2-deoxyglucose transiently inhibits yeast AMPK signaling and triggers glucose transporter endocytosis, potentiating the drug toxicity.

2-deoxyglucose is a glucose analog that impacts many aspects of cellular physiology. After its uptake and its phosphorylation into 2-deoxyglucose-6-phosphate (2DG6P), it interferes with several metabolic pathways including glycolysis and protein N-glycosylation. Despite this systemic effect, resistance can arise through strategies that are only partially understood. In yeast, 2DG resistance is often associated with mutations causing increased activity of the yeast 5'-AMP activated protein kinase (AMPK), Snf1. Here we focus on the contribution of a Snf1 substrate in 2DG resistance, namely the alpha-arrestin Rod1 involved in nutrient transporter endocytosis. We report that 2DG triggers the endocytosis of many plasma membrane proteins, mostly in a Rod1-dependent manner. Rod1 participates in 2DG-induced endocytosis because 2DG, following its phosphorylation by hexokinase Hxk2, triggers changes in Rod1 post-translational modifications and promotes its function in endocytosis. Mechanistically, this is explained by a transient, 2DG-induced inactivation of Snf1/AMPK by protein phosphatase 1 (PP1). We show that 2DG-induced endocytosis is detrimental to cells, and the lack of Rod1 counteracts this process by stabilizing glucose transporters at the plasma membrane. This facilitates glucose uptake, which may help override the metabolic blockade caused by 2DG, and 2DG export-thus terminating the process of 2DG detoxification. Altogether, these results shed a new light on the regulation of AMPK signaling in yeast and highlight a remarkable strategy to bypass 2DG toxicity involving glucose transporter regulation.

Role of glutamine synthetase in angiogenesis beyond glutamine synthesis.

Glutamine synthetase, encoded by the gene GLUL, is an enzyme that converts glutamate and ammonia to glutamine. It is expressed by endothelial cells, but surprisingly shows negligible glutamine-synthesizing activity in these cells at physiological glutamine levels. Here we show in mice that genetic deletion of Glul in endothelial cells impairs vessel sprouting during vascular development, whereas pharmacological blockade of glutamine synthetase suppresses angiogenesis in ocular and inflammatory skin disease while only minimally affecting healthy adult quiescent endothelial cells. This relies on the inhibition of endothelial cell migration but not proliferation. Mechanistically we show that in human umbilical vein endothelial cells GLUL knockdown reduces membrane localization and activation of the GTPase RHOJ while activating other Rho GTPases and Rho kinase, thereby inducing actin stress fibres and impeding endothelial cell motility. Inhibition of Rho kinase rescues the defect in endothelial cell migration that is induced by GLUL knockdown. Notably, glutamine synthetase palmitoylates itself and interacts with RHOJ to sustain RHOJ palmitoylation, membrane localization and activation. These findings reveal that, in addition to the known formation of glutamine, the enzyme glutamine synthetase shows unknown activity in endothelial cell migration during pathological angiogenesis through RHOJ palmitoylation.

SARS-CoV-2's brain impact: revealing cortical and cerebellar differences via cluster analysis in COVID-19 recovered patients.

BACKGROUND: COVID-19 is a disease known for its neurological involvement. SARS-CoV-2 infection triggers neuroinflammation, which could significantly contribute to the development of long-term neurological symptoms and structural alterations in the gray matter. However, the existence of a consistent pattern of cerebral atrophy remains uncertain. OBJECTIVE: Our study aimed to identify patterns of brain involvement in recovered COVID-19 patients and explore potential relationships with clinical variables during hospitalization. METHODOLOGY: In this study, we included 39 recovered patients and 39 controls from a pre-pandemic database to ensure their non-exposure to the virus. We obtained clinical data of the patients during hospitalization, and 3 months later; in addition we obtained T1-weighted magnetic resonance images and performed standard screening cognitive tests. RESULTS: We identified two groups of recovered patients based on a cluster analysis of the significant cortical thickness differences between patients and controls. Group 1 displayed significant cortical thickness differences in specific cerebral regions, while Group 2 exhibited significant differences in the cerebellum, though neither group showed cognitive deterioration at the group level. Notably, Group 1 showed a tendency of higher D-dimer values during hospitalization compared to Group 2, prior to p-value correction. CONCLUSION: This data-driven division into two groups based on the brain structural differences, and the possible link to D-dimer values may provide insights into the underlying mechanisms of SARS-COV-2 neurological disruption and its impact on the brain during and after recovery from the disease.

