Evaluation of a Lung Ultrasound Score in Hospitalized Adult Patients with COVID-19 in Barcelona, Spain.

Background/Objectives: During the COVID-19 pandemic and the burden on hospital resources, the rapid categorization of high-risk COVID-19 patients became essential, and lung ultrasound (LUS) emerged as an alternative to chest computed tomography, offering speed, non-ionizing, repeatable, and bedside assessments. Various LUS score systems have been used, yet there is no consensus on an optimal severity cut-off. We assessed the performance of a 12-zone LUS score to identify adult COVID-19 patients with severe lung involvement using oxygen saturation (SpO2)/fractional inspired oxygen (FiO2) ratio as a reference standard to define the best cut-off for predicting adverse outcomes. Methods: We conducted a single-centre prospective study (August 2020-April 2021) at Hospital del Mar, Barcelona, Spain. Upon admission to the general ward or intensive care unit (ICU), clinicians performed LUS in adult patients with confirmed COVID-19 pneumonia. Severe lung involvement was defined as a SpO2/FiO2 ratio <315. The LUS score ranged from 0 to 36 based on the aeration patterns. Results: 248 patients were included. The admission LUS score showed moderate performance in identifying a SpO2/FiO2 ratio <315 (area under the ROC curve: 0.71; 95%CI 0.64-0.77). After adjustment for COVID-19 risk factors, an admission LUS score ≥17 was associated with an increased risk of in-hospital death (OR 5.31; 95%CI: 1.38-20.4), ICU admission (OR 3.50; 95%CI: 1.37-8.94) and need for IMV (OR 3.31; 95%CI: 1.19-9.13). Conclusions: Although the admission LUS score had limited performance in identifying severe lung involvement, a cut-off ≥17 score was associated with an increased risk of adverse outcomes. and could play a role in the rapid categorization of COVID-19 pneumonia patients, anticipating the need for advanced care.

Neurobehavioral Progress and Signs of Transition in Children With Prolonged Disorders of Consciousness: A Retrospective Longitudinal Study With the Coma Recovery Scale-Revised.

BACKGROUND: Research on disorders of consciousness in children is scarce and includes disparate and barely comparable participants and assessment instruments and therefore provides inconclusive information on the clinical progress and recovery in this population. This study retrospectively investigated the neurobehavioral progress and the signs of transition between states of consciousness in a group of children admitted to a rehabilitation program either with an unresponsive wakefulness syndrome (UWS) or in a minimally conscious state (MCS). METHODS: Systematic weekly assessments were conducted with the Coma Recovery Scale-Revised (CRS-R) until emergence from MCS, discharge, or death. RESULTS: Twenty-one children, nine admitted with a UWS and 12 admitted in an MCS, were included in the study. Four children with a UWS transitioned to an MCS with a CRS-R of 10 (9.2 to 12.2) by showing visual pursuit, visual fixation, or localization to noxious stimulation. Twelve children emerged from the MCS with a CRS-R of 20.5 (19 to 21.7). Children who emerged from the MCS had had a shorter time postinjury and higher CRS-R at admission, compared with those who did not emerge. CONCLUSIONS: Almost half of the children who were admitted with a UWS transitioned to an MCS, and almost all who were admitted in an MCS emerged from this state. Children who emerged had shorter times since injury and higher scores on the CRS-R at admission, compared with those who did not emerge.

Minimally conscious state plus versus minus: Likelihood of emergence and long-term functional independence.

OBJECTIVE: Severe brain injuries can result in disorders of consciousness, such as the Minimally Conscious State (MCS), where individuals display intermittent yet discernible signs of conscious awareness. The varied levels of responsiveness and awareness observed in this state have spurred the progressive delineation of two subgroups within MCS, termed "plus" (MCS+) and "minus" (MCS-). However, the clinical validity of these classifications remains uncertain. This study aimed to investigate and compare the likelihood of emergence from MCS, as well as the functional independence after emergence, in individuals categorized as in MCS+ and MCS-. METHODS: Demographic and behavioral data of 80 participants, admitted as either in MCS+ (n = 30) or MCS- (n = 50) to a long-term neurorehabilitation unit, were retrospectively analyzed. The neurobehavioral condition of each participant was evaluated weekly until discharge, demise, or emergence from MCS. The functional independence of those participants who emerged from MCS was assessed 6 months after emergence. RESULTS: While only about half of the individuals classified as in MCS- (n = 24) emerged from the MCS, all those admitted as in MCS+ did, and in a shorter postinjury period. Despite these differences, all individuals who emerged from the MCS demonstrated similar high disability and low functional independence 6 months after emergence, regardless of their state at admission. INTERPRETATION: Individuals classified as MCS+ exhibited a higher likelihood of emergence and a shorter time to emergence compared to those in MCS-. However, the level of functional independence 6 months after emergence was found to be unrelated to the initial state at admission.

