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Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Introduction: Coagulopathy associated with isolated traumatic brain injury (C-iTBI) is a frequent complication associated with poor outcomes, primarily due to its role in the development or progression of haemorrhagic brain lesions. The independent risk factors for its onset are age, severity of traumatic brain injury (TBI), volume of fluids administered during resuscitation, and pre-injury use of antithrombotic drugs. Although the pathophysiology of C-iTBI has not been fully elucidated, two distinct stages have been identified: an initial hypocoagulable phase that begins within the first 24 h, dominated by platelet dysfunction and hyperfibrinolysis, followed by a hypercoagulable state that generally starts 72 h after the trauma. The aim of this study was to design an acronym as a mnemonic device to provide clinicians with an auxiliary tool in the treatment of this complication., Methods: A narrative analysis was performed in which intensive care physicians were asked to list the key factors related to C-iTBI. The initial sample was comprised of 33 respondents. Respondents who were not physicians, not currently working in or with experience in coagulopathy were excluded. Interviews were conducted for a month until the sample was saturated. Each participant was asked a single question: Can you identify a factor associated with coagulopathy in patients with TBI? Factors identified by respondents were then submitted to a quality check based on published studies and proven evidence. Because all the factors identified had strong support in the literature, none was eliminated. An acronym was then developed to create the mnemonic device., Results and Conclusion: Eleven factors were identified: cerebral computed tomography, oral anticoagulant & antiplatelet use, arterial blood pressure (Hypotension), goal-directed haemostatic therapy, use fluids cautiously, low calcium levels, anaemia-transfusion, temperature, international normalised ratio (INR), oral antithrombotic reversal, normal acid-base status, forming the acronym "Coagulation." This acronym is a simple mnemonic device, easy to apply for anyone facing the challenge of treating patients of moderate or severe TBI on a daily basis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Quintana-Diaz, Anania, Juárez-Vela, Echaniz-Serrano, Tejada-Garrido, Sanchez-Conde, Nanwani-Nanwani, Serrano-Lázaro, Marcos-Neira, Gero-Escapa, García-Criado and Godoy.)

Aneurysmal subarachnoid hemorrhage (aSAH) is an uncommon and severe subtype of stroke leading to the loss of many years of productive life. We analyzed NLRP3 activity as well as key components of the inflammasome cascade in monocytes and plasma from 28 patients with aSAH and 14 normal controls using flow cytometry, western blot, ELISA, and qPCR technologies. Our data reveal that monocytes from patients with aSAH present an overactivation of the NLRP3 inflammasome, which results in the presence of high plasma levels of interleukin (IL)-1β, IL-18, gasdermin D, and tissue factor. Although further research is needed, we propose that serum tissue factor concentration might be a useful prognosis biomarker for clinical outcome, and for Tako-Tsubo cardiomyopathy and cerebral vasospasm prediction. Remarkably, MCC-950 inhibitor effectively blocks NLRP3 activation in aSAH monocyte culture and supresses tissue factor release to the extracellular space. Finally, our findings suggest that NLRP3 activation could be due to the release of erythrocyte breakdown products to the subarachnoid space during aSAH event. These data define NLRP3 activation in monocytes from aSAH patients, indicating systemic inflammation that results in serum TF upregulation which in turns correlates with aSAH severity and might serve as a prognosis biomarker for aSAH clinical outcome and for cerebral vasospasm and Tako-Tsubo cardiomyopathy prediction., (© 2022. The Author(s).)

