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    Analysis of the effectiveness of a computerized cognitive stimulation program designed from Occupational Therapy according to the level of cognitive reserve in older adults in Primary Care: Stratified randomized clinical trial protocol.

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    Normal aging presents subtle cognitive changes that can be detected before meeting the criteria for Mild cognitive impairment (MCI). Older people with low cognitive reserve and who receive limited cognitive stimulation are at greater risk of deterioration. In this regard, cognitive stimulation (CS) has been identified as an intervention that reduces this risk, provided that its design takes into account the differences in the level of cognitive reserve (CR) acquired throughout life and the baseline level of cognitive functioning. The general objective of this study is to evaluate, through a randomized clinical trial, the effectiveness of a computerized cognitive stimulation program, designed and adapted from Occupational Therapy based on the level of cognitive reserve in older adults in Primary Care. 100 participants will be randomized in a stratified manner according to the level of cognitive reserve (low/moderate/high), assigning 50 participants to the control group and 50 participants to the intervention group. The intervention group will carry out a computerized cognitive stimulation intervention designed and adapted from occupational therapy according to the level of cognitive reserve, through the "stimulus" platform. The main result expected to be achieved is the improvement of higher brain functions. As secondary results, we expect that those cognitive aspects most vulnerable to aging will decrease more slowly (in areas such as memory, executive function, attention and processing speed), and that the cognitive reserve of the participants will increase, in addition to being able to balance gender differences in these aspects. We think that these results can have a positive impact on the creation of adapted, meaningful and stimulating CS programs in older adults to prevent MCI and experience healthier aging

    Health-related quality of life determinants in Spanish children with eosinophilic esophagitis.

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    20.500.12530/87858To study the health-related quality of life (HRQoL) and its possible determinant factors in Spanish children with eosinophilic esophagitis (EoE) and their parents. Multicenter observational cross-sectional study. The Spanish version of the Pediatric Quality of Life Eosinophilic Esophagitis Module was filled out by EoE patients aged 8-18 and their parents. Demographic, psychosocial, and clinical variables were studied. Multiple linear regression was performed to identify related factors of HRQoL. A total of 279 children and their parents participated (72.7% males). 39.1% received swallowed corticosteroids, 35.5% proton pump inhibitors and 16.8% diet. 1.1% received other treatments and 7.5% received no treatment. Poor compliance to treatment was observed in 11.5% and 6.5% of patients were referred to mental health. The Total Scale Scores were 72.71 ± 17.50 and 75.62 ± 16.73 for children and parents, respectively. "Communication" was the dimension with the highest scores (82.14 ± 21.65 and 81.59 ± 24.13) while "Food and Eating" (48.92 ± 32.94 and 62.85 ± 28.78), and "Food Feelings" (53.55 ± 29.96 and 53.95 ± 27.78) had the lower scores. Patients and parents under dietary treatment showed lower scores than those under pharmacological treatment, 65.77 ± 16.96 versus 74.28 ± 16.96, p = 0.001 and 68.33 ± 17.32 versus 77.24 ± 15.97, p = 0.001, respectively. Factors associated with worse HRQoL scores were symptom frequency, diet, food allergies, and the need for mental health assistance. The HRQoL of children and their parents was "good." However, diet, frequency of symptoms, food allergies, and the need for mental health care were the factors that had a negative impact on HRQoL of children with EoE

    Thrombotic risk and features of patients with inferior vena cava agenesis: a multicentre, retrospective, observational study.

