Evaluation of functional warm ischemia time during controlled donation after circulatory determination of death using normothermic regional perfusion (ECMO-TT): A prospective multicenter cohort study.

BACKGROUND: Controlled donation after circulatory determination of death (cDCD) seems an effective way to mitigate the critical shortage of available organs for transplant worldwide. As a recently developed procedure for organ retrieval, some questions remain unsolved such as the uncertainty regarding the effect of functional warm ischemia time (FWIT) on organs´ viability. METHODS: We developed a multicenter prospective cohort study collecting all data from evaluated organs during cDCD from 2017 to 2020. All the procedures related to cDCD were performed with normothermic regional perfusion. The analysis included organ retrieval as endpoint and FWIT as exposure of interest. The effect of FWIT on the likelihood for organ retrieval was evaluated with Relative distribution analysis. RESULTS: A total amount of 507 organs´ related information was analyzed from 95 organ donors. Median donor age was 62 years, and 63% of donors were male. Stroke was the most common diagnosis before withdrawal of life-sustaining therapy (61%), followed by anoxic encephalopathy (21%). This analysis showed that length of FWIT was inversely associated with organ retrieval rates for liver, kidneys, and pancreas. No statistically significant association was found for lungs. CONCLUSIONS: Results showed an inverse association between functional warm ischemia time (FWIT) and retrieval rate. We also have postulated optimal FWIT's thresholds for organ retrieval. FWIT for liver retrieval remained between 6 and less than 11 min and in case of kidneys and pancreas, the optimal FWIT for retrieval was 6 to 12 min. These results could be valuable to improve organ utilization and for future analysis.

Anidulafungin dosing in critically ill patients with continuous venovenous haemodiafiltration.

BACKGROUND: Anidulafungin is indicated as a first-line treatment for invasive candidiasis in critically ill patients. In the intensive care unit, sepsis is the main cause of acute renal failure, and treatment with continuous renal replacement therapy (CRRT) has increased in recent years. Antimicrobial pharmacokinetics is affected by CRRT, but few studies have addressed the optimal dosage for anidulafungin during CRRT. PATIENTS AND METHODS: We included 12 critically ill patients who received continuous venovenous haemodiafiltration to treat acute renal failure. Anidulafungin was infused on 3 consecutive days, starting with a loading dose (200 mg) on Day 1, and doses of 100 mg on Days 2 and 3. Blood and ultradiafiltrate samples were collected on Day 3 (during steady-state) before, and at regular intervals after, the infusion had started. Anidulafungin concentrations were determined with HPLC. RESULTS: On Day 3, peak plasma concentrations with the 100 mg dose were 6.2 ±â€Š1.7 mg/L and 7.1 ±â€Š1.9 mg/L in the arterial and venous samples, respectively. The mean, pre-filter trough concentration was 3.0 ±â€Š0.6 mg/L. The mean AUC0-24 values for plasma anidulafungin were 93.9 ±â€Š19.4 and 104.1 ±â€Š20.3mg·h/L in the arterial and venous samples, respectively. There was no adsorption to synthetic surfaces, and the anidulafungin concentration in the ultradiafiltrate was below the limit of detection. CONCLUSION: The influence of CRRT on anidulafungin elimination appeared to be negligible. Therefore, we recommend no adjustments to the anidulafungin dose for patients receiving CRRT.

Looking for biological factors to predict the risk of active cytomegalovirus infection in non-immunosuppressed critically ill patients.

