Assessment of PaO2/FiO2 for stratification of patients with moderate and severe acute respiratory distress syndrome

Objectives: A recent update of the definition of acute respiratory distress syndrome (ARDS) proposed an empirical classification based on ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) at ARDS onset. Since the proposal did not mandate PaO2/FiO2 calculation under standardised ventilator settings (SVS), we hypothesised that a stratification based on baseline PaO2/FiO2 would not provide accurate assessment of lung injury severity. Design: A prospective, multicentre, observational study. Setting: A network of teaching hospitals. Participants: 478 patients with eligible criteria for moderate (100300). Primary and secondary outcomes Group severity and hospital mortality. Results: At ARDS onset, 173 patients had a PaO2/FiO2≤100 but only 38.7% met criteria for severe ARDS at 24 h under SVS. When assessed under SVS, 61.3% of patients with severe ARDS were reclassified as moderate, mild and non-ARDS, while lung severity and hospital mortality changed markedly with every PaO2/FiO2 category (p<0.000001). Our model of risk stratification outperformed the stratification using baseline PaO2/FiO2 and non-standardised PaO2/FiO2 at 24 h, when analysed by the predictive receiver operating characteristic (ROC) curve: area under the ROC curve for stratification at baseline was 0.583 (95% CI 0.525 to 0.636), 0.605 (95% CI 0.552 to 0.658) at 24 h without SVS and 0.693 (95% CI 0.645 to 0.742) at 24 h under SVS (p<0.000001). Conclusions: Our findings support the need for patient assessment under SVS at 24 h after ARDS onset to assess disease severity, and have implications for the diagnosis and management of ARDS patients. Trial registration numbers NCT00435110 and NCT00736892

Identification of COVID-19 patients at risk of hospital admission and mortality: a European multicentre retrospective analysis of mid-regional pro-adrenomedullin

Background: Mid-Regional pro-Adrenomedullin (MR-proADM) is an inflammatory biomarker that improves the prognostic assessment of patients with sepsis, septic shock and organ failure. Previous studies of MR-proADM have primarily focussed on bacterial infections. A limited number of small and monocentric studies have examined MR-proADM as a prognostic factor in patients infected with SARS-CoV-2, however there is need for multicenter validation. An evaluation of its utility in predicting need for hospitalisation in viral infections was also performed. Methods: An observational retrospective analysis of 1861 patients, with SARS-CoV-2 confirmed by RT-qPCR, from 10 hospitals across Europe was performed. Biomarkers, taken upon presentation to Emergency Departments (ED), clinical scores, patient demographics and outcomes were collected. Multiclass random forest classifier models were generated as well as calculation of area under the curve analysis. The primary endpoint was hospital admission with and without death. Results: Patients suitable for safe discharge from Emergency Departments could be identified through an MR-proADM value of ≤ 1.02&nbsp;nmol/L in combination with a CRP (C-Reactive Protein) of ≤ 20.2&nbsp;mg/L and age ≤ 64, or in combination with a SOFA (Sequential Organ Failure Assessment) score &lt; 2 if MR-proADM was ≤ 0.83&nbsp;nmol/L regardless of age. Those at an increased risk of mortality could be identified upon presentation to secondary care with an MR-proADM value of &gt; 0.85&nbsp;nmol/L, in combination with a SOFA score ≥ 2 and LDH &gt; 720 U/L, or in combination with a CRP &gt; 29.26&nbsp;mg/L and age ≤ 64, when MR-proADM was &gt; 1.02&nbsp;nmol/L. Conclusions: This international study suggests that for patients presenting to the ED with confirmed SARS-CoV-2 infection, MR-proADM in combination with age and CRP or with the patient’s SOFA score could identify patients at low risk where outpatient treatment may be safe

Endothelial dysfunction is an early indicator of sepsis and neutrophil degranulation of septic shock in surgical patients

