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Abstract Emergency medical services (EMSs) face critical situations that require patient risk classification based on analytical and vital signs. We aimed to establish clustering-derived phenotypes based on prehospital analytical and vital signs that allow risk stratification. This was a prospective, multicenter, EMS-delivered, ambulance-based cohort study considering six advanced life support units, 38 basic life support units, and four tertiary hospitals in Spain. Adults with unselected acute diseases managed by the EMS and evacuated with discharge priority to emergency departments were considered between January 1, 2020, and June 30, 2023. Prehospital point-of-care testing and on-scene vital signs were used for the unsupervised machine learning method (clustering) to determine the phenotypes. Then phenotypes were compared with the primary outcome (cumulative mortality (all-cause) at 2, 7, and 30 days). A total of 7909 patients were included. The median (IQR) age was 64 (51–80) years, 41% were women, and 26% were living in rural areas. Three clusters were identified: alpha 16.2% (1281 patients), beta 28.8% (2279), and gamma 55% (4349). The mortality rates for alpha, beta and gamma at 2 days were 18.6%, 4.1%, and 0.8%, respectively; at 7 days, were 24.7%, 6.2%, and 1.7%; and at 30 days, were 33%, 10.2%, and 3.2%, respectively. Based on standard vital signs and blood test biomarkers in the prehospital scenario, three clusters were identified: alpha (high-risk), beta and gamma (medium- and low-risk, respectively). This permits the EMS system to quickly identify patients who are potentially compromised and to proactively implement the necessary interventions.

Inflammation plays a pivotal role in the pathogenesis of primary and post-essential thrombocythemia or post-polycythemia vera myelofibrosis (MF) in close cooperation with the underlying molecular drivers. This inflammatory state is induced by a dynamic spectrum of inflammatory cytokines, although recent evidence points to the participation of additional soluble inflammatory mediators. Damage-associated molecular patterns (DAMPs) represent endogenous signals released upon cell death or damage which trigger a potent innate immune response. We assessed the contribution of two prototypical DAMPs, HMGB1 and S100A8/A9, to MF inflammation. Circulating HMGB1 and S100A8/A9 were elevated in MF patients in parallel to the degree of systemic inflammation and levels increased progressively during advanced disease stages. Patients with elevated DAMPs had higher frequency of adverse clinical features, such as anemia, and inferior survival, suggesting their contribution to disease progression. Monocytes, which are key players in MF inflammation, were identified as a source of S100A8/A9 but not HMGB1 release, while both DAMPs correlated with cell death parameters, such as serum LDH and cell-free DNA, indicating that passive release is an additional mechanism leading to increased DAMPs. HMGB1 and S100A8/A9 promote inflammation through binding to Toll-like receptor (TLR) 4, whereas the former also binds TLR2. Monocytes from MF patients were shown to be hyperactivated at baseline, as reflected by higher CD11b and tissue factor exposure and increased expression levels of proinflammatory cytokines IL-1β and IL-6. Patient monocytes showed preserved TLR4 and TLR2 expression and were able to mount normal or even exacerbated functional responses and cytokine upregulation following stimulation of TLR4 and TLR2. Elevated levels of endogenous TLR ligands HMGB1 and S100A8/A9 coupled to the finding of preserved or hyperreactive TLR-triggered responses indicate that DAMPs may promote monocyte activation and cytokine production in MF, fueling inflammation. Plasma IL-1β and IL-6 were elevated in MF and correlated with DAMPs levels, raising the possibility that DAMPs could contribute to cytokine generation in vivo. In conclusion, this study highlights that, in cooperation with classic proinflammatory cytokines, DAMPs represent additional inflammatory mediators that may participate in the generation of MF inflammatory state, potentially providing novel biomarkers of disease progression and new therapeutic targets.

