Primary Cilia as a Tumor Marker in Pituitary Neuroendocrine Tumors.

Pituitary neuroendocrine tumors (PitNETs) account for approximately 15% of all intracranial neoplasms. Although they usually appear to be benign, some tumors display worse behavior, displaying rapid growth, invasion, refractoriness to treatment, and recurrence. Increasing evidence supports the role of primary cilia (PC) in regulating cancer development. Here, we showed that PC are significantly increased in PitNETs and are associated with increased tumor invasion and recurrence. Serial electron micrographs of PITNETs demonstrated different ciliation phenotypes (dot-like versus normal-like cilia) that represented PC at different stages of ciliogenesis. Molecular findings demonstrated that 123 ciliary-associated genes (eg, doublecortin domain containing protein 2, Sintaxin-3, and centriolar coiled-coil protein 110) were dysregulated in PitNETs, representing the upregulation of markers at different stages of intracellular ciliogenesis. Our results demonstrate, for the first time, that ciliogenesis is increased in PitNETs, suggesting that this process might be used as a potential target for therapy in the future.

Effectiveness, tolerability, and response predictors of preventive anti-CGRP mAbs for migraine in patients over 65 years old: a multicenter real-world case-control study.

OBJECTIVE: To evaluate clinical characteristics, effectiveness, and tolerability of preventive anti- calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) in the elderly. Anti-CGRP mAbs have demonstrated efficacy and safety in patients with migraine although there is limited information regarding the elderly. DESIGN: We performed a multicenter case-control study of cases (patients over 65 years old) and controls (sex-matched patients under 55 years old) with migraine receiving anti-CGRP mAbs. METHODS: We included the demographic characteristics, effectiveness-reduction in the number of monthly headache days (MHD) and monthly migraine days (MMD), 30%, 50%, and 75% responder rates-and treatment emergent adverse events (TEAEs). The primary endpoint was the 50% response rate regarding MHD at weeks 20-24; exploratory 50% response predictors in the elderly were evaluated. RESULTS: In total, 228 patients were included: 114 cases , 114 controls-. Among cases 84.2% (96/114) were women, 79.8% (91/114) CM; mean age of cases 70.1 years old (range: 66-86); mean age of controls was 42.9 years old(range: 38-49). Cases had a higher percentage of vascular risk factors (P < .05),older age of onset (P < .001) and more reported prior preventive treatments (P < .001). Regarding effectiveness in cases, 50% response rate was achieved by 57.5% (42/73) at 20-24 weeks, with lower reduction in the MHD at 8-12 weeks (5 [7.2], 8 [9.1]; P = .001) and a higher reduction in MMD at 20-24 weeks (10.7 [9.1], 9.2 [7.7]; P = .04) compared to the control group. The percentage of TEAEs was similar in the 2 groups. Diagnosis of episodic migraine (EM) (P = .03) and lower number of MHD at baseline (P = .001) were associated with a 50% response in the elderly in univariate analysis. CONCLUSIONS: Our study provides real world evidence of effectiveness and safety of anti-CGRP mAbs for migraine in patients without upper age-limit and possible predictors of anti-CGRP response in the elderly.

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.

Headache in patients with inflammatory bowel disease: Migraine prevalence according to the Migraine Screening-Questionnaire (MS-Q) and headache characteristics.

BACKGROUND: The gut-brain axis describes a complex bidirectional association between neurological and gastrointestinal (GI) disorders. In patients with migraine, GI comorbidities are common. We aimed to evaluate the presence of migraine among patients with inflammatory bowel disease (IBD) according to Migraine Screen-Questionnaire (MS-Q) and describe the headache characteristics compared to a control group. Additionally, we explored the relationship between migraine and IBD severities. METHODS: We performed a cross-sectional study through an online survey including patients from the IBD Unit at our tertiary hospital. Clinical and demographic variables were collected. MS-Q was used for migraine evaluation. Headache disability scale HIT-6, anxiety-depression scale HADS, sleep scale ISI, and activity scale Harvey-Bradshaw and Partial Mayo scores were also included. RESULTS: We evaluated 66 IBD patients and 47 controls. Among IBD patients, 28/66 (42%) were women, mean age 42 years and 23/66 (34.84%) had ulcerative colitis. MS-Q was positive in 13/49 (26.5%) of IBD patients and 4/31 (12.91%) controls (p=0.172). Among IBD patients, headache was unilateral in 5/13 (38%) and throbbing in 10/13 (77%). Migraine was associated with female sex (p=0.006), lower height (p=0.003) and weight (p=0.002), anti-TNF treatment (p=0.035). We did not find any association between HIT-6 and IBD activity scales scores. CONCLUSIONS: Migraine presence according to MS-Q could be higher in patients with IBD than controls. We recommend migraine screening in these patients, especially in female patients with lower height and weight and anti-TNF treatment.