Integrative approach to elucidate the embryological effects of caffeine in Cyprinus carpio: Bioconcentration and alteration of oxidative stress-related gene expression patterns.

Caffeine (CAF) is an alkaloid, which acts as a central nervous system (CNS) stimulant drug. In recent years, CAF has been recurrently detected in water bodies, generating deleterious effects in aquatic organisms. The information on the toxic effects of CAF in the environment is still limited. Thus, the objective of this work was to determine whether CAF at environmentally relevant concentrations (CAF concentrations were selected based on studies on the worldwide occurrence of this compound and on the toxicity of CAF in aquatic species) is capable of inducing alterations to embryonic development and alteration of oxidative stress-related gene expression patterns in Cyprinus carpio. For this purpose, common carp embryos (2 hpf) were exposed to realistic concentrations of CAF until 96 hpf. Alterations to embryonic development and teratogenic effects were evaluated at 12, 24, 48, 72 and 96 hpf. In addition, oxidative stress in carp embryos at 72 and 96 hpf was evaluated by cellular oxidation biomarkers (lipoperoxidation level, hydroperoxide content and carbonyl protein content) and antioxidant enzymes activities (superoxide dismutase and catalase). Oxidative stress-related gene expression (sod, cat and gpx1) was also evaluated. Our results showed that CAF concentrations above 500 ng/L are capable of producing teratogenic effects. Furthermore, CAF was able to induce alterations such cardiac malformations, somite alterations, pericardial edema and chorda malformations. Concerning oxidative stress, the results demonstrated that CAF induce oxidative damage on the embryos of C. carpio. Our outcomes also showed up-regulations in genes related to antioxidant activity sod, cat and gpx by CAF exposure. In conclusion CAF at environmentally relevant concentrations is able to alter the embryonic development of common carp by the oxidative stress pathway. Based on the above evidence, it can be inferred that acute exposure to CAF can lead to a toxic response that significantly harms fish's health, adversely affecting their essential organs' functioning.

Functional and physicochemical properties of protein from giant squid (Dosidicus gigas) extracted using foam-aided pH-shift processing.

Jumbo squid (Dosidicus gigas) is a commercially valuable mollusk in Mexico; 80% of its body is edible. Despite the high protein content (∼18%) and low cholesterol content of this species, its high proteolytic activity (microbial and endogenous enzymes) induces protein degradation and consequent reduction in functional properties from a structural viewpoint. Gelation capacity (texture profile of the gels obtained), solubility, water holding capacity, foaming capacity, emulsification capacity, and emulsion stability were evaluated in protein concentrates obtained by foam-aided pH-shift processing: (A) myofibrillar protein extraction with distilled water and no pH-shifting; (B) alkaline solubilization and isoelectric precipitation; (C) acidic solubilization and isoelectric precipitation; and (D) process A and isoelectric precipitation. Process B showed superior gelation capacity, D had high emulsion stability across a wide range of pH values (4.0-8.0) and C lower plate counts of aerobic mesophilic. Therefore, all three alternative extraction processes showed techno-functional advantages. PRACTICAL APPLICATION: Jumbo squid is an abundant protein source in México, most of which is exported. Functional and physicochemical properties of muscle protein were improved by pH-shift processing. The recovered protein showed modifications of technological properties, using one of the methods described can lead to produce a protein extract with the most desirable attributes, such as foaming, emulsifying, or gelling capacities. The functional and physicochemical properties of protein from squid can be enhanced by selecting a certain pH-shift processing, depending on the desirable use. There is a broad perspective on the use of these protein extracts as ingredients or additives.