COVID-19 has emerged as a devastating disease in the last 2 years. Many authors appointed to the importance of kallikrein-kinin system (KKS) in COVID-19 pathophysiology as it is involved in inflammation, vascular homeostasis, and coagulation. We aim to study the bradykinin cascade and its involvement in severity of patients with COVID-19. This is an observational cohort study involving 63 consecutive patients with severe COVID-19 pneumonia and 27 healthy subjects as control group. Clinical laboratory findings and plasma protein concentration of KKS peptides [bradykinin (BK), BK1-8], KKS proteins [high-molecular weight kininogen (HK)], and KKS enzymes [carboxypeptidase N subunit 1 (CPN1), kallikrein B1 (KLKB1), angiotensin converting enzyme 2 (ACE2), and C1 esterase inhibitor (C1INH)] were analyzed. We detected dysregulated KKS in patients with COVID-19, characterized by an accumulation of BK1-8 in combination with decreased levels of BK. Accumulated BK1-8 was related to severity of patients with COVID-19. A multivariate logistic regression model retained BK1-8, BK, and D-dimer as independent predictor factors to intensive care unit (ICU) admission. A Youden's optimal cutoff value of -0.352 was found for the multivariate model score with an accuracy of 92.9%. Multivariate model score-high group presented an odds ratio for ICU admission of 260.0. BK1-8 was related to inflammation, coagulation, and lymphopenia. Our data suggest that BK1-8/BK plasma concentration in combination with D-dimer levels might be retained as independent predictors for ICU admission in patients with COVID-19. Moreover, we reported KKS dysregulation in patients with COVID-19, which was related to disease severity by means of inflammation, hypercoagulation, and lymphopenia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Alfaro, Díaz-García, García-Tovar, Zamarrón, Mangas, Galera, Nanwani-Nanwani, Pérez-de-Diego, López-Collazo, García-Río and Cubillos-Zapata.)

Coronavirus disease 19 (COVID-19) patients usually require long periods of mechanical ventilation and sedation, which added to steroid therapy, favours a predisposition to the development of delirium and subsequent mental health disorders, as well as physical and respiratory sequelae. The aim of this study was to determine the prevalence of post-intensive care syndrome (PICS) at 3 months after hospital discharge, in a cohort of mechanically ventilated patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). An ambispective, observational study was conducted in three hospitals with intensive care unit (ICU) follow-up clinics. We studied adults who survived a critical illness due to SARS-CoV-2 infection requiring invasive mechanical ventilation. A physical (muscle strength and pulmonary function), functional [12-Item Short Form Health Survey (SF-12), and Barthel score], psychological [hospital anxiety and depression (HADS) and posttraumatic stress disorder symptom severity scales], and cognitive [Montreal cognitive assessment (MoCA) test] assessment were performed. A total of 186 patients were evaluated at 88 days (IQR 68-121) after hospital discharge. Mean age was 59 ± 12 years old, 126 (68%) patients were men, and median length of mechanical ventilation was 14 days (IQR 8-31). About 3 out of 4 patients (n = 139, 75%) met PICS criteria. Symptoms of cognitive and psychiatric disorders were found in 59 (32%) and 58 (31%) patients, respectively. Ninety-one (49%) patients had muscle weakness. Pulmonary function tests in patients with no respiratory comorbidities showed a normal pattern in 93 (50%) patients, and a restrictive disorder in 62 (33%) patients. Also, 69 patients (37%) were on sick leave, while 32 (17%) had resumed work at the time of assessment. In conclusion, survivors of critical illness due to SARS-CoV-2 infection requiring mechanical ventilation have a high prevalence of PICS. Physical domain is the most frequently damaged, followed by cognitive and psychiatric disorders. ICU follow-up clinics enable the assistance of this vulnerable population., (© 2022. The Author(s).)

CD39/NTPDase1 has emerged as an important molecule that contributes to maintain inflammatory and coagulatory homeostasis. Various studies have hypothesized the possible role of CD39 in COVID-19 pathophysiology since no confirmatory data shed light in this regard. Therefore, we aimed to quantify CD39 expression on COVID-19 patients exploring its association with severity clinical parameters and ICU admission, while unraveling the role of purinergic signaling on thromboinflammation in COVID-19 patients. We selected a prospective cohort of patients hospitalized due to severe COVID-19 pneumonia (n=75), a historical cohort of Influenza A pneumonia patients (n=18) and sex/age-matched healthy controls (n=30). CD39 was overexpressed in COVID-19 patients' plasma and immune cell subsets and related to hypoxemia. Plasma soluble form of CD39 (sCD39) was related to length of hospital stay and independently associated with intensive care unit admission (adjusted odds ratio 1.04, 95%CI 1.0-1.08, p=0.038), with a net reclassification index of 0.229 (0.118-0.287; p=0.036). COVID-19 patients showed extracellular accumulation of adenosine nucleotides (ATP and ADP), resulting in systemic inflammation and pro-coagulant state, as a consequence of purinergic pathway dysregulation. Interestingly, we found that COVID-19 plasma caused platelet activation, which was successfully blocked by the P2Y 12 receptor inhibitor, ticagrelor. Therefore, sCD39 is suggested as a promising biomarker for COVID-19 severity. As a conclusion, our study indicates that CD39 overexpression in COVID-19 patients could be indicating purinergic signaling dysregulation, which might be at the basis of COVID-19 thromboinflammation disorder., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Díaz-García, García-Tovar, Alfaro, Zamarrón, Mangas, Galera, Ruíz-Hernández, Solé-Violán, Rodríguez-Gallego, Van-Den-Rym, Pérez-de-Diego, Nanwani-Nanwani, López-Collazo, García-Rio and Cubillos-Zapata.)