Utility of non-invasive monitoring of exhaled carbon dioxide and perfusion index in adult patients in the emergency department.

BACKGROUND: Several noninvasive solutions are available for the assessment of patients at risk of deterioration. Capnography, in the form of end-tidal exhaled CO2 (ETCO2) and perfusion index (PI), could provide relevant information about patient prognosis. The aim of the present project was to determine the association of ETCO2 and PI with mortality of patients admitted to the emergency department (ED). METHODS: Multicenter, prospective, cohort study of adult patients with acute disease who needed continuous monitoring in the ED. The study included two tertiary hospitals in Spain between October 2022 and June 2023. The primary outcome of the study was in-hospital mortality (all-cause). Demographics, vital signs, ETCO2 and PI were collected. RESULTS: A total of 687 patients were included in the study. The in-hospital mortality rate was 6.8%. The median age was 79 years (IQR: 69-86), and 63.3% were males. The median ETCO2 value was 30 mmHg (26-35) in survivors and 23 mmHg (16-30) in nonsurvivors (p = 0.001). For the PI, the medians were 4.7% (2.8-8.1) for survivors and 2.5% (0.98-4-4) for nonsurvivors (p < 0.001). The model that presented the best AUC was age (odds ratio (OR): 1.02 (1.00-1.05)), the respiratory rate (OR: 1.06 (1.02-1.11)), and the PI (OR: 0.83 (0.75-0.91)), with a result of 0.840 (95% CI: 0.795-0.886); the model with the respiratory rate (OR: 1.05 (1.01-1.10)), the PI (OR: 0.84 (0.76-0.93)), and the ETCO2 (no statistically significant OR), with an AUC of 0.838 (95% CI: 0.787-0.889). CONCLUSIONS: The present study showed that the PI and respiratory rate are independently associated with in-hospital mortality. Both the PI and ETCO2 are predictive parameters with improved prognostic performance compared with that of standard vital signs.

Adoption of community monitoring improves common pool resource management across contexts.

Pervasive overuse and degradation of common pool resources (CPRs) is a global concern. To sustainably manage CPRs, effective governance institutions are essential. A large literature has developed to describe the institutional design features employed by communities that successfully manage their CPRs. Yet, these designs remain far from universally adopted. We focus on one prominent institutional design feature, community monitoring, and ask whether nongovernmental organizations or governments can facilitate its adoption and whether adoption of monitoring affects CPR use. To answer these questions, we implemented randomized controlled trials in six countries. The harmonized trials randomly assigned the introduction of community monitoring to 400 communities, with data collection in an additional 347 control communities. Most of the 400 communities adopted regular monitoring practices over the course of a year. In a meta-analysis of the experimental results from the six sites, we find that the community monitoring reduced CPR use and increased user satisfaction and knowledge by modest amounts. Our findings demonstrate that community monitoring can improve CPR management in disparate contexts, even when monitoring is externally initiated rather than homegrown. These findings provide guidance for the design of future programs and policies intended to develop monitoring capabilities in communities. Furthermore, our harmonized, multisite trial provides sustainability science with a new way to study the complexity of socioecological systems and builds generalizable insights about how to improve CPR management.

Identification of a measles variant displaying mutations impacting molecular diagnostics, Geneva, Switzerland, 2023.

Real-time PCR is one of the most widely used techniques to diagnose measles cases. Here we report measles virus variants with three genetic mutations in the reverse primer annealing site of a widely used PCR. The mutations result in a slight loss of the PCR sensitivity. Variants bearing the three mutations presently circulate in different countries since at least the end of 2021. Our findings highlight the usefulness of molecular surveillance in monitoring if oligonucleotides in diagnostic tests remain adequate.

