Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Proyecto de investigación para determinar estrategias para la consolidación de la marca País Ecuador para Canadá

En las actuales condiciones de globalización, es desarrollo del comercio exterior puede ofrecer oportunidades de mayor bienestar social, progreso técnico y desarrollo económico para todos los países y habitantes del planeta. En este contexto, es primordial para las economías nacionales desarrollar mecanismos que les permitan mostrar sus fortalezas al resto del mundo, tomando en cuenta el punto de vista de los clientes actuales y potenciales que se encuentran en el mercado internacional

Association between serum tissue inhibitor of matrix metalloproteinase-1 levels and mortality in patients with severe brain trauma injury.

OBJECTIVE: Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) play a role in neuroinflammation after brain trauma injury (TBI). Previous studies with small sample size have reported higher circulating MMP-2 and MMP-9 levels in patients with TBI, but no association between those levels and mortality. Thus, the aim of this study was to determine whether serum TIMP-1 and MMP-9 levels are associated with mortality in patients with severe TBI. METHODS: This was a multicenter, observational and prospective study carried out in six Spanish Intensive Care Units. Patients with severe TBI defined as Glasgow Coma Scale (GCS) lower than 9 were included, while those with Injury Severity Score (ISS) in non-cranial aspects higher than 9 were excluded. Serum levels of TIMP-1, MMP-9 and tumor necrosis factor (TNF)-alpha, and plasma levels of tissue factor (TF) and plasminogen activator inhibitor (PAI)-1 plasma were measured in 100 patients with severe TBI at admission. Endpoint was 30-day mortality. RESULTS: Non-surviving TBI patients (n = 27) showed higher serum TIMP-1 levels than survivor ones (n = 73). We did not find differences in MMP-9 serum levels. Logistic regression analysis showed that serum TIMP-1 levels were associated 30-day mortality (OR = 1.01; 95% CI = 1.001-1.013; P = 0.03). Survival analysis showed that patients with serum TIMP-1 higher than 220 ng/mL presented increased 30-day mortality than patients with lower levels (Chi-square = 5.50; P = 0.02). The area under the curve (AUC) for TIMP-1 as predictor of 30-day mortality was 0.73 (95% CI = 0.624-0.844; P<0.001). An association between TIMP-1 levels and APACHE-II score, TNF- alpha and TF was found. CONCLUSIONS: The most relevant and new findings of our study, the largest series reporting data on TIMP-1 and MMP-9 levels in patients with severe TBI, were that serum TIMP-1 levels were associated with TBI mortality and could be used as a prognostic biomarker of mortality in TBI patients

Survival curves at 30 days using 220/mL of TIMP-1 serum levels as cut-off.

<p>Survival curves at 30 days using 220/mL of TIMP-1 serum levels as cut-off.</p

Multiple binomial logistic regression analysis of variables to predict 30-day mortality.

<p>TIMP  =  tissue inhibitor of matrix metalloproteinase; APACHE II  =  Acute Physiology and Chronic Health Evaluation; GCS Glasgow Coma Scale</p

Baseline clinical and biochemical characteristics of survivor and non-survivor patients.

<p>P 25–75 = percentile 25^th–75^th; PaO₂ = pressure of arterial oxygen/fraction inspired oxygen; FIO₂  =  pressure of arterial oxygen/fraction inspired oxygen; ISS  =  Injury Severity Score; INR  =  international normalized ratio; aPTT  =  activated partial thromboplastin time; APACHE II  =  Acute Physiology and Chronic Health Evaluation; ICP  =  intracranial pressure; CPP  =  cerebral perfusion pressure; TIMP  =  tissue inhibitor of matrix metalloproteinase; MMP  =  matrix metalloproteinase; TNF  =  tumor necrosis factor; PAI  =  plasminogen activator inhibitor</p

Receiver operation characteristic analysis using TIMP-1 serum levels as predictor of mortality at 30 days.

<p>Receiver operation characteristic analysis using TIMP-1 serum levels as predictor of mortality at 30 days.</p

Correlation between serum TIMP-1 levels and other baseline clinical and biochemical characteristics.

<p>TIMP =  tissue inhibitor of matrix metalloproteinase; GCS =  Glasgow Coma Scale; TNF  =  tumor necrosis factor; PAI  =  plasminogen activator inhibitor; INR  =  international normalized ratio; aPTT  =  activated partial thromboplastin time; MMP  =  matrix metalloproteinase. Bonferroni correction to control the multiple testing problem (0.05/11 = 0.004) was used. Only <i>P</i>-values lower than 0.004 were considered statistically significant.</p