Neuronal and astrocytic tetraploidy is increased in drug-resistant epilepsy.

AIMS: Epilepsy is one of the most prevalent neurological diseases. A third of patients with epilepsy remain drug-resistant. The exact aetiology of drug-resistant epilepsy (DRE) is still unknown. Neuronal tetraploidy has been associated with neuropathology. The aim of this study was to assess the presence of tetraploid neurons and astrocytes in DRE. METHODS: For that purpose, cortex, hippocampus and amygdala samples were obtained from patients subjected to surgical resection of the epileptogenic zone. Post-mortem brain tissue of subjects without previous records of neurological, neurodegenerative or psychiatric diseases was used as control. RESULTS: The percentage of tetraploid cells was measured by immunostaining of neurons (NeuN) or astrocytes (S100ß) followed by flow cytometry analysis. The results were confirmed by image cytometry (ImageStream X Amnis System Cytometer) and with an alternative astrocyte biomarker (NDRG2). Statistical comparison was performed using univariate tests. A total of 22 patients and 10 controls were included. Tetraploid neurons and astrocytes were found both in healthy individuals and DRE patients in the three brain areas analysed: cortex, hippocampus and amygdala. DRE patients presented a higher number of tetraploid neurons (p = 0.020) and astrocytes (p = 0.002) in the hippocampus than controls. These results were validated by image cytometry. CONCLUSIONS: We demonstrated the presence of both tetraploid neurons and astrocytes in healthy subjects as well as increased levels of both cell populations in DRE patients. Herein, we describe for the first time the presence of tetraploid astrocytes in healthy subjects. Furthermore, these results provide new insights into epilepsy, opening new avenues for future treatment.

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.

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.

Risk of recurrent stroke and mortality after cryptogenic stroke in diabetic patients.

BACKGROUND: Diabetes mellitus is a highly prevalent and growing chronic disease that is associated with increased risk of recurrence among several stroke subtypes. However, evidence on the prognostic role of diabetes in the setting of cryptogenic stroke (CS) remains scarce. METHODS: From April 2019 to November 2021, we recruited prospectively 78 consecutive patients with CS. Patients were classified according to the presence of diabetes. Main outcome was the composite of stroke recurrence and death. Secondary outcome was stroke recurrence. RESULTS: Mean age of the cohort was 78 ± 7.7 years and 18 patients (23%) had diabetes. After a median clinical follow-up of 23 months the incidence of stroke recurrence and mortality [HR 5.8 (95% CI 1.9-19), p = 0.002] and the incidence of stroke recurrence [HR 16.6 (95% CI 1.8-149), p = 0.012], were higher in patients with diabetes. After adjusting for potential confounders diabetes was identified as an independent predictor of stroke recurrence and death in patients with CS [HR 33.8 (95% CI 2.1-551), p = 0.013]. Other independent predictors of stroke recurrence and mortality were hypertension [HR 31.4 (95% CI 1.8-550), p = 0.018], NTproBNP [HR 1.002 (95% CI 1.001-1.004), p = 0.013] and chronic kidney disease (CKD) [HR 27.4 (95% CI 1.4-549) p = 0.03]. Furthermore, diabetes was an independent predictor of stroke recurrence [HR 103 (95% CI 1.3-8261), p = 0.038]. CONCLUSION: Diabetic patients with CS are at higher risk of stroke recurrence and death. Hypertension CKD and NTproBNP are also independent predictors of stroke recurrence and death after CS.

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.

Prognostic Involvement of Lymph Node Density in Oral Squamous Cell Carcinoma. A New Predictive Model.

