Paradigm shift in transfusion practices during early COVID-19 pandemic: A single center retrospective study.

BACKGROUND: The advent of coronavirus disease 2019 (COVID-19) unveiled the worst national blood crisis that the United States had witnessed in over a decade. With the pandemic influencing the different stages of the acquisition of blood products outside the hospital setting, we aimed to explore the possible barriers contributing to the shortage of blood products within the medical community. AIM: To assess the adherence to restrictive blood transfusion practices for patients in the COVID era and pre-COVID era. METHODS: We conducted a retrospective cross-sectional study on hospitalized patients distinguishing the pattern of blood transfusion during the COVID and pre-COVID era in a community hospital. Data was tabulated to include the number of red blood cell (RBC) transfusions and if transfusions met restrictive blood transfusion criteria as per institutional guidelines. Chi-square was applied to test the statistical association between qualitative variables. Unpaired t test and Mann Whitney U test were applied respectively to test the mean difference of quantitative variables. RESULTS: A total of 208 patients were included in the study, of which 108 were during COVID era and 100 were during pre-COVID era. The leading reason for admission in both the COVID era and pre-COVID era transfused patients was shortness of breath (53.7% and 36% P = 0.001), followed by gastrointestinal bleeding (25.9% and 21% P = 0.001). There was a higher percentage of RBC transfusions in the intensive care unit in the COVID-era group than in the pre-COVID era group (38.9% vs 22%, P = 0.008). The restrictive transfusion criteria were met in 62% vs 79% in the COVID and pre-COVID eras, respectively (P = 0.008). CONCLUSION: The COVID-era group received RBC transfusions with less stringent adherence to restrictive blood transfusion practices in comparison to pre-COVID era group.

Using microfluidic shear to assess transfusion requirements in trauma patients.

Background: Viscoelastic assays have widely been used for evaluating coagulopathies but lack the addition of shear stress important to in vivo clot formation. Stasys technology subjects whole blood to shear forces over factor-coated surfaces. Microclot formation is analyzed to determine clot area (CA) and platelet contractile forces (PCFs). We hypothesize the CA and PCF from this novel assay will provide information that correlates with trauma-induced coagulopathy and transfusion requirements. Methods: Blood samples were collected on adult trauma patients from a single-institution prospective cohort study of high-level activations. Patient and injury characteristics, transfusion data, and outcomes were collected. Thromboelastography, coagulation studies, and Stasys assays were run on paired samples collected at admission. Stasys CA and PCFs were quantified as area under the curve calculations and maximum values. Normal ranges for Stasys assays were determined using healthy donors. Data were compared using Kruskal-Wallis tests and simple linear regression. Results: From March 2021 to January 2023, 108 samples were obtained. Median age was 37.5 (IQR 27.5-52) years; patients were 77% male. 71% suffered blunt trauma, 26% had an Injury Severity Score of ≥25. An elevated international normalized ratio significantly correlated with decreased cumulative PCF (p=0.05), maximum PCF (p=0.05) and CA (p=0.02). Lower cumulative PCF significantly correlated with transfusion of any products at 6 and 24 hours (p=0.04 and p=0.05) as well as packed red blood cells (pRBCs) at 6 and 24 hours (p=0.04 and p=0.03). A decreased maximum PCF showed significant correlation with receiving any transfusion at 6 (p=0.04) and 24 hours (p=0.02) as well as transfusion of pRBCs, fresh frozen plasma, and platelets in the first 6 hours (p=0.03, p=0.03, p=0.03, respectively). Conclusions: Assessing coagulopathy in real time remains challenging in trauma patients. In this pilot study, we demonstrated that microfluidic approaches incorporating shear stress could predict transfusion requirements at time of admission as well as requirements in the first 24 hours. Level of evidence: Level II.

Synergistic treatment of infected burn wound utilizing maggot debridement and acellular fish skin grafting - a case report.