Visualization is essential for interpreting data, especially in scientific research where datasets often come from experiments or simulations. Data visualization techniques vary based on the data type. For example, mapping can illustrate city traffic incidents, while bar plots can identify the most common incidents. This paper presents VisUAM (Visualizador UAM), a web-based tool for creating graphics from various datasets across any domain. The current version of VisUAM supports data from three scientific software tools: Pore Networks, Voronoi Diagrams, and Particle Diffusive Simulator. VisUAM’s architecture allows easy integration of any data type and supports multi-dimensional visualizations, including 2D, 3D, and animations. Its flexibility, web-based accessibility, and adaptability to new visualization needs make VisUAM a versatile and comprehensive platform for researchers.

Myelofibrosis (MF) is a clonal hematopoietic stem cell disorder classified among chronic myeloproliferative neoplasms, characterized by exacerbated myeloid and megakaryocytic proliferation and bone marrow fibrosis. It is induced by driver (JAK2/CALR/MPL) and high molecular risk mutations coupled to a sustained inflammatory state that contributes to disease pathogenesis. Patient outcome is determined by stratification into risk groups and refinement of current prognostic systems may help individualize treatment decisions. Circulating cell-free (cf)DNA comprises short fragments of double-stranded DNA, which promotes inflammation by stimulating several pathways, including inflammasome activation, which is responsible for IL-1β and IL-18 maturation and release. In this work, we assessed the contribution of cfDNA as a marker of disease progression and mediator of inflammation in MF. cfDNA was increased in MF patients and higher levels were associated with adverse clinical outcome, a high-risk molecular profile, advanced disease stages and inferior overall survival, indicating its potential value as a prognostic marker. Cell-free DNA levels correlated with tumor burden parameters and markers of systemic inflammation. To mimic the effects of cfDNA, monocytes were stimulated with poly(dA:dT), a synthetic double-stranded DNA. Following stimulation, patient monocytes released higher amounts of inflammasome-processed cytokine, IL-18 to the culture supernatant, reflecting enhanced inflammasome function. Despite overexpression of cytosolic DNA inflammasome sensor AIM2, IL-18 release from MF monocytes was shown to rely mainly on the NLRP3 inflammasome, as it was prevented by NLRP3-specific inhibitor MCC950. Circulating IL-18 levels were increased in MF plasma, reflecting in vivo inflammasome activation, and highlighting the previously unrecognized involvement of this cytokine in MF cytokine network. Monocyte counts were higher in patients and showed a trend towards correlation with IL-18 levels, suggesting monocytes represent a source of circulating IL-18. The close correlation shown between IL-18 and cfDNA levels, together with the finding of enhanced DNA-triggered IL-18 release from monocytes, suggest that cfDNA promotes inflammation, at least in part, through inflammasome activation. This work highlights cfDNA, the inflammasome and IL-18 as additional players in the complex inflammatory circuit that fosters MF progression, potentially providing new therapeutic targets.

Objective To compare the predictive value of the quick COVID-19 Severity Index (qCSI) and the National Early Warning Score (NEWS) for 90-day mortality amongst COVID-19 patients. Methods Multicenter retrospective cohort study conducted in adult patients transferred by ambulance to an emergency department (ED) with suspected COVID-19 infection subsequently confirmed by a SARS-CoV-2 test (polymerase chain reaction). We collected epidemiological data, clinical covariates (respiratory rate, oxygen saturation, systolic blood pressure, heart rate, temperature, level of consciousness and use of supplemental oxygen) and hospital variables. The primary outcome was cumulative all-cause mortality during a 90-day follow-up, with mortality assessment monitoring time points at 1, 2, 7, 14, 30 and 90 days from ED attendance. Comparison of performances for 90-day mortality between both scores was carried out by univariate analysis. Results From March to November 2020, we included 2,961 SARS-CoV-2 positive patients (median age 79 years, IQR 66–88), with 49.2% females. The qCSI score provided an AUC ranging from 0.769 (1-day mortality) to 0.749 (90-day mortality), whereas AUCs for NEWS ranging from 0.825 for 1-day mortality to 0.777 for 90-day mortality. At all-time points studied, differences between both scores were statistically significant (p

