Update on the Effects of Antioxidants on Diabetic Retinopathy: In Vitro Experiments, Animal Studies and Clinical Trials

Current therapies for diabetic retinopathy (DR) incorporate blood glucose and blood pressure control, vitrectomy, photocoagulation, and intravitreal injections of anti-vascular endothelial growth factors or corticosteroids. Nonetheless, these techniques have not been demonstrated to completely stop the evolution of this disorder. The pathophysiology of DR is not fully known, but there is more and more evidence indicating that oxidative stress is an important mechanism in the progression of DR. In this sense, antioxidants have been suggested as a possible therapy to reduce the complications of DR. In this review we aim to assemble updated information in relation to in vitro experiments, animal studies and clinical trials dealing with the effect of the antioxidants on DR

Effect of the implementation of clinical guidelines on management of candidemia in elderly patients

Introduction: Mortality from candidemia is higher in elderly population than in younger patients, which may be related to suboptimal management. The aim of the present study is to evaluate adherence to the recommendations for the clinical management of candidemia in a population over 75 years before and after implementing specific training. Patients and Methods: We recorded retrospectively data from candidemia episodes in elderly patients during two periods of time: 2010–2015 years (before training) and 2017–2022 years (after training), as well as adherence to the recommendations of the clinical practice guidelines, mortality and consultation to infectious disease specialists. Results: Forty-five episodes of candidemia were recorded in the first period and 29 episodes in the second period. A better compliance to the recommendations of the clinical practice guidelines was observed in the second period: echocardiogram performance (75.9% vs. 48.9% p= .021), fundoscopy (65.5% vs. 44.4% p= .076), follow-up blood cultures (72.4% vs. 42.2% p= .011), removal of central venous catheter (80% vs. 52.9% p= .080) and adequate antifungal treatment (82.6% vs. 52.6% p= .018). A trend towards lower mortality was observed during the second period (27.6% vs. 44.4% p= .144). Conclusion: The improvement of knowledge of clinical guidelines on candidemia and the participation of infectious disease specialists may increase the quality of care in elderly patients with candidemia. It would be necessary to enlarge the sample size to evaluate the real impact of this intervention on mortality

Use of Monoclonal Antibodies in Immunocompromised Patients Hospitalized with Severe COVID-19: A Retrospective Multicenter Cohort

This work was supported by the Research Institute Puerta de Hierro-Segovia de Aranda (IDIPHSA), funding number 0040200108 (2.400€).Objective: We aim to describe the safety and efficacy of sotrovimab in severe cases of COVID-19 in immunocompromised hosts. Methods: We used a retrospective multicenter cohort including immunocompromised hospitalized patients with severe COVID-19 treated with sotrovimab between October 2021 and December 2021. Results: We included 32 patients. The main immunocompromising conditions were solid organ transplantation (46.9%) and hematological malignancy (37.5%). Seven patients (21.9%) had respiratory progression: 12.5% died and 9.4% required mechanical ventilation. Patients treated within the first 14 days of their symptoms had a lower progression rate: 12.0% vs. 57.1%, p = 0.029. No adverse event was attributed to sotrovimab. Conclusions: Sotrovimab was safe and may be effective in its use for immunocompromised patients with severe COVID-19. More studies are needed to confirm these preliminary data.Depto. de MedicinaFac. de MedicinaTRUEResearch Institute Puerta de Hierro-Segovia de Aranda (IDIPHSA)pu