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    20.500.12530/87855Inferior vena cava agenesis (IVCA) is a rare anomaly predisposing affected people to lower-limb venous thrombosis with low frequency of pulmonary embolism. Antenatal thrombosis and inherited thrombophilia have been suggested as causes of IVCA. However, there is little evidence on the clinical course and management of this condition. We designed a patient registry to assess the thrombotic risk and features of IVCA. In this this multicentre, retrospective, observational study, we included patients with IVCA diagnosed by routine imaging from 20 hospitals in Spain (n=18), Portugal (n=1), and Italy (n=1). Patients were identified from a systematic search in radiology databases using data extraction software (cohort A) and alternative searches in medical records for confirmed IVCA (cohort B; option allowed when systematic approaches were unapplicable). Primary outcomes were clinical and imaging features, thrombotic risk, phenotype of IVCA-associated thrombosis, anticoagulant treatment, and the results of thrombophilia testing. We included patients with IVCA diagnosed by routine imaging studies done between Jan 1, 2010, and Dec 31, 2022. In the systematic search, 4 341 333 imaging exams were screened from the radiology databases of eight centres. 122 eligible patients were enrolled in cohort A. A further 95 patients were identified by screening medical records at 12 centres, of whom 88 were eligible and included in cohort B, making a combined cohort of 210 patients. 96 (46%) of 210 patients were female and 200 (95%) were European or Hispanic. 60 (29%) of 210 patients had hepatic IVC interruption, whereas 150 (71%) had extrahepatic IVCA. In cohort A, 65 (53%) of 122 patients had venous thrombosis, with an estimated annual risk of 1·15% (95% CI 0·89-1·46). Extrahepatic IVCA was associated with a greater risk of venous thrombosis than hepatic IVCA (56 [67%] of 84 patients vs nine [24%] of 38 patients, odds ratio 5·31, 95% CI 2·27-12·43; p This evaluation of a large patient cohort demonstrates the high thrombotic burden of IVCA. We have identified two distinct forms of IVCA, hepatic and extrahepatic, suggesting different underlying mechanisms. Beyond clinical characterisation, we draw attention to this orphan disease and highlight the need for its study and improved care. Spanish Society of Thrombosis and Haemostasis, Instituto de Salud Carlos III, FEDER, Fundación Séneca

    Foetal gluten immunogenic peptides during pregnancy: a new determinant on the coeliac exposome.

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    20.500.12530/87913The increasing incidence of coeliac disease is leading to a growing interest in active search for associated factors, even the intrauterine and early life. The exposome approach to disease encompasses a life course perspective from conception onwards has recently been highlighted. Knowledge of early exposure to gluten immunogenic peptides (GIP) in utero could challenge the chronology of early prenatal tolerance or inflammation, rather than after the infant's solid diet after birth. We developed an accurate and specific immunoassay to detect GIP in amniotic fluid (AF) and studied their accumulates, excretion dynamics and foetal exposure resulting from AF swallowing. One hundred twenty-five pregnant women with different gluten diets and gestational ages were recruited. GIP were detectable in AF from at least the 16th gestational week in gluten-consuming women. Although no significant differences in GIP levels were observed during gestation, amniotic GIP late pregnancy was not altered by maternal fasting, suggesting closed-loop entailing foetal swallowing of GIP-containing AF and subsequent excretion via the foetal kidneys. The study shows evidence, for the first time, of the foetal exposure to gluten immunogenic peptides and establishes a positive correlation with maternal gluten intake. The results obtained point to a novel physiological concept as they describe a plausible closed-loop circuit entailing foetal swallowing of GIP contained in AF and its subsequent excretion through the foetal kidneys. The study adds important new information to understanding the coeliac exposome

    The Impact of Complementary Feeding on Fecal Microbiota in Exclusively Breast-Fed Infants with Cystic Fibrosis (A Descriptive Study).

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    20.500.12530/87908Early life gut microbiota plays a pivotal role in shaping immunity, metabolism, and overall health outcomes. This is relevant in healthy infants but may be even more crucial in infants with chronic devastating diseases, such as cystic fibrosis (CF). While the introduction of solid foods in healthy infants modifies the composition of colonic microbiota, less knowledge is available on those with CF. The aim of this descriptive observational study was to assess the composition of fecal microbiota in six exclusively breast-fed infants with CF, and then explore the changes induced upon the introduction of different foods. two types of fecal samples were collected from each subject: one during the exclusive-breastfeeding period, and the other after incorporating each new food in the ad libitum diet. The microbiota composition was analyzed by 16S rRNA amplicon sequencing. Wide heterogenicity in the composition at the phylum level (variable proportions of Actinobacteriota, Proteobacteria, and Firmicutes, and the absence of Bacteroidota in all subjects) was found, and different enterotypes were characterized in each subject by the main presence of one genus: Bifidobacterium in Subject 1 (relative abundance of 54.4%), Klebsiella in Subject 3 (49.1%), Veillonella in Subjects 4 and 5 (32.7% and 36.9%, respectively), and Clostridium in Subject 6 (48.9%). The transition to complementary feeding induced variable changes in microbiota composition, suggesting a subject-specific response and highlighting the importance of inter-individual variation. Further studies are required to identify which foods contribute to shaping colonic microbiota in the most favorable way for patients with CF using a personalized approach

