Publications by authors named "Ancor Sanz-García"

35 Publications

Publisher Correction: Analyzing artificial intelligence systems for the prediction of atrial fibrillation from sinus-rhythm ECGs including demographics and feature visualization.

Sci Rep 2021 Dec 9;11(1):24030. Epub 2021 Dec 9.

Biometrics and Data Pattern Analytics Lab, Escuela Politecnica Superior, Universidad Autonoma de Madrid, Calle Francisco Tomas Y Valiente, 11, C-235, 28049, Madrid, Spain.

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http://dx.doi.org/10.1038/s41598-021-03535-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8660788PMC
December 2021

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

Prehosp Emerg Care 2022 Jan 12:1-9. Epub 2022 Jan 12.

Servicio de Urgencias, Hospital Universitario Rio Hortega de Valladolid, Gerencia Regional de Salud de Castilla y León (SACYL), Valladolid, Spain.

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.: 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. 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. 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.
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http://dx.doi.org/10.1080/10903127.2021.2011995DOI Listing
January 2022

Analyzing artificial intelligence systems for the prediction of atrial fibrillation from sinus-rhythm ECGs including demographics and feature visualization.

Sci Rep 2021 11 23;11(1):22786. Epub 2021 Nov 23.

Biometrics and Data Pattern Analytics Lab, Escuela Politecnica Superior, Universidad Autonoma de Madrid, Calle Francisco Tomas Y Valiente, 11, C-235, 28049, Madrid, Spain.

Atrial fibrillation (AF) is an abnormal heart rhythm, asymptomatic in many cases, that causes several health problems and mortality in population. This retrospective study evaluates the ability of different AI-based models to predict future episodes of AF from electrocardiograms (ECGs) recorded during normal sinus rhythm. Patients are divided into two classes according to AF occurrence or sinus rhythm permanence along their several ECGs registry. In the constrained scenario of balancing the age distributions between classes, our best AI model predicts future episodes of AF with area under the curve (AUC) 0.79 (0.72-0.86). Multiple scenarios and age-sex-specific groups of patients are considered, achieving best performance of prediction for males older than 70 years. These results point out the importance of considering different demographic groups in the analysis of AF prediction, showing considerable performance gaps among them. In addition to the demographic analysis, we apply feature visualization techniques to identify the most important portions of the ECG signals in the task of AF prediction, improving this way the interpretability and understanding of the AI models. These results and the simplicity of recording ECGs during check-ups add feasibility to clinical applications of AI-based models.
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http://dx.doi.org/10.1038/s41598-021-02179-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8610971PMC
November 2021

Usefulness of the CONUT index upon hospital admission as a potential prognostic indicator of COVID-19 health outcomes.

Chin Med J (Engl) 2021 Oct 26;135(2):187-193. Epub 2021 Oct 26.

Servicios de Neumología, Admisión y Documentación Clínica, Cuidados Intensivos y Nutrición y Dietética; Hospital Universitario de La Princesa, Madrid, Spain.

Background: In-hospital mortality in patients with coronavirus disease 2019 (COVID-19) is high. Simple prognostic indices are needed to identify patients at high-risk of COVID-19 health outcomes. We aimed to determine the usefulness of the CONtrolling NUTritional status (CONUT) index as a potential prognostic indicator of mortality in COVID-19 patients upon hospital admission.

Methods: Our study design is of a retrospective observational study in a large cohort of COVID-19 patients. In addition to descriptive statistics, a Kaplan-Meier mortality analysis and a Cox regression were performed, as well as receiver operating curve (ROC).

Results: From February 5, 2020 to January 21, 2021, there was a total of 2969 admissions for COVID-19 at our hospital, corresponding to 2844 patients. Overall, baseline (within 4 days of admission) CONUT index could be scored for 1627 (57.2%) patients. Patients' age was 67.3 ± 16.5 years and 44.9% were women. The CONUT severity distribution was: 194 (11.9%) normal (0-1); 769 (47.2%) light (2-4); 585 (35.9%) moderate (5-8); and 79 (4.9%) severe (9-12). Mortality of 30 days after admission was 3.1% in patients with normal risk CONUT, 9.0% light, 22.7% moderate, and 40.5% in those with severe CONUT (P < 0.05). An increased risk of death associated with a greater baseline CONUT stage was sustained in a multivariable Cox regression model (P < 0.05). An increasing baseline CONUT stage was associated with a longer duration of admission, a greater requirement for the use of non-invasive and invasive mechanical ventilation, and other clinical outcomes (all P < 0.05). The ROC of CONUT for mortality had an area under the curve (AUC) and 95% confidence interval of 0.711 (0.676-0746).

Conclusion: The CONUT index upon admission is potentially a reliable and independent prognostic indicator of mortality and length of hospitalization in COVID-19 patients.
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http://dx.doi.org/10.1097/CM9.0000000000001798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8769140PMC
October 2021

A Comprehensive Model to Predict Atrial Fibrillation in Cryptogenic Stroke: The Decryptoring Score.

J Stroke Cerebrovasc Dis 2022 Jan 21;31(1):106161. Epub 2021 Oct 21.

Cardiology Department, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid. IIS-IP, CIBER-CV, Madrid, Spain. Electronic address:

Objetive: Cryptogenic stroke (CS) represents up to 30% of ischemic strokes (IS). Since atrial fibrillation (AF) can be detected in up to 30% of CS, there is a clinical need for estimating the probability of underlying AF in CS to guide the optimal secondary prevention strategy. The aim of the study was to develop the first comprehensive predictive score including clinical conditions, biomarkers, and left atrial strain (LAS), to predict AF detection in this setting.

Methods: Sixty-three consecutive patients with IS or transient ischemic attack with ABCD2 scale ≥ 4 of unknown etiology were prospectively recruited. Clinical, laboratory, and echocardiographic variables were collected. All patients underwent 15 days wearable Holter-ECG monitoring. Main objective was the Decryptoring score creation to predict AF in CS. Score variables were selected by a univariate analysis and, thereafter, score points were derived according to a multivariant analysis.

