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Multitarget Effects of Nrf2 Signalling in the Brain: Common and Specific Functions in Different Cell Types.
No full text20.500.12530/87854Nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial regulator of cellular defence mechanisms, essential for maintaining the brain's health. Nrf2 supports mitochondrial function and protects against oxidative damage, which is vital for meeting the brain's substantial energy and antioxidant demands. Furthermore, Nrf2 modulates glial inflammatory responses, playing a pivotal role in preventing neuroinflammation. This review explores these multifaceted functions of Nrf2 within the central nervous system, focusing on its activity across various brain cell types, including neurons, astrocytes, microglia, and oligodendrocytes. Due to the brain's vulnerability to oxidative stress and metabolic challenges, Nrf2 is emerging as a key therapeutic target to enhance resilience against oxidative stress, inflammation, mitochondrial dysfunction, and demyelination, which are central to many neurodegenerative diseases
A Prospective, Observational Study of the Effect of a High-Calorie, High-Protein Oral Nutritional Supplement with HMB in an Old and Malnourished or at-Risk-of-Malnutrition Population with Hip Fractures: A FracNut Study.
No full text20.500.12530/87857Hip fractures are prevalent among older people, often leading to reduced mobility, muscle loss, and bone density decline. Malnutrition exacerbates the prognosis post surgery. This study aimed to evaluate the impact of a 12-week regimen of a high-calorie, high-protein oral supplement with β-hydroxy-β-methylbutyrate (HC-HP-HMB-ONS) on nutritional status, daily activities, and compliance in malnourished or at-risk older patients with hip fractures receiving standard care. A total of 270 subjects ≥75 years of age, residing at home or in nursing homes, malnourished or at risk of malnutrition, and post hip fracture surgery, received HC-HP-HMB-ONS for 12 weeks. Various scales and questionnaires assessed outcomes. During the 12 weeks of follow-up, 82.8% consumed ≥75% of HC-HP-HMB-ONS. By week 12, 62.4% gained or maintained weight (+0.3 kg), 29.2% achieved normal nutritional status (mean MNA score +2.8), and 46.8% improved nutritional status. Biochemical parameters improved significantly. Subjects reported good tolerability (mean score 8.5/10), with 87.1% of healthcare providers concurring. The administration of HC-HP-HMB-ONS markedly enhanced nutritional status and biochemical parameters in older hip-fracture patients, with high compliance and tolerability. Both patients and healthcare professionals expressed satisfaction with HC-HP-HMB-ONS
SEOM-GEICO clinical guideline on epithelial ovarian cancer (2023).
No full text20.500.12530/87854In recent years, the incorporation of new strategies to the therapeutic armamentarium has completely changed the outcomes of epithelial ovarian cancer (EOC). The identification of new predictive and prognostic biomarkers has also enabled the selection of those patients more likely to respond to targeted agents. Nevertheless, EOC is still a highly lethal disease and resistance to many of these new agents is common. The objective of this guideline is to summarize the most relevant strategies to manage EOC, to help the clinician throughout the challenging diagnostic and therapeutic processes and to provide evidence-based recommendations
Alopecia Areata Treatment Patterns and Satisfaction: Results of a Real-World Cross-Sectional Survey in Europe.
No full text20.500.12530/87854Alopecia areata (AA) is an autoimmune disease that causes scalp, face, and/or body hair loss. Recently, oral treatments with kinases inhibition became the first approved therapies for severe AA. An understanding of the use and effectiveness of traditional therapies in real-world treatment settings is needed to guide integration of novel therapies into the treatment paradigm. This study aimed to describe traditional treatment patterns, dermatologists' reasons for therapy choice, and dermatologists' satisfaction with disease control among patients with AA. Data were drawn from the 2021-2022 Adelphi Real World AA Disease Specific Programme™, a cross-sectional survey of dermatologists and adult patients with AA, conducted in France, Germany, Italy, Spain, and the UK. For each patient, using data from patient consultation and medical records, dermatologists reported % scalp hair loss (SHL), characteristics of current and prior AA therapies, and satisfaction with disease control. Overall, 239 dermatologists provided data for 1720 patients with AA. Mean (SD) patient age was 35.8 (11.6) years, and 51% were male. Based on dermatologist perception, among patients with ≤ 10% SHL, 74% were experiencing mild AA, while ≥ 95% of patients with ≥ 50% SHL were experiencing severe/very severe AA. In patients with ≥ 50% SHL, the most common therapies received included systemic immunosuppressants (31%), topical corticosteroids (24%), and oral corticosteroids (24%). Among all patients who had switched therapies, 49%, 26%, and 24% switched because of worsening AA, lack of initial efficacy with prior treatment, and loss of response over time, respectively. Among those with SHL ≥ 50%, dermatologists reported satisfaction with current therapy in Dermatologists reported low satisfaction with traditional AA therapies used in patients with extensive SHL, with some patients discontinuing treatment because of worsening disease. This suggests more effective treatments are needed for patients with severe AA