Chronic intake of an enriched diet with spirulina (Arthrospira maxima) alleviates the embryotoxic effects produced by realistic concentrations of tetracycline in Danio rerio.

Tetracycline (TC) is one of the most consumed antibiotics worldwide. Due to its high consumption, recent studies have reported its presence in aquatic environments and have assessed its effects on fish, algae, and daphniids. However, in most of those works, authors have tested TC toxicity at concentrations higher than the ones reported in the water matrix. Herein, we aimed to assess the likely embryotoxic and oxidative damage induced by environmentally relevant concentrations of TC in embryos of Danio rerio. Moreover, we seek to determine whether or not an enriched diet with spirulina can alleviate the embryotoxic damage produced by TC. Our findings indicated that TC at concentrations of 50 to 500 ng/L induced pericardial edema, tail deformities, and absence of head and fin in embryos after 96 h of exposure. Moreover, this antibiotic prompted the death of embryos in a concentration-dependent manner. According to our integrated biomarker response index, TC induced oxidative damage on Danio rerio embryos, as star plots showed a tendency to lipoperoxidation, hydroperoxides, and protein carbonyl content. Spirulina reduced the toxicity of TC by diminishing the levels of oxidative damage biomarkers, which resulted in a decrease in the rate of death and malformed embryos. Overall, TC at concentrations of ng/L prompted oxidative stress and embryotoxicity in the early life stages of Danio rerio; nonetheless, the algae spirulina was able to reduce the severity of those effects.

Identifying and regulating emotions after acquired brain injury: the role of interoceptive sensibility.

Introduction: Interoceptive deficits are associated with difficulties in identifying and regulating emotions. However, research on interoception after acquired brain injury (ABI) is scarce, and its relationship with emotional difficulties in this population is unknown. This study aimed to (1) examine differences in self-reported alexithymia, performance-based emotional awareness, emotion regulation, depression, and interoceptive sensibility between ABI and control individuals; and (2) analyze the role of adaptive interoceptive dimensions in these emotional processes after ABI. Methods: Forty-three individuals with ABI and 42 matched control individuals completed the Multidimensional Assessment of Interoceptive Awareness-2, the Toronto Alexithymia Scale, the Levels of Emotional Awareness Scale, the Difficulties in Emotion Regulation Scale, and the Hospital Anxiety and Depression Scale. Results: Compared to the control group, individuals with ABI showed reduced tendency to ignore unpleasant sensations increased severity of depressive symptoms, as well as tendencies to have greater difficulties in emotion regulation and lower emotional awareness. Additionally, interoceptive dimensions such as trusting, as well as not-distracting from and not-worrying about bodily sensations, played a relevant role in explaining lower alexithymia and difficulties in emotion regulation. Moreover, lower alexithymia and emotion dysregulation were related to less depressive symptoms. These relationships were invariant across ABI and control individuals. Discussion: Although individuals with ABI may have different levels of emotional abilities compared to non-ABI individuals, the relationship patterns between interoceptive and emotional processes appear to be similar between the two groups. This study suggests the potential benefit of addressing both interoceptive and emotional difficulties in treatments targeting such prevalent sequelae of ABI as depressive symptoms.

Chronic exposure to realistic concentrations of metformin prompts a neurotoxic response in Danio rerio adults.

Metformin (MET) is among the most consumed drugs around the world, and thus, it is considered the uppermost drug in mass discharged into water settings. Nonetheless, data about the deleterious consequences of MET on water organisms are still scarce and require further investigation. Herein, we aimed to establish whether or not chronic exposure to MET (1, 20, and 40 µg/L) may alter the swimming behavior and induce neurotoxicity in Danio rerio adults. After 4 months of exposure, MET-exposed fish exhibited less swimming activity when compared to control fish. Moreover, compared with the control group, MET significantly inhibited the activity of AChE and induced oxidative damage in the brain of fish. Concerning gene expression, MET significantly upregulated the expression of Nrf1, Nrf2, BAX, p53, BACE1, APP, PSEN1, and downregulated CASP3 and CASP9. Although MET did not overexpress the CASP3 gene, we saw a meaningful rise in the activity of this enzyme in the blood of fish exposed to MET compared to the control group, which we then confirmed by a high number of apoptotic cells in the TUNEL assay. Our findings demonstrate that chronic exposure to MET may impair fish swimming behavior, making them more vulnerable to predators.