The identification of non-immunosuppressed critically ill patients most at risk for developing cytomegalovirus (CMV) reactivation is potentially of great clinical relevance. The current study was aimed at determining (i) whether single nucleotide polymorphisms in the genes coding for chemokine receptor 5 (CCR5), interleukin-10 IL-10), and monocyte chemoattractant protein-1 (MCP-1) have an impact on the incidence rate of active CMV infection, (ii) whether serum levels of CMV-specific IgGs are associated with the risk of CMV reactivation, and (iii) whether detection of CMV DNA in saliva precedes that in the lower respiratory tract or the blood compartment. A total of 36 out of 78 patients (46%) developed an episode of active CMV infection. The incidence rate of active CMV infection was not significantly associated with any single nucleotide polymorphisms. A trend towards a lower incidence of active CMV infection (P = 0.06) was noted in patients harboring the IL10 C/C genotype. Patients carrying the CCR5 A/A genotype had high CMV DNA loads in tracheal aspirates. The serum levels of CMV IgGs did not differ significantly between patients with a subsequent episode of active CMV infection (median, 217 IU/mL) or without one (median, 494 IU/mL). Detection of CMV DNA in saliva did not usually precede that in plasma and/or tracheal aspirates. In summary, the analysis of single nucleotide polymorphisms in the IL10 and CCR5 genes might help to determine the risk of active CMV infection or the level of CMV replication within episodes, respectively, in non-immunosuppressed critically ill patients.

Effects of different flow patterns and end-inspiratory pause on oxygenation and ventilation in newborn piglets: an experimental study.

BACKGROUND: Historically, the elective ventilatory flow pattern for neonates has been decelerating flow (DF). Decelerating flow waveform has been suggested to improve gas exchange in the neonate when compared with square flow (SF) waveform by improving the ventilation perfusion. However, the superiority of DF compared with SF has not yet been demonstrated during ventilation in small infants. The aim of this study was to compare SF vs. DF, with or without end-inspiratory pause (EIP), in terms of oxygenation and ventilation in an experimental model of newborn piglets. METHODS: The lungs of 12 newborn Landrace/LargeWhite crossbred piglets were ventilated with SF, DF, SF-EIP and DF-EIP. Tidal volume (VT), inspiratory to expiratory ratio (I/E), respiratory rate (RR), and FiO2 were keep constant during the study. In order to assure an open lung during the study while preventing alveolar collapse, a positive end-expiratory pressure (PEEP) of 6 cmH2O was applied after a single recruitment maneuver. Gas exchange, lung mechanics and hemodynamics were measured. RESULTS: The inspiratory flow waveform had no effect on arterial oxygenation pressure (PaO2) (276 vs. 278 mmHg, p = 0.77), alveolar dead space to alveolar tidal volume (VDalv/VTalv) (0.21 vs. 0.19 ml, p = 0.33), mean airway pressure (Pawm) (13.1 vs. 14.0 cmH2O, p = 0.69) and compliance (Crs) (3.5 vs. 3.5 ml cmH2O(-1), p = 0.73) when comparing SF and DF. A short EIP (10%) did not produce changes in the results. CONCLUSION: The present study showed that there are no differences between SF, DF, SF-EIP and DF-EIP in oxygenation, ventilation, lung mechanics, or hemodynamics in this experimental model of newborn piglets with healthy lungs.

Plasticity and associated epigenetic mechanisms play a role in thermal evolution during range expansion.

Due to global change, many species are shifting their distribution and are thereby confronted with novel thermal conditions at the moving range edges. Especially during the initial phases of exposure to a new environment, it has been hypothesized that plasticity and associated epigenetic mechanisms enable species to cope with environmental change. We tested this idea by capitalizing on the well-documented southward range expansion of the damselfly Ischnura elegans from France into Spain where the species invaded warmer regions in the 1950s in eastern Spain (old edge region) and in the 2010s in central Spain (new edge region). Using a common garden experiment at rearing temperatures matching the ancestral and invaded thermal regimes, we tested for evolutionary changes in (thermal plasticity in) larval life history and heat tolerance in these expansion zones. Through the use of de- and hypermethylating agents, we tested whether epigenetic mechanisms play a role in enabling heat tolerance during expansion. We used the phenotype of the native sister species in Spain, I. graellsii, as proxy for the locally adapted phenotype. New edge populations converged toward the phenotype of the native species through plastic thermal responses in life history and heat tolerance while old edge populations (partly) constitutively evolved a faster life history and higher heat tolerance than the core populations, thereby matching the native species. Only the heat tolerance of new edge populations increased significantly when exposed to the hypermethylating agent. This suggests that the DNA methylation machinery is more amenable to perturbation at the new edge and shows it is able to play a role in achieving a higher heat tolerance. Our results show that both (evolved) plasticity as well as associated epigenetic mechanisms are initially important when facing new thermal regimes but that their importance diminishes with time.