Adapting response to a measles outbreak in a context of high vaccination and breakthrough cases: an example from Vaud, Switzerland, January to March 2024.

A measles outbreak with 51 cases occurred in the canton of Vaud, Switzerland, between January and March 2024. The outbreak was triggered by an imported case, and 37 (72.5%) subsequent cases were previously vaccinated individuals. Epidemiological investigations showed that vaccinated measles cases were symptomatic and infectious. In a highly vaccinated population, it is important to raise awareness among healthcare professionals to suspect and test for measles virus when an outbreak is declared, irrespective of the vaccination status of the patients.

Forestry Applications of Space-Borne LiDAR Sensors: A Worldwide Bibliometric Analysis.

The 21st century has seen the launch of new space-borne sensors based on LiDAR (light detection and ranging) technology developed in the second half of the 20th century. Nowadays, these sensors offer novel opportunities for mapping terrain and canopy heights and estimating aboveground biomass (AGB) across local to regional scales. This study aims to analyze the scientific impact of these sensors on large-scale forest mapping to retrieve 3D canopy information, monitor forest degradation, estimate AGB, and model key ecosystem variables such as primary productivity and biodiversity. A worldwide bibliometric analysis of this topic was carried out based on up to 412 publications indexed in the Scopus database during the period 2004-2022. The results showed that the number of published documents increased exponentially in the last five years, coinciding with the commissioning of two new LiDAR space missions: Ice, Cloud, and Land Elevation Satellite (ICESat-2) and Global Ecosystem Dynamics Investigation (GEDI). These missions have been providing data since 2018 and 2019, respectively. The journal that demonstrated the highest productivity in this field was "Remote Sensing" and among the leading contributors, the top five countries in terms of publications were the USA, China, the UK, France, and Germany. The upward trajectory in the number of publications categorizes this subject as a highly trending research topic, particularly in the context of improving forest resource management and participating in global climate treaty frameworks that require monitoring and reporting on forest carbon stocks. In this context, the integration of space-borne data, including imagery, SAR, and LiDAR, is anticipated to steer the trajectory of this research in the upcoming years.

Character variation in separate body regions of Gerreidae (Osteichthyes: Teleostei) fishes inferred from geometric morphometrics.

Body morphology is a valuable feature for distinguishing teleostean fishes. However, the utility of character variation in separate body regions has yet to be tested. The taxonomy of the Gerreidae family is controversial due to character overlapping among its fish species. This work aims to analyze and compare the body shape variation in three regions, cephalic, trunk, and caudal peduncle, using landmark data and geometric morphometric methods in 17 species and five genera of the family Gerreidae. The pattern of shape variation for the cephalic region consisted of well-defined character states exclusive of each species analyzed. Shape variation in the trunk and caudal peduncle regions does not distinguish all species in this study. This study showed that the dorsal cephalic profile is highly variable among the species, therefore, shape variation in this region is useful for distinguishing Gerreidae species. In contrast, some species within the same genus share similar shape states in the trunk and caudal peduncle regions, with the most shape variation in the dorsal profile and anal fin for the trunk and in the middle of the caudal peduncle.

A Missense Variant in TP53 Could Be a Genetic Biomarker Associated with Bone Tissue Alterations.

Metabolic bone diseases cover a broad spectrum of disorders that share alterations in bone metabolism that lead to a defective skeleton, which is associated with increasing morbidity, disability, and mortality. There is a close connection between the etiology of metabolic bone diseases and genetic factors, with TP53 being one of the genes associated therewith. The single nucleotide polymorphism (SNP) Arg72Pro of TP53 is a genetic factor associated with several pathologies, including cancer, stroke, and osteoporosis. Here, we aim to analyze the influence of the TP53 Arg72Pro SNP on bone mass in humanized Tp53 Arg72Pro knock-in mice. This work reports on the influence of the TP53 Arg72Pro polymorphism in bone microarchitecture, OPG expression, and apoptosis bone status. The results show that the proline variant of the TP53 Arg72Pro polymorphism (Pro72-p53) is associated with deteriorated bone tissue, lower OPG/RANK ratio, and lower apoptosis in bone tissue. In conclusion, the TP53 Arg72Pro polymorphism modulates bone microarchitecture and may be a genetic biomarker that can be used to identify individuals with an increased risk of suffering metabolic bone alterations.