Optimization of the Physical, Optical and Mechanical Properties of Composite Edible Films of Gelatin, Whey Protein and Chitosan.

The aim of this work was to evaluate the effect of the concentration of gelatin (G) (3-6 g), whey protein (W) (2.5-7.5 g) and chitosan (C) (0.5-2.5 g) on the physical, optical and mechanical properties of composite edible films (CEFs) using the response surface methodology (RSM), as well as optimizing the formulation for the packaging of foods. The results of the study were evaluated via first- and second-order multiple regression analysis to obtain the determination coefficient values with a good fit (R ˃ 0.90) for each of the response variables, except for the values of solubility and b*. The individual linear effect of the independent variables (the concentrations of gelatin, whey protein and chitosan) significantly affected (p ≤ 0.05) the water vapor permeability (WVP), strength and solubility of the edible films. The WVP of the edible films varied from 0.90 to 1.62 × 10-11 g.m/Pa.s.m2, the resistance to traction varied from 0.47 MPa to 3.03 MPa and the solubility varied from 51.06% to 87%. The optimized values indicated that the CEF prepared with a quantity of 4 g, 5 g and 3 g of gelatin, whey protein and chitosan, respectively, provided the CEF with a smooth, continuous and transparent surface, with L values that resulted in a light-yellow hue, a lower WVP, a maximum strength (resistance to traction) and a lower solubility. The results revealed that the optimized formulation of the CEF of G-W-C allowed a good validation of the prediction model and could be applied, in an effective manner, to the food packaging industry, which could help in mitigating the environmental issues associated with synthetic packaging materials.

Behavioral signs of recovery from unresponsive wakefulness syndrome to emergence of minimally conscious state after severe brain injury.

Precise description of behavioral signs denoting transition from unresponsive wakefulness syndrome/vegetative state (UWS/VS) to minimally conscious state (MCS) or emergence from MCS after severe brain injury is crucial for prognostic purposes. A few studies have attempted this goal but involved either non-standardized instruments, limited temporal accuracy or samples, or focused on (sub)acute patients. The objective of this study was to describe the behavioral signs that led to a change of diagnosis, as well as the factors influencing this transition, in a large sample of patients with chronic disorders of consciousness after severe brain injury. In this retrospective cohort study, 185 patients in UWS/VS or MCS were assessed with the Coma Recovery Scale Revised (CRS-R) five times within the two weeks following their admission to a neurorehabilitation center and then weekly until emergence from MCS, discharge or death. Of these 185 patients, 33 patients in UWS/VS and 45 patients in MCS transitioned to another state. Transition to MCS was mostly denoted by one behavioral sign (72%), predominantly visual fixation (57%), followed by localization to noxious stimulation (27%), visual pursuit (21%) and object manipulation (12%), and could be predicted by etiology, time post-injury and age. Emergence from MCS was characterized by one sign in 64% of patients and by two signs (functional communication and objects use) in the remaining cases, and could be predicted by time post-injury and number of behavioral signs at admission. Clinicians should be therefore advised to pay particular attention to visual and motor subscales of the CRS-R to detect behavioral recovery.

Oxidative stress as a potential mechanism by which guanylurea disrupts the embryogenesis of Danio rerio.

Metformin is one the most prescribed drug to treat type 2 diabetes. In wastewater treatment plants, this drug is bacterially transformed to guanylurea, which occurs at higher concentrations in the aquatic environments than its parent compound. Since there is a huge knowledge gap about the toxicity of this metabolite on aquatic organisms, we aimed to investigate the impact of guanylurea on the embryonic development and oxidative stress biomarkers of zebrafish (Danio rerio). For this effect, zebrafish embryos (4 h post fertilization) were exposed to 25, 50, 100, 200, 250, 25,000, 50,000, 75,000 µg/L guanylurea until 96 h post fertilization. Guanylurea led to a significant delay in the hatching process in all exposure groups. Furthermore, this transformation product affected the embryonic development of fish, inducing severe body alterations and consequently leading to their death. The most pronounced malformations were malformation of tail, scoliosis, pericardial edema, yolk deformation and craniofacial malformation. Concerning oxidative stress response, we demonstrated that guanylurea induced the antioxidant activity of superoxide dismutase, catalase, and glutathione peroxidase in zebrafish embryos. In addition, the levels of lipid peroxidation, protein carbonyl and hydroperoxide content were also increased in the embryos exposed to this transformation product. However, the integrated biomarker response (IBR) analysis carried out in this study demonstrated that oxidative damage biomarkers got more influence over the embryos than antioxidant enzymes. Thus, we can conclude that guanylurea induces oxidative stress in zebrafish embryos, and that this transformation product impair the normal development of this freshwater organism.

