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    Cytotoxicity, Epidermal Barrier Function and Cytokine Evaluation after Antiseptic Treatment in Bioengineered Autologous Skin Substitute.

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    Bioengineered autologous skin substitutes (BASS) technology is an emerging field for skin burn therapy. However, further studies on BASS characterization, viability against standard procedures for wound healing, and protocol optimization are necessary for the improvement of BASS technology for clinical use. The aim of this study is to evaluate the effect of common antiseptics for clinical use in BASS, focusing on cell viability, inflammatory cytokine pattern, and epithelium and skin barrier integrity, in order to establish the most adequate treatment for wound care after BASS grafting. Human keratinocytes (hKT) and dermal fibroblasts (hDF) were isolated from foreskin samples and integrated into hyaluronic acid-based BASS. The following antiseptics were applied every 48 h: ethanol (70%), chlorhexidine digluconate (1%), sodium hypochlorite (0.02%), povidone iodine (100 mg/mL), and polyhexanide (0.1%), during a follow-up of 16 days. Sodium hypochlorite was the only treatment that showed a high cell viability percentage throughout the evaluation time compared to other antiseptic treatments, as well as a similar cytokine secretion pattern as control BASS. No significant differences were found regarding epidermal barrier function. These findings point towards sodium hypochlorite being the least aggressive antiseptic treatment for BASS post-transplantation wound care.We gratefully acknowledge financial support from the Ministry of Health and Families of the Andalusian Regional Government (PIGE-0242-2019) and from the Carlos III Health Institute (PI17/02083). The work of María I. Quiñones Vico was supported by a predoctoral fellowship (BOE22/10/2019) from the Ministry of Science, Innovation and Universities of Spain.S

    Seven-versus 14-day course of antibiotics for the treatment of bloodstream infections by Enterobacterales: a randomized, controlled trial

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    Objective: To prove that 7-day courses of antibiotics for bloodstream infections caused by members of the Enterobacterales (eBSIs) allow a reduction in patients' exposure to antibiotics while achieving clinical outcomes similar to those of 14-day schemes.Methods: A randomized trial was performed. Adult patients developing eBSI with appropriate source control were assigned to 7 or 14 days of treatment, and followed 28 days after treatment cessation; treatments could be resumed whenever necessary. The primary endpoint was days of treatment at the end of follow-up. Clinical outcomes included clinical cure, relapse of eBSI and relapse of fever. A superiority margin of 3 days was set for the primary endpoint, and a non-inferiority margin of 10% was set for clinical outcomes. Efficacy and safety were assessed together with a DOOR/RADAR (desirability of outcome ranking and response adjusted for duration of antibiotic risk) analysis.Results: 248 patients were assigned to 7 (n = 119) or 14 (n = 129) days of treatment. In the intention-to-treat analysis, median days of treatment at the end of follow-up were 7 and 14 days (difference 7, 95%CI 7-7). The non-inferiority margin was also met for clinical outcomes, except for relapse of fever (-0.2%, 95%CI -10.4 to 10.1). The DOOR/RADAR showed that 7-day schemes had a 77.7% probability of achieving better results than 14-day treatments.Conclusions: 7-day schemes allowed a reduction in antibiotic exposure of patients with eBSI while achieving outcomes similar to those of 14-day schemes. The possibility of relapsing fever in a limited number of patients, without relevance to final outcomes, may not be excluded, but was overcome by the benefits of shortening treatments.S

    EHO-85: A Multifunctional Amorphous Hydrogel for Wound Healing Containing Olea europaea Leaf Extract: Effects on Wound Microenvironment and Preclinical Evaluation.

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    The prevalence of chronic wounds is increasing due to the population aging and associated pathologies, such as diabetes. These ulcers have an important socio-economic impact. Thus, it is necessary to design new products for their treatment with an adequate cost/effectiveness ratio. Among these products are amorphous hydrogels. Their composition can be manipulated to provide a favorable environment for ulcer healing. The aim of this study was to evaluate a novel multifunctional amorphous hydrogel (EHO-85), containing Olea europaea leaf extract, designed to enhance the wound healing process. For this purpose, its moistening ability, antioxidant capacity, effect on pH in the wound bed of experimental rats, and the effect on wound healing in a murine model of impaired wound healing were assessed. EHO-85 proved to be a remarkable moisturizer and its application in a rat skin wound model showed a significant antioxidant effect, decreasing lipid peroxidation in the wound bed. EHO-85 also decreased the pH of the ulcer bed from day 1. In addition, in mice (BKS. Cg-m +/+ Leprdb) EHO-85 treatment showed superior wound healing rates compared to hydrocolloid dressing. In conclusion, EHO-85 can speed up the closure of hard-to-heal wounds due to its multifunctional properties that are able to modulate the wound microenvironment, mainly through its remarkable effect on reactive oxygen species, pH, and moistening regulation.S

    Cardiometabolic and Nutritional Morbidities of a Large, Adult, PKU Cohort from Andalusia.