Producción CientíficaBackground: Stratification of the severity of infection is currently based on the Sequential Organ Failure Assessment (SOFA) score, which is difficult to calculate outside the ICU. Biomarkers could help to stratify the severity of infection in surgical patients. Methods: Levels of ten biomarkers indicating endothelial dysfunction, 22 indicating emergency granulopoiesis, and six denoting neutrophil degranulation were compared in three groups of patients in the first 12 h after diagnosis at three Spanish hospitals. Results: There were 100 patients with infection, 95 with sepsis and 57 with septic shock. Seven biomarkers indicating endothelial dysfunction (mid-regional proadrenomedullin (MR-ProADM), syndecan 1, thrombomodulin, angiopoietin 2, endothelial cell-specific molecule 1, vascular cell adhesion molecule 1 and E-selectin) had stronger associations with sepsis than infection alone. MR-ProADM had the highest odds ratio (OR) in multivariable analysis (OR 11·53, 95 per cent c.i. 4·15 to 32·08; P = 0·006) and the best area under the curve (AUC) for detecting sepsis (0·86, 95 per cent c.i. 0·80 to 0·91; P < 0·001). In a comparison of sepsis with septic shock, two biomarkers of neutrophil degranulation, proteinase 3 (OR 8·09, 1·34 to 48·91; P = 0·028) and lipocalin 2 (OR 6·62, 2·47 to 17·77; P = 0·002), had the strongest association with septic shock, but lipocalin 2 exhibited the highest AUC (0·81, 0·73 to 0·90; P < 0·001). Conclusion: MR-ProADM and lipocalin 2 could be alternatives to the SOFA score in the detection of sepsis and septic shock respectively in surgical patients with infection.Instituto de Salud Carlos III (grants PI15/01959, PI15/01451 and PI16/01156

The Immune System in Stroke

Stroke represents an unresolved challenge for both developed and developing countries and has a huge socio-economic impact. Although considerable effort has been made to limit stroke incidence and improve outcome, strategies aimed at protecting injured neurons in the brain have all failed. This failure is likely to be due to both the incompleteness of modelling the disease and its causes in experimental research, and also the lack of understanding of how systemic mechanisms lead to an acute cerebrovascular event or contribute to outcome. Inflammation has been implicated in all forms of brain injury and it is now clear that immune mechanisms profoundly influence (and are responsible for the development of) risk and causation of stroke, and the outcome following the onset of cerebral ischemia. Until very recently, systemic inflammatory mechanisms, with respect to common comorbidities in stroke, have largely been ignored in experimental studies. The main aim is therefore to understand interactions between the immune system and brain injury in order to develop novel therapeutic approaches. Recent data from clinical and experimental research clearly show that systemic inflammatory diseases -such as atherosclerosis, obesity, diabetes or infection - similar to stress and advanced age, are associated with dysregulated immune responses which can profoundly contribute to cerebrovascular inflammation and injury in the central nervous system. In this review, we summarize recent advances in the field of inflammation and stroke, focusing on the challenges of translation between pre-clinical and clinical studies, and potential anti-inflammatory/immunomodulatory therapeutic approaches

Cardiovascular features and risk of mortality in COVID-19 hospitalized patients in Spain during 2020. A nationwide study from the Minimum Basic Data Set