Antidiabetic drug metformin disrupts the embryogenesis in zebrafish through an oxidative stress mechanism.

In recent years, the consumption of metformin has increased not only due to the higher prevalence of type 2 diabetes, but also due to their usage for other indications such as cancer and polycystic ovary syndrome. Consequently, metformin is currently among the highest drug by weight released into the aquatic environments. Since the toxic effects of this drug on aquatic species has been scarcely explored, the aim of this work was to investigate the influence of metformin on the development and redox balance of zebrafish (Danio rerio) embryos. For this purpose, zebrafish embryos (4 hpf) were exposed to 1, 10, 20, 30, 40, 50, 75 and 100 µg/L metformin until 96 hpf. Metformin significantly accelerated the hatching process in all exposure groups. Moreover, this drug induced several morphological alterations on the embryos, affecting their integrity and consequently leading to their death. The most frequent malformations found on the embryos included malformation of tail, scoliosis, pericardial edema and yolk deformation. Regarding oxidative balance, metformin significantly induced the activity of antioxidant enzymes and the levels of oxidative damage biomarkers. However, our IBR analisis demonstrated that oxidative damage biomarkers got more influence over the embryos. Together these results demonstrated that metformin may affect the embryonic development of zebrafish and that oxidative stress may be involved in the generation of this embryotoxic process.

Role of asymptomatic bacteriuria on early periprosthetic joint infection after hip hemiarthroplasty. BARIFER randomized clinical trial.

PURPOSE: To evaluate preoperative asymptomatic bacteriuria (ASB) treatment to reduce early-periprosthetic joint infections (early-PJIs) after hip hemiarthroplasty (HHA) for fracture. METHODS: Open-label, multicenter RCT comparing fosfomycin-trometamol versus no intervention with a parallel follow-up cohort without ASB. PRIMARY OUTCOME: early-PJI after HHA. RESULTS: Five hundred ninety-four patients enrolled (mean age 84.3); 152(25%) with ASB (77 treated with fosfomycin-trometamol/75 controls) and 442(75%) without. Despite the study closed without the intended sample size, ASB was not predictive of early-PJI (OR: 1.06 [95%CI: 0.33-3.38]), and its treatment did not modify early-PJI incidence (OR: 1.03 [95%CI: 0.15-7.10]). CONCLUSIONS: Neither preoperative ASB nor its treatment appears to be risk factors of early-PJI after HHA. ClinicalTrials.gov Identifier: Eudra CT 2016-001108-47.

When, How, and to What Extent Are Individuals with Unresponsive Wakefulness Syndrome Able to Progress? Neurobehavioral Progress.

Accurate estimation of the neurobehavioral progress of patients with unresponsive wakefulness syndrome (UWS) is essential to anticipate their most likely clinical course and guide clinical decision making. Although different studies have described this progress and possible predictors of neurobehavioral improvement in these patients, they have methodological limitations that could restrict the validity and generalization of the results. This study investigates the neurobehavioral progress of 100 patients with UWS consecutively admitted to a neurorehabilitation center using systematic weekly assessments based on standardized measures, and the prognostic factors of changes in their neurobehavioral condition. Our results showed that, during the analyzed period, 34% of the patients were able to progress from UWS to minimally conscious state (MCS), 12% of the total sample (near one third from those who progressed to MCS) were able to emerge from MCS, and 10% of the patients died. Transition to MCS was mostly denoted by visual signs, which appeared either alone or in combination with motor signs, and was predicted by etiology and the score on the Coma Recovery Scale-Revised at admission with an accuracy of 75%. Emergence from MCS was denoted in the same proportion by functional communication and object use. Predictive models of emergence from MCS and mortality were not valid and the identified predictors could not be accounted for.