BackgroundNowadays, there is no gold standard score for prehospital sepsis and sepsis-related mortality identification. The aim of the present study was to analyze the performance of qSOFA, NEWS2 and mSOFA as sepsis predictors in patients with infection-suspected in prehospital care. The second objective is to study the predictive ability of the aforementioned scores in septic-shock and in-hospital mortality.MethodsProspective, ambulance-based, and multicenter cohort study, developed by the emergency medical services, among patients (n = 535) with suspected infection transferred by ambulance with high-priority to the emergency department (ED). The study enrolled 40 ambulances and 4 ED in Spain between 1 January 2020, and 30 September 2021. All the variables used in the scores, in addition to socio-demographic data, standard vital signs, prehospital analytical parameters (glucose, lactate, and creatinine) were collected. For the evaluation of the scores, the discriminative power, calibration curve and decision curve analysis (DCA) were used.ResultsThe mSOFA outperformed the other two scores for mortality, presenting the following AUCs: 0.877 (95%CI 0.841–0.913), 0.761 (95%CI 0.706–0.816), 0.731 (95%CI 0.674–0.788), for mSOFA, NEWS, and qSOFA, respectively. No differences were found for sepsis nor septic shock, but mSOFA’s AUCs was higher than the one of the other two scores. The calibration curve and DCA presented similar results.ConclusionThe use of mSOFA could provide and extra insight regarding the short-term mortality and sepsis diagnostic, backing its recommendation in the prehospital scenario.

IntroductionCOVID-19 has initially been studied in terms of an acute-phase disease, although recently more attention has been given to the long-term consequences. In this study, we examined COVID-19 as an independent risk factor for long-term mortality in patients with acute illness treated by EMS (emergency medical services) who have previously had the disease against those who have not had the disease.MethodsA prospective, multicenter, ambulance-based, ongoing study was performed with adult patients with acute disease managed by EMS and transferred with high priority to the emergency department (ED) as study subjects. The study involved six advanced life support units, 38 basic life support units, and five emergency departments from Spain. Sociodemographic inputs, baseline vital signs, pre-hospital blood tests, and comorbidities, including COVID-19, were collected. The main outcome was long-term mortality, which was classified into 1-year all-cause mortality and 1-year in- and out-of-hospital mortality. To compare both the patients with COVID-19 vs. patients without COVID-19 and to compare survival vs non-survival, two main statistical analyses were performed, namely, a longitudinal analysis (Cox regression) and a logistic regression analysis.ResultsBetween 12 March 2020 and 30 September 2021, a total of 3,107 patients were included in the study, with 2,594 patients without COVID-19 and 513 patients previously suffering from COVID-19. The mortality rate was higher in patients with COVID-19 than in patients without COVID-19 (31.8 vs. 17.9%). A logistic regression showed that patients previously diagnosed with COVID-19 presented higher rates of nursing home residency, a higher number of breaths per minute, and suffering from connective disease, dementia, and congestive heart failure. The longitudinal analysis showed that COVID-19 was a risk factor for mortality [hazard ratio 1.33 (1.10–1.61); p < 0.001].ConclusionThe COVID-19 group presented an almost double mortality rate compared with the non-COVID-19 group. The final model adjusted for confusion factors suggested that COVID-19 was a risk factor for long-term mortality.

(1) Background: The Modified Sequential Organ Failure Assessment (mSOFA) is an Early Warning Score (EWS) that has proven to be useful in identifying patients at high risk of mortality in prehospital care. The main objective of this study was to evaluate the predictive validity of prehospital mSOFA in estimating 2- and 90-day mortality (all-cause) in patients with acute cardiovascular diseases (ACVD), and to compare this validity to that of four other widely-used EWS. (2) Methods: We conducted a prospective, observational, multicentric, ambulance-based study in adults with suspected ACVD who were transferred by ambulance to Emergency Departments (ED). The primary outcome was 2- and 90-day mortality (all-cause in- and out-hospital). The discriminative power of the predictive variable was assessed and evaluated by the area under the curve (AUC) of the receiver operating characteristic (ROC). (3) Results: A total of 1540 patients met the inclusion criteria. The 2- and 90-day mortality rates were 5.3% and 12.7%, respectively. The mSOFA showed the highest AUC of all the evaluated scores for both 2- and 90-day mortality, AUC = 0.943 (0.917–0.968) and AUC = 0.874 (0.847–0.902), respectively. (4) Conclusions: The mSOFA is a quick and easy-to-use EWS with an excellent ability to predict mortality at both 2 and 90 days in patients treated for ACVD, and has proved to be superior to the other EWS evaluated in this study.