Neuroinflammation-Related Proteins NOD2 and Spp1 Are Abnormally Upregulated in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of unknown etiology and poorly understood pathophysiology. There is no specific biomarker either for diagnosis or prognosis. The aim of our study was to investigate differentially expressed proteins in the CSF and serum from patients with ALS to determine their role in the disease process and evaluate their utility as diagnostic or prognostic biomarkers. We performed mass spectrometry in the CSF from 3 patients with ALS and 3 healthy controls (HCs). The results were compared with motor cortex dysregulated transcripts obtained from 11patients with sporadic ALS and 8 HCs. Candidate proteins were tested using ELISA in the serum of 123 patients with ALS, 30 patients with Alzheimer disease (AD), 28 patients with frontotemporal dementia (FTD), and 102 HCs. Patients with ALS, AD, and FTD were prospectively recruited from January 2003 to December 2020. A group of age-matched HCs was randomly selected from the Sant Pau Initiative on Neurodegeneration cohort of the Sant Pau Memory Unit. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and osteopontin (Spp1) were differentially expressed in the CSF and the motor cortex transcriptome of patients with ALS compared with that in HCs (p < 0.05). NOD2 and Spp1 levels were significantly higher in sera from patients with ALS than in HCs (p < 0.001). Receiver operating characteristic analysis showed an area under the curve of 0.63 for NOD2 and 0.81 for Spp1. NOD2 levels were significantly lower in patients with AD and FTD than in patients with ALS (p < 0.0001), but we found no significant differences in Spp1 levels between patients with ALS, AD (p = 0.51), and FTD (p = 0.42). We found a negative correlation between Spp1 levels and ALS functional rating scale (r = −0.24, p = 0.009). Our discovery-based approach identified NOD2 as a novel biomarker in ALS and adds evidence to the contribution of Spp1 in the disease process. Both proteins are involved in innate immunity and autophagy and are increased in the serum from patients with ALS. Our data support a relevant role of neuroinflammation in the pathophysiology of the disease and may identify targets for disease-modifying treatments in ALS. Further longitudinal studies should investigate the diagnostic and prognostic value of NOD2 and Spp1 in clinical practice

Multi-touch gestures for pre-kindergarten children

The direct manipulation interaction style of multi-touch technology makes it the ideal mechanism for learning activities from pre-kindergarteners to adolescents. However, most commercial prekindergarten applications only support tap and drag operations. This paper investigates pre-kindergarteners' (2–3 years of age) ability to perform other gestures on multi-touch surfaces. We found that these infants could effectively perform additional gestures, such as one-finger rotation and two-finger scale up and down, just as well as basic gestures, despite gender and age differences. We also identified cognitive and precision issues that may have an impact on the performance and feasibility of several types of interaction (double tap, long press, scale down and two-finger rotation) and propose a set of design guidelines to mitigate the associated problems and help designers envision effective interaction mechanisms for this challenging age range. & 2014 Elsevier Ltd. All rights reserved.We would like to thank the Universitat Politecnica de Valencia2 and the Itultu3 Pre-kindergarten Schools for their collaboration in this study as well as the anonymous reviewers for their helpful comments. This research has been funded by the Spanish Ministry of Economy and Competitiveness and by the FEDER funds of the EU under the project Grants CreateWorlds (TIN2010-20488) and insPIre (TIN2012-34003). The work is also supported by a post-doctoral fellowship within the VALi+d program from Conselleria d'Educacio, Cultura i Esport (Generalitat Valenciana) to A. Catala (APOSTD/2013/013). Vicente Nacher received a Research Collaboration Scholarship (Project 2012/32/00004) for this work from the Spanish Ministry of Education.Nácher Soler, VE.; Jaén Martínez, FJ.; Navarro, E.; Catalá Bolós, A.; Gonzalez, P. (2015). Multi-touch gestures for pre-kindergarten children. International Journal of Human-Computer Studies. 73:37-51. https://doi.org/10.1016/j.ijhcs.2014.08.004S37517

A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

Introduction: A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy.&lt;p&gt;&lt;/p&gt; Methods: Sixty-six non-HLA SNPs showing a P value &#60;10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays. Results: We observed nominal associations for both PPARG rs310746 (PMH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (PMH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis.&lt;p&gt;&lt;/p&gt; Conclusion: Our results suggest a role of PPARG gene in the development of SSc

Safety and efficacy of ribociclib plus letrozole in patients with HR+, HER2– advanced breast cancer: Results from the Spanish sub-population of the phase 3b CompLEEment-1 trial