Obstructive sleep apnoea is related to melanoma aggressiveness through paraspeckle protein-1 upregulation.

BACKGROUND: In patients with obstructive sleep apnoea (OSA), intermittent hypoxia induces overexpression of paraspeckle component (PSPC)1, a master modulator of transforming growth factor (TGF)-ß signalling, which promotes cell cancer progression through epithelial-mesenchymal transition (EMT) and acquisition of cancer stem cell (CSC)-like features. However, the persistence of intermittent hypoxia-induced effects on PSPC1, and their consequences in cancer patients are not known. To this effect, circulating PSPC1 levels were compared in patients with cutaneous melanoma with or without OSA, and their relationship with tumour aggressiveness along with the in vitro effects of soluble PSPC1 and intermittent hypoxia on melanoma cell aggressiveness mechanisms were assessed. METHODS: In 292 cutaneous melanoma patients, sleep studies and serum levels of PSPC1 and TGF-ß were evaluated. The effect of PSPC1 on expression of EMT and CSC transcription factors was assessed using melanoma cell lines with patient sera under both normoxia and intermittent hypoxia conditions. RESULTS: PSPC1 levels were higher in patients with moderate-severe OSA compared with mild OSA or non-OSA patients. Serum levels of PSPC1 were associated with several cutaneous melanoma clinical aggressiveness indicators. Both intermittent hypoxia exposures and serum from OSA patients upregulated TGF-ß expression and amplified the expression of transcription factors associated with EMT activation and acquisition of CSC characteristics. CONCLUSION: In cutaneous melanoma patients, OSA severity is associated with higher PSPC1 serum levels, which jointly with intermittent hypoxia would enhance the self-reprogramming capabilities of EMT and CSC feature acquisition of melanoma cells, promoting their intrinsic aggressiveness.

Normal tissue content impact on the GBM molecular classification.

Molecular classification of glioblastoma has enabled a deeper understanding of the disease. The four-subtype model (including Proneural, Classical, Mesenchymal and Neural) has been replaced by a model that discards the Neural subtype, found to be associated with samples with a high content of normal tissue. These samples can be misclassified preventing biological and clinical insights into the different tumor subtypes from coming to light. In this work, we present a model that tackles both the molecular classification of samples and discrimination of those with a high content of normal cells. We performed a transcriptomic in silico analysis on glioblastoma (GBM) samples (n = 810) and tested different criteria to optimize the number of genes needed for molecular classification. We used gene expression of normal brain samples (n = 555) to design an additional gene signature to detect samples with a high normal tissue content. Microdissection samples of different structures within GBM (n = 122) have been used to validate the final model. Finally, the model was tested in a cohort of 43 patients and confirmed by histology. Based on the expression of 20 genes, our model is able to discriminate samples with a high content of normal tissue and to classify the remaining ones. We have shown that taking into consideration normal cells can prevent errors in the classification and the subsequent misinterpretation of the results. Moreover, considering only samples with a low content of normal cells, we found an association between the complexity of the samples and survival for the three molecular subtypes.

Prehospital Respiratory Early Warning Score for airway management in-ambulance: A score comparison.