Results: AF was detected in 15 patients (24%). Age > 75 (9 points), hypertension (1 point), Troponin T > 40 ng/L (8.5 points), NTproBNP > 200 pg/ml (0.5 points), LAS reservoir < 25.3% (24.5 points) and LAS conduct < 10.4% (0.5 points) were included in the score. The rate of AF detection was 0% among patients with a score of < 10 and 80% among patients with a score > 35. The comparison of the predictive validity between the proposed score and AF-ESUS score resulted in an AUC of 0.94 for Decryptoring score and of 0.65 for the AF-ESUS score(p < 0.001).

Conclusion: This novel score offers an accurate AF prediction in patients with CS; however these results will require validation in an independent cohort using this model before they may be translated into clinical practice.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.106161DOI Listing
January 2022

Comorbidity-adjusted NEWS predicts mortality in suspected patients with COVID-19 from nursing homes: Multicentre retrospective cohort study.

J Adv Nurs 2021 Sep 14. Epub 2021 Sep 14.

Servicio de Urgencias, Hospital Universitario Rio Hortega de Valladolid, Gerencia Regional de Salud de Castilla y León (SACYL), Valladolid, Spain.

Aims: To assess the prognostic accuracy of comorbidity-adjusted National Early Warning Score in suspected Coronavirus disease 2019 patients transferred from nursing homes by the Emergency Department.

Design: Multicentre retrospective cohort study.

Methods: Patients transferred by high-priority ambulances from nursing homes to Emergency Departments with suspected severe acute respiratory syndrome coronavirus 2 infection, from March 12 to July 31 2020, were considered. Included variables were: clinical covariates (respiratory rate, oxygen saturation, systolic blood pressure, heart rate, temperature, level of consciousness and supplemental oxygen use), the presence of comorbidities and confirmatory analytical diagnosis of severe acute respiratory syndrome coronavirus 2 infection. The primary outcome was a 2-day mortality rate. The discriminatory capability of the National Early Warning Score was assessed by the area under the receiver operating characteristic curve in two different cohorts, the validation and the revalidation, which were randomly selected from the main cohort.

Results: A total of 337 nursing homes, 10 advanced life support units, 51 basic life support units and 8 hospitals in Spain entailing 1,324 patients (median age 87 years) was involved in this study. Two-day mortality was 11.5% (152 cases), with a positivity rate of severe acute respiratory syndrome coronavirus 2 of 51.2%, 77.7% of hospitalization from whom 1% was of intensive care unit admission. The National Early Warning Score results for the revalidation cohort presented an AUC of 0.771, and of 0.885, 0.778 and 0.730 for the low-, medium- and high-level groups of comorbidities.

Conclusion: The comorbidity-adjusted National Early Warning Score provides a good short-term prognostic criterion, information that can help in the decision-making process to guide the best strategy for each older adult, under the current pandemic.

Impact: What problem did the study address? Under the current coronavirus disease 2019 pandemic, targeting older adults at high risk of deterioration in nursing homes remains challenging. What were the main findings? Comorbidity-adjusted National Early Warning Score helps to forecast the risk of clinical deterioration more accurately. Where and on whom will the research have impact? A high NEWS, with a low level of comorbidity is associated with optimal predictive performance, making these older adults likely to benefit from continued follow up and potentially hospital referral under the current coronavirus disease 2019 pandemic.
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http://dx.doi.org/10.1111/jan.15039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657335PMC
September 2021

Role of SpO2/FiO2 Ratio and ROX Index in Predicting Early Invasive Mechanical Ventilation in COVID-19. A Pragmatic, Retrospective, Multi-Center Study.

Biomedicines 2021 Aug 18;9(8). Epub 2021 Aug 18.

Emergency Department, Hospital Universitario Rio Hortega de Valladolid, Gerencia Regional de Salud de Castilla y León (SACYL), c/Dulzaina, 2, 47012 Valladolid, Spain.

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 ( = 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.
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http://dx.doi.org/10.3390/biomedicines9081036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392288PMC
August 2021

Systematic review and meta-analysis of fluid therapy protocols in acute pancreatitis: type, rate and route.

HPB (Oxford) 2021 11 8;23(11):1629-1638. Epub 2021 Jul 8.

HPB Unit, Department of General and Digestive Surgery, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Madrid, Spain.

Background: Adequate fluid resuscitation is paramount in the management of acute pancreatitis (AP). The aim of this study is to assess benefits and harms of fluid therapy protocols in patients with AP.

Methods: MEDLINE, Embase, Science Citation Index and clinical trial registries were searched for randomised clinical trials published before May 2020, assessing types of fluids, routes and rates of administration.

Results: A total 15 trials (1073 participants) were included. Age ranged from 38 to 73 years; follow-up period ranged from 0.5 to 6 months. Ringer lactate (RL) showed a reduced number of severe adverse events (SAE) when compared to normal saline (NS) (OR 0.48; 95%CI 0.29-0.81, p = 0.006); additionally, NS showed reduced SAE (RR 0.38; 95%IC 0.27-0.54, p < 0.001) and organ failure (RR 0.30; 95%CI 0.21-0.44, p < 0.001) in comparison with hydroxyethyl starch (HES). High fluid rate fluid infusion showed increased mortality (OR 2.88; 95%CI 1.41-5.88, p = 0.004), increased number of SAE (RR 1.42; 95%CI 1.04-1.93, p = 0.030) and higher incidence of sepsis (RR 2.80; 95%CI 1.51-5.19, p = 0.001) compared to moderate fluid rate infusion.

Conclusions: In patients with AP, RL should be preferred over NS and HES should not be recommended. Based on low-certainty evidence, moderate-rate fluid infusion should be preferred over high-rate infusion.
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http://dx.doi.org/10.1016/j.hpb.2021.06.426DOI Listing
November 2021

Mortality risk model for patients with suspected COVID-19 based on information available from an emergency dispatch center.

Emergencias 2021 08;33(4):265-272

Hospital Universitario Río Hortega de Valladolid, Gerencia Regional de Salud de Castilla y León (SACYL).

Objectives: To develop and validate a scale to stratify risk of 2-day mortality based on data collected during calls to an emergency dispatch center from patients with suspected coronavirus disease 2019 (COVID-19).