Evaluation of cytomegalovirus (CMV)-specific T-cell immunity for the assessment of the risk of active CMV infection in non-immunosuppressed surgical and trauma intensive care unit patients.

The current study was designed to assess the predictive value of the evaluation of cytomegalovirus (CMV)-specific T-cell immunity early following admission to the intensive care unit for inferring the risk of active CMV infection in non-immunosuppressed surgical and trauma patients. A total of 31 CMV-seropositive patients were included. Patients were screened for the presence of CMV DNA in plasma and in tracheal aspirates by real-time PCR. Enumeration of CMV pp65 and IE-1-specific IFN-γ CD8(+) and CD4(+) T cells was performed by flow cytometry for intracellular cytokine staining. Virological and immunological monitoring was conducted once or twice a week. Active CMV infection occurred in 17 out of 31 patients. Undetectable levels of pp65 and IE-1-specific IFN-γ CD8(+) and CD4(+) T-cell subsets cells were observed in 10 patients who developed active CMV infection and in one who did not (at a median of 2 days following ICU admission). Peak CMV DNA loads in both tracheal aspirates and plasma were substantially higher (P = 0.018 and P = 0.091, respectively) in patients with undetectable IFN-γ T-cell responses than in patients with detectable responses. The expansion of both CMV-specific T-cell subsets following detection of active CMV infection was demonstrated in 9 out of 14 patients with active CMV infection. In conclusion, the evaluation of CMV pp65 and IE-1-specific IFN-γ-producing CD8(+) and CD4(+) T cells early following ICU admission may allow the identification of patients most at risk of either having or developing an episode of active CMV infection, particularly those associated with high-level virus replication.

Convergence of life history and physiology during range expansion toward the phenotype of the native sister species.

In our globally changing planet many species show range expansions whereby they encounter new thermal regimes that deviate from those of their source region. Pressing questions are to what extent and through which mechanisms, plasticity and/or evolution, species respond to the new thermal regimes and whether these trait changes are adaptive. Using a common-garden experiment, we tested for plastic and evolutionary trait changes in life history and a set of understudied biochemical/physiological traits during the range expansion of the damselfly Ischnura elegans from France into a warmer region in Spain. To assess the adaptiveness of the trait changes we used the phenotype of its native sister species in Spain, I. graellsii, as proxy for the locally adapted phenotype. While our design cannot fully exclude maternal effects, our results suggest that edge populations adapted to the local conditions in the newly invaded region through the evolution of a faster pace-of-life (faster development and growth rates), a smaller body size, a higher energy budget and increased expression levels of the heat shock gene DnaJ. Notably, based on convergence toward the phenotype of the native sister species and its thermal responses, and the fit with predictions of life history theory these potential evolutionary changes were likely adaptive. Nevertheless, the convergence toward the native sister species is incomplete for thermal plasticity in traits associated with anaerobic metabolism and melanization. Our results highlight that evolution might at least partly contribute in an adaptive way to the persistence of populations during range expansion into new thermal environments and should be incorporated when predicting and understanding species' range expansions.

The importance of eco-evolutionary dynamics for predicting and managing insect range shifts.

Evolutionary change impacts the rate at which insect pests, pollinators, or disease vectors expand or contract their geographic ranges. Although evolutionary changes, and their ecological feedbacks, strongly affect these risks and associated ecological and economic consequences, they are often underappreciated in management efforts. Greater rigor and scope in study design, coupled with innovative technologies and approaches, facilitates our understanding of the causes and consequences of eco-evolutionary dynamics in insect range shifts. Future efforts need to ensure that forecasts allow for demographic and evolutionary change and that management strategies will maximize (or minimize) the adaptive potential of range-shifting insects, with benefits for biodiversity and ecosystem services.

Atlas of Iberian water beetles (ESACIB database).