BACKGROUND: Prehospital Respiratory Early Warning Scores to estimate the requirement for advanced respiratory support is needed. To develop a prehospital Respiratory Early Warning Score to estimate the requirement for advanced respiratory support. METHODS: Multicentre, prospective, emergency medical services (EMS)-delivered, longitudinal cohort derivationvalidation study carried out in 59 ambulances and five hospitals across five Spanish provinces. Adults with acute diseases evaluated, supported and discharged to the Emergency Department with high priority were eligible. The primary outcome was the need for invasive or non-invasive respiratory support (NIRS or IRS) in the prehospital scope at the first contact with the patient. The measures included the following: epidemiological endpoints, prehospital vital signs (respiratory rate, pulse oximetry saturation, fraction of inspired oxygen, systolic and diastolic mean blood pressure, heart rate, tympanic temperature and consciousness level by the GCS). RESULTS: Between 26 Oct 2018 and 26 Oct 2021, we enrolled 5793 cases. For NIRS prediction, the final model of the logistic regression included respiratory rate and pulse oximetry saturation/fraction of inspired oxygen ratio. For the IRS case, the motor response from the Glasgow Coma Scale was also included. The REWS showed an AUC of 0.938 (95% CI: 0.918-0.958), a calibration-in-large of 0.026 and a higher net benefit as compared with the other scores. CONCLUSIONS: Our results showed that REWS is a remarkably aid for the decision-making process in the management of advanced respiratory support in prehospital care. Including this score in the prehospital scenario could improve patients' care and optimise the resources' management.

Modified Rapid Emergency Medicine Score-Lactate (mREMS-L) performance to screen non-anticipated 30-day-related-mortality in emergency department.

BACKGROUND: The aim of this study was to compare the ability to predict 30-day in-hospital mortality of lactate versus the modified Rapid Emergency Medicine Score (mREMS) versus the arithmetic sum of the mREMS plus the numerical value of lactate (mREMS-L). METHODS: A prospective, multicentric, emergency department delivery, pragmatic study was conducted. To determine the predictive capacity of the scales, lactate was measured and the mREMS and mREMS-L were calculated in adult patients (aged>18 years) transferred with high priority by ambulance to the emergency department in five hospitals of Castilla y Leon between 1 January 2020 and 31 December 2021. The area under the receiver operating characteristic (ROC) curve of each of the scales was calculated in terms of mortality for 30 days. RESULTS: A total of 5371 participants were included, and the in-hospital mortality rate at 30 days was of 11.4% (615 cases). The best cut-off point determined in the mREMS was 7.0 points (sensitivity of 67% and specificity of 84%), and for lactate, the cut-off point was 1.4 mmol/L (sensitivity of 88% and specificity of 67%). Finally, the combined mREMS-L showed a cut-off point of 7.9 (sensitivity of 83% and a specificity of 83%). The area under the ROC curve of the mREMS, lactate and mREMS-L for 30-day mortality was 0.851, 0.853, and 0.903, respectively (p < 0.001 in all cases). CONCLUSIONS: The new score generated, mREMS-L, obtained better statistical results than its components (mREMS and lactate) separately.

Prehospital seizures: Short-term outcomes and risk stratification based in point-of-care testing.

BACKGROUND: Information for treatment or hospital derivation of prehospital seizures is limited, impairing patient condition and hindering patients risk assessment by the emergency medical services (EMS). This study aimed to determine the associated factors to clinical impairment, and secondarily, to determine risk factors associated to cumulative in-hospital mortality at 2, 7 and 30 days, in patients presenting prehospital seizures. METHODS: Prospective, multicentre, EMS-delivery study involving adult subjects with prehospital seizures, including five advanced life support units, 27 basic life support units and four emergency departments in Spain. All bedside variables: including demographic, standard vital signs, prehospital laboratory tests and presence of intoxication or traumatic brain injury (TBI), were analysed to construct a risk model using binary logistic regression and internal validation methods. RESULTS: A total of 517 patients were considered. Clinical impairment was present in 14.9%, and cumulative in-hospital mortality at 2, 7 and 30-days was 3.4%, 4.6% and 7.7%, respectively. The model for the clinical impairment indicated that respiratory rate, partial pressure of carbon dioxide, blood urea nitrogen, associated TBI or stroke were risk factors; higher Glasgow Coma Scale (GCS) scores mean a lower risk of impairment. Age, potassium, glucose, prehospital use of mechanical ventilation and concomitant stroke were risk factors associated to mortality; and oxygen saturation, a high score in GCS and haemoglobin were protective factors. CONCLUSION: Our study shows that prehospital variables could reflect the clinical impairment and mortality of patients suffering from seizures. The incorporation of such variables in the prehospital decision-making process could improve patient outcomes.

