Características nutricionales de los pacientes con cirrosis hepática

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 16-01-202

Quantification of the uranium concentration in human urine by inductively coupled plasma-sector field mass spectrometry (ICP-SFMS)

In this study, the validation of a method for analyzing the uranium (U) concentration in human urine samples by inductively coupled plasma-sector field mass spectrometry (ICP-SFMS) was conducted. PROCORAD (the Association for the Promotion of Quality Control in Radiotoxicological Analysis) provided two urine samples spiked with unknown contents of U (Sample A = 33.6 ± 1.0 µg/L and Sample B = 3.3 ± 0.1 µg/L) and one unspiked sample as a blank. The analyses were directly performed on the diluted urine samples (dilution factor = 1:20) in 5% v/v HNO3. The results obtained by ICP-SFMS corresponded well with the reference values, and the limits of detection were 235U = 0.049 × 10-3 µg/L and 238U = 7.37 × 10-3 µg/L. The ICP-SFMS technique has been shown to be successful in the analysis of the U concentration in human urine samples and for the quantification of isotopic ratios

Predictors of cognitive decline in Alzheimer"s disease and mild cognitive impairment using the CAMCOG: a five-year follow-up

Background: There are discrepant findings regarding which subscales of the Cambridge Cognitive Examination(CAMCOG) are able to predict cognitive decline. The study aimed to identify the baseline CAMCOG subscales that can discriminate between patients and predict cognitive decline in Alzheimer"s disease (AD)and mild cognitive impairment (MCI). Methods: This was a five-year case-control study of patients with cognitive impairment and a control group.Participants were grouped into AD (n = 121), MCI converted to dementia (MCI-Ad, n = 43), MCI-stable(MCI-St, n = 66), and controls (CTR, n = 112). Differences in the mean scores obtained by the four groupswere examined. Receiver operating characteristic curves were used to compare subscale scores in the AD and MCI-Ad groups with those of controls. The influence of age, gender, schooling, and depression on baseline subscale scores was assessed. Results: Of the CAMCOG subscales, Orientation and Memory (learning and recent) (OR + MEM) showed the highest discriminant capacity in the baseline analysis of the four groups. This baseline analysis indicated that OR + MEM was the best predictor of conversion to AD in the MCI-Ad group (area under the curve, AUC = 0.81), whereas the predictive capacity of the global MMSE and CAMCOG scores was poor (AUC = 0.59 and 0.53, respectively). Conclusions: In the baseline analysis, the Orientation and Memory (learning and recent) subscales showed the highest discriminant and predictive capacity as regards both cognitive decline in the AD group and conversion to AD among MCI-Ad patients. This was not affected by age, gender, schooling, or depression

Declive cognitivo en la enfermedad de Alzheimer. Seguimiento de más de 3 años de una muestra de pacientes

Introducción. Las tasas de declive cognitivo en los pacientes con enfermedad de Alzheimer (EA) presentan variaciones debido a diversos factores. El objetivo del estudio fue determinar la influencia de la edad, escolaridad, género, actividades de la vida diaria (AVD) e inhibidores de la acetilcolinesterasa (IAChE) y memantina en el ritmo y tasas de declive cognitivo. Pacientes y métodos. Estudio retrospectivo de una muestra de 383 pacientes con EA, con evaluaciones neuropsicológicas durante un período superior a 3 años. Se utilizó como medida cognitiva el Cambridge Cognitive Examination (CAMCOG). Se agruparon los pacientes según su tasa de declive anual (TDA) y se realizaron análisis bivariante y de regresión lineal multivariante utilizando como variable dependiente la diferencia de puntuaciones en el CAMCOG (basal-final). Resultados. La menor edad (β = -0,23; p < 0,001), la mayor escolaridad (β = 0,26; p < 0,001) y el mayor deterioro de las AVD (β = 0,24; p < 0,001) estuvieron asociados a un mayor declive en todos los pacientes. Los fármacos tuvieron un efecto benéfico (β = -0,18; p = 0,011) en el grupo con menor y más lento declive (TDA < 5%). Conclusiones. La menor edad, la mayor escolaridad y el deterioro de las AVD se relacionan con un mayor declive cognitivo. Los IAChE y memantina tuvieron un efecto benéfico, enlenteciendo el declive en el grupo de pacientes con menor TD