Material And Methods: Retrospective multicenter study of consecutive patients over the age of 18 years with suspected COVID-19 who were transported from home over the course of 3 months after telephone interviews with dispatchers. We analyzed clinical and epidemiologic variables and comorbidities in relation to death within 2 days of the call. Using data from the development cohort, we built a risk model by means of logistic regression analysis of categorical variables that were independently associated with 2-day mortality. The scale was validated first in a validation cohort in the same province and then in a cohort in a different province.

Results: A total of 2320 patients were included. The mean age was 79 years, and 49.8% were women. The overall 2-day mortality rate was 22.6% (376 deaths of patients with severe acute respiratory syndrome coronavirus 2 infection). The model included the following factors: age, location (rural location as a protective factor), institutionalization, desaturation, lung sounds (rhonchi), and altered mental status. The area under the receiver operating characteristic curve for death within 2 days was 0.763 (95% CI, 0.725-0.802; P .001). Mortality in patients at high risk (more than 2.4 points on the scale) was 60%.

Conclusion: This risk scale derived from information available to an emergency dispatch center is applicable to patients with suspected COVID-19. It can stratify patients by risk of early death (within 2 days), possibly helping with decision making regarding whether to transport from home or what means of transport to use, and destination.
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August 2021

Time for a prehospital-modified sequential organ failure assessment score: An ambulance-Based cohort study.

Am J Emerg Med 2021 Nov 24;49:331-337. Epub 2021 Jun 24.

Servicio de Urgencias, Hospital Universitario Rio Hortega de Valladolid, Gerencia Regional de Salud de Castilla y León (SACYL), Spain.

Background: To adapt the Sequential Organ Failure Assessment (SOFA) score to fit the prehospital care needs; to do that, the SOFA was modified by replacing platelets and bilirubin, by lactate, and tested this modified SOFA (mSOFA) score in its prognostic capacity to assess the mortality-risk at 2 days since the first Emergency Medical Service (EMS) contact.

Methods: Prospective, multicentric, EMS-delivery, ambulance-based, pragmatic cohort study of adults with acute diseases, referred to two tertiary care hospitals (Spain), between January 1st and December 31st, 2020. The discriminative power of the predictive variable was assessed through a prediction model trained using the derivation cohort and evaluated by the area under the curve (AUC) of the receiver operating characteristic (ROC) on the validation cohort.

Results: A total of 1114 participants comprised two separated cohorts recruited from 15 ambulance stations. The 2-day mortality rate (from any cause) was 5.9% (66 cases). The predictive validity of the mSOFA score was assessed by the calculation of the AUC of ROC in the validation cohort, resulting in an AUC of 0.946 (95% CI, 0.913-0.978, p < .001), with a positive likelihood ratio was 23.3 (95% CI, 0.32-46.2).

Conclusions: Scoring systems are now a reality in prehospital care, and the mSOFA score assesses multiorgan dysfunction in a simple and agile manner either bedside or en route. Patients with acute disease and an mSOFA score greater than 6 points transferred with high priority by EMS represent a high early mortality group.

Trial Registration: ISRCTN48326533, Registered Octuber 312,019, Prospectively registered (doi:https://doi.org/10.1186/ISRCTN48326533).
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http://dx.doi.org/10.1016/j.ajem.2021.06.042DOI Listing
November 2021

Electrocardiographic biomarkers to predict atrial fibrillation in sinus rhythm electrocardiograms.

Heart 2021 11 4;107(22):1813-1819. Epub 2021 Jun 4.

Cardiology Department, Hospital Universitario de la Princesa, Madrid, Spain.

Objective: Early prediction of atrial fibrillation (AF) development would improve patient outcomes. We propose a simple and cheap ECG based score to predict AF development.

Methods: A cohort of 16 316 patients was analysed. ECG measures provided by the computer-assisted ECG software were used to identify patients. A first group included patients in sinus rhythm who showed an ECG with AF at any time later (n=505). A second group included patients with all their ECGs in sinus rhythm (n=15 811). By using a training set (75% of the cohort) the initial sinus rhythm ECGs of both groups were analysed and a predictive risk score based on a multivariate logistic model was constructed.

Results: A multivariate regression model was constructed with 32 variables showing a predictive value characterised by an area under the curve (AUC) of 0.776 (95% CI: 0.738 to 0.814). The subsequent risk score included the following variables: age, duration of P-wave in aVF, V4 and V5; duration of T-wave in V3, mean QT interval adjusted for heart rate, transverse P-wave clockwise rotation, transverse P-wave terminal angle and transverse QRS complex terminal vector magnitude. Risk score values ranged from 0 (no risk) to 5 (high risk). The predictive validity of the score reached an AUC of 0.764 (95% CI: 0.722 to 0.806) with a global specificity of 61% and a sensitivity of 55%.

Conclusions: The automatic assessment of ECG biomarkers from ECGs in sinus rhythm is able to predict the risk for AF providing a low-cost screening strategy for early detection of this pathology.
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http://dx.doi.org/10.1136/heartjnl-2021-319120DOI Listing
November 2021

Prehospital troponin as a predictor of early clinical deterioration.

Eur J Clin Invest 2021 Nov 18;51(11):e13591. Epub 2021 May 18.

Emergency Department, Hospital Universitario Rio Hortega de Valladolid, Gerencia Regional de Salud de Castilla y León (SACYL), Salamanca, Spain.

Background And Objectives: Elevated troponin T (cTnT) values are associated with comorbidities and early mortality, in both cardiovascular and noncardiovascular diseases. The objective of this study is to evaluate the prognostic accuracy of the sole utilization of prehospital point-of-care cardiac troponin T to identify the risk of early in-hospital deterioration, including mortality within 28 days.

Methods: We conducted a prospective, multicentric, controlled, ambulance-based, observational study in adults with acute diseases transferred with high priority by ambulance to emergency departments, between 1 January and 30 September 2020. Patients with hospital diagnosis of acute coronary syndrome were excluded. The discriminative power of the predictive cTnT was assessed through a discrimination model trained using a derivation cohort and evaluated by the area under the curve of the receiver operating characteristic on a validation cohort.