Dopamine receptors D1 and D2 show prognostic significance and potential therapeutic applications for endometrial cancer patients.

OBJECTIVE: Catecholaminergic signaling has been a target for therapy in different type of cancers. In this work, we characterized the ADRß2, DRD1 and DRD2 expression in healthy tissue and endometrial tumors to evaluate their prognostic significance in endometrial cancer (EC), unraveling their possible application as an antitumor therapy. METHODS: 109 EC patients were included. The expression of the ADRß2, DRD1 and DRD2 proteins was evaluated by immunohistochemistry and univariate and multivariate analysis to assess their association with clinic-pathological and outcome variables. Finally, HEC1A and AN3CA EC cell lines were exposed to different concentrations of selective dopaminergic agents alone or in combination to study their effects on cellular viability. RESULTS: ADRß2 protein expression was not associated with clinico-pathological parameters or prognosis. DRD1 protein expression was reduced in tumors samples but showed a significant inverse association with tumor size and stage. DRD2 protein expression was significantly associated with non-endometrioid EC, high grade tumors, tumor size, worse disease-free survival (HR = 3.47 (95%CI:1.35-8.88)) and overall survival (HR = 2.98 (95%CI:1.40-6.34)). The DRD1 agonist fenoldopam showed a reduction of cellular viability in HEC1A and AN3CA cells. The exposure to domperidone, a DRD2 antagonist, significantly reduced cell viability compared to the control. Finally, DRD1 agonism and DRD2 antagonism combination induced a significant reduction in cell viability of the AN3CA cells compared to monotherapy, close to being an additive response than a synergistic effect (CI of 1.1 at 0.5% Fa). CONCLUSION: DRD1 and DRD2 expression levels showed a significant association with clinico-pathological parameters. Both the combined activation of DRD1 and blockage of DRD2 may form an innovative strategy to inhibit tumor growth in EC.

Amino-OPE glycosides and blue light: a powerful synergy in photodynamic therapy.

Herein we report the synthesis and biological properties of sugar-conjugated oligophenylene ethynylene (OPE) dyes, used as novel photosensitizers (PSs) for photodynamic treatment (PDT) under blue light. The OPE-bearing glycosides at both ends are successfully prepared by a Pd-catalyzed Sonogashira cross-coupling reaction. The live-cell imaging studies have shown that these OPE glycosides (including glucose, mannose and maltose derivatives) efficiently penetrate the cytoplasm of cultured HeLa cancer cells. No dark toxicity was observed, but upon irradiating the cells under blue light an extraordinary photodynamic effect was observed at low concentrations (10-6-10-8 M). The localization studies indicate that OPE-glucose 1 and OPE-mannose 2 have Golgi patterns, whereas OPE-maltose 3 could be in lysosomes. The PDT and morphological studies in HeLa cells treated with sublethal doses of PS 1-3 revealed that cell death occurs by necrosis.

Trace Organic Contaminant Removal from Municipal Wastewater by Styrenic ß-Cyclodextrin Polymers.

Trace organic contaminants (TrOCs) present major removal challenges for wastewater treatment. TrOCs, such as perfluoroalkyl and polyfluoroalkyl substances (PFAS), are associated with chronic toxicity at ng L-1 exposure levels and should be removed from wastewater to enable safe reuse and release of treated effluents. Established adsorbents, such as granular activated carbon (GAC), exhibit variable TrOC removal and fouling by wastewater constituents. These shortcomings motivate the development of selective novel adsorbents that also maintain robust performance in wastewater. Cross-linked ß-cyclodextrin (ß-CD) polymers are promising adsorbents with demonstrated TrOC removal efficacy. Here, we report a simplified and potentially scalable synthesis of a porous polymer composed of styrene-linked ß-CD and cationic ammonium groups. Batch adsorption experiments demonstrate that the polymer is a selective adsorbent exhibiting complete removal for six out of 13 contaminants with less adsorption inhibition than GAC in wastewater. The polymer also exhibits faster adsorption kinetics than GAC and ion exchange (IX) resin, higher adsorption affinity for PFAS than GAC, and is regenerable by solvent wash. Rapid small-scale column tests show that the polymer exhibits later breakthrough times compared to GAC and IX resin. These results demonstrate the potential for ß-CD polymers to remediate TrOCs from complex water matrices.