The ESACIB ('EScarabajos ACuáticos IBéricos') database is provided, including all available distributional data of Iberian and Balearic water beetles from the literature up to 2013, as well as from museum and private collections, PhD theses, and other unpublished sources. The database contains 62,015 records with associated geographic data (10×10 km UTM squares) for 488 species and subspecies of water beetles, 120 of them endemic to the Iberian Peninsula and eight to the Balearic Islands. This database was used for the elaboration of the "Atlas de los Coleópteros Acuáticos de España Peninsular". In this dataset data of 15 additional species has been added: 11 that occur in the Balearic Islands or mainland Portugal but not in peninsular Spain and an other four with mainly terrestrial habits within the genus Helophorus (for taxonomic coherence). The complete dataset is provided in Darwin Core Archive format.

Epidemiology of invasive candidiasis in a surgical intensive care unit: an observational study.

BACKGROUND: Invasive candidiasis (IC) is a frequent and life-threatening infection in critically ill patients. The aim of this study was to evaluate the epidemiology of IC and the antifungal susceptibility of etiological agents in patients admitted to our surgical intensive care unit (SICU) in Spain. METHODS: We designed a prospective, observational, single center, population-based study in a SICU. We included all consecutive adult patients (≥18 years old) who had documented IC, either on admission or during their stay, between January 2012 and December 2013. RESULTS: There were a total of 22 episodes of IC in the 1149 patients admitted during the 24-month study. The overall IC incidence was 19.1 cases per 1000 admissions. Thirteen cases of IC (59.1%) were intra-abdominal candidiasis (IAC) and 9 (40.9%) were candidemias. All cases of IAC were patients with secondary peritonitis and severe sepsis or septic shock. The overall crude mortality rate was 13.6%; while, it was 33% in patients with candidemia. All patients with IAC survived, including one patient with concomitant candidemia. The most common species causing IC was Candida albicans (13; 59.1%) followed by Candida parapsilosis (5; 22.7%), and Candida glabrata (2; 9.1%). There was also one case each (4.5%) of Candida krusei and Candida tropicalis. Thus, the ratio of non-C. albicans (9) to C. albicans (13) was 1:1.4. There was resistance to fluconazole and itraconazole in 13.6% of cases. Resistance to other antifungals was uncommon. CONCLUSIONS: Candida parapsilosis was the second most common species after C. albicans, indicating the high prevalence of non-C. albicans species in the SICU. Resistance to azoles, particularly fluconazole, should be considered when starting an empirical treatment. Although IAC is a very frequent form of IC in critically ill surgical patients, prompt antifungal therapy and adequate source control appears to lead to a good outcome. However, our results are closely related to our ICU and any generalization must be taken with caution. Therefore, further investigations are needed.

Expresión de diferentes requerimientos nutritivos en Trypanosoma cruzi incubados a diferentes temperaturas en medios de cultivo con o sin suplementos proteicos / Expression of differents nutritional requirements of Trypanosoma cruzi incubates on different temperature in culture media with or not protein

Se presenta un medio de cultivo sintético suplementado con péptidos de bajo peso molecular que permite el crecimiento del Trypanosoma cruzi en la forma de epimastigotes entre 26 grados y 37 grados C. El análisis de los requerimientos nutritivos del parásito en este medio de cultivo revela que 9 aminoácidos son esenciales en el medio suplementado con suero fetal bovino o con péptidos desde el primer pasaje a todas las temperaturas, mientras que otros aminoácidos o sus precursores fueron necesarios para permitir el crecimiento después de un segundo pasaje. Cuando la temperatura de crecimiento fue entre 30-37 grado C también fueron necesarios 5 aminoácidos: B-alamina, glutamina, cisteína, ornitina y treonina. Nueve vitaminas fueron necesarias a todas las temperaturas que el ácido ascórnico y el ergocalciferol no se necesitaron en ningún caso. El resto de los aminoácidos y de las vitaminas variaron su papel de factor de crecimiento dependiendo de la temperatura de incubación del medio de cultivo. en el caso de los medios de cultivo suplementados con péptidos, aumentaron en forma ostensible al compararlos con los medios suplementados con proteínas. Un péptido compuesto por un ácido glutámico, dos alaninas y una lisina puede substituir como factor de crecimiento al suero fetal bovino a todas las temperaturas. Se han preparado medios de cultivo mínimo donde epimastigotes de T. cruzi pueden crecer entre 26 y 37 grados C por más de 30 pasajes