Results: A total of 848 patients were included in our study. The median age was 68 years (25th-75th percentiles: 50-81 years), and 385 (45.4%) were women. The mortality rate within 28 days was 12.4% (156 cases). The predictive ability of cTnT to predict mortality presented an area under the curve of 0.903 (95% CI: 0.85-0.954; P < .001). Risk stratification was performed, resulting in three categories with the following optimal cTnT cut-off points: high risk greater than or equal to 100, intermediate risk 40-100 and low risk less than 40 ng/L. In the high-risk group, the mortality rate was 61.7%, and on the contrary, the low-risk group presented a mortality of 2.3%.

Conclusions: The implementation of a routine determination of cTnT on the ambulance in patients transferred with high priority to the emergency department can help to stratify the risk of these patients and to detect unknown early clinical deterioration.
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http://dx.doi.org/10.1111/eci.13591DOI Listing
November 2021

Differential miRNAs in acute spontaneous coronary artery dissection: Pathophysiological insights from a potential biomarker.

EBioMedicine 2021 Apr 15;66:103338. Epub 2021 Apr 15.

Department of Immunology, Instituto de Investigación Sanitaria, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Madrid, Spain; CIBER de Enfermedades Cardiovasculares, Spain. Electronic address:

Background: Spontaneous Coronary Artery Dissection (SCAD) is an important cause of acute coronary syndromes, particularly in young to middle-aged women. Differentiating acute SCAD from coronary atherothrombosis remains a major clinical challenge.

Methods: A case-control study was used to explore the usefulness of circulating miRNAs to discriminate both clinical entities. The profile of miRNAs was evaluated using an unbiased human RT-PCR platform and confirmed using individual primers. miRNAs were evaluated in plasma samples from acute SCAD and atherothrombotic acute myocardial infarction (AT-AMI) from two independent cohorts; discovery cohort (SCAD n = 15, AT-AMI n = 15), and validation cohort (SCAD n = 11, AT-AMI n = 41) with 9 healthy control subjects. Plasma levels of IL-8, TGFB1, TGBR1, Endothelin-1 and MMP2 were analysed by ELISA assays.

Findings: From 15 differentially expressed miRNAs detected in cohort 1, we confirmed in cohort 2 the differential expression of 4 miRNAs: miR-let-7f-5p, miR-146a-5p, miR-151a-3p and miR-223-5p, whose expression was higher in SCAD compared to AT-AMI. The combined expression of these 4 miRNAs showed the best predictive value to distinguish between both entities (AUC: 0.879, 95% CI 0.72-1.0) compared to individual miRNAs. Functional profiling of target genes identified an association with blood vessel biology, TGF-beta pathway and cytoskeletal traction force. ELISA assays showed high plasma levels of IL-8, TGFB1, TGFBR1, Endothelin-1 and MMP2 in SCAD patients compared to AT-AMI.

Interpretation: We present a novel signature of plasma miRNAs in patients with SCAD. miR-let-7f-5p, miR-146a-5p, miR-151a-3p and miR-223-5p discriminate SCAD from AT-AMI patients and also shed light on the pathological mechanisms underlying this condition.

Funding: Spanish Ministry of Economy and Competitiveness (MINECO): Plan Nacional de Salud SAF2017-82886-R, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV). Fundación BBVA a equipos de Investigación Científica 2018 and from Caixa Banking Foundation under the project code HR17-00016 to F.S.M. Instituto de Salud Carlos III (AES 2019): PI19/00565 to F.R, PI19/00545 to P.M. CAM (S2017/BMD-3671-INFLAMUNE-CM) from Comunidad de Madrid to FSM and PM. The UK SCAD study was supported by BeatSCAD, the British Heart Foundation (BHF) PG/13/96/30608 the NIHR rare disease translational collaboration and the Leicester NIHR Biomedical Research Centre.
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http://dx.doi.org/10.1016/j.ebiom.2021.103338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079473PMC
April 2021

Association of Prehospital Oxygen Saturation to Inspired Oxygen Ratio With 1-, 2-, and 7-Day Mortality.

JAMA Netw Open 2021 04 1;4(4):e215700. Epub 2021 Apr 1.

Data Analysis Unit, Health Research Institute, Hospital de la Princesa, Madrid, Spain.

Importance: The early identification of patients at high risk of clinical deterioration represents one of the greatest challenges for emergency medical services (EMS).

Objective: To assess whether use of the ratio of prehospital oxygen saturation measured by pulse oximetry (Spo2) to fraction of inspired oxygen (Fio2) measured during initial contact by EMS with the patient (ie, the first Spo2 to Fio2 ratio) and 5 minutes before the patient's arrival at the hospital (ie, the second Spo2 to Fio2 ratio) can predict the risk of early in-hospital deterioration.

Design, Setting, And Participants: A prospective, derivation-validation prognostic cohort study of 3606 adults with acute diseases referred to 5 tertiary care hospitals in Spain was conducted between October 26, 2018, and June 30, 2020. Eligible patients were recruited from among all telephone requests for EMS assistance for adults who were later evacuated with priority in advanced life support units to the referral hospitals during the study period.

Main Outcomes And Measures: The primary outcome was hospital mortality from any cause within the first, second, third, or seventh day after EMS transport to the hospital. The main measure was the Spo2 to Fio2 ratio.

Results: A total of 3606 participants comprised 2 separate cohorts: the derivation cohort (3081 patients) and the validation cohort (525 patients). The median age was 69 years (interquartile range, 54-81 years), and 2122 patients (58.8%) were men. The overall mortality rate of the patients in the study cohort ranged from 3.6% for 1-day mortality (131 patients) to 7.1% for 7-day mortality (256 patients). The best model performance was for 2-day mortality with the second Spo2 to Fio2 ratio with an area under the curve of 0.890 (95% CI, 0.829-0.950; P < .001), although the other outcomes also presented good results. In addition, a risk-stratification model was generated. The optimal cutoff resulted in the following ranges of Spo2 to Fio2 ratios: 50 to 100 for high risk of mortality, 101 to 426 for intermediate risk, and 427 to 476 for low risk.

Conclusions And Relevance: This study suggests that use of the prehospital Spo2 to Fio2 ratio was associated with improved management of patients with acute disease because it accurately predicts short-term mortality.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.5700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044733PMC
April 2021

DNA Copy Number Variation Associated with Anti-tumour Necrosis Factor Drug Response and Paradoxical Psoriasiform Reactions in Patients with Moderate-to-severe Psoriasis.