PURPOSE: Lymph node density (LND) has been reported to be a significant predictor of survival in oral squamous cell carcinoma (OSCC). The aim of this study was to analyze LND as a prognostic factor in OSCC and create a predictive model that determines the probability of death in these patients. METHODS: A retrospective cohort study was carried out with a cohort of patients who underwent cervical dissection and primary resection of OSCC between 1980 and 2020. The primary predictor variable in this study was LND, which is defined as the number of positive lymph nodes divided by the total number of lymph nodes removed. The cutoff values for prediction of disease-specific survival (DSS) were calculated by receiver operating characteristic curve analysis, which determined the best cutoff value was 0.07. Patients were divided into binary subgroups (low and high risk) using the best cutoff value of LND. The outcome variable was DSS, defined as the duration from the date of diagnosis to death due to OSCC and not due to other causes or secondary tumors. Other variables were type of neck dissection, postsurgical treatment, surgical margin, pathological T category stage, pathological N category (pN) stage, extranodal extension, perineural invasion, bone invasion, and presence of recurrence. A predictive model (score) was generated by selecting variables using a log-rank test and by using the Cox proportional-hazards regression (multivariate analysis). RESULTS: The sample consisted of 368 patients, 252 (68.5%) male and 116 (31.5%) female patients, with a mean age of 60.3 years. According to the LND cutoff value, there were 289 patients with a low LND (≤0.07) and 79 with a high LND (>0.07). The univariate analysis showed LND as a significant predictor of DSS at 5 years (67.1% in LND ≤ 0.07 vs 32.9% in LND > 0.07; P < .001). The Cox multivariate analysis identified LND (hazard ratio [HR] = 27.2; 95% confidence interval [CI], 3.18-231; P = .002), recurrence (HR = 4.45; 95% CI, 2.3-8.4; P < .001), and type of treatment (HR = 0.52; 95% CI, 0.34-0.81; P < .001) as independent predictive factors for DSS. In the predictive model, the presence of recurrence was the most important factor with 8 points, whereas LND >0.07 contributed only 1 point; however, the 2 categories resulting from this limit were statistically significant. CONCLUSIONS: Our study demonstrates that LND is an additional prognostic factor in patients with a pN+ disease. In addition, our predictive model could be useful in the therapeutic algorithm of OSCC patients, as it can predict the probability of death in these patients.

Esophageal biomechanics assessed by impedance planimetry (EndoFLIPTM) in healthy subjects and in patients with eosinophilic esophagitis. Normality values.

BACKGROUND: active eosinophilic esophagitis is associated with esophageal caliber, distensibility and motility changes that may be reversed with treatment. OBJECTIVES: to study esophageal diameter, distensibility and contractility in healthy subjects compared to patients with eosinophilic esophagitis, both before and after treatment. METHODS: a quasi-experimental study, EndoFLIP™, was used to analyze the esophageal body and esophago-gastric junction (EGJ) in all three groups, and a program was designed to obtain esophageal diameter, distensibility and contractility values. RESULTS: ten healthy volunteers (24-61 years, six men) and nine patients with eosinophilic esophagitis (21-52 years, seven men) were included. The esophagogastric junction distensibility index was 5.07 mm2/Hg in the control subjects, 2.40 mm2/Hg in the subjects with eosinophilic esophagitis before treatment and 2.46 mm2/Hg after treatment. The distensibility plateau was 20.02 mm, 15.43 mm and 17.41 mm, respectively, and the diameter was 21.90 mm, 17.73 mm and 18.30 mm, showing significant differences (p < 0.05), except between control subjects and patients after treatment (p = 0.079). Repetitive antegrade contractions developed in 90 % of control subjects, 66.7 % of eosinophilic esophagitis patients before treatment and 88.9 % of the latter after treatment (p > 0.05). CONCLUSIONS: esophago-gastric junction distensibility index, distensibility plateau and diameter values were higher in controls than in patients, although six weeks of treatment seems a short period to observe significant changes in esophageal biomechanics. Repetitive antegrade contractions are the predominant pattern in healthy subjects and eosinophilic esophagitis. We provide normality values for esophageal biomechanics, measured by impedance planimetry in our setting.

Relevant SARS-CoV-2 viremia is associated with COVID-19 severity: Prospective cohort study and validation cohort.

