Objetivo: Diferentes polimorfismos genéticos de los antígenos leucocitarios humanos (HLA) están asociados con el riesgo y el pronóstico de enfermedades autoinmunes e infecciosas. Los objetivos de estudio fueron determinar si existe una asociación entre polimorfismos genéticos de HLA y la susceptibilidad y mortalidad de pacientes con la enfermedad del coronavirus 2019 (COVID-19). Diseño: Estudio observacional y prospectivo Ámbito: Ocho Unidades de Cuidados Intensivos (UCI) de 6 hospitales de las islas canarias (España). Pacientes: Pacientes COVID-19 ingresados en UCI y sujetos sanos. Intervenciones: Se determinaron los polimorfismos genéticos de HLA Variable de interés principal: Mortalidad a los 30 días Resultados: Se incluyeron 3886 sujetos sanos y 72 pacientes COVID-19 (10 fallecidos y 62 supervivientes a 30 días). Encontramos una tendencia a una mayor frecuencia de los alelos HLA-A*32 (p=0.004) en sujetos sanos que en pacientes COVID-19, y de los alelos HLA-B*39 (p=0.02) y HLA-C*16 (p=0.02) en pacientes COVID-19 que en sujetos sanos; sin embargo, no fueron significativos al corregir por comparaciones múltiples. En la regresión logística encontramos que la presencia de ciertos alelos estuvo asociada con mayor mortalidad, como el alelo HLA-A*11 controlando por SOFA (OR=7.693; 95% CI=1.063-55.650; p=0.04) o APACHE-II (OR=11.858; 95% CI=1.524-92.273; p=0.02), el alelo HLA-C*01 controlando por SOFA (OR=11.182; 95% CI=1.053-118.700; p=0.04) o APACHE-II (OR=17.604; 95% CI=1.629-190.211; p=0.02), y el alelo HLA-DQB1*04 controlando por SOFA (OR=9.963; 95% CI=1.235-80.358; p=0.03). Conclusiones: Los nuevos hallazgos de nuestro preliminar estudio de pequeño tamaño muestral fueron que determinados polimorfismos genéticos de HLA podrían estar asociados con la mortalidad de pacientes COVID-19; sin embargo, estudios de mayor tamaño muestral son necesarios para concluirlo definitivamente.

PCT has a high negative predictive value (94%) and lower PCT levels seems to be a good tool for excluding coinfection, particularly for patients without shock.

Our findings suggest that early oseltamivir administration was associated with favourable outcomes among critically ill ventilated patients with 2009 H1N1 virus infection.

There is a hyperoxidative state in patients with trauma brain injury (TBI). Malondialdehyde (MDA) is an end-product formed during oxidative stress, concretely lipid peroxidation. In small studies (highest sample size 50 patients), higher levels of MDA have been found in nonsurviving than surviving patients with TBI. An association between serum MDA levels and mortality in patients with TBI, however, has not been reported. Thus, the objective of this prospective, observational, multicenter study, performed in six Spanish intensive care units, was to determine whether MDA serum levels are associated with early mortality in a large series of patients with severe TBI. Serum MDA levels were measured in 100 patients with severe TBI on day 1 and in 75 healthy controls. The end-point of the study was 30-day mortality. We found higher serum MDA levels in patients with severe TBI than in healthy controls (p < 0.001). Nonsurviving patients with TBI (n = 27) showed higher serum MDA levels (p < 0.001) than survivors (n = 73). Logistic regression analysis showed that serum MDA levels were associated with 30-day mortality (odds ratio [OR] = 4.662; 95% confidence interval [CI] = 1.466-14.824; p = 0.01), controlling for Glasgow Coma Score, age, and computed tomography findings. Survival analysis showed that patients with serum MDA levels higher than 1.96 nmol/mL presented increased 30-day mortality than patients with lower levels (hazard ratio = 3.5; 95% CI = 1.43-8.47; p < 0.001). Thus, the most relevant new finding of our study, the largest to date on serum MDA levels in patients with severe TBI, was an association between serum MDA levels and early mortality.

Objective: Development of a risk-stratification model to predict severe Covid-19 related illness, using only presenting symptoms, comorbidities and demographic data. Materials and methods: We performed a case-control study with cases being those with severe disease, defined as ICU admission, mechanical ventilation, death or discharge to hospice, and controls being those with non-severe disease. Predictor variables included patient demographics, symptoms and past medical history. Participants were 556 patients with laboratory confirmed Covid-19 and were included consecutively after presenting to the emergency department at a tertiary care center from March 1, 2020 to April 21, 2020 Results: Most common symptoms included cough (82%), dyspnea (75%), and fever/chills (77%), with 96% reporting at least one of these. Multivariable logistic regression analysis found that increasing age (adjusted odds ratio [OR], 1.05; 95% confidence interval [CI], 1.03-1.06), dyspnea (OR, 2.56; 95% CI: 1.51-4.33), male sex (OR, 1.70; 95% CI: 1.10-2.64), immunocompromised status (OR, 2.22; 95% CI: 1.17-4.16) and CKD (OR, 1.76; 95% CI: 1.01-3.06) were significant predictors of severe Covid-19 infection. Hyperlipidemia was found to be negatively associated with severe disease (OR, 0.54; 95% CI: 0.33-0.90). A predictive equation based on these variables demonstrated fair ability to discriminate severe vs non-severe outcomes using only this historical information (AUC: 0.76). Conclusions: Severe Covid-19 illness can be predicted using data that could be obtained from a remote screening. With validation, this model could possibly be used for remote triage to prioritize evaluation based on susceptibility to severe disease while avoiding unnecessary waiting room exposure. Published by Elsevier Inc. 1.2. Importance Given that most patients presenting with symptoms concerning for Covid-19 infection have ultimately been negative [8], there is a concern