Here we report about a patient with a full thickness burn injury of the left lower extremity with approximately 8% of total body surface area affected. Initial therapy consisted of necrosectomy and wound coverage with split thickness graft. The patient developed a wound infection with Pseudomonas aeruginosa, resulting in the failure of the skin graft to achieve complete healing. The case was further complicated by the patient's concurrent presentation of anemia, characterized by a hematocrit level of 19.8% on 11th day after admission. Additionally, the patient refused acceptance of any blood transfusion, adding a significant layer of complexity to the management strategy. In summary, the patient's critical state required an immediate intervention. Due to the contraindication for a further surgical debridement and autograft, we changed the treatment strategy to a conservative approach. First, the wound was debrided employing maggot therapy 17 days after admission. Subsequently, free soft tissue coverage was accomplished using decellularized fish skin dressings on 45th day. This approach yielded satisfactory wound closure. Following an approximately two-month hospitalization period (52nd day after admission), the patient was discharged with a stable wound condition, nearing complete healing.

The Magic Number 63 - Redefining the Geriatric Age for Massive Transfusion in Trauma.

INTRODUCTION: The arbitrary geriatric age cutoff of 65 may not accurately define older adults at higher risk of mortality following massive transfusion (MT). We sought to redefine a new geriatric age threshold for MT and understand its association with outcomes. MATERIAL AND METHODS: The 2013-2018 Trauma Quality Improvement Program database was queried for all adults who received ≥10 units of packed red blood cells (pRBCs) within 24 h of admission. A bootstrap analysis using multiple logistic regression established transfusion futility thresholds (TTs), where additional pRBCs no longer improved mortality for various age cutoffs. The age cutoff at which the TT for those relatively older and relatively younger was statistically significant was used to define the new "geriatric" age for MT. Outcomes were then compared between the newly defined geriatric and nongeriatric patients. RESULTS: The difference in TT first became significant when the age cutoff was 63 y. The TT for patients aged ≥63 y (new geriatric, n = 2870) versus <63 y (nongeriatric, n = 17,302) was 34 and 40 units of pRBCs, respectively (P = 0.04). Although geriatric patients had a higher Glasgow coma scale score (9 versus 6, P < 0.01) and lower abbreviated injury score-abdomen (3 versus 4, P < 0.01) than the nongeriatric, they suffered higher overall mortality (62% versus 45%, P < 0.01). A lower percentage of geriatric patients were discharged to home (7% versus 35%, P < 0.01). CONCLUSIONS: The new geriatric age for MT is 63 y, with a TT of 34 units. Despite suffering less severe injuries, physiologically "geriatric" patients have worse outcomes following MT.

'Of One Blood?': Gendered Propaganda and Blood Donor Behaviour in Wartime Bristol and South West England, 1939-1945.

This article explores civilian responses to the British army's blood donor recruitment campaign in wartime Britain, revealing it to be an underexplored medium for the examination of the contribution of women to Britain's war effort. However, despite extensive gender-targeted propaganda, it reveals evidence of a significant disparity between levels of volunteering to donate and actual donation throughout the war. Wartime donor behaviour was influenced by perceptions of personal or familial risk, with donor recruitment propaganda emphasising kinship ties to those in military service and promoting blood donation as a mutual insurance policy. Ultimately, this article argues that evidence of donor behaviour further undermines the mythologised narrative of Britain's 'People's War' and provides nuance to the understanding of blood donor motivation.

Irregular red blood cell antibodies, abnormal hemoglobin and dangerous universal blood donor insights from a public blood center in a Brazilian metropolitan area.

BACKGROUND: Immunohematology tests are crucial in transfusion safety. This study aimed to assess irregular red blood cell (RBC) antibodies, abnormal hemoglobin and dangerous universal blood donors at a public blood center in a Brazilian metropolitan area. METHODS: A cross-sectional study included all consecutive blood donors from January 2018 to December 2021 at the Brasília Blood Center Foundation, Federal District (FD), Brazil. RESULTS: Among 205,965 blood donations, irregular RBC antibodies were found in 743 (0.4 %). Abnormal hemoglobin was observed in 5396 (2.6 %): 3959 (1.9 %) with Hb AS, 1344 (0.7 %) with Hb AC, and 93 (< 0,1 %) with other hemoglobin variants. Of O group donors, 12.5 % (9646) had hemolysins: 12.5 % (2410) both anti-A and anti-B, 8.7 % (9646) only anti-A, and 1.6 % (1763) only anti-B hemolysins. Female sex (p < 0.001) and increasing age (p < 0.001) were associated with irregular RBC antibodies. O and/or Rh(D)-positive blood groups had a lower prevalence of irregular RBC antibodies compared to other ABO and/or Rh(D)-negative groups. Age (p < 0.001) and female sex (p < 0.001) were associated with anti-A/anti-B hemolysins, while FD residency was associated with reduced incidence (p < 0.001). CONCLUSION: Anti-A/anti-B hemolysins in O group donors, abnormal hemoglobin and irregular RBC antibodies pose risks to transfusion practice and should not be overlooked. Advancing age, female sex, ABO blood group other than O, or Rh(D)- negative are independently associated with the presence of irregular RBC antibodies. Dangerous universal blood donors were associated with advanced age, female gender, Rh(D)-positive blood type, and individuals residing in a Brazilian state other than where the blood center was located.