Role of poplar DNA demethylases in controlling winter dormancy

Trees have developed the mechanism of winter dormancy to survive the harsh conditions of winter in temperate and cold regions. It determines the geographical distribution of tree species and the long of the growing period. Epigenetic control of winter dormancy in woody plants is barely known. 5-methyl cytosine (5mC) is an important epigenetic mark that regulates gene expression in animals and plants. The profile of DNA methylation changes in the transition of developmental stages in plants such as chestnut bud set and burst, flowering in azalea, aging in pine trees among other. So far, the enzymes involved in the modification of the methylome and the molecular mechanism behind the control over those development processes remain to be understood. Our previous results showed higher DNA methylation and less acetylated Lys 8 of histone H4 global levels in poplar stem during winter dormancy compared to active growing season. Analysis of the 5-methyl cytosine levels by the application of the immunofluorescence-based method set up in our lab showed that global DNA methylation decrease significantly when trees are near to restore the growing season after the winter dormancy. We have identified two poplar homologs to Arabidopsis DME gene: PtaDML8/PtaDML10. DME protein promotes global DNA demethylation along the genome during the endosperm development. Our RT-PCR analyses indicate that the expression of PtaDML8/PtaDML10 genes increases significantly when trees are near to restart growing after the winter. Functional characterization showed that PtaDML8/PtaDML10 knockdown plants have a delayed in resuming of growth after dormancy. Taken together, we hypothesize that an active control of the 5mC DNA methylation play a key role in winter dormancy and that 5mC demethylases would be crucial for poplar dormant-growth transitio

Prevalence estimation of significant fibrosis because of NASH in Spain combining transient elastography and histology

Acord transformatiu CRUE-CSICBackground & Aims: Non-alcoholic fatty liver disease (NAFLD) has become a major public health problem, but the prevalence of fibrosis associated with non-alcoholic steatohepatitis (NASH) is largely unknown in the general population. This study aimed to provide an updated estimation of the prevalence of NASH fibrosis in Spain. Methods: This was an observational, retrospective, cross-sectional, population-based study with merged data from two Spanish datasets: a large (N = 12 246) population-based cohort (ETHON), including transient elastography (TE) data, and a contemporary multi-centric biopsy-proven NASH cohort with paired TE data from tertiary centres (N = 501). Prevalence for each NASH fibrosis stage was estimated by crossing TE data from ETHON dataset with histology data from the biopsy-proven cohort. Results: From the patients with valid TE in ETHON dataset (N = 11 440), 5.61% (95% confidence interval [95% CI]: 2.53-11.97) had a liver stiffness measurement (LSM) ≥ 8 kPa. The proportion attributable to NAFLD (using clinical variables and Controlled Attenuation Parameter) was 57.3% and thus, the estimated prevalence of population with LSM ≥ 8 kPa because of NAFLD was 3.21% (95% CI 1.13-8.75). In the biopsy-proven NASH cohort, 389 patients had LSM ≥ 8 kPa. Among these, 37% did not have significant fibrosis (F2-4). The estimated prevalence of NASH F2-3 and cirrhosis in Spain's adult population were 1.33% (95% CI 0.29-5.98) and 0.70% (95% CI 0.10-4.95) respectively. Conclusions: These estimations provide an accurate picture of the current prevalence of NASH-related fibrosis in Spain and can serve as reference point for dimensioning the therapeutic efforts that will be required as NASH therapies become available

Increased risk of MAFLD and liver fibrosis in inflammatory bowel disease independent of classic metabolic risk factors

ackground & Aims There is conflicting evidence regarding the prevalence of and risk factors for metabolic-associated fatty liver disease (MAFLD) in patients with inflammatory bowel disease (IBD). We aimed to determine MAFLD prevalence and risk factors in IBD patients. Methods Cross-sectional, case-control study included all consecutive IBD patients treated at 2 different university hospitals. Controls were subjects randomly selected from the general population and matched by age, sex, type 2 diabetes status, and body mass index in a 1:2 ratio. MAFLD was confirmed by controlled attenuation parameter. Liver biopsies were collected when MAFLD with significant liver fibrosis was suspected. In addition, age- and fibrosis stage-paired non-IBD patients with biopsy-proven MAFLD served as a secondary control group. Results Eight hundred thirty-one IBD patients and 1718 controls were included. The prevalence of MAFLD and advanced liver fibrosis (transient elastography ≥9.7 kPa) was 42.00% and 9.50%, respectively, in IBD patients and 32.77% and 2.31%, respectively, in the general population (P < .001). A diagnosis of IBD was an independent predictor of MAFLD (adjusted odds ratio, 1.99; P < .001) and an independent risk factor for advanced liver fibrosis (adjusted odds ratio, 5.55; P < .001). Liver biopsies were obtained from 40 IBD patients; MAFLD was confirmed in all cases, and fibrosis of any degree was confirmed in 25 of 40 cases (62.5%). Body mass index and type 2 diabetes prevalence were significantly lower in IBD-MAFLD patients than in severity-paired patients with biopsy-proven MAFLD. Conclusions MAFLD and liver fibrosis are particularly prevalent in IBD patients, regardless of the influence of classic metabolic risk factors.Acknowledgements: The authors report funding support from the Spanish Instituto de Salud Carlos III-FEDER Grant (FIS - PI18/01304) related to this manuscript

Immunogenic dynamics and SARS-CoV-2 variant neutralisation of the heterologous ChAdOx1-S/BNT162b2 vaccination: Secondary analysis of the randomised CombiVacS study