INTRODUCTION: During the last two years scientific evidence has been gathered regarding the cardiovascular complications of Covid-19. Nevertheless nationwide studies are still required to better understand both the incidence of less frequent clinical findings, and the prognostic implications of cardiovascular COVID-19 complications. PURPOSE: The aim of this study was to estimate the incidence of cardiovascular diseases among COVID-19 hospitalized patients in Spain during 2020, as well as their association with mortality, besides other clinical and epidemiological factors. METHODS: We used the Minimum Basic Data Set from the Spanish Ministry of Health (RAE-CMBD) to analyze the data of all COVID-19 hospitalized patients in Spain during 2020. This national database includes concurrent diagnostics of all studied patients codified according to the Tenth International Classification of Diseases (ICD-10). Logistic regression analysis was performed to evaluate the influence of the different clinical and epidemiological variables in the evolution of COVID-19 hospitalized patients. Odds ratios were obtained for each variable adjusting by age and sex, and also adjusting by the rest of clinical factors. The software used for analysis was STATA v 16.1. RESULTS: 75585 men (55.15%) and 61468 women (44.85%) were hospitalized due to COVID-19 during 2020 in Spain. The median age was 66 in men and 71 in women. Mortality was 14.92% in males, and 13.81% in females. 9.62% of patients were admitted to intensive care unit (ICU). Mortality in ICU was 29.13%. Heart Failure (7.8%), Atrial Fibrillation (7.7%), Pulmonary Embolism (3.46%), Supraventricular Arrythmias (1.18%), Cardiomyopathy (1.06%), Acute Coronary Syndrome (0.87%), Ischemic Stroke (0.33%), Myocarditis (0.12%) Pericarditis (0.06%), or Takotsubo Disease (0.05%), were relevant cardiovascular findings in COVID-19 hospitalized patients (Table 1). In the logistic regression multivariate analysis in COVID-19 patients we found epidemiological predictors of in-hospital mortality such as age (OR 2.38 for each decade), or male sex (OR 1.39). Among the clinical predictors of mortality we differentiated cardiovascular ones as Acute Coronary Syndrome (OR 1.51), Ischemic Stroke (OR 1.46), or Heart Failure (OR 1.43); and non cardiovascular ones such as admission to ICU (OR 3.12), Adult Respiratory Distress Syndrome (OR 2.74), need for Mecanical Ventilation (OR 2.52), Acute Kidney Failure (OR 2.07), Liver damage (OR 1.67), or Dementia (OR 1.66), (Table 2) CONCLUSION(S): Heart Failure, Pulmonary Embolism, Ischaemic Heart Disease, Atrial fibrillation, Ischemic Stroke, or Cardiomyopathy were among the main cardiovascular diseases associated to COVID-19. They increased in a different measure the risk of mortality in COVID-19, together with factors such as Mecanical ventilation, ICU admission, Acute kidney failure, Dementia, Liver damage, Adult Respiratory Distress Syndrome, older age, or male sex. FUNDING ACKNOWLEDGEMENT: Type of funding sources: None

The protective association of endogenous immunoglobulins against sepsis mortality is restricted to patients with moderate organ failure

Abstract Background Pre-evaluation of endogenous immunoglobulin levels is a potential strategy to improve the results of intravenous immunoglobulins in sepsis, but more work has to be done to identify those patients who could benefit the most from this treatment. The objective of this study was to evaluate the impact of endogenous immunoglobulins on the mortality risk in sepsis depending on disease severity. Methods This was a retrospective observational study including 278 patients admitted to the ICU with sepsis fulfilling the SEPSIS-3 criteria, coming from the Spanish GRECIA and ABISS-EDUSEPSIS cohorts. Patients were distributed into two groups depending on their Sequential Organ Failure Assessment score at ICU admission (SOFA < 8, n = 122 and SOFA ≥ 8, n = 156), and the association between immunoglobulin levels at ICU admission with mortality was studied in each group by Kaplan–Meier and multivariate logistic regression analysis. Results ICU/hospital mortality in the SOFA < 8 group was 14.8/23.0%, compared to 30.1/35.3% in the SOFA ≥ 8 group. In the group with SOFA < 8, the simultaneous presence of total IgG < 407 mg/dl, IgM < 43 mg/dl and IgA < 219 mg/dl was associated with a reduction in the survival mean time of 6.6 days in the first 28 days and was a robust predictor of mortality risk either during the acute or during the post-acute phase of the disease (OR for ICU mortality: 13.79; OR for hospital mortality: 7.98). This predictive ability remained in the absence of prior immunosuppression (OR for ICU mortality: 17.53; OR for hospital mortality: 5.63). Total IgG < 407 mg/dl or IgG1 < 332 mg/dl was also an independent predictor of ICU mortality in this group. In contrast, in the SOFA ≥ 8 group, we found no immunoglobulin thresholds associated with neither ICU nor hospital mortality. Conclusions Endogenous immunoglobulin levels may have a different impact on the mortality risk of sepsis patients based on their severity. In patients with moderate organ failure, the simultaneous presence of low levels of IgG, IgA and IgM was a consistent predictor of both acute and post-acute mortalities