Acute intravascular haemolysis associated with scrub typhus.

Scrub typhus, a prevalent tropical infection, may sometimes manifest with unusual complications. Here, we present the case of a young man who was admitted to our facility with a fever for the past 3 days and passage of dark-coloured urine since that morning. On investigation, we identified intravascular haemolytic anaemia. Through meticulous examination, a black necrotic lesion (eschar) was discovered on his right buttock, a pathognomonic sign of scrub typhus infection. Treatment was initiated with oral doxycycline 100 mg two times a day. Subsequently, diagnosis of scrub typhus was confirmed through positive results from scrub typhus IgM via ELISA and PCR analysis from the eschar tissue. The patient responded well to oral doxycycline and his symptoms resolved within the next few days. This case highlights severe intravascular haemolysis associated with scrub typhus infection.

Excessive use of preoperative blood type and antibody screening: A retrospective observational study conducted in a hospital in Norway.

INTRODUCTION: This study aimed to identify the blood transfusion rates for several surgical procedures in a single district general hospital and assess the value of preoperative blood type and antibody screen across all relevant surgical procedures. We hypothesized that there was an overuse of blood type and antibody screen in our general surgical population. METHODS: A database containing transfusions of patients who underwent elective- or emergency surgery from January 2015 to September 2020 was matched to a database of preoperative type-and-screen performed in the same period. Registered procedures where the incidence of transfusion is deemed low were excluded. The included procedures were assessed for the intraoperative usefulness of type- and-screen testing. RESULTS: In the included 68.892 surgeries, 36.134 (52.0%) blood samples were preoperatively tested for the blood type and screened for antibodies according to the hospital's routine. Overall 3.517 (5.1%) of surgeries had patients that received a transfusion in the perioperative period and 1.2% (n = 850) during the surgery. CONCLUSION: Most surgeries had a very low incidence of transfusion. Despite this, type-and-screen tests were widely used. This suggests the need for a more focused pre-surgery type-and-screen approach, and a more data driven approach to local guidelines in collaboration with surgical specialties.

Extranodal diffuse large B-cell lymphoma involving the uterine cervix.

This is a case of primary diffuse large B-cell lymphoma involving the uterine cervix which presented with irregular vaginal bleeding. The diagnosis was confirmed following multiple cervical biopsies. Treatment with a combination of immunotherapy, chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP)) and radiotherapy produced a good response.

Evaluating the Shock Index, Revised Assessment of Bleeding and Transfusion (RABT), Assessment of Blood Consumption (ABC) and novel PTTrauma score to predict critical transfusion threshold (CAT) in penetrating thoracic trauma.

The shock index (SI) has been associated with predicting transfusion needs in trauma patients. However, its utility in penetrating thoracic trauma (PTTrauma) for predicting the Critical Administration Threshold (CAT) has not been well-studied. This study aimed to evaluate the prognostic value of SI in predicting CAT in PTTrauma patients and compare its performance with the Assessment of Blood Consumption (ABC) and Revised Assessment of Bleeding and Transfusion (RABT) scores. We conducted a prognostic type 2, single-center retrospective observational cohort study on patients with PTTrauma and an Injury Severity Score (ISS) > 9. The primary exposure was SI at admission, and the primary outcome was CAT. Logistic regression and decision curve analysis were used to assess the predictive performance of SI and the PTTrauma score, a novel model incorporating clinical variables. Of the 620 participants, 53 (8.5%) had more than one CAT. An SI > 0.9 was associated with CAT (adjusted OR 4.89, 95% CI 1.64-14.60). The PTTrauma score outperformed SI, ABC, and RABT scores in predicting CAT (AUC 0.867, 95% CI 0.826-0.908). SI is a valuable predictor of CAT in PTTrauma patients. The novel PTTrauma score demonstrates superior performance compared to existing scores, highlighting the importance of developing targeted predictive models for specific injury patterns. These findings can guide clinical decision-making and resource allocation in the management of PTTrauma.