Acta Derm Venereol 2021 May 4;101(5):adv00448. Epub 2021 May 4.

Data Analysis Unit, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria La Princesa (IIS-IP), Madrid, Spain.

Biological drugs targeting tumour necrosis factor are effective for psoriasis. However, 30-50% of patients do not respond to these drugs and may even develop paradoxical psoriasiform reactions. This study search-ed for DNA copy number variations that could predict anti-tumour necrotic factor drug response or the appearance of anti-tumour necrotic factor induced psoriasiform reactions. Peripheral blood samples were collected from 70 patients with anti-tumour necrotic factor drug-treated moderate-to-severe plaque psoriasis. Samples were analysed with an Illumina 450K methylation microarray. Copy number variations were obtained from raw methylation data using conumee and Chip Analysis Methylation Pipeline (ChAMP) R packages. One copy number variation was found, harbouring one gene (CPM) that was significantly associated with adalimumab response (Bonferroni-adjusted p-value < 0.05). Moreover, one copy number variation was identified harbouring 3 genes (ARNT2, LOC101929586 and MIR5572) related to the development of paradoxical psoriasiform reactions. In conclusion, this study has identified DNA copy number variations that could be good candidate markers to predict response to adalimumab and the development of anti-tumour necrotic factor paradoxical psoriasiform reactions.
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http://dx.doi.org/10.2340/00015555-3794DOI Listing
May 2021

Early Warning Scores in Patients with Suspected COVID-19 Infection in Emergency Departments.

J Pers Med 2021 Mar 2;11(3). Epub 2021 Mar 2.

Emergency Department, Hospital Universitario Rio Hortega de Valladolid, Gerencia Regional de Salud de Castilla y León (SACYL), c/Dulzaina, 2, 47012 Valladolid, Spain.

Early warning scores (EWSs) help prevent and recognize and thereby act as the first signs of clinical and physiological deterioration. The objective of this study is to evaluate different EWSs (National Early Warning Score 2 (NEWS2), quick sequential organ failure assessment score (qSOFA), Modified Rapid Emergency Medicine Score (MREMS) and Rapid Acute Physiology Score (RAPS)) to predict mortality within the first 48 h in patients suspected to have Coronavirus disease 2019 (COVID-19). We conducted a retrospective observational study in patients over 18 years of age who were treated by the advanced life support units and transferred to the emergency departments between March and July of 2020. Each patient was followed for two days registering their final diagnosis and mortality data. A total of 663 patients were included in our study. Early mortality within the first 48 h affected 53 patients (8.3%). The scale with the best capacity to predict early mortality was the National Early Warning Score 2 (NEWS2), with an area under the curve of 0.825 (95% CI: 0.75-0.89). The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients presented an area under the curve (AUC) of 0.804 (95% CI: 0.71-0.89), and the negative ones with an AUC of 0.863 (95% CI: 0.76-0.95). Among the EWSs, NEWS2 presented the best predictive power, even when it was separately applied to patients who tested positive and negative for SARS-CoV-2.
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http://dx.doi.org/10.3390/jpm11030170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001393PMC
March 2021

Can anxiety in undergraduate students in a high-fidelity clinical simulation be predicted? A randomized, sham-controlled, blinded trial.

Nurse Educ Today 2021 Mar 19;98:104774. Epub 2021 Jan 19.

Data Analysis Unit, Health Research Institute, Hospital de la Princesa, Madrid (IIS-IP), Spain. Electronic address:

Introduction: High-fidelity clinical simulation has implied a revolution in health science training. Despite its benefits, some drawbacks could hinder the learning process, especially the anxiety produced during such scenarios.

Objectives: The aim of the present work is to develop a predictive model capable of determining which students will present high levels of anxiety.

Design: We performed a randomized, sham-controlled, blinded trial in which students were randomly assigned to four scenarios and played one of two possible roles.

Methods: Before and after the simulation we assessed the anxiety level along with physiological and analytical parameters. The main analyzed outcome was an increase of ≥25% in anxiety compared with baseline.

Results: The type of scenario or the role played had no effect on anxiety. The predictive model presented an Area Under the Receiver Operating Characteristics of 0.798 (95% CI: 0.69-0.90; p < 0.001), with age and systolic blood pressure being protective factors against anxiety.

Conclusions: Our results showed that the anxiety level developed during simulation could be predicted. The application of this predictive model when associated to appropriate techniques to deal with increased anxiety levels could improve the learning process of medical students during simulations.
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http://dx.doi.org/10.1016/j.nedt.2021.104774DOI Listing
March 2021

Blood Biomarkers for Assessing Headaches in Healthcare Workers after Wearing Biological Personal Protective Equipment in a COVID-19 Field Hospital.

J Pers Med 2021 Jan 4;11(1). Epub 2021 Jan 4.

Faculty of Health Sciences, Universidad de Castilla la Mancha, 45600 Talavera de la Reina, Spain.

The coronavirus disease 2019 (COVID-19) has led to a pandemic, which among other things, has highlighted biosafety as a key cornerstone in the management of disease transmission. The aim of this work was to analyze the role played by different blood biomarkers in predicting the appearance of headaches in healthcare workers wearing personal protective equipment (PPE) in a COVID-19 treatment unit. A prospective cohort study of 38 healthcare workers was performed during April 2020. Blood analysis, performed just before the start of a 4 hour shift, was carried out on all volunteers equipped with PPE. At the end of their shifts and after decontamination, they were asked if they had suffered from headache in order to obtain a binary outcome. The baseline creatinine value reflected a specific odds ratio of 241.36 (95% CI: 2.50-23,295.43; = 0.019) and an area under the curve (AUC) value of 0.737 (95%CI: 0.57-0.90; < 0.01). Blood creatinine is a good candidate for predicting the appearance of a de novo headache in healthcare workers after wearing PPE for four hours in a COVID-19 unit.
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http://dx.doi.org/10.3390/jpm11010027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823801PMC
January 2021

Serum adipokines as non-invasive biomarkers in Crohn's disease.

Sci Rep 2020 10 22;10(1):18027. Epub 2020 Oct 22.

Servicio de Aparato Digestivo, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain.