When, How, and to What Extent Are Individuals with Unresponsive Wakefulness Syndrome Able to Progress? Functional Independence.

Accurate estimation of the functional independence of patients with unresponsive wakefulness syndrome (UWS) is essential to adjust family and clinical expectations and plan long-term necessary resources. Although different studies have described the clinical course of these patients, they have methodological limitations that could restrict generalization of the results. This study investigates the neurobehavioral progress of 100 patients with UWS consecutively admitted to a neurorehabilitation center using systematic weekly assessments based on standardized measures, and the functional independence staging of those patients who emerged from a minimally conscious state (MCS) during the first year post-emergence. Our results showed that one year after emergence, most patients were severely dependent, although some of them showed extreme or moderate severity. Clinically meaningful functional improvement was less likely to occur in cognitively-demanding activities, such as activities of daily living and executive function. Consequently, the use of specific and staging functional independence measures, with domain-specific evaluations, are recommended to detect the functional changes that might be expected in these patients. The information provided by these instruments, together with that obtained from repeated assessments of the preserved consciousness with standardized instruments, could help clinicians to adjust expectations and plan necessary resources for this population.

Competition Enhances the Effectiveness and Motivation of Attention Rehabilitation After Stroke. A Randomized Controlled Trial.

Attention deficits are among the most common cognitive impairments observed after experiencing stroke. However, a very limited number of studies have investigated the effectiveness of interventions that specifically focus on the rehabilitation of attention deficits among subjects with impaired attention. Although several interventions have included the use of computerized programs to provide dynamic stimuli, real-time performance feedback, and motivating tasks, existing studies have not exploited the potential benefits of multi-user interactions. Group-based and competitive interventions have been reported to be more enjoyable and motivating, depending on individual traits, and may potentially be more demanding, which may increase their effectiveness. This study investigated the effectiveness and motivating abilities of an intervention specifically designed to address attention deficits. This intervention combined paper-and-pencil tasks and interactive, computerized, multi-touch exercises, which were administered, either non-competitively or competitively, to a group of 43 individuals with chronic stroke. The mediating effects of competitiveness were evaluated for both intervention effectiveness and motivation. Participants were randomly sorted into two groups and underwent 20 one-hour group-based sessions, during which they either worked individually or competed with peers, according to their group allocation. Participants were assessed before and after the intervention, using the Conners' Continuous Performance Test, the d2 Test of Attention, the Color Trail Test, the Digit Span Test, and the Spatial Span Test. The competitiveness and subjective experiences of the participants after the intervention were investigated with the Revised Competitiveness Index and the Intrinsic Motivation Inventory, respectively. The results showed that participants who competed demonstrated significantly greater improvements in all cognitive abilities, except for divided attention, and reported greater enjoyment than their non-competitive peers. Both groups reported comparable levels of perceived competence, pressure, and usefulness. Interestingly, the competitiveness of the participants did not alter either the effectiveness or the subjective experience of the intervention. These findings suggest that competition might enhance the effectiveness and enjoyment of rehabilitation interventions designed to address attention deficits in individuals post-stroke, regardless of their level of competitiveness and without having a negative effect on their perceived pressure and competence.

Efficacy and safety of a comprehensive educational antimicrobial stewardship program focused on antifungal use.