Ozone Improves Oxygenation and Offers Organ Protection after Autologous Blood Transfusion in a Simulated Carbon Dioxide Pneumoperitoneal Environment in a Rabbit Hemorrhagic Shock Model.

Objectives: Autologous blood transfusion techniques are well applied in surgery, but the red blood cells (RBCs) collected during laparoscopic surgery may forfeit their ability to oxygenate. O3 is a potent oxidation gas. This study investigates whether O3 could improve the oxygen-carrying capacity of RBCs, reduce inflammatory reactions, and offer organ protection. Methods: We established a hemorrhagic shock model in rabbits, and simulated CO2 pneumoperitoneum and O3 were applied before autologous blood transfusion. Perioperative mean arterial pressure and arterial blood gas were recorded, blood gas and RBC morphology of collected blood were analyzed, plasma IL-6, ALT, AST, CRE, and lung histopathology POD0 and POD3 were tested, as well as postoperative survival quality. Results: Autologous blood that underwent simulated CO2 pneumoperitoneum had a lower pH and SaO2 and a higher PaCO2 than the control group. After O3 treatment, PaO2 and SaO2 increased significantly, with unchanged pH values and PaCO2. RBCs in autologous blood were drastically deformed after CO2 conditioning and then reversed to normal by O3 treatment. Rabbits that received CO2-conditioned autologous blood had a compromised survival quality after surgery, higher plasma IL-6 levels, higher lung injury scores on POD0, higher ALT and AST levels on POD3, and O3 treatment alleviated these adverse outcomes. Conclusion: O3 can restore RBC function, significantly improve blood oxygenation under simulated CO2 pneumoperitoneum, offer organ protection, and improve the postoperative survival quality in the rabbit hemorrhage shock model.

Hemoglobin C Disorder in Anemic Patients Referred to the National Center for Thalassemia and Genetic Counseling in Damascus.

Background: Hemoglobinopathies are common inherited blood disorders in our Mediterranean area. The main structural hemoglobin variants are hemoglobin S and hemoglobin C, due to their prevalence. We conducted this retrospective study to investigate and characterize hemoglobin C patients referred to the National Center for Thalassemia and Genetic Counseling and the management of hemoglobin C disease in Damascus. Materials and Methods: The study included patients referred to the National Center for Thalassemia and Genetic Counseling in Damascus between 2000 and 2022 for hemoglobin C detection. Gender, age, geographical origin, hemoglobin electrophoresis profile, and blood transfusion were considered for hemoglobin C patient classification. Blood transfusion in five consecutive years and linear regression with hemoglobin S and C values were determined. Results: 30 (14 males and 16 females) out of 624 patients between 3 and 46 years old (mean ± SD: 17.3 ± 9.7 years) showed hemoglobin C disease. Only eight patients (one male and seven females) received blood transfusions, and the remaining patients (13 males and 9 females) did not receive any transfusion. Only one patient with 100% hemoglobin C was detected; 19 showed HbSC, and 10 had HbAC. There was a significant correlation between hemoglobin S and geographical origin (P-value=0). Conclusion: A Homozygote hemoglobin C patient has mild hemolytic anemia, whereas the hemoglobin C 100% patient has only a one-time blood transfusion (he was 17 years old) in our study. The inherited combination of hemoglobin C and S is less severe than hemoglobin S alone. There is a significant relationship between hemoglobin S and geographical origin (p-value=0).

Factor Eight Inhibitor Bypassing Activity as First-line Therapy for Coagulopathy in Cardiac Surgery.