Early kinetics of SARS-CoV-2 viral load (VL) in plasma determined by quantitative reverse-transcription polymerase chain reaction (RT-PCR) was evaluated as a predictor of poor clinical outcome in a prospective study and assessed in a retrospective validation cohort. Prospective observational single-center study including consecutive adult patients hospitalized with COVID-19 between November 2020 and January 2021. Serial plasma samples were obtained until discharge. Quantitative RT-PCR was performed to assess SARS-CoV-2 VL. The main outcomes were in-hospital mortality, admission to the Intensive Care Unit (ICU), and their combination (Poor Outcome). Relevant viremia (RV), established in the prospective study, was assessed in a retrospective cohort including hospitalized COVID-19 patients from April 2021 to May 2022, in which plasma samples were collected according to clinical criteria. Prospective cohort: 57 patients were included. RV was defined as at least a twofold increase in VL within ≤2 days or a VL > 300 copies/ml, in the first week. Patients with RV (N = 14; 24.6%) were more likely to die than those without RV (35.7% vs. 0%), needed ICU admission (57% vs. 0%) or had Poor Outcome (71.4% vs. 0%), (p < 0.001 for the three variables). Retrospective cohort: 326 patients were included, 18.7% presented RV. Patients with RV compared with patients without RV had higher rates of ICU-admission (odds ratio [OR]: 5.6 [95% confidence interval [CI]: 2.1-15.1); p = 0.001), mortality (OR: 13.5 [95% CI: 6.3-28.7]; p < 0.0001) and Poor Outcome (OR: 11.2 [95% CI: 5.8-22]; p < 0.0001). Relevant SARS-CoV-2 viremia in the first week of hospitalization was associated with higher in-hospital mortality, ICU admission, and Poor Outcome. Findings observed in the prospective cohort were confirmed in a larger validation cohort.

Machine-learning-based approach for predicting response to anti-calcitonin gene-related peptide (CGRP) receptor or ligand antibody treatment in patients with migraine: A multicenter Spanish study.

BACKGROUND AND PURPOSE: Several variables have been reported to be associated with anti-calcitonin gene-related peptide (CGRP) receptor or ligand antibody response, but with differing results. Our objective was to determine whether machine-learning (ML)-based models can predict 6-, 9- and 12-month responses to anti-CGRP receptor or ligand therapies among migraine patients. METHODS: We performed a multicenter analysis of prospectively collected data from patients with migraine receiving anti-CGRP therapies. Demographic and clinical variables were collected. Response rates in the 30% to 50% range, or at least 30%, in the 50% to 75% range, or at least 50%, and response rate of at least 75% regarding the reduction in the number of headache days per month at 6, 9 and 12 months were calculated. A sequential forward feature selector was used for variable selection and ML-based predictive models for the response to anti-CGRP therapies at 6, 9 and 12 months, with model accuracy not less than 70%, were generated. RESULTS: A total of 712 patients were included, 93% were women, and the mean (SD) age was 48 (11.6) years. Eighty-four percent of patients had chronic migraine. ML-based models using headache days/month, migraine days/month and the Headache Impact Test (HIT-6) yielded predictions with an F1 score range of 0.70-0.97 and an area under the receiver-operating curve score range of 0.87-0.98. SHAP (SHapley Additive exPlanations) summary plots and dependence plots were generated to evaluate the relevance of the factors associated with the prediction of the above-mentioned response rates. CONCLUSIONS: Our results show that ML models can predict anti-CGRP response at 6, 9 and 12 months. This study provides a predictive tool that can be used in a real-world setting.

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

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.

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

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.

Novel Prehospital Phenotypes and Outcomes in Adult-Patients with Acute Disease.

An early identification of prehospital phenotypes may allow health care workers to speed up and improve patients' treatment. To determine emergency phenotypes by exclusively using prehospital clinical data, a multicenter, prospective, and observational ambulance-based study was conducted with a cohort of 3,853 adult patients treated consecutively and transferred with high priority from the scene to the hospital emergency department. Cluster analysis determined three clusters with highly different outcome scores and pathological characteristics. The first cluster presented a 30-day mortality after the index event of 45.9%. The second cluster presented a mortality of 26.3%, while mortality of the third cluster was 5.1%. This study supports the detection of three phenotypes with different risk stages and with different clinical, therapeutic, and prognostic considerations. This evidence could allow adapting treatment to each phenotype thereby helping in the decision-making process.

Prehospital troponin as a predictor of early clinical deterioration.

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.

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

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.

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

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. Methods: 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. Results: 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. Conclusions: 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.