A 54-year-old woman with a mechanical mitral valve replacement presented with recurrent admissions for pneumonia and pulmonary edema. Multimodality imaging revealed mobile masses on the prosthesis and discrepant point of care and inpatient international normalized ratio levels owing to antiphospholipid antibody cross-reactivity on the outpatient assay. The prosthetic valve thromboses resolved with therapeutic anticoagulation. (Level of Difficulty: Beginner.)

Essential thrombocythemia (ET) is comprised among chronic myeloproliferative neoplasms (MPN) and is caused by driver mutations in JAK2, CALR, and MPL, which lead to megakaryocyte proliferation and prominent thrombocytosis. Thrombosis remains the main cause of morbidity in ET and is driven by the interplay between blood cells, the endothelium, the clotting cascade, and host-derived inflammatory mediators. Platelet activation plays a key role in the thrombotic predisposition, although the underlying mechanisms remain poorly defined. In addition to their role in hemostasis, platelets participate in innate immunity and inflammation owing to the expression of toll-like receptors (TLR), which recognize inflammatory signals, triggering platelet functional responses. Considering the impact of inflammation on ET procoagulant state, we assessed the contribution of TLR2 and TLR4 to platelet hemostatic and inflammatory properties in ET patients, by using Pam3CSK4 and lipopolysaccharide (LPS) as specific TLR2 and TLR4 ligands, respectively. TLR2 ligation induced increased surface translocation of α-granule-derived P-selectin and CD40L, which mediate platelet interaction with leukocytes and endothelial cells, respectively, and higher levels of dense granule-derived CD63 in patients, whereas PAC-1 binding was not increased and LPS had no effect on these platelet responses. Platelet-neutrophil aggregate formation was elevated in ET at baseline and after stimulation of both TLR2 and TLR4. In addition, ET patients displayed higher TLR2- and TLR4-triggered platelet secretion of the chemokine RANTES (CCL5), whereas von Willebrand factor release was not enhanced, revealing a differential releasate pattern for α-granule-stored inflammatory molecules. TLR-mediated hyperresponsiveness contrasted with impaired or preserved responses to classic platelet hemostatic agonists, such as TRAP-6 and thrombin. TLR2 and TLR4 expression on the platelet surface was normal, whereas phosphorylation of downstream effector ERK1/2 was higher in patients at baseline and after incubation with Pam3CSK4, which may partly explain the enhanced TLR2 response. In conclusion, exacerbated response to TLR stimulation may promote platelet activation in ET, boosting platelet/leukocyte/endothelial interactions and secretion of inflammatory mediators, overall reinforcing the thromboinflammatory state. These findings highlight the role of platelets as inflammatory sentinels in MPN prothrombotic scenario and provide additional evidence for the close intertwining between thrombosis and inflammation in this setting.

The ability of COVID-19 to compromise the respiratory system has generated a substantial proportion of critically ill patients in need of invasive mechanical ventilation (IMV). The objective of this paper was to analyze the prognostic ability of the pulse oximetry saturation/fraction of inspired oxygen ratio (SpO2/FiO2) and the ratio of SpO2/FiO2 to the respiratory rate–ROX index–as predictors of IMV in an emergency department in confirmed COVID-19 patients. A multicenter, retrospective cohort study was carried out in four provinces of Spain between March and November 2020. The discriminative power of the predictive variable was assessed through a prediction model trained using a derivation sub-cohort and evaluated by the area under the curve (AUC) of the receiver operating characteristic (ROC) on the validation sub-cohort. A total of 2040 patients were included in the study. The IMV rate was 10.1%, with an in-hospital mortality rate of 35.3%. The performance of the SpO2/FiO2 ratio was better than the ROX index–AUC = 0.801 (95% CI 0.746–0.855) and AUC = 0.725 (95% CI 0.652–0.798), respectively. In fact, a direct comparison between AUCs resulted in significant differences (p = 0.001). SpO2 to FiO2 ratio is a simple and promising non-invasive tool for predicting risk of IMV in patients infected with COVID-19, and it is realizable in emergency departments.