OBJECTIVES: To compare the outcomes of factor eight inhibitor bypassing activity (FEIBA) versus fresh frozen plasma (FFP) as the primary treatment for postoperative coagulopathy in patients undergoing cardiac surgery. DESIGN: A retrospective, propensity-matched study. SETTING: A single, tertiary hospital. PARTICIPANTS: Patients who underwent noncoronary cardiac surgery with cardiopulmonary bypass between 2015 and 2023. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We stratified patients into 2 groups based on whether they received intraoperative FFP or FEIBA; cases using both were excluded. We analyzed 434 cases, with 197 receiving FFP and 237 receiving FEIBA. After propensity matching, there was no significant difference in the proportion of the patients who required packed red blood cell transfusions (p = 0.08). However, of those who required packed red blood cell transfusions, patients in the FEIBA group required significantly fewer units of packed red blood cells (p < 0.001). Significantly fewer patients in the FEIBA group required platelet (p < 0.001) and cryoprecipitate (p < 0.001) transfusions. The FEIBA group showed decreased prolonged postoperative intubation (p = 0.05), decreased intensive care unit length of stay (p = 0.04), and lower 30-day readmission rates (p = 0.03). There were no differences in the rates of thrombotic complications between the 2 cohorts. CONCLUSIONS: In the initial treatment of postcardiopulmonary bypass coagulopathy, FEIBA may be more effective than FFP in decreasing blood product transfusions and readmission rates. Further studies are needed to explore the potential routine use of FEIBA as first-line agent in this patient population.

Atypical haemolytic uremic syndrome in a patient with severe Babesiosis.

Babesiosis is a tick-borne parasitic infection that can result in various haematological complications. This case report discusses a patient with severe Babesiosis complicated by an unorthodox presentation of Babesiosis-associated haemolytic uremic syndrome. Discussed here is the patient's clinical course and the management strategies employed, with an emphasis on early recognition and treatment of renal failure in the context of severe Babesiosis. Haematologic manifestations of Babesia are common and the severity of disease is dependent on parasite load. While treatment options such as red blood cell exchange have been proposed for severe cases, their impact on clinical outcomes is limited and they may not be readily available in resource-limited settings. Traditional management using antimicrobials has been proposed but there is limited discussion about managing unique presentations such as renal failure in Babesiosis. Hence, understanding the pathophysiology, early recognition and aggressive treatment strategies can optimise clinical outcomes and reduce mortality.

Potential Association of Blood Transfusion in Deceased Donors With Outcomes of Liver Transplantation in the United States.

BACKGROUND: Donor blood transfusion may potentially affect transplant outcomes through an inflammatory response, recipient sensitization, or transmission of infection. The aim of this study was to evaluate the association of donor blood transfusion with outcomes of liver transplantation (LT). METHODS: From January 2004 to December 2022, donor blood transfusion information was available for 113,017 adult recipients of LT in the United Network for Organ Sharing database and was classified into 4 levels of transfusion: no-transfusion (N = 68,130), transfusion of 1-5 units (N = 33,629), 6-10 units (N = 8067), and >10 units (N = 5329). Recipient survival analysis was performed by Kaplan-Meier method and multivariable Cox-hazard model. RESULTS: Among this cohort, 40.8% of donors (N = 46,261) received blood transfusion during the index hospitalization. Compared to no-blood transfusion donors, blood transfusion donors were younger (median age 37 versus 46 y P < 0.001) and were more brain death donors (94.5% versus 92.1%, P < 0.001). An increased risk of rejection at 6-mo (transfusion 10.3% versus no-transfusion 9.9%, P = 0.055) and 1 y (transfusion 12.5% versus no-transfusion 11.9%, P = 0.0036) post-LT was noted in this cohort. Multivariable Cox-hazard model showed blood transfusion was associated with increased 1-y mortality (transfusion 1.07; 95% CI 1.02-1.12, P = 0.007) and graft failure (transfusion 1.09; 95% CI 1.04-1.13, P < 0.001). CONCLUSIONS: Donor blood transfusion was associated with an increased risk of rejection at 6 mo and 1 y among LT recipients and worse post-transplant graft and overall survival. Additional information regarding donor blood transfusion, along with other known factors, may be considered when deciding the optimization of overall immune suppression in LT recipients to decrease the risk of delayed rejection.

Generation of a human iPSC cell line (MUSIi017-A) from a donor with O negative blood type.

The Rh-negative type O blood group (O Rh-) is considered a universal donor for emergency blood transfusions. Due to the constant shortage of this rare blood group, the production of blood cells from iPSCs derived from the O Rh- donor could potentially serve as a limitless blood source for transfusions. In this report, we establish a MUSIi017-A iPSC line from peripheral blood mononuclear cells of a healthy donor with the O Rh- blood group. The established iPSC line exhibited a normal karyotype, showed identical STR compared to donor peripheral blood mononuclear cells, and could differentiate to all three germ layers.