Tracking the National Early Warning Score 2 from Prehospital Care to the Emergency Department: A Prospective, Ambulance-Based, Observational Study.

Aim of the study: To assess the prognostic ability of the National Early Warning Score 2 (NEWS2) at three time points of care -at the emergency scene (NEWS2-1), just before starting the transfer by ambulance to the hospital (NEWS2- 2), and at the hospital triage box (NEWS2-3)- to estimate in-hospital mortality after two days since the index event.Methods: Prospective, multicenter, ambulance-based, cohort ongoing study in adults (>18 years) consecutively attended by advanced life support (ALS) and evacuated with high-priority to the emergency departments (ED) between October 2018 and May 2021. Vital sign measures were used to calculate the NEWS2 score at each time point, then this score was entered in a logistic regression model as the single predictor. Two outcomes were considered: first, all-cause mortality of the patients within 2 days of presentation to EMS, and second, unplanned ICU admission. The calibration and scores comparison was performed by representing the predicted vs the observed risk curves according to NEWS score value.Results: 4943 patients were enrolled. Median age was 69 years (interquartile range 53- 81). The NEWS2-3 presented the better performance for all-cause two-day in-hospital mortality with an AUC of 0.941 (95% CI: 0.917-0.964), showing statistical differences with both the NEWS2-1 (0.872 (95% CI: 0.833-0.911); p < 0.003) and with the NEWS2- 2 (0.895 (95% CI: 0.866-0.925; p < 0.05). The calibration and scores comparison results showed that the NEWS2-3 was the best predictive score followed by the NEWS2-2 and the NEWS2-1, respectively.Conclusions: The NEWS2 has an excellent predictive performance. The score showed a very consistent response over time with the difference between "at the emergency scene" and "pre-evacuation" presenting the sharpest change with decreased threshold values, thus displaying a drop in the risk of acute clinical impairment.

Development of a prehospital lactic acidosis score for early-mortality. A prospective, multicenter, ambulance-based, cohort study.

BACKGROUND: Lactic acidosis is a clinical status related to clinical worsening. Actually, higher levels of lactate is a well-established trigger of emergency situations. The aim of this work is to build-up a prehospital early warning score to predict 2-day mortality and intensive care unit (ICU) admission, constructed with other components of the lactic acidosis besides the lactate. METHODS: Prospective, multicenter, observational, derivation-validation cohort study of adults evacuated by ambulance and admitted to emergency department with acute diseases, between January 1st, 2020 and December 31st, 2021. Including six advanced life support, thirty-eight basic life support units, referring to four hospitals (Spain). The primary and secondary outcome of the study were 2-day all-cause mortality and ICU-admission. The prehospital lactic acidosis (PLA) score was derived from the analysis of prehospital blood parameters associated with the outcome using a logistic regression. The calibration, clinical utility, and discrimination of PLA were determined and compared to the performance of each component of the score alone. RESULTS: A total of 3334 patients were enrolled. The final PLA score included: lactate, pCO2, and pH. For 2-day mortality, the PLA showed an AUC of 0.941 (95%CI: 0.914-0.967), a better performance in calibration, and a higher net benefit as compared to the other score components alone. For the ICU admission, the PLA only showed a better performance for AUC: 0.75 (95%CI: 0.706-0.794). CONCLUSIONS: Our results showed that PLA predicts 2-day mortality better than other lactic acidosis components alone. Including PLA score in prehospital setting could improve emergency services decision-making.