Aim of the Study. To evaluate the ability of the prehospital National Early Warning Score 2 scale (NEWS2) to predict early mortality (within 48 hours) after the index event based on the triage priority assigned for any cause in the emergency department. Methods. This is a multicenter longitudinal observational cohort study on patients attending Advanced Life Support units and transferred to the emergency department of their reference hospital. We collected demographic, physiological, and clinical variables, main diagnosis, and hospital triage level as well as mortality. The main outcome variable was mortality from any cause within two days of the index event. Results. Between April 1 and November 30, 2018, a total of 1054 patients were included in our study. Early mortality within the first 48 hours after the index event affected 55 patients (5.2%), of which 23 cases (41.8%) had causes of cardiovascular origin. In the stratification by triage levels, the AUC of the NEWS2 obtained for short-term mortality varied between 0.77 (95% CI: 0.65-0.89) for level I and 0.94 (95% CI: 0.79-1) for level III. Conclusions. The Prehospital Emergency Medical Services should evaluate the implementation of the NEWS2 as a routine evaluation, which, together with the structured hospital triage system, effectively serves to predict early mortality and detect high-risk patients.

One of the challenges in the emergency department (ED) is the early identification of patients with a higher risk of clinical deterioration. The objective is to evaluate the prognostic capacity of ΔLA (correlation between prehospital lactate (pLA) and hospital lactate (hLA)) with respect to in-hospital two day mortality. We conducted a pragmatic, multicentric, prospective and blinded-endpoint study in adults who consecutively attended and were transported in advanced life support with high priority from the scene to the ED. The corresponding area under the receiver operating characteristics curve (AUROC) was obtained for each of the outcomes. In total, 1341 cases met the inclusion criteria. The median age was 71 years (interquartile range: 54–83 years), with 38.9% (521 cases) females. The total 2 day mortality included 106 patients (7.9%). The prognostic precision for the 2 day mortality of pLA and hLA was good, with an AUROC of 0.800 (95% CI: 0.74–0.85; p < 0.001) and 0.819 (95% CI: 0.76–0.86; p < 0.001), respectively. Of all patients, 31.5% (422 cases) had an ΔLA with a decrease of

The characterization of colleters in Rubiaceae is crucial for understanding their role in plant function. Analyzing colleters in Palicourea tetraphylla and Palicourea rudgeoides aims to deepen the understanding of these structures morphoanatomical and functional characteristics. The study reveals colleters with palisade epidermis and a parenchymatic central axis, classified as standard type, featuring vascularization and crystals. Colleter secretion, abundant in acidic mucopolysaccharides, proteins, and phenolic compounds, protects against desiccation. The ontogenesis, development, and senescence of the colleters are quite rapid and fulfill their role well in biotic and abiotic protection because these structures are present at different stages of development in the same stipule. Pronounced protrusions on the colleters surface, coupled with the accumulation of secretion in the intercellular and subcuticular spaces, suggest that the secretory process occurs through the wall, driven by pressure resulting from the accumulation of secretion. The microorganisms in the colleters' secretion, especially in microbiota-rich environments such as the Atlantic Forest, provide valuable information about plant–microorganism interactions, such as resistance to other pathogens and organisms and ecological balance. This enhanced understanding of colleters contributes to the role of these structures in the plant and enriches knowledge about biological interactions within specific ecosystems and the family taxonomy. [ABSTRACT FROM AUTHOR]