Cultural competences among future nurses and midwives: a case of attitudes toward Jehovah's witnesses' stance on blood transfusion.

BACKGROUND: Transcultural nursing recognises the significance of cultural backgrounds in providing patients with quality care. This study investigates the opinions of master's students in nursing and midwifery regarding the attitudes of Jehovah's Witnesses towards refusing blood transfusions. METHODS: 349 master's students in nursing and midwifery participated in a quantitative study and were surveyed via the Web to evaluate their awareness of the stance of Jehovah's Witnesses on blood transfusions and the ethical and legal dilemmas associated with caring for Jehovah's Witness (JW) patients. RESULTS: The study yielded three significant findings. It unequivocally demonstrates that nursing and midwifery students possess inadequate knowledge regarding Jehovah's Witnesses' stance on blood transfusions and their acceptance of specific blood products and medical procedures. Despite being cognisant of the ethical and legal dilemmas of caring for JW patients, students lack an understanding of patients' autonomy to reject blood transfusions and their need for bloodless medicine. Students also articulated educational needs regarding cultural competencies regarding the Jehovah's Witnesses' beliefs on blood transfusions and non-blood management techniques. CONCLUSIONS: Healthcare professionals need the knowledge and skills necessary to provide holistic, patient-centred and culturally sensitive care. This study emphasises the urgent need for university curricula and nursing postgraduate training to include modules on transcultural nursing and strategies for minimising blood loss.

Haemoglobin values, transfusion practices, and long-term outcomes in critically ill patients with traumatic brain injury: a secondary analysis of CENTER-TBI.

Haemoglobin (Hb) thresholds and red blood cells (RBC) transfusion strategies in traumatic brain injury (TBI) are controversial. Our objective was to assess the association of Hb values with long-term outcomes in critically ill TBI patients. We conducted a secondary analysis of CENTER-TBI, a large multicentre, prospective, observational study of European TBI patients. All patients admitted to the Intensive Care Unit (ICU) with available haemoglobin data on admission and during the first week were included. During the first seven days, daily lowest haemoglobin values were considered either a continous variable or categorised as < 7.5 g/dL, between 7.5-9.5 and > 9.5 g/dL. Anaemia was defined as haemoglobin value < 9.5 g/dL. Transfusion practices were described as "restrictive" or "liberal" based on haemoglobin values before transfusion (e.g. < 7.5 g/dL or 7.5-9.5 g/dL). Our primary outcome was the Glasgow outcome scale extended (GOSE) at six months, defined as being unfavourable when < 5. Of 1590 included, 1231 had haemoglobin values available on admission. A mean Injury Severity Score (ISS) of 33 (SD 16), isolated TBI in 502 (40.7%) and a mean Hb value at ICU admission of 12.6 (SD 2.2) g/dL was observed. 121 (9.8%) patients had Hb < 9.5 g/dL, of whom 15 (1.2%) had Hb < 7.5 g/dL. 292 (18.4%) received at least one RBC transfusion with a median haemoglobin value before transfusion of 8.4 (IQR 7.7-8.5) g/dL. Considerable heterogeneity regarding threshold transfusion was observed among centres. In the multivariable logistic regression analysis, the increase of haemoglobin value was independently associated with the decrease in the occurrence of unfavourable neurological outcomes (OR 0.78; 95% CI 0.70-0.87). Congruous results were observed in patients with the lowest haemoglobin values within the first 7 days < 7.5 g/dL (OR 2.09; 95% CI 1.15-3.81) and those between 7.5 and 9.5 g/dL (OR 1.61; 95% CI 1.07-2.42) compared to haemoglobin values > 9.5 g/dL. Results were consistent when considering mortality at 6 months as an outcome. The increase of hemoglobin value was associated with the decrease of mortality (OR 0.88; 95% CI 0.76-1.00); haemoglobin values less than 7.5 g/dL was associated with an increase of mortality (OR 3.21; 95% CI 1.59-6.49). Anaemia was independently associated with long-term unfavourable neurological outcomes and mortality in critically ill TBI patients.Trial registration: CENTER-TBI is registered at ClinicalTrials.gov, NCT02210221, last update 2022-11-07.