Background: Tracheostomy is one of the most frequent techniques in intensive care units (ICU). Fiberoptic bronchoscopy (FB) is a safety measure when performing a percutaneous dilatational tracheostomy (PDT), but the controversy surrounding the routine use of FB as part of the procedure remains open. National surveys in some European countries showed that the use of FB is non-standardized. Retrospective studies have not shown a significant difference in complications between procedures performed with or without a bronchoscope. International guidelines have not been able to establish recommendations regarding the use of FB in PDT due to lack of evidence., Design: This is a multicenter (three centers at the time of  publishing this paper) randomized controlled clinical trial to examine the safety of percutaneous tracheostomy using FB. We will include all consecutive adult patients admitted to the ICU in whom percutaneous tracheostomy for prolonged mechanical ventilation is indicated and with no exclusion criteria for using FB. Eligible patients will be randomly assigned to receive blind PDT or PDT under endoscopic guidance. All procedures will be performed by experienced intensivists in PDT and FB. A Data Safety and Monitoring Board (DSMB) will monitor the trial. The primary outcome is the incidence of perioperative complications., Discussion: FB is a safe technique when performing PDT although its use is not universally accepted in all ICUs as a routine practice. Should PDT be monitored routinely with endoscopic guidance? This study will assess the role of FB monitoring during PDT., Trial Registration: ClinicalTrials.gov NCT04265625. Registered on February 11, 2020.

Objective: To describe the transfusion practice in the ICUs in Spain, according to national and international recommendations (guidelines)., Design: Prospective, cross-sectional, multi-centre study., Scope: Data collection was carried out by means of a questionnaire sent electronically to the Heads of Service of 111 ICUs in Spain., Participants: 1,448 patients were included, aged 61.8 (SD 15.7) years, 66.2% male, with an SOFA of 4.7±3.8 and average stay of 10.62±17.49 days., Variables: Demographic and clinical variables of the patients were collected, as well as variables related to the transfusion act., Results: Of the 1,448 patients, 9.9% received al least one transfusion of any blood product, 3.7% fresh plasma, 3.9% platelets and 8.9% red blood cell concentrate, mainly by analytical criteria (36.2%). Hemoglobin had a mean of 7.8g/dL (95% CI: 6-9-8.5) and 9.8g/dL (95% CI: 8.5-11.2) before and after the transfusion, respectively, p<0.001. The transfusion units had a mean of 2.5±2.4 per patient. The most commonly used blood product was red blood cell concentrate (90.2%). Patients admitted for surgery had a higher transfusion rate (14.4%) than those admitted for medical pathology (8.9%) (p=0.006). 5.4% (7/129) of patients who received red blood cell concentrate died compared to 2.4% (31/1302) who did not (p=0.04). Mortality of transfused patients was higher. The transfusion rate in most of hospitals was 5% to 20%, with 18 hospitals (16.21%) having transfusion rates between 20% and 50%. Hospitals with PBM programs and mass transfusion programs had a lower transfusion rate, although not statistically significant., Conclusions: In this multicenter cross-sectional study, a transfusion prevalence of 9.9% was observed in Spanish critical care units. The most frequent blood product transfused was red blood cells and the main reasons for transfusion were acute anemia with hemodynamic impact and analytical criteria. Mortality of transfused patients was higher., (Copyright © 2020 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.)