    Determinants of adverse outcomes following patent foramen ovale closure in elderly patients.

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    Limited data are available on transcatheter patent foramen ovale (PFO) closure outcomes in the elderly. Through this study, we aimed to determine the incidence and predictors of adverse events (recurrent cerebrovascular events [CVE] and atrial fibrillation [AF]) post-PFO closure in older patients with cryptogenic events. This multicentre international study included patients over 60 years undergoing PFO closure for cryptogenic thromboembolic events. A dedicated database compiled baseline, procedural, and follow-up data. Competing risk and adjusted outcome predictor analyses were conducted. A total of 689 patients were included (median age 65 years, 41.2% female, mean Risk of Paradoxical Embolism [RoPE] score 4.5). The procedural success rate was 99.4%. After a median follow-up of 2 (interquartile range 1-5) years, 66 patients (9.6%) had died. CVE and stroke rates were 1.21 and 0.55 per 100 patient-years, respectively. Diabetes (hazard ratio [HR] 3.89, 95% confidence interval [CI]: 1.67-9.07; p=0.002) and atrial septal aneurysm (ASA; HR 5.25, 95% CI: 1.56-17.62; p=0.007) increased the CVE risk. New-onset AF occurred at a rate of 3.30 per 100 patient-years, with 51.3% within one month post-procedure. Older age (HR 1.05 per year, 95% CI: 1.00-1.09; p=0.023) and the absence of hypertension (HR 2.04, 95% CI: 1.19-3.57; p=0.010) were associated with an increased risk of AF. Older patients undergoing PFO closure had a relatively low rate of CVE and new-onset AF after a median follow-up of 2 years. The presence of diabetes, ASA, and a more advanced age determined an increased risk of adverse clinical events. These factors may be considered in the clinical decision-making process regarding PFO closure in this challenging population

    Use of Eltrombopag to Improve Thrombocytopenia and Tranfusion Requirement in Anti-CD19 CAR-T Cell-Treated Patients.

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    20.500.12530/87852Background/Objectives: Immune effector cell-associated hematotoxicity (ICAHT) is a frequent adverse event after chimeric antigen receptor (CAR)-T cell therapy. Grade ≥ 3 thrombocytopenia occurs in around one-third of patients, and many of them become platelet transfusion-dependent. Eltrombopag is a thrombopoietin receptor agonist (TPO-RA) able to accelerate megakaryopoiesis, which has been used successfully in patients with bone marrow failure and immune thrombocytopenia (ITP). Its role in managing thrombocytopenia and other cytopenias in CAR-T cell-treated patients has been scarcely addressed. Our aim was to report the safety and efficacy of this approach in patients included in the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC) registry. Methods: This is a retrospective, multicenter, observational study. Patients who developed platelet transfusion dependence subsequently to CAR-T cells and received eltrombopag to improve platelet counts were recruited in 10 Spanish hospitals. Results: Thirty-eight patients were enrolled and followed up for a median (interquartile range [IQR]) of 175 (99, 489) days since CAR-T cell infusion. At the moment eltrombopag was indicated, 18 patients had thrombocytopenia and another severe cytopenia, while 8 patients had severe pancytopenia. After 32 (14, 38) days on eltrombopag, 29 (76.3%) patients recovered platelet transfusion independence. The number of platelet units transfused correlated with the time needed to restore platelet counts higher than 20 × 109/L (Rho = 0.639,

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