ObjectiveData on circulating total antioxidant capacity (TAC) levels in ischemic stroke patients compared with healthy controls are limited and provided conflicting findings. There are not data about the association between circulating TAC levels, peroxidation state and outcome in patients with severe ischemic stroke. The objective of this study was to examine the relationship of TAC with 30-day mortality after severe ischemic stroke.Methods This multicenter study included 58 patients with coma (Glasgow Coma Scale < 9) following severe malignant middle cerebral artery infarction (MMCAI). We measured circulating levels of TAC and malondialdehyde (MDA, a biomarker of lipid peroxidation) on day 1 of severe MMCAI diagnosis. The study endpoint was 30-day mortality.ResultsNon-survivors (n = 29) showed higher serum TAC levels (p < 0.001) and higher serum MDA levels (p = 0.004) than survivors (n = 29). Multiple binomial logistic regression analysis showed that serum TAC levels were associated with 30-day mortality, after controlling for Glasgow Coma Scale and age (odds ratio 1.92; 95 % confidence interval 1.201–3.072; p = 0.006). There was a correlation between serum TAC and MDA levels (rho = 0.35; p = 0.008).ConclusionsThis single-center study in severe MMCAI patients found an association between higher serum TAC levels and 30-day mortality and further identified a relationship between serum TAC levels, lipid peroxidation state and mortality after severe ischemic stroke.

IntroductionSubstance P (SP) is a member of the tachykinin family of neuropeptides, which are widely distributed throughout the central nervous system (CNS) and actively involved in inflammatory processes. SP is released early following acute injury to the CNS, promoting a neurogenic inflammatory response characterized by an increase in the permeability of the blood–brain barrier and the development of vasogenic edema. High levels of SP could lead to an exacerbated inflammatory response that could be fatal for patients with traumatic brain injury (TBI). Thus, the main goal of the present study was to determine whether serum SP levels are associated with injury severity and mortality in patients with severe TBI.MethodsThis multicenter, observational, prospective study was carried out in six Spanish intensive care units and included patients with Glasgow Coma Scale (GCS) scores ≤8. Patients with an Injury Severity Score ≥10 in non-cranial aspects were excluded. Blood samples were collected on day 1 of TBI to measure serum SP levels. The endpoint was 30-day mortality.ResultsWe found higher serum SP levels (P =0.002) in non-surviving patients (n =27) than in surviving patients (n =73). The area under the curve for serum SP levels with regard to predicting 30-day mortality was 0.70 (95% confidence interval (CI), 0.60 to 0.79; P <0.001). Survival analysis showed that patients with serum SP levels >299 pg/ml had higher 30-day mortality than patients with lower levels (hazard ratio =3.7; 95% CI, 1.75 to 7.94; P <0.001). Multiple binomial logistic regression analysis showed that serum SP levels >299 pg/ml were associated with 30-day mortality when we controlled for APACHE II score and Marshall computed tomography lesion classification (odds ratio (OR) =5.97; 95% CI, 1.432 to 24.851; P =0.01) and for GCS score and age (OR =5.71; 95% CI, 1.461 to 22.280; P =0.01). We found a negative association between serum SP levels and GCS score (Spearman’s ρ = −0.22; P =0.03).ConclusionsWe report, for the first time to our knowledge, that serum SP levels were associated with injury severity and mortality in patients with severe TBI. These results open the possibility that SP antagonists may be useful in the treatment of patients with severe TBI.

ObjectiveThere have been found apoptotic changes in brain tissue samples from animals and humans after a traumatic brain injury (TBI). The protein cytokeratin 18 (CK-18), present in epithelial cells, is cleaved by the action of caspases during apoptosis, and the resulting fragments are released into the blood as caspase-cleaved CK (CCCK)-18. Circulating levels of CCCK-18, as biomarker of apoptosis, have been determined in patients with different processes; however, it has not been explored in TBI patients. Thus, the objective of this study was to determine whether there is an association between serum CCCK-18 levels and mortality and whether such levels could be used as a biomarker to predict outcomes in TBI patients.MethodsA prospective, observational, multicenter study carried out in six Spanish Intensive Care Units. We included patients with severe TBI defined as Glasgow Coma Scale (GCS) lower than 9; and were excluded those patients with Injury Severity Score (ISS) in non-cranial aspects higher than 9. We measured serum CCCK-18 levels at admission. The end-point of the study was 30-day mortality.ResultsSurviving patients (n = 73) showed lower serum CCCK-18 levels (P = 0.003) than non-survivors (n = 27). On ROC analysis, the area under the curve (AUC) for serum CCCK-18 levels as predictor of 30-day mortality was 0.69 (95% CI = 0.59–0.78; P = 0.006). We found in survival analysis that patients with serum CCCK-18 higher than 201 u/L had higher 30-day mortality than patients with lower levels (Hazard ratio = 3.9; 95% CI = 1.81–8.34; P<0.001). Regression analyses showed that serum CCCK-18 levels higher than 201 u/L were associated with 30-day mortality (OR = 8.476; 95% CI = 2.087–34.434; P = 0.003) after controlling for age and GCS.ConclusionsThe novel finding of our study was that serum CCCK-18 levels are associated with 30-day mortality and could be used as a prognostic biomarker in patients with severe TBI.