CG02N Analyzer Accurately Measures Fibrinogen Level in Whole Blood in the Presence of Low- or High-Dose Heparin.

Rapid fibrinogen (Fbg) evaluation is important in patients with massive bleeding during severe trauma and those undergoing major surgery. However, there are only a few studies on the point-of-care Fbg analyzer. In this study, we aimed to investigate the accuracy of Fbg level measured using CG02N, with whole blood contained in lithium-heparinized syringes with two different concentrations of heparin. Blood samples were collected in lithium-heparinized tubes, namely PREZA-PAK®II (low-dose heparin group [LG], 7 IU/mL) and Pro-Vent® Plus (high-dose heparin group [HG], 70.5 IU/mL). The Fbg levels in LG and HG were compared with those of citrated plasma Fbg (standard-Fbg). Strong correlations with respect to the Fbg level were observed between standard-Fbg and LG or HG (r = 0.968, p < 0.0001; r = 0.970, p < 0.0001, respectively). We demonstrated that the Fbg level in whole-blood samples was accurately assessed by CG02N and not affected by low- or high-dose heparin.

Net reclassification index in comparison of prognostic value of disseminated intravascular coagulation diagnostic criteria by Japanese Society on Thrombosis and Hemostasis and International Society on Thrombosis and Haemostasis: a multicenter prospective cohort study.

BACKGROUND: We compared the prognostic value of the Japanese Society on Thrombosis and Hemostasis (JSTH) disseminated intravascular coagulation (DIC) diagnostic criteria with that of the International Society on Thrombosis and Haemostasis (ISTH) DIC diagnostic criteria for 28-day in-hospital mortality. METHODS: We conducted a multicenter prospective cohort study involving two hematology departments, four emergency departments, and one general medicine department in Japan between August 2017 and July 2021. We assessed three ISTH DIC diagnostic criteria categories using low cutoff levels of D-dimer (low D-dimer), high cutoff levels of D-dimer (high D-dimer), and fibrinogen/fibrin degradation products (FDP) as fibrin-related markers. The main outcome was diagnosis-based category additive net reclassification index (NRI). RESULTS: A total of 222 patients were included: 82 with hematopoietic disorders, 86 with infections, and 54 with other diseases. The 28-day in-hospital mortality rate was 14% (n = 31). The DIC rates diagnosed by the JSTH, ISTH-low D-dimer, high D-dimer, and FDP DIC diagnosis were 52.7%, 47.3%, 42.8%, and 27.0%, respectively. The overall category additive NRI by JSTH DIC diagnosis vs. ISTH-low D-dimer, high D-dimer, and FDP DIC diagnosis were - 10 (95% confidence interval [CI]: -28 to 8, p = 0.282), - 7.8 (95% CI: -26 to 10, p = 0.401), and - 11 (95% CI: -26 to 3, p = 0.131), respectively. CONCLUSIONS: JSTH criterion showed the highest sensitivity for DIC diagnosis that did not improve but reflected the same prognostic value for mortality evaluated using ISTH DIC diagnosis criteria. This finding may help clinicians to use JSTH DIC criterion as an early intervention strategy in patients with coagulopathy.

The Restrictive Red Blood Cell Transfusion Strategy for Critically Injured Patients (RESTRIC) trial: a cluster-randomized, crossover, non-inferiority multicenter trial of restrictive transfusion in trauma.

BACKGROUND: The efficacies of fresh frozen plasma and coagulation factor transfusion have been widely evaluated in trauma-induced coagulopathy management during the acute post-injury phase. However, the efficacy of red blood cell transfusion has not been adequately investigated in patients with severe trauma, and the optimal hemoglobin target level during the acute post-injury and resuscitation phases remains unclear. Therefore, this study aimed to examine whether a restrictive transfusion strategy was clinically non-inferior to a liberal transfusion strategy during the acute post-injury phase. METHODS: This cluster-randomized, crossover, non-inferiority multicenter trial was conducted at 22 tertiary emergency medical institutions in Japan and included adult patients with severe trauma at risk of major bleeding. The institutions were allocated a restrictive or liberal transfusion strategy (target hemoglobin levels: 7-9 or 10-12 g/dL, respectively). The strategies were applied to patients immediately after arrival at the emergency department. The primary outcome was 28-day survival after arrival at the emergency department. Secondary outcomes included transfusion volume, complication rates, and event-free days. The non-inferiority margin was set at 3%. RESULTS: The 28-day survival rates of patients in the restrictive (n = 216) and liberal (n = 195) strategy groups were 92.1% and 91.3%, respectively. The adjusted odds ratio for 28-day survival in the restrictive versus liberal strategy group was 1.02 (95% confidence interval: 0.49-2.13). Significant non-inferiority was not observed. Transfusion volumes and hemoglobin levels were lower in the restrictive strategy group than in the liberal strategy group. No between-group differences were noted in complication rates or event-free days. CONCLUSIONS: Although non-inferiority of the restrictive versus liberal transfusion strategy for 28-day survival was not statistically significant, the mortality and complication rates were similar between the groups. The restrictive transfusion strategy results in a lower transfusion volume. TRIAL REGISTRATION NUMBER: umin.ac.jp/ctr: UMIN000034405, registration date: 8 October 2018.