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    The establishment of national neonatal screening systems has resulted in improved quality of life and life expectancy in patients with phenylketonuria (PKU). This has led to the development of multidisciplinary treatment units for adult patients with PKU. We present a retrospective descriptive study of a cohort of 90 adult patients (>16 years) with PKU under active follow-up in two reference centers in Andalusia. We analyzed disease severity, treatment type, demographic variables, cardiovascular risk factors, vitamin and hormone profiles, and bone metabolism. The median (interquartile range)age was 29 (23−38) years, 47 (52.2%) were women and 43 (47.8%) were men. Eighty (88.9%) had classical PKU, five (5.6%) moderate PKU, and five (5.6%) mild PKU. Diagnosis was by neonatal screening in 62 (68.9%) of the patients. The rest had late diagnosis. Treatment with sapropterin was given to 18 (20%) patients and diet and nutrition therapy to 72 (80%). There was adequate metabolic control according to Phe levels in 43 (47.78%) patients. Body mass index was 26.61 (22.7−31.1) kg/m2. Twenty-six (29.2%) patients had obesity, 7 (7.9%) hypertension, 2 (2.2%) type 2 diabetes, 26 (28.89%) dyslipidemia, 14 (15.6%) elevated total cholesterol, 9 (15.8%) decreased high-density lipoprotein cholesterol and 16 (17.8%) hypertriglyceridemia. Seven (10.3%) patients had osteoporosis and 28 (41.17%) osteopenia. Twenty-six (30.6%) had vitamin D (25OH) deficiency and four (4.5%) vitamin B12 deficiency. Although we observed no differences with most vascular risk factors, we found a high prevalence of obesity in relation to the age of the cohort. A continued evaluation of comorbidities in these patients is therefore needed, despite adequate metabolic control.S

    The Gut Microbiota of Obese Children Releases Lower Antioxidant Capacity from Food than That of Lean Children.

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    The prevalence of obesity has been increasing in children over the last few decades, becoming a concern for health professionals and governments. Gut microbial community structure in obese people have been found to differ from that of lean subjects for some taxa which could result in different production of microbial metabolites. The aim of the present work was to study whether the gut microbiota from obese children extracts a different concentration of antioxidant capacity than the gut microbiota from lean children. For this purpose, different foods were in vitro digested and in vitro fermented using fecal material from obese and lean children. FRAP, DPPH and Folin-Ciocalteu methods were used to measure the antioxidant capacity released during digestion and fermentation. Overall, when using lean gut microbiota, antioxidant capacity released was higher when measured via DPPH and FRAP. Moreover, according to DPPH results, lean gut microbiota could potentially release more antioxidant power from vegetables than from animal products, while obese gut microbiota did the opposite. On the contrary, with the FRAP method obese gut microbiota released higher levels of antioxidant power from plant products than from animal products, but the final antioxidant capacity was still lower than that released by lean gut microbiota. Therefore, these results reflect that the total antioxidant capacity of foods is influenced by the gut microbiota, although whether that antioxidant capacity is released from plant or animal products can be slightly influenced by the method used for analysis.This work was supported by the European Research Commission (Research Executive Agency) under de research project Stance4Health under Grant (Contract Nº 816303) granted to José Á. Rufián Henares and by the Plan Propio de Investigación y Transferencia of the University of Granada under the program “Intensificación de la Investigación, modalidad B”, granted to José Á. Rufián HenaresS

    Cognitive, behavioural or cognitive-behavioural self-help interventions for subclinical depression in older adults: A systematic review and meta-analysis.

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    Subclinical depression is a risk factor for the development of major depression in older adults. We aimed to determine the effectiveness of pure self-help or self-help with minimal support to reduce depressive symptoms and to prevent the onset of major depression in this population. This was a systematic review and meta-analysis of trials that used self-administrated cognitive, behavioural or cognitive-behavioural interventions for older adults with subclinical depression compared to control groups. Medline, Embase, PsycInfo and Cochrane databases were searched for relevant studies. We analysed eight trials involving 1449 participants. A small but significant effect favouring the intervention was found at short-term [d = 0.33; 95% CI (Confidence Interval): 0.20-0.47] and at long-term (d = 0.22; 95% CI: 0.04-0.40) for depressive symptoms. None of the studies looked at the preventive effect of self-help interventions in reducing the probability of a subsequent diagnosis of major depression. The low number of studies meant that it was not possible to test for publication bias. The absence of pre-published protocols for many of the studies meant that there is a possibility of selective reporting bias for some of the primary studies. There is some evidence that cognitive-behavioural self-help interventions may reduce depressive symptoms in older adults with subclinical depression. However, no study examined whether the intervention had a preventative effect in reducing the likelihood of a subsequent diagnosis of major depression.S

    Proinflammatory Polyphosphate Increases in Plasma of Obese Children with Insulin Resistance and Adults with Severe Type 2 Diabetes.