Adipose tissue secretes molecules that can promote activity in Crohn's disease. We aimed to evaluate the role of serum adipokines as possible biomarkers in Crohn's disease. Serum samples were obtained from 40 patients with endoscopically active or quiescent Crohn's disease and 36 healthy controls. Serum leptin, ghrelin, resistin and adiponectin levels were analysed by Multiplex in a Luminex 200 system technology. Receiver Operating Characteristic curves were performed to evaluate the adipokines discriminatory capacity. A logistic regression adjusted by possible confounders (i.e. gender, age, BMI) was performed for those adipokines that showed an area under the curve > 0.7. No differences were found in age, gender or BMI among groups. Distribution for serum resistin was different among the three groups of study, and only this adipokine showed an area under the curve of 0.75 comparing actives patients and healthy control groups. Resistin median concentration was selected as a cut-off for a logistic regression analysis; odds ratio along its 95% confidence interval adjusted by gender, age, and BMI yielded a value of 5.46 (1.34-22.14) comparing actives patients and healthy controls. High concentration of serum resistin is probably associated to activity, being this association independent of gender, age or BMI.
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http://dx.doi.org/10.1038/s41598-020-74999-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582883PMC
October 2020

Usefulness of computer-assisted ECG analysis in the pre-operative evaluation of noncardiac surgery.

Eur J Anaesthesiol 2020 11;37(11):1075-1077

From the Data Analysis Unit, Instituto de Investigación Sanitaria, Hospital Universitario de la Princesa (AS-G, MP-R, GJO), Cardiology Service, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, IIS-IP, CIVER-CV (AC, FA, LJJ-B), Anaesthesiology and Critical Care Service, Hospital Universitario de la Princesa, Madrid, Spain (EA, AP), Department Anaesthesia and Intensive Care Units, IRCCS Istituto Clinico Humanitas, Humanitas University, Milan, Italy (MC), Biostatistics, Methodology Unit, Instituto de Investigación Sanitaria (JMCM), Informatic's Department, Hospital Universitario de la Princesa, Madrid, Spain and The National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina (GJO).

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http://dx.doi.org/10.1097/EJA.0000000000001256DOI Listing
November 2020

Predicting Health Care Workers' Tolerance of Personal Protective Equipment: An Observational Simulation Study.

Clin Simul Nurs 2020 Oct 2;47:65-72. Epub 2020 Sep 2.

Data Analysis Unit, Health Research Institute, Hospital de la Princesa, 28006 Madrid, Spain.

Background: More recently, due to the coronavirus disease 2019 pandemic, health care workers have to deal with clinical situations wearing personal protective equipment (PPE); however, there is a question of whether everybody will tolerate PPE equally. The main objective of this study was to develop a risk model to predict whether health care workers will tolerate wearing PPE, C category, 4B/5B/6B type, during a 30-minute simulation.

Methods: A nonexperimental simulation study was conducted at the Advanced Simulation Center, Faculty of Medicine, Valladolid University (Spain) from April 3rd to 28th, 2017. Health care students and professionals were equipped with PPE and performed a 30-minute simulation. Anthropometric, physiological, and analytical variables and anxiety levels were measured before and after simulation. A scoring model was constructed.

Results: Ninety-six volunteers participated in the study. Half the sample presented metabolic fatigue in the 20 minutes after finishing the simulation. The predictive model included female sex, height, muscle and bone mass, and moderate level of physical activity. The validity of the main model using all the variables presented an area under the curve of 0.86 (95% confidence interval: 0.786-0.935), and the validity of the model had an area under the curve of 0.725 (95% confidence interval: 0.559-0.89).

Conclusions: Decision-making in biohazard incidents is a challenge for emergency team leaders. Knowledge of health care workers' physiological tolerance of PPE could improve their performance.
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http://dx.doi.org/10.1016/j.ecns.2020.07.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467653PMC
October 2020

The Value of Prehospital Early Warning Scores to Predict in - Hospital Clinical Deterioration: A Multicenter, Observational Base-Ambulance Study.

Prehosp Emerg Care 2021 Sep-Oct;25(5):597-606. Epub 2020 Sep 15.

Objectives: Early warning scores are clinical tools capable of identifying prehospital patients with high risk of deterioration. We sought here to contrast the validity of seven early warning scores in the prehospital setting and specifically, to evaluate the predictive value of each score to determine early deterioration-risk during the hospital stay, including mortality at one, two, three and seven- days since the index event. : A prospective multicenter observational based-ambulance study of patients treated by six advanced life support emergency services and transferred to five Spanish hospitals between October 1, 2018 and December 31, 2019. We collected demographic, clinical, and laboratory variables. Seven risk score were constructed based on the analysis of prehospital variables associated with death within one, two, three and seven days since the index event. The area under the receiver operating characteristics was used to determine the discriminant validity of each early warning score. : A total of 3,273 participants with acute diseases were accurately linked. The median age was 69 years (IQR, 54-81 years), 1,348 (41.1%) were females. The overall mortality rate for patients in the study cohort ranged from 3.5% for first-day mortality (114 cases), to 7% for seven-day mortality (228 cases). The scores with the best performances for one-day mortality were Vitalpac Early Warning Score with an area under the receiver operating characteristic (AUROC) of 0.873 (95% CI: 0.81-0.9), for two-day mortality, Triage Early Warning Score with an AUROC of 0.868 (95% CI: 0.83-0.9), for three and seven-days mortality the Modified Rapid Emergency Medicine Score with an AUROC of 0.857 (0.82-0.89) and 0.833 (95% CI: 0.8-0.86). In general, there were no significant differences between the scores analyzed. : All the analyzed scores have a good predictive capacity for early mortality, and no statistically significant differences between them were found. The National Early Warning Score 2, at the clinical level, has certain advantages. Early warning scores are clinical tools that can help in the complex decision-making processes during critical moments, so their use should be generalized in all emergency medical services.
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http://dx.doi.org/10.1080/10903127.2020.1813224DOI Listing
September 2021

Accuracy of prehospital point-of-care lactate in early in-hospital mortality.

Eur J Clin Invest 2020 Dec 16;50(12):e13341. Epub 2020 Aug 16.

Data Analysis Unit, Health Research Institute, Hospital de la Princesa (IIS-IP), Madrid, Spain.

