaje relevante, son pocos los trabajos que hasta la fecha han evaluado la efectividad del tratamiento secuencial en este grupo de pacientes. El objetivo principal del presente estudio fue evaluar la efectividad de un tratamiento anti-TNFα en pacientes con enfermedad de Crohn que no habían alcanzado la remisión previamente con otro fármaco del mismo grupo terapéutico. Con este fin se incluyeron un total de 118 pacientes procedentes de 24 hospitales españoles con diagnóstico previo de enfermedad de Crohn y que hubieran recibido un segundo tratamiento anti-TNFα habiendo tenido falta de remisión con el previo. El primer anti-TNFα se había suspendido por ausencia de respuesta en el 54% de los casos y por respuesta parcial en el 46%. El 51% de los pacientes alcanzó la remisión clínica a corto plazo con el segundo tratamiento anti-TNFα. El porcentaje de remisión alcanzado con el segundo fármaco fue menor en aquellos pacientes en los que el tratamiento biológico se indicó por enfermedad perianal (OR = 0,3, IC 95% = 0,1-0,7, p = 0,005). La probabilidad de mantener la remisión fue del 76%, 68% y 64% a los 12, 18 y 24 meses, respectivamente. Durante el seguimiento, el 33% de los pacientes requirió intensificación del segundo anti-TNFα y, de ellos, el 37% logró alcanzar la remisión clínica. A la luz de estos resultados, podemos concluir que el tratamiento con un segundo fármaco anti-TNFα tras no haber alcanzado la remisión con el anterior es una estrategia efectiva en aproximadamente la mitad de los pacientes, teniendo menos probabilidades de responder aquellos pacientes con enfermedad perianal. No obstante, una proporción relevante de pacientes pierde la respuesta a lo largo del tiempo y, en estos casos, la intensificación del tratamiento es una opción terapéutica válida

Reduction of net sulfide production rate by nitrate in wastewater bioreactors. Kinetics and changes in the microbial community

15 páginas, 7 figuras, 5 tablas, 44 referencias.-- [email protected] addition stimulated sulfide oxidation by increasing the activity of nitrate-reducing sulfide-oxidizing bacteria (NR-SOB), decreasing the concentration of dissolved H2S in the water phase and, consequently, its release to the atmosphere of a pilot-scale anaerobic bioreactor. The effect of four different concentrations of nitrate (0.12, 0.24, 0.50, and 1.00 mM) was investigated for a period of 3 days in relation to sulfide concentration in two bioreactors set up at Guadalete wastewater treatment plant (Jerez de la Frontera, Spain). Physicochemical variables were measured in water and air, and the activity of bacteria implicated in the sulfur and nitrogen cycles was analyzed in the biofilms and in the water phase of the bioreactors. Biofilms were a net source of sulfide for the water and gas phases (7.22±5.3 μmol s−1) in the absence of nitrate dosing. Addition of nitrate resulted in a quick (within 3 h) decrease of sulfide both in the water and atmospheric phases. Sulfide elimination efficiency in the water phase increased with nitrate concentrations following the Michaelis–Menten kinetics (Ks=0.63 mM NO3 −). The end of nitrate addition resulted in a recovery or increase of initial net sulfide production in about 3 h. Addition of nitrate increased the activity of NR-SOB and decreased the activity of sulfate-reducing bacteria. Results confirmed the role of NR-SOB on hydrogen sulfide consumption coupled with nitrate reduction and sulfate recycling, revealing Sulfurimonas denitrificans and Paracoccus denitrificans as NR-SOB of great importance in this process.We acknowledge the support of the grants P06-RNM-01787, P11-RNM-7199, the PAI groups RNM-214 and BIO-288 from Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía, Spain and CTM2009-10736 from the Ministerio de Innovación y Ciencia, Spain, which include cofinancing from FEDER funds. S. Papaspyrou was funded by a JAE-Doc fellowship (Programa JAE, JAE-Doc109, Spanish National Research Council) and a Marie Curie ERG action (NITRICOS, 235005, European Union).Peer reviewe

Genomic Characterization of Host Factors Related to SARS-CoV-2 Infection in People with Dementia and Control Populations: The GR@ACE/DEGESCO Study

Emerging studies have suggested several chromosomal regions as potential host genetic factors involved in the susceptibility to SARS-CoV-2 infection and disease outcome. We nested a COVID-19 genome-wide association study using the GR@ACE/DEGESCO study, searching for susceptibility factors associated with COVID-19 disease. To this end, we compared 221 COVID-19 confirmed cases with 17,035 individuals in whom the COVID-19 disease status was unknown. Then, we performed a meta-analysis with the publicly available data from the COVID-19 Host Genetics Initiative. Because the APOE locus has been suggested as a potential modifier of COVID-19 disease, we added sensitivity analyses stratifying by dementia status or by disease severity. We confirmed the existence of the 3p21.31 region (LZTFL1, SLC6A20) implicated in the susceptibility to SARS-CoV-2 infection and TYK2 gene might be involved in COVID-19 severity. Nevertheless, no statistically significant association was observed in the COVID-19 fatal outcome or in the stratified analyses (dementia-only and non-dementia strata) for the APOE locus not supporting its involvement in SARS-CoV-2 pathobiology or COVID-19 prognosis

Valoración de las metodologías y herramientas docentes por el alumnado. Impulso del mentoring para profesores en la enseñanza online y presencial

Depto. de Derecho CivilFac. de DerechoFALSEsubmitte

Impact of Biological Agents on Postsurgical Complications in Inflammatory Bowel Disease : A Multicentre Study of Geteccu