Impact of dementia on 30-, 180-, and 365-day mortality during the first pandemic wave in older adults seen in spanish emergency departments diagnosed with or without COVID-19
No full text20.500.12530/87849Objectives: To assess whether dementia is an independent predictor of death after a hospital emergency department (ED) visit by older adults with or without a COVID-19 diagnosis during the first pandemic wave. Method: We used data from the EDEN-Covid (Emergency Department and Elderly Needs during Covid) cohort formed by all patients >= 65 years seen in 52 Spanish EDs from March 30 to April 5, 2020. The association of prior history of dementia with mortality at 30, 180 and 365 d was evaluated in the overall sample and according to a COVID-19 or non COVID diagnosis. Results: We included 9,770 patients aged 78.7 +/- 8.3 years, 51.1% men, 1513 (15.5%) subjects with prior history of dementia and 3055 (31.3%) with COVID-19 diagnosis. 1399 patients (14.3%) died at 30 d, 2008 (20.6%) at 180 days and 2456 (25.1%) at 365 d. The adjusted Hazard Ratio (aHR) for age, sex, comorbidity, disability and diagnosis for death associated with dementia were 1.16 (95% CI 1.01-1.34) at 30 d; 1.15 at 180 d (95% CI 1.03-1.30) and 1.19 at 365 d (95% CI 1.07-1.32), p = 65 years seen in 52 Spanish EDs from March 30 to April 5, 2020. The association of prior history of dementia with mortality at 30, 180 and 365 d was evaluated in the overall sample and according to a COVID-19 or non COVID diagnosis. Results: We included 9,770 patients aged 78.7 +/- 8.3 years, 51.1% men, 1513 (15.5%) subjects with prior history of dementia and 3055 (31.3%) with COVID-19 diagnosis. 1399 patients (14.3%) died at 30 d, 2008 (20.6%) at 180 days and 2456 (25.1%) at 365 d. The adjusted Hazard Ratio (aHR) for age, sex, comorbidity, disability and diagnosis for death associated with dementia were 1.16 (95% CI 1.01-1.34) at 30 d; 1.15 at 180 d (95% CI 1.03-1.30) and 1.19 at 365 d (95% CI 1.07-1.32),
Antioxidant Therapies in the Treatment of Multiple Sclerosis.
No full text20.500.12530/87861Several studies have proposed a potential role for oxidative stress in the development of multiple sclerosis (MS). For this reason, it seems tentative to think that treatment with antioxidant substances could be useful in the treatment of this disease. In this narrative review, we provide a summary of the current findings on antioxidant treatments, both in experimental models of MS, especially in experimental autoimmune encephalomyelitis (EAE) and in the cuprizone-induced demyelination model, and clinical trials in patients diagnosed with MS. Practically all the antioxidants tested in experimental models of MS have shown improvement in clinical parameters, in delaying the evolution of the disease, and in improving histological and biochemical parameters, including decreased levels of markers of inflammation and oxidative stress in the central nervous system and other tissues. Only a few clinical trials have been carried out to investigate the potential efficacy of antioxidant substances in patients with MS, most of them in the short term and involving a short series of patients, so the results of these should be considered inconclusive. In this regard, it would be desirable to design long-term, randomized, multicenter clinical trials with a long series of patients, assessing several antioxidants that have demonstrated efficacy in experimental models of MS
PKC Inhibition Improves Human Penile Vascular Function and the NO/cGMP Pathway in Diabetic Erectile Dysfunction: The Role of NADPH Oxidase
No full text20.500.12530/87897Erectile dysfunction (ED) is a frequent and difficult-to-treat condition in diabetic men. Protein kinase C (PKC) is involved in diabetes-related vascular and cavernosal alterations. We aimed to evaluate the role of PKC in endothelial dysfunction and NO/cGMP impairment associated with diabetic ED in the human corpus cavernosum (CC) and penile resistance arteries (PRAs) and the potential mechanisms involved. Functional responses were determined in the CC and PRAs in patients with non-diabetic ED and diabetic ED undergoing penile prosthesis insertion. PKC activator 12,13-phorbol-dibutyrate (PDBu) impaired endothelial relaxations and cGMP generation in response to acetylcholine in the CC from non-diabetic ED. PDBu also impaired responses to a PDE5 inhibitor, sildenafil, in non-diabetic ED patients. Conversely, a PKC inhibitor, GF109203X, improved endothelial, neurogenic, and PDE5-inhibitor-induced relaxations and cGMP generation only in the CC in diabetic ED patients. Endothelial and PDE5-inhibitor-induced vasodilations of PRAs were potentiated only in diabetes. Improvements in endothelial function in diabetes were also achieved with a specific inhibitor of the PKC beta 2 isoform or an NADPH-oxidase inhibitor, apocynin, which prevented PDBu-induced impairment in non-diabetic patients. PKC inhibition counteracted NO/cGMP impairment and endothelial dysfunction in diabetes-related ED, potentially improving response to PDE5 inhibition
CureMate: A clinical decision support system for breast cancer treatment.