Background: Emergency medical services (EMS) routinely face complex scenarios where decisions should be taken with limited clinical information. The development of fast, reliable and easy to perform warning biomarkers could help in such decision-making processes. The present study aims at characterizing the validity of point-of-care lactate (pLA) during prehospital tasks for predicting in-hospital mortality within two days after the EMS assistance.

Materials And Methods: Prospective, multicentric, ambulance-based and controlled observational study without intervention, including six advanced life support and five hospitals. The pLA levels were recorded during EMS assistance of adult patients. The validity of pLA to determine the in-hospital mortality was assessed by the area under the curve (AUC) of the receiver operating curve (ROC).

Results: A total of 2997 patients were considered in the study, with a median of 69 years (IQR 54-81) and 41.4% of women. The median pLA value was 2.7 mmol/L (1.9-3.8) in survivors and 5.7 mmol/L (4.4-7.6) in nonsurvivors. The global discrimination level of pLA reached an AUC of 0.867, being 1.9 mmol/L and 4 mmol/L the cut-off point for low and high mortality. The discrimination value of pLA was not affected by sex, age or pathology.

Conclusions: Our results highlight the clinical importance of prehospital pLA to determine the in-hospital risk of mortality. The incorporation of pLA into the EMS protocols could improve the early identification of risky patients, leading to a better care of such patients.
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http://dx.doi.org/10.1111/eci.13341DOI Listing
December 2020

Expression of miR-135b in Psoriatic Skin and Its Association with Disease Improvement.

Cells 2020 07 2;9(7). Epub 2020 Jul 2.

Dermatology Department, Instituto de Investigación Sanitaria Hospital Universitario de la Princesa (IISP), 28006 Madrid, Spain.

miRNAs have been associated with psoriasis since just over a decade. However, we are far from a complete understanding of their role during the development of this disease. Our objective was to characterize the cutaneous expression of miRNAs not previously described in psoriasis, the changes induced following the treatment with biologicals and their association with disease improvement. Next generation sequencing was performed from five skin samples from psoriasis patients (lesional and non-lesional skin) and five controls, and from this cohort, 12 microRNAs were selected to be analyzed in skin samples from 44 patients with plaque psoriasis. In 15 patients, an additional sample was obtained after three months of biological treatment. MiR-9-5p, miR-133a-3p and miR-375 were downregulated in the lesional skin of psoriasis patients. After treatment, expression of miR-133a-3p, miR-375, miR-378a and miR-135b in residual lesions returned towards the levels observed in non-lesional skin. The decrease in miR-135b levels after treatment with biologics was associated with both the improvement of patients evaluated through Psoriasis Area and Severity Index score and the decrease in local inflammatory response. Moreover, basal expression of miR-135b along with age was associated with the improvement of psoriasis, suggesting its possible usefulness as a prognostic biomarker.
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http://dx.doi.org/10.3390/cells9071603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408353PMC
July 2020

Risk for early death in acutely ill older adults attended by prehospital emergency medical services.

Emergencias 2020 06;32(3):177-184

Unidad de Análisis de Datos (UAD) del Instituto de Investigación Sanitaria del Hospital de la Princesa (IIS-IP), Madrid, España.

Objectives: To develop and validate a prehospital risk model to predict early in-hospital mortality (#48 hours) in patients aged 65 years or older.

Material And Methods: Prospective multicenter observational study in a cohort of patients aged 65 years or older attended by advanced life support emergency services and transferred to 5 Spanish hospitals between April 2018 and July 2019. We collected demographic, clinical and laboratory variables. A risk score was constructed and validated based on the analysis of prehospital variables associated with death within 48 hours. Predictors were selected by logistic regression.

Results: A total of 1759 patients were recruited. The median age was 79 years (interquartile range, 72-85 years), and 766 (43.5%) were women. One hundred eight patients (6.1%) died within 48 hours. Predictors in the Prehospital Older Adults Warning Scale (POAWS) were age, systolic blood pressure, temperature, the ratio of oxygen saturation to the fraction of inspired oxygen, score on the Glasgow coma scale, and lactic acid concentration in venous blood. The area under the receiver operating characteristic curve of the model to predict early mortality was 0.853 (95% CI, 0.80-0.91; P<.001). Mortality in patients at high risk (POAWS score, >7) was 69%.

Conclusion: The prehospital POAWS score can be used to stratify risk for death within 48 hours in patients aged 65 years or older.
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June 2020

Utility of circulating serum miRNA profiles to evaluate the potential risk and severity of immune-mediated inflammatory disorders.

J Autoimmun 2020 07 5;111:102472. Epub 2020 May 5.

Department of Endocrinology, Hospital Universitario de La Princesa, Instituto de Investigación Princesa, Universidad Autónoma de Madrid, C/ Diego de León 62, 28006, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER GCV14/ER/12), Spain. Electronic address:

Immune-mediated inflammatory disorders (IMID) are a group of diseases that present inflammation as a major pathogenic mechanism. They affect 15% of the population and pose a heavy socio-economic burden. Despite the growing knowledge on the etiopathogenesis of these diseases and the marked improvement in their management, there is a lack of predictive markers of IMID development or severity suitable for early diagnosis and adjustment of treatment intensity. The possibility that certain circulating miRNA profiles could be used as biomarkers of risk of development and/or severity of several autoimmune diseases has fuelled the interest in using them to improve the selection of successful treatments. The multi-pronged approach proposed here sought to reveal circulating miRNAs and miRNA signatures that could act as new predictive biomarkers of IMID development and severity. Our results showed that the circulating levels of miR-19b and miR-26b were significantly decreased (p < 0.001) in IMID patients compared to controls. Furthermore, receiver operating characteristic (ROC) curve analysis showed that these miRNAs were suitable discriminators capable to identify an IMID, with areas under the curve (AUC) of 0.85 and 0.83, respectively. In addition, we established that miR-19a and miR-143 were significantly increased in IMID patients with severe disease (p < 0.05). In summary, our findings identify two different miRNA signatures. One of them is associated with the presence of IMIDs and could lead to the development of tools for their early detection. The second signature is able to discriminate between mild and severe forms of these disorders and could be a putative tool to select patient candidates for a more intense treatment.
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http://dx.doi.org/10.1016/j.jaut.2020.102472DOI Listing
July 2020

Prehospital Point-Of-Care Lactate Increases the Prognostic Accuracy of National Early Warning Score 2 for Early Risk Stratification of Mortality: Results of a Multicenter, Observational Study.