OBJECTIVE: Few data exist regarding the impact of antimicrobial stewardship programs on antifungal use. We evaluated the efficacy and safety of a comprehensive long-term antimicrobial stewardship program (ASP) focused on antifungal use. METHODS: During a 9-year period, we quarterly assessed antifungal consumption, incidence density of hospital-acquired candidemia, Candida spp. distribution, antifungal resistance, and crude death rate per 1000 occupied bed days (OBDs) of hospital-acquired candidemia. We performed segmented regression analysis of interrupted time series. RESULTS: A significant change in trend was observed for antifungal consumption, with a sustained reduction of -0.87% per quarter (95% confidence interval [CI], -1.36 -0.38, p < 0.001), accounting for a final reduction of -38.4%. The main reduction was produced in fluconazole, with a sustained reduction of -1.37% per quarter (95%CI, -1.96 -0.68, p<0.001). The incidence density of hospital-acquired candidemia decreased, with a change in slope of -5.06% cases per 1000 OBDs per year (95%CI, -8.23 -1.77, p = 0.009). The 14-day crude death rate per 1000 OBDs dropped from 0.044 to 0.017 (-6.36% deaths per 1000 OBDs per year; 95%CI, -13.45 -1.31, p = 0.09). CONCLUSIONS: This ASP has succeeded in optimizing the use of antifungal with a long-lasting reduction without increasing the incidence, neither the mortality, of hospital-acquired candidemia.

Embryotoxic and teratogenic profile of tretracycline at environmentally relevant concentrations on Cyprinus carpio.

The objective of this work was to evaluate whether tetracycline (TC) in environmentally relevant concentrations was able to induce alterations to embryonic development and teratogenic effects in oocytes and embryos of Cyprinus carpio. For this purpose, an embryolethality study was conducted and the lethal concentration 50 (LC50) and effective concentration 50 of malformations (EC50) were calculated, and with these data the teratogenic index (TI) was determined. The main alterations to embryonic development and the teratogenic effects produced by TC on embryos of C. carpio were determined using the Kimmel and Hersem scale adapted for Cyprinus carpio. LC50 and EC50 were respectively 500.08 and 145.3 µg L-1.TC was shown to be teratogenic with teratogenic index of 3.44, and the main malformations identified in concentrations of 90-900 µg L-1 were malformation in tail, modified chorda structure, pericardical edema, scoliosis and malformations of the heart. A significant decrease in concentration-dependent in Kimmel and Hersem score was observed. The results allow us to conclude that TC at environmentally relevant concentrations is capable of inducing embryotoxic and teratogenic effects, generating risk in the integrity of the common carp C. Carpio.

Early outcomes of kidney transplantation from elderly donors after circulatory death (GEODAS study).

BACKGROUND: Spain has dramatically increased the number of controlled circulatory death donors (cDCD). The initial selection criteria for considering cDCD for kidney transplantation (KT) have been expanded progressively, with practically no limits in donor age during the last years. We aimed to analyze the early clinical outcomes using expanded (> 65 years) cDCD in comparison with standard ones. METHODS: Observational multicenter study including 19 transplant centers in Spain. We performed a systematic inclusion in a central database of every KT from expanded cDCD at each participant unit from January-2012 to January-2017. Surgical procedures and immunosuppressive protocols were based on local practices. Data was analyzed in the central office using logistic and Cox regression or competitive-risk models for multivariate analysis. Median time of follow-up was 18.1 months. RESULTS: 561 KT were performed with kidneys from cDCD, 135 from donors older than 65 years. As expected, recipients from older cDCD were also older (65.8 (SD 8.8) vs 53.7 (SD 11.4) years; p < 0.001) and with higher comorbidity. At 1 year, no differences were found amongst older and younger cDCD KT recipients in terms of serum creatinine (1.6 (SD 0.7) vs 1.5 (SD 0.8) mg/dl; p = 0.29). Non-death censored graft survival was inferior, but death-censored graft survival was not different (95.5 vs 98.2% respectively; p = 0.481). They also presented a trend towards higher delayed graft function (55.4 vs 46.7%; p = 0.09) but a similar rate of primary non-function (3.7 vs 3.1%; p = 0.71), and acute rejection (3.0 vs 6.3%; p = 0.135). In the multivariate analysis, in short follow-up, donor age was not related with worse survival or poor kidney function (eGFR < 30 ml/min). CONCLUSIONS: The use of kidneys from expanded cDCD is increasing for older and comorbid patients. Short-term graft outcomes are similar for expanded and standard cDCD, so they constitute a good-enough source of kidneys to improve the options of KT wait-listed patients.