No full text20.500.12530/87908Breast Cancer (BC) poses significant challenges in treatment decision-making. Multiple first treatment lines are currently available, determined by several patient-specific factors that need to be considered in the decision-making process. To present CureMate, a Clinical Decision Support System to predict the most effective initial treatment for BC patients. Different artificial intelligence models based on demographic, anatomopathological and magnetic resonance imaging variables are studied. CureMate's web application allows for easy use of the best model. A database of 232 BCE patients, each described by 29 variables, was established. Out of four machine learning algorithms, specifically Decision Tree Classifier (DTC), Gaussian Naïve Bayes (GNB), k-Nearest Neighbor (K-NN), and Support Vector Machine (SVM), the most suitable model for the task was identified, optimized and independently tested. SVM was identified as the best model for BC treatment planning, resulting in a test accuracy of 0.933. CureMate's web application, including the SVM model, allows for introducing the relevant patient variables and displays the suggested first treatment step, as well as a diagram of the following steps. The results demonstrate CureMate's high accuracy and effectiveness in clinical settings, indicating its potential to aid practitioners in making informed therapeutic decisions
Clinical Profile and Prognosis of Patients with Left-Sided Infective Endocarditis with Surgical Indication Who Are Not Operated.
No full text20.500.12530/87885Approximately a quarter of patients with infective endocarditis (IE) who have surgical indication only receive antibiotic treatment. Their short-term prognosis is dismal. We aimed to describe the characteristics of this group of patients to evaluate the mortality according to the cause of rejection and type of surgical indication and to analyze their prognostic factors of mortality. From 2005 to 2022, 1105 patients with definite left-sided IE were consecutively attended in three tertiary hospitals. Of them, 912 (82.5%) had formal surgical indication according to the most recent European Guidelines available in each period of the study and 303 (33%) only received medical treatment. These were older, had more comorbidities and higher in-hospital (46% vs. 24%;
Myocarditis and pericarditis risk with mRNA COVID-19 vaccination compared to unvaccinated individuals: A retrospective cohort study in a Spanish Tertiary Hospital.
No full text20.500.12530/87913This study compared the incidence of pericarditis and myocarditis in patients exposed to mRNA COVID-19 vaccines to the incidence in those who were not vaccinated, considering the incidence of these conditions resulting from COVID-19 infection. This was a retrospective cohort study of individuals assigned to health area of La Paz University Hospital in Spain. The exposure factor was vaccination with mRNA COVID-19 vaccines between December 27th, 2020 and January 9th, 2022 with a minimum follow-up of one month. The outcome was the incidence of pericarditis or myocarditis in these individuals. The incidence of pericarditis and myocarditis in the total population exposed to at least one dose of mRNA COVID-19 vaccines was 5/100,000 (CI95%:3 to 8 per 100,000), compared to 70/100,000 (CI95%: 66 to 92 per 100,000) in those who were not vaccinated. In the adolescent population (aged 12-17), the incidence was 10/100,000 in vaccinated population (CI95%: 5 to 45 per 100,000) compared to 20/100,000 in unvaccinated (CI95%: 6 to 79 per 100,000). The incidence of pericarditis or myocarditis in patients with COVID-19 infection was 200/100,000 people (CI95%: 114 to 306 per 100,000). The most common cause of pericarditis and myocarditis in the cohort was idiopathic/infectious (74 cases). Cases of myocarditis attributed to COVID-19 infection were more severe and had higher mortality rates compared to cases with other causes. The incidence of pericarditis and myocarditis in patients exposed to mRNA COVID-19 vaccines was lower than in those who were not vaccinated, especially in adults.The most common cause of pericarditis and myocarditis was idiopathic/infectious, but the most frequent cause in adolescent patients was mRNA COVID-19 vaccination. Cases of myocarditis due to COVID-19 infection were more severe and had greater mortality