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    Obesity increases the risk of insulin resistance and type 2 diabetes through increased inflammation at cellular and tissue levels. Therefore, study of the molecular elements involved in obesity-related inflammation may contribute to preventing and controlling it. Inorganic polyphosphate is a natural phosphate polymer that has recently been attracting more attention for its role in inflammation and hemostasis processes. Polyphosphates are one of the main constituents of human platelets, which are secreted after platelet activation. Among other roles, they interact with multiple proteins of the coagulation cascade, trigger bradykinin release, and inhibit the complement system. Despite its importance, determinations of polyphosphate levels in blood plasma had been elusive until recently, when we developed a method to detect these levels precisely. Here, we perform cross sectional studies to evaluate plasma polyphosphate in: 25 children, most of them with obesity and overweight, and 20 adults, half of them with severe type 2 diabetes. Our results show that polyphosphate increases, in a significant manner, in children with insulin resistance and in type 2 diabetes patients. As we demonstrated before that polyphosphate decreases in healthy overweight individuals, these results suggest that this polymer could be an inflammation biomarker in the metabolic disease onset before diabetes.S

    Mortality and biochemical recurrence after surgery, brachytherapy, or external radiotherapy for localized prostate cancer: a 10-year follow-up cohort study.

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    To compare the effectiveness at ten years of follow-up of radical prostatectomy, brachytherapy and external radiotherapy, in terms of overall survival, prostate cancer-specific mortality and biochemical recurrence. Cohort of men diagnosed with localized prostate cancer (T1/T2 and low/intermediate risk) from ten Spanish hospitals, followed for 10 years. The treatment selection was decided jointly by patients and physicians. Of 704 participants, 192 were treated with open radical retropubic prostatectomy, 317 with 125I brachytherapy alone, and 195 with 3D external beam radiation. We evaluated overall survival, prostate cancer-specific mortality, and biochemical recurrence. Kaplan-Meier estimators were plotted, and Cox proportional-hazards regression models were constructed to estimate hazard ratios (HR), adjusted by propensity scores. Of the 704 participants, 542 patients were alive ten years after treatment, and a total of 13 patients have been lost during follow-up. After adjusting by propensity score and Gleason score, brachytherapy and external radiotherapy were not associated with decreased 10-year overall survival (aHR = 1.36, p = 0.292 and aHR = 1.44, p = 0.222), but presented higher biochemical recurrence (aHR = 1.93, p = 0.004 and aHR = 2.56, p <0.001) than radical prostatectomy at ten years of follow-up. Higher prostate cancer-specific mortality was also observed in external radiotherapy (aHR = 9.37, p = 0.015). Novel long-term results on the effectiveness of brachytherapy to control localized prostate cancer ten years after treatment, compared to radical prostatectomy and external radiotherapy, showed high overall survival, similar to radical prostatectomy, but with a higher risk of biochemical progression. These findings provide valuable information to facilitate shared clinical decision-making.T he study was funded through competitive grants from the Instituto de Salud Carlos III FEDER: Fondo Europeo de Desarrollo Regional (Grant numbers PI02/0668, PI08/90090, PI13/00412, PI21/00023, and FI19/00229); Generalitat de Catalunya, Spain (Grant numbers 086/24/2000 and 2017 SGR 452); and CIBER de Epidemiología y Salud Pública CIBERESP (research funding CB06/02/0046).S

    Long-Term Outcomes of Dose-Escalated Hypofractionated Radiotherapy in Localized Prostate Cancer.

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    This retrospective study aimed to provide some clinical outcomes regarding effectiveness, toxicity, and quality of life in PCa patients treated with dose-escalated moderately hypofractionated radiation therapy (HFRT). Patients received HFRT to a total dose of 66 Gy in 22 fractions (3 Gy/fraction) delivered via volume modulated arc therapy (VMAT) in 2011-2016. Treatment effectiveness was measured by the biochemical failure-free survival rate. Toxicity was assessed according to the criteria of the Radiation Therapy Oncology Group (RTOG) and quality of life according to the criteria of the European Organization for Research and Treatment of Cancer (EORTC). In this regard, quality of life (QoL) was measured longitudinally, at a median of 2 and 5 years after RT. Enrolled patients had low-risk (40.2%), intermediate-risk (47.5%), and high-risk (12.3%) PCa. Median follow-up was 75 months. The biochemical failure-free survival rate was 94.2%. The incidence of acute grade 2 or higher gastrointestinal (GI) and genitourinary (GU) toxicity was 9.84% and 28.69%, respectively. The incidence rate of late grade 2 or higher GI and GU toxicity was 1.64% and 4.10%, respectively. Expanded Prostate Cancer Index Composite (EPIC) scores showed that the majority of patients maintained their QoL. HFRT to 66 Gy with VMAT was associated with adequate biochemical control, low toxicity and good reported GU and GI quality of life.S

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