Background: The impact of biologics on the risk of postoperative complications (PC) in inflammatory bowel disease (IBD) is still an ongoing debate. This lack of evidence is more relevant for ustekinumab and vedolizumab. Aims: To evaluate the impact of biologics on the risk of PC. Methods: A retrospective study was performed in 37 centres. Patients treated with biologics within 12 weeks before surgery were considered "exposed". The impact of the exposure on the risk of 30-day PC and the risk of infections was assessed by logistic regression and propensity score-matched analysis. Results: A total of 1535 surgeries were performed on 1370 patients. Of them, 711 surgeries were conducted in the exposed cohort (584 anti-TNF, 58 vedolizumab and 69 ustekinumab). In the multivariate analysis, male gender (OR: 1.5; 95% CI: 1.2-2.0), urgent surgery (OR: 1.6; 95% CI: 1.2-2.2), laparotomy approach (OR: 1.5; 95% CI: 1.1-1.9) and severe anaemia (OR: 1.8; 95% CI: 1.3-2.6) had higher risk of PC, while academic hospitals had significantly lower risk. Exposure to biologics (either anti-TNF, vedolizumab or ustekinumab) did not increase the risk of PC (OR: 1.2; 95% CI: 0.97-1.58), although it could be a risk factor for postoperative infections (OR 1.5; 95% CI: 1.03-2.27). Conclusions: Preoperative administration of biologics does not seem to be a risk factor for overall PC, although it may be so for postoperative infections

Association Between Preexisting Versus Newly Identified Atrial Fibrillation and Outcomes of Patients With Acute Pulmonary Embolism

Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90-day all-cause (odds ratio [OR], 2.81; 95% CI, 2.33-3.38) and PE-related mortality (OR, 2.38; 95% CI, 1.37-4.14) and increased 1-year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10-9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all-cause mortality (OR, 1.91; 95% CI, 1.57-2.32) but not PE-related mortality (OR, 1.50; 95% CI, 0.85-2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR, 2.28; 95% CI, 1.75-2.97) and PE-related (OR, 3.64; 95% CI, 2.01-6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.info:eu-repo/semantics/publishedVersio

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks : The GR@ACE project

Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

Impact of Biological Agents on Postsurgical Complications in Inflammatory Bowel Disease: A Multicentre Study of Geteccu

Background: The impact of biologics on the risk of postoperative complications (PC) in inflammatory bowel disease (IBD) is still an ongoing debate. This lack of evidence is more relevant for ustekinumab and vedolizumab. Aims: To evaluate the impact of biologics on the risk of PC. Methods: A retrospective study was performed in 37 centres. Patients treated with biologics within 12 weeks before surgery were considered “exposed”. The impact of the exposure on the risk of 30-day PC and the risk of infections was assessed by logistic regression and propensity score-matched analysis. Results: A total of 1535 surgeries were performed on 1370 patients. Of them, 711 surgeries were conducted in the exposed cohort (584 anti-TNF, 58 vedolizumab and 69 ustekinumab). In the multivariate analysis, male gender (OR: 1.5; 95% CI: 1.2–2.0), urgent surgery (OR: 1.6; 95% CI: 1.2–2.2), laparotomy approach (OR: 1.5; 95% CI: 1.1–1.9) and severe anaemia (OR: 1.8; 95% CI: 1.3–2.6) had higher risk of PC, while academic hospitals had significantly lower risk. Exposure to biologics (either anti-TNF, vedolizumab or ustekinumab) did not increase the risk of PC (OR: 1.2; 95% CI: 0.97–1.58), although it could be a risk factor for postoperative infections (OR 1.5; 95% CI: 1.03–2.27). Conclusions: Preoperative administration of biologics does not seem to be a risk factor for overall PC, although it may be so for postoperative infections

Non-motor symptom burden in patients with Parkinson's disease with impulse control disorders and compulsive behaviours : results from the COPPADIS cohort

The study was aimed at analysing the frequency of impulse control disorders (ICDs) and compulsive behaviours (CBs) in patients with Parkinson's disease (PD) and in control subjects (CS) as well as the relationship between ICDs/CBs and motor, nonmotor features and dopaminergic treatment in PD patients. Data came from COPPADIS-2015, an observational, descriptive, nationwide (Spain) study. We used the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) for ICD/CB screening. The association between demographic data and ICDs/CBs was analyzed in both groups. In PD, this relationship was evaluated using clinical features and treatment-related data. As result, 613 PD patients (mean age 62.47 ± 9.09 years, 59.87% men) and 179 CS (mean age 60.84 ± 8.33 years, 47.48% men) were included. ICDs and CBs were more frequent in PD (ICDs 12.7% vs. 1.6%, p < 0.001; CBs 7.18% vs. 1.67%, p = 0.01). PD patients had more frequent previous ICDs history, premorbid impulsive personality and antidepressant treatment (p < 0.05) compared with CS. In PD, patients with ICDs/CBs presented younger age at disease onset, more frequent history of previous ICDs and premorbid personality (p < 0.05), as well as higher comorbidity with nonmotor symptoms, including depression and poor quality of life. Treatment with dopamine agonists increased the risk of ICDs/CBs, being dose dependent (p < 0.05). As conclusions, ICDs and CBs were more frequent in patients with PD than in CS. More nonmotor symptoms were present in patients with PD who had ICDs/CBs compared with those without. Dopamine agonists have a prominent effect on ICDs/CBs, which could be influenced by dose

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research