Background: Breast cancer is the most common malignancy and the second leading cause of cancer-related mortality in Spanish women. Ribociclib in combination with endocrine therapy (ET) has shown superiority in prolonging survival in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) vs. ET alone.Methods: CompLEEment-1 is a single-arm, open-label phase 3b trial evaluating ribociclib plus letrozole in a broad population of patients with HR+, HER2- ABC. The primary endpoints were safety and tolerability. Here we report data for Spanish patients enrolled in CompLEEment-1.Results: A total of 526 patients were evaluated (median follow-up: 26.97 months). Baseline characteristics showed a diverse population with a median age of 54 years. At study entry, 56.5% of patients had visceral metastases and 8.7% had received prior chemotherapy for advanced disease. Rates of all-grade and Grade >= 3 adverse events (AEs) were 99.0% and 76.2%, respectively; 21.3% of patients experienced a serious AE, and 15.8% of AEs led to treatment discontinuation. AEs of special interest of neutropenia, increased alanine aminotransferase, increased aspartate aminotransferase and QTcF prolongation occurred in 77.8%, 14.8%, 11.4% and 4.0% of patients, respectively. Patients aged >70 years experienced increased rates of all-grade and Grade >= 3 neutropenia and anemia. Efficacy results were consistent with the global study.Conclusions: Results from Spanish patients enrolled in CompLEEment-1 are consistent with global data showing efficacy and a manageable safety profile for ribociclib plus letrozole treatment in patients with HR+, HER2-ABC, including populations of interest (NCT02941926).Trial registration: ClinicalTrials.gov NCT0294192

A Large Multicenter Prospective Study of Community-Onset Healthcare Associated Bacteremic Urinary Tract Infections in the Era of Multidrug Resistance: Even Worse than Hospital Acquired Infections?

Introduction: Healthcare-associated (HCA) infections represent a growing public health problem. The aim of this study was to compare community-onset healthcare associated (CO-HCA) bacteremic urinary tract infections (BUTI) and hospital-acquired (HA)-BUTI with special focus on multidrug resistances (MDR) and outcomes. Methods: ITUBRAS-project is a prospective multicenter cohort study of patients with HCA-BUTI. All consecutive hospitalized adult patients with CO-HCA-BUTI or HA-BUTI episode were included in the study. Exclusion criteria were: patients < 18 years old, non-hospitalized patients, bacteremia from another source or primary bacteremia, non-healthcare-related infections and infections caused by unusual pathogens of the urinary tract. The main outcome variable was 30-day all-cause mortality with day 1 as the first day of positive blood culture. Logistic regression was used to analyze factors associated with clinical cure at hospital discharge and with receiving inappropriate initial antibiotic treatment. Cox regression was used to evaluate 30-day all-cause mortality. Results: Four hundred forty-three episodes were included, 223 CO-HCA-BUTI. Patients with CO-HCA-BUTI were older (p < 0.001) and had more underlying diseases (p = 0.029) than those with HA-BUTI. The severity of the acute illness (Pitt score) was also higher in CO-HCA-BUTI (p = 0.026). Overall, a very high rate of MDR profiles (271/443, 61.2%) was observed, with no statistical differences between groups. In multivariable analysis, inadequate empirical treatment was associated with MDR profile (aOR 3.35; 95% CI 1.77–6.35), Pseudomonas aeruginosa (aOR 2.86; 95% CI 1.27–6.44) and Charlson index (aOR 1.11; 95% CI 1.01–1.23). Mortality was not associated with the site of acquisition of the infection or the presence of MDR profile. However, in the logistic regression analyses patients with CO-HCA-BUTI (aOR 0.61; 95% CI 0.40–0.93) were less likely to present clinical cure. Conclusion: The rate of MDR infections was worryingly high in our study. No differences in MDR rates were found between CO-HCA-BUTI and HA-BUTI, in the probability of receiving inappropriate empirical treatment or in 30-day mortality. However, CO-HCA-BUTIs were associated with worse clinical cure. © 2021, The Author(s)