J Clin Med 2020 Apr 18;9(4). Epub 2020 Apr 18.

Data Analysis Unit, Health Research Institute, Hospital de la Princesa, 28006 Madrid, Spain.

The objective of this study was to assess whether the use of prehospital lactate (pLA) can increase the prognostic accuracy of the National Early Warning Score 2 (NEWS2) to detect the risk of death within 48 h. A prospective, multicenter study in adults treated consecutively by the emergency medical services (EMS) included six advanced life support (ALS) services and five hospitals. Patients were assigned to one of four groups according to their risk of mortality (low, low-medium, medium, and high), as determined by the NEWS2 score. For each group, the validity of pLA in our cohort was assessed by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. In this study, 3081 participants with a median age of 69 years (Interquartile range (IQR): 54-81) were included. The two-day mortality was 4.4% (137 cases). The scale derived from the implementation of the pLA improved the capacity of the NEWS2 to discriminate low risk of mortality, with an AUC of 0.910 (95% CI: 0.87-0.94; < 0.001). The risk stratification provided by the NEWS2 can be improved by incorporating pLA measurement to more accurately predict the risk of mortality in patients with low risk.
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http://dx.doi.org/10.3390/jcm9041156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231108PMC
April 2020

Systemic administration of a fibroblast growth factor receptor 1 agonist rescues the cognitive deficit in aged socially isolated rats.

Neurobiol Aging 2019 06 20;78:155-165. Epub 2019 Feb 20.

Department of Psychobiology, Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain. Electronic address:

Social isolation predominantly occurs in elderly people and it is strongly associated with cognitive decline. However, the mechanisms that produce isolation-related cognitive dysfunction during aging remain unclear. Here, we evaluated the cognitive, electrophysiological, and morphological effects of short- (4 weeks) and long-term (12 weeks) social isolation in aged male Wistar rats. Long-term but not short-term social isolation increased the plasma corticosterone levels and impaired spatial memory in the Morris water maze. Moreover, isolated animals displayed dampened hippocampal long-term potentiation in vivo, both in the dentate gyrus (DG) and CA1, as well as a specific reduction in the volume of the stratum oriens and spine density in CA1. Interestingly, social isolation induced a transient increase in hippocampal basic fibroblast growth factor (FGF2), whereas fibroblast growth factor receptor 1 (FGFR1) levels only increased after long-term isolation. Importantly, subchronic systemic administration of FGL, a synthetic peptide that activates FGFR1, rescued spatial memory in long-term isolated rats. These findings provide new insights into the neurobiological mechanisms underlying the detrimental effects on memory of chronic social isolation in the aged.
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http://dx.doi.org/10.1016/j.neurobiolaging.2019.02.011DOI Listing
June 2019

Potential EEG biomarkers of sedation doses in intensive care patients unveiled by using a machine learning approach.

J Neural Eng 2019 04 31;16(2):026031. Epub 2019 Jan 31.

Instituto de Investigación Sanitaria, Hospital de la Princesa, Madrid, España.

Objective: Sedation of neurocritically ill patients is one of the most challenging situation in ICUs. Quantitative knowledge on the sedation effect on brain activity in that complex scenario could help to uncover new markers for sedation assessment. Hence, we aim to evaluate the existence of changes of diverse EEG-derived measures in deeply-sedated (RASS-Richmond agitation-sedation scale  -4 and  -5) neurocritically ill patients, and also whether sedation doses are related with those eventual changes.

Approach: We performed an observational prospective cohort study in the intensive care unit of the Hospital de la Princesa. Twenty-six adult patients suffered from traumatic brain injury and subarachnoid hemorrhage were included in the present study. Long-term continuous electroencephalographic (EEG) recordings (2141 h) and hourly annotated information were used to determine the relationship between intravenous sedation infusion doses and network and spectral EEG measures. To do that, two different strategies were followed: assessment of the statistical dependence between both variables using the Spearman correlation rank and by performing an automatic classification method based on a machine learning algorithm.

Main Results: More than 60% of patients presented a correlation greater than 0.5 in at least one of the calculated EEG measures with the sedation dose. The automatic classification method presented an accuracy of 84.3% in discriminating between different sedation doses. In both cases the nodes' degree was the most relevant measurement.

Significance: The results presented here provide evidences of brain activity changes during deep sedation linked to sedation doses. Particularly, the capability of network EEG-derived measures in discriminating between different sedation doses could be the framework for the development of accurate methods for sedation levels assessment.
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http://dx.doi.org/10.1088/1741-2552/ab039fDOI Listing
April 2019

Identifying causal relationships between EEG activity and intracranial pressure changes in neurocritical care patients.

J Neural Eng 2018 12 5;15(6):066029. Epub 2018 Sep 5.

Instituto de Investigación Sanitaria, Hospital de la Princesa, Madrid, Spain.

Objective: To explore and assess the relationship between electroencephalography (EEG) activity and intracranial pressure (ICP) in patients suffering from traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) during their stay in an intensive care unit.

Approach: We performed an observational prospective cohort study of adult patients suffering from TBI or SAH. Continuous EEG-ECG was performed during ICP monitoring. In every patient, variables derived from the EEG were calculated and the Granger causality (GC) methodology was employed to assess whether, and in which direction, there is any relationship between EEG and ICP.

Main Results: One-thousand fifty-five hours of continuous multimodal monitoring were analyzed in 21 patients using the GC test. During 37.88% of the analyzed time, significant GC statistic was found in the direction from the EEG activity to the ICP, with typical lags of 25-50 s between them. When recordings were adjusted by sedation-perfusion and/or bolus-and handling, these percentages hardly changed.

Significance: Long-lasting, continuous and simultaneous EEG and ICP recordings from TBI and SAH patients provide highly rich and useful information, which has allowed for uncovering a strong relationship between both signals. The use of this relationship could lead to developing a medical device to measure ICP in a non-invasive way.
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http://dx.doi.org/10.1088/1741-2552/aadeeaDOI Listing
December 2018
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