Background Coagulation abnormalities in COVID-19 patients have not been addressed in depth. Objective To perform a longitudinal evaluation of coagulation profile of patients admitted to the ICU with COVID-19. Methods Conventional coagulation tests, rotational thromboelastometry (ROTEM), platelet function, fibrinolysis, antithrombin, protein C and S were measured at days 0, 1, 3, 7 and 14. Based on median total maximum SOFA score, patients were divided in two groups: SOFA ≤ 10 and SOFA > 10. Results Thirty patients were studied. Some conventional coagulation tests, as aPTT, PT and INR remained unchanged during the study period, while alterations on others coagulation laboratory tests were detected. Fibrinogen levels were increased in both groups. ROTEM maximum clot firmness increased in both groups from Day 0 to Day 14. Moreover, ROTEM–FIBTEM maximum clot firmness was high in both groups, with a slight decrease from day 0 to day 14 in group SOFA ≤ 10 and a slight increase during the same period in group SOFA > 10. Fibrinolysis was low and decreased over time in all groups, with the most pronounced decrease observed in INTEM maximum lysis in group SOFA > 10. Also, D-dimer plasma levels were higher than normal reference range in both groups and free protein S plasma levels were low in both groups at baseline and increased over time, Finally, patients in group SOFA > 10 had lower plasminogen levels and Protein C ​​than patients with SOFA <10, which may represent less fibrinolysis activity during a state of hypercoagulability. Conclusion COVID-19 patients have a pronounced hypercoagulability state, characterized by impaired endogenous anticoagulation and decreased fibrinolysis. The magnitude of coagulation abnormalities seems to correlate with the severity of organ dysfunction. The hypercoagulability state of COVID-19 patients was not only detected by ROTEM but it much more complex, where changes were observed on the fibrinolytic and endogenous anticoagulation system.

Background: Coagulation abnormalities in severe COVID-19 patients have not been addressed in depth. Methods: Prospective longitudinal single-center study involving COVID-19 patients admitted to the ICU. Conventional coagulation tests (prothrombin time, international normalized ratio and activated partial thromboplastin time), rotational thromboelastometry (ROTEM), platelet function, plasma fibrinolysis markers, antithrombin, protein C and S were measured at the time of study inclusion (baseline), and at days 1, 3, 7 and 14 after enrollment. Based on median total maximum SOFA score, patients were divided in two groups: SOFA ≤ 10 and SOFA > 10.Results: From March, 2020 through May, 2020, 30 patients [median (IQR) age: 61 (52-83) yrs; SAPS III score: 49 (41-61) points] were included in this study. Conventional coagulation tests remained unchanged during the study period, while the majority of patients exhibited a hypercoagulability state based on ROTEM. Fibrinogen levels were increased in both groups. ROTEM (INTEM and EXTEM) maximum clot firmness increased in both study groups from day 0 to day 14. ROTEM – FIBTEM maximum clot firmness was high in both groups during the study period, with a slight decrease from day 0 to day 14 in group SOFA ≤ 10 and a slight increase during the same period in group SOFA > 10. Fibrinolysis (INTEM and EXTEM maximum lysis) was low and decreased over time in all groups, with the most pronounced decrease observed in INTEM maximum lysis in group SOFA > 10. Antithrombin slightly increased over time in group SOFA ≤ 10 while it remained stable in group SOFA > 10. Protein C plasma levels increased over time in both groups, although patients in group SOFA > 10 exhibited lower values in comparison to patients in group SOFA ≤ 10. Protein S plasma levels were low in both groups at baseline and increased over time with no between-group differences.Conclusion: COVID-19 patients have a pronounced hypercoagulability state, characterized by impaired endogenous anticoagulation and decreased fibrinolysis. The magnitude of coagulation abnormalities seems to correlate with the severity of organ dysfunction. The hypercoagulability state of COVID-19 patients was detected by ROTEM, but not with conventional coagulation tests.

Goal: The present work aims to improve the project portfolio selection processes under uncertainty of pharmaceutical companies by integrating two Multicriteria Decision Making (MCDM) methods in a fuzzy environment: the AHP and the VIKOR methods. Design / Methodology / Approach: We employed normative axiomatic modeling as the methodology for our work. The MCDM are subjective methods representing decision-makers preferences and assisting the project portfolio selection process. Thus, the model is founded on integrating the fuzzy-AHP and fuzzy-VIKOR methods; the first one determines the importance of the company's strategy and the second for elaborating the project ranking. We validated this methodology in a Brazilian subsidiary of one of the biggest pharmaceutical enterprises worldwide. Results: The developed model considers the evaluators' scores' indecision, enhancing the project portfolio selection process and optimizing its decision-making. Limitations of the investigation: The proposed method does not verify the correlation, interdependence, or cannibalization between the criteria and the projects, which are common limitations to MCDM subjective approaches. In addition, resource constraints are not considered and scheduling routines. Practical implications: The pharmaceutical market is heated by the increase in life expectancy, greater access to medications, and the most recurrent disease outbreaks, resulting in greater competitiveness, increasing the need for companies to seek greater strategic projects selection efficiency. Originality / Value: A well-structured and assertive project portfolio selection becomes extremely important for the pharmaceutical market to keep the company competitive in the market, which explains the importance of this work.