Background The CombiVacS study was designed to assess immunogenicity and reactogenicity of the heterologous ChAdOx1-S/BNT162b2 combination, and 14-day results showed a strong immune response. The present secondary analysis addresses the evolution of humoral and cellular response up to day 180. Methods Between April 24 and 30, 2021, 676 adults primed with ChAdOx1-S were enrolled in five hospitals in Spain, and randomised to receive BNT162b2 as second dose (interventional group [IG]) or no vaccine (control group [CG]). Individuals from CG received BNT162b2 as second dose and also on day 28, as planned based on favourable results on day 14. Humoral immunogenicity, measured by immunoassay for SARS-CoV-2 receptor binding domain (RBD), antibody functionality using pseudovirus neutralisation assays for the reference (G614), Alpha, Beta, Delta, and Omicron variants, as well as cellular immune response using interferon-γ and IL-2 immunoassays were assessed at day 28 after BNT162b2 in both groups, at day 90 (planned only in the interventional group) and at day 180 (laboratory data cut-off on Nov 19, 2021). This study was registered with EudraCT (2021-001978-37) and ClinicalTrials.gov (NCT04860739). Findings In this secondary analysis, 664 individuals (441 from IG and 223 from CG) were included. At day 28 post vaccine, geometric mean titres (GMT) of RBD antibodies were 5616·91 BAU/mL (95% CI 5296·49–5956·71) in the IG and 7298·22 BAU/mL (6739·41–7903·37) in the CG (p 1:100 at day 180 (19% and 22%, respectively). Interpretation Titres of RBD antibodies decay over time, similar to homologous regimes. Our findings suggested that delaying administration of the second dose did not have a detrimental effect after vaccination and may have improved the response obtained. Lower neutralisation was observed against Omicron and Beta variants at day 180.Funded by Instituto de Salud Carlos III (ISCIII). AMB, AJC, JO, and JF are members of the VACCELERATE (European Corona Vaccine Trial Accelerator Platform) Network, which aims to facilitate and accelerate the design and implementation of COVID-19 phase 2 and 3 vaccine trials. JO is a member of the INsTRuCT (Innovative Training in Myeloid Regulatory Cell Therapy) Consortium, a network of European scientists from academia and industry focused on developing innovative immunotherapies. This work is funded by Instituto de Salud Carlos III, a Spanish public body assigned to the Ministry of Science and Innovation that manages and promotes public clinical research related to public health. The Spanish Clinical Trials Platform is a public network funded by the Instituto de Salud Carlos III (grant numbers PTC20/00018 and PT17/0017), the State Plan for Research, Development, and Innovation 2013–16, the State Plan for Scientific and Technical Research and Innovation 2017–20, and the Subdirectorate General for Evaluation and Promotion of Research, Instituto de Salud Carlos III, cofinanced with FEDER funds. CombiVacS was designed under the umbrella of the VACCELERATE project. VACCELERATE and INsTRuCT received funding from the EU's Horizon 2020 Research and Innovation Programme (grant agreement numbers 101037867 and 860003). The Instituto de Salud Carlos III is the Spanish partner in the VACCELERATE project. This work is partially funded by Institute of Health Carlos III (Instituto de Salud Carlos III – ISCIII –), (grants PI19CIII/00004 to JA and PI21CIII/00025 to MPO and JGP), and COVID-19 FUND (grants COV20/00679 and COV20/00072 to MPO and JA) and CIBERINFEC, co-financed by the European Regional Development Fund (FEDER) “A way to make Europe”

Epidemiology, use, and practice of the intraosseous route in an out-of-hospital emergency department: a retrospective cross-sectional study

IntroductionThe Spanish Emergency Medical Services, according to the model we know today, were formed during the 80s and 90s of the 20th century. The Health Emergency Service (EMS), 061 La Rioja, began to assist the population of La Rioja in November 1999. An essential part of the mission of the SES is the provision of care and the transfer of critical patients using advanced life support unit (ALSU) techniques. In daily practice, out-of-hospital emergency services are faced with situations in which they must deal with the care of serious or critically ill patients, in which the possibility of being able to channel peripheral vascular access as part of ALSU quickly may be difficult or impossible. In these cases, cannulation of intraosseous (IO) vascular access may be the key to early and adequate care.AimThis study aimed to determine the incidence and epidemiology use of IO vascular access in SES 061 La Rioja during the year 2022.Matherial and methodsWe performed observational retrospective cross-sectional studies conducted in 2022. It included a population of 4.364 possible patients as a total of interventions in the community of La Rioja in that year.ResultsA total of 0.66% of patients showed a clinical situation that required the establishment of IO vascular access to enable out-of-hospital stabilization; this objective was achieved in 41.3%. A total of 26.1% of patients who presented with cardiorespiratory arrest (CA) were stabilized, while 100% presented with shock and severe trauma.DiscussionIO vascular access provides a suitable route for out-of-hospital stabilization of critically ill patients when peripheral vascular access is difficult or impossible