Trasplante renal con órganos procedentes de donación tras parada circulatoria controlada: resultados del estudio multicéntrico GEODAS-3 / Kidney transplant from controlled donors following circulatory death: Results from the GEODAS-3 multicentre study

Introducción: Varios países eu:ropeos disponen de programas de donación tras parada cardiaca controlada (cDCD). Veintidós centros participan en el grupo GEODAS, cuyos resultados clínicos presentamos desde una perspectiva nefrológica. Métodos: Estudio multicéntrico retrospectivo observacional con inclusión sistemática de todos los trasplantes renales (TR) procedentes de cDCD, siguiendo protocolos locales de extracción e inmunosupresión. Resultados: Se incluyó a 335 donantes tras cDCD (edad media 57,2 años) fallecidos mayoritariamente por eventos cardiovasculares. Se analizan 566 receptores (edad media de 56,5 años; el 91,9% con primer trasplante renal), con una mediana de seguimiento de 1,9 años. La terapia de inducción fue casi universal (timoglobulina 67,4%; simulect 32,8%) con mantenimiento con prednisona-MMF-tacrolimus (91,3%) o combinaciones con mTOR (6,5%). El tiempo medio de isquemia fría (CIT) fue 12,3 h. Hubo un 3,4% de fallo primario del injerto (n = 19), asociado fundamentalmente al tiempo de isquemia fría (solo el CIT ≥ 14 h se asoció a fallo primario del injerto). La función retrasada del injerto (DGF) fue 48,8%. Los factores de riesgo para la DGF fueron: CIT ≥ 14 h OR 1,6, procedencia de hemodiálisis (vs. diálisis peritoneal) OR 2,1 y edad del donante OR 1,01 (por año). Veintiún pacientes fallecieron con injerto funcionante (3,7%), con una supervivencia de paciente e injerto (censurada para muerte) al segundo año del 95% y del 95,1%, respectivamente. El filtrado glomerular estimado al año de seguimiento fue 60,9ml/min. Conclusiones: El CIT es un factor modificable para mejorar la incidencia del fallo primario del injerto en trasplante renal procedente de cDCD. El trasplante renal con cDCD tiene mayor incidencia en la función retrasada del injerto, pero igual supervivencia de paciente e injerto que la referencia histórica para donación en muerte encefálica. Los resultados son satisfactorios para continuar promoviendo este tipo de donación. Conclusiones: El CIT es un factor modificable para mejorar la incidencia del fallo primario del injerto en trasplante renal procedente de cDCD. El trasplante renal con cDCD tiene mayor incidencia en la función retrasada del injerto, pero igual supervivencia de paciente e injerto que la referencia histórica para donación en muerte encefálica. Los resultados son satisfactorios para continuar promoviendo este tipo de donación

Introduction: Many European countries have transplant programmes with controlled donors after cardiac death (cDCD). Twenty-two centres are part of GEODAS group. We analysed clinical results from a nephrological perspective. Methods: Observational, retrospective and multicentre study with systematic inclusion of all kidney transplant recipients from cDCD, following local protocols regarding extraction and immunosuppression. Results: A total of 335 cDCD donors (mean age 57.2 years) whose deaths were mainly due to cardiovascular events were included. Finally, 566 recipients (mean age 56.5 years; 91.9% first kidney transplant) were analysed with a median of follow-up of 1.9 years. Induction therapy was almost universal (thymoglobulin 67.4%; simulect 32.8%) with maintenance with prednisone-MMF-tacrolimus (91.3%) or combinations with mTOR (6.5%). Mean cold ischaemia time (CIT) was 12.3 h. Approximately 3.4% (n = 19) of recipients experienced primary non-function, essentially associated with CIT (only CIT ≥ 14 h was associated with primary non-function). Delayed graft function (DGF) was 48.8%. DGF risk factors were CIT ≥ 14 h OR 1.6, previous haemodialysis (vs. peritoneal dialysis) OR 2.1 and donor age OR 1.01 (per year). Twenty-one patients (3.7%) died with a functioning graft, with a recipient and death-censored graft survival at 2-years of 95% and 95.1%, respectively. The estimated glomerular filtration rate at one year of follow-up was 60.9 ml/min. Conclusions: CIT is a modifiable factor for improving the incidence of primary non-function in kidney transplant arising from cDCD. cDCD kidney transplant recipients have higher delayed graft function rate, but the same patient and graft survival compared to brain-dead donation in historical references. These results are convincing enough to continue fostering this type of donation