Purpose: To investigate clinical and laboratory tissue perfusion in addition to near-infrared spectroscopy (NIRS) static and dynamic-derived parameters in critically ill COVID-19 patients. Methods: A cross-sectional single-center exploratory study was performed. Twenty adult patients with confirmed COVID-19 admitted to the intensive care unit (ICU) within 24 hours were prospectively included in this study. A control group without COVID-19 was composed by forty patients included in recently published study. Accessed NIRS-derived parameters included basal tissue oxygen saturation (StO2), descending slope (%/min), ascending slope (%/min), maximum value of StO2 (StO2max), recovery time (s) and the area under the curve of reactive hyperemia. Results: The median (IQR) age of included patients was 58 (46-69) years. Patients with COVID-19 presented higher SAPS III score [50 (46-53) vs. 45 (30-53), p=0.04] compared with control patients. Patients with SARS-CoV-2 infection showed higher StO2 min [60 (49-79) vs. 54 (48-58) %; p=0.04] and lower descending slope [5.7 (3.4-8.8) vs. 8.1 (6.4-9.7) %/min; p<0.01] compared with ICU patients without COVID-19. Basal StO2 [80 (74-90) vs. 82 (76-86) %; p=0.89], StO2 max [(91 (83-95) vs. 90 (84-94) %; p=0.86], ascending slope [2.0 (1.1-2.9) vs. 2.2 (1.5-3.3) %/min; p=0.43], recovery time [14.5 (12.0-22.0) vs. 21.5 (14.3-28.3) s; p=0.13] and hyperemia area [10.3 (5.8-13.0) vs. 8.6 (4.0-14.3); p=0.55] did not differ between, respectively, COVID-19 and control groups. Conclusion: Severe COVID-19 patients exhibited a lower rate of oxygen extraction by peripheral tissues than non-COVID-19 critically ill patients, which may represent an adaptive mechanism to hypoxemia. This hypothesis needs to be further investigated.

Objective The main objective was to assess the clinical characteristics, associated factors, and outcomes of patients admitted to the ICU for candidemia. The secondary objective was to examine the relationship of candidemia with the length of stay and mortality. Methods The analysis was a retrospective single-center cohort study addressing the effect of invasive candidemia on outcomes. This study was performed in a medical-surgical ICU located in a tertiary private hospital in São Paulo, Brazil. Data was collected through the review of the hospital database. Results In total, 18,442 patients were included in our study, including 22 patients with candidemia. The median age was similar in patients with and without candidemia [67 (56–84) vs. 67 (51–80)]. Most patients were male, and the proportion of men was higher among patients with candidemia (77% vs. 55.3%). The rates of renal replacement therapy (40.9% vs. 3.3%), mechanical ventilation (63.6% vs. 29.6%), and parenteral nutrition (40.9% vs. 4.8%) were higher in patients with candidemia than in those without candidemia. The mortality rate (77.3% vs. 11.9%) and length of hospital stay [42 days (23.0–78.8) vs. 8 days (5.0–17.0)] were significantly higher in patients with candidemia. Conclusions Patients with candidemia are prone to longer hospital stay and mortality. In addition, we found associations of candidemia with the use of invasive mechanical ventilation, renal replacement therapy, and parenteral nutrition.

Objective: To evaluate clinical practices and hospital resource organization during the early COVID-19 pandemic in Brazil. Methods: This was a multicenter, cross-sectional survey. An electronic questionnaire was provided to emergency department and intensive care unit physicians attending COVID-19 patients. The survey comprised four domains: characteristics of the participants, clinical practices, COVID-19 treatment protocols and hospital resource organization. Results: Between May and June 2020, 284 participants [median (interquartile ranges) age 39 (33 - 47) years, 56.3% men] responded to the survey; 33% were intensivists, and 9% were emergency medicine specialists. Half of the respondents worked in public hospitals. Noninvasive ventilation (89% versus 73%; p = 0.001) and highflow nasal cannula (49% versus 32%; p = 0.005) were reported to be more commonly available in private hospitals than in public hospitals. Mechanical ventilation was more commonly used in public hospitals than private hospitals (70% versus 50%; p = 0,024). In the Emergency Departments, positive endexpiratory pressure was most commonly adjusted according to SpO 2, while in the intensive care units, positive end-expiratory pressure was adjusted according to the best lung compliance. In the Emergency Departments, 25% of the respondents did not know how to set positive end-expiratory pressure. Compared to private hospitals, public hospitals had a lower availability of protocols for personal protection equipment during tracheal intubation (82% versus 94%; p = 0.005), managing mechanical ventilation [64% versus 75%; p = 0.006] and weaning patients from mechanical ventilation [34% versus 54%; p = 0.002]. Finally, patients spent less time in the emergency department before being transferred to the intensive care unit in private hospitals than in public hospitals [2 (1 - 3) versus 5 (2 - 24) hours; p < 0.001]. Conclusion: This survey revealed significant heterogeneity in the organization of hospital resources, clinical practices and treatments among physicians during the early COVID-19 pandemic in Brazil.

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