Glial fibrillary acidic protein level on admission can predict severe traumatic brain injury in patients with severe multiple trauma: A single-center retrospective observational study.

Objective: This study aimed to clarify whether the glial fibrillary acidic protein (GFAP) and soluble protein-100ß (S100ß) can predict severe traumatic brain injury (TBI) in patients with severe multiple trauma. Methods: This is a single-center retrospective observational study of 179 patients with severe multiple trauma. The GFAP and S100ß were measured upon patient arrival at the hospital. We divided the patients into the severe TBI group (with a Traumatic Coma Data Bank classification of ≥III), the non-severe TBI group (non-TBI group [absence of abnormality on the computed tomography scan and extracranial injury], and the mild to moderate TBI group [TCDB classification I and II]). We compared biomarker levels between the two groups and then evaluated the accuracy of predicting severe TBI using a receiver operating characteristic curve. Results: A total of 41 patients had severe TBI, and 138 had non-severe TBI. Mean GFAP levels were significantly higher in the severe TBI group (median, 6000 pg/mL; interquartile range [IQR], 651-15,548 pg/mL) than in the non-severe TBI group (median, 149 pg/mL; IQR, 0-695 pg/mL) (p < 0.0001). In contrast, there was no significant difference in S100ß levels between the severe TBI group (median, 64 pg/mL; IQR, 0-536 pg/mL) and non-severe TBI group (median, 117 pg/mL; IQR, 0-403 pg/mL) (p = 0.637). The area under the receiver operating characteristic curve was 0.810 (p < 0.0001) for GFAP and 0.476 (p = 0.908) for S100ß. For the GFAP, the optimal cutoff value for detecting severe TBI was 947 pg/mL (sensitivity, 75.6%; specificity, 78.3%). Conclusions: In patients with severe multiple trauma, the GFAP level at hospital arrival could predict severe TBI, whereas the S100ß level was not a useful predictor.

Prognostic value of serum high mobility group box 1 protein and histone H3 levels in patients with disseminated intravascular coagulation: a multicenter prospective cohort study.

BACKGROUND: We compared the prognostic value of serum high mobility group box 1 protein (HMGB1) and histone H3 levels with the International Society on Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) scores for 28-day in-hospital mortality in patients with DIC caused by various underlying diseases. METHODS: We conducted a multicenter prospective cohort study including two hematology departments, four emergency departments, and one general medicine department in Japan, between August 2017 and July 2021. We included patients diagnosed with DIC by the ISTH DIC scoring system. RESULTS: Overall, 104 patients were included: 50 with hematopoietic disorders, 41 with infections, and 13 with the other diseases. The 28-day in-hospital mortality rate was 21%. The receiver operator characteristic (ROC) curve showed that a DIC score of 6 points, serum HMGB1 level of 8 ng/mL, and serum histone H3 level of 2 ng/mL were the optimal cutoff points. The odds ratios of more than these optimal cutoff points of the DIC score, serum HMGB1, and histone H3 levels were 1.58 (95% confidence interval [CI]: 0.60 to 4.17, p = 0.36), 5.47 (95% CI: 1.70 to 17.6, p = 0.004), and 9.07 (95% CI: 2.00 to 41.3, p = 0.004), respectively. The area under the ROC curve of HMGB1 (0.74, 95% CI: 0.63 to 0.85) was better than that of the ISTH DIC scores (0.55, 95% CI: 0.43 to 0.67, p = 0.03), whereas that of histone H3 was not (0.71, 95% CI: 0.60 to 0.82, p = 0.07). Calibration and net reclassification plots of HMGB1 identified some high-risk patients, whereas the ISTH DIC scores and histone H3 did not. The category-free net reclassification improvement of HMGB1 was 0.45 (95% CI: 0.01 to 0.90, p = 0.04) and that of histone H3 was 0.37 (95% CI: - 0.05 to 0.78, p = 0.08). CONCLUSIONS: Serum HMGB1 levels have a prognostic value for mortality in patients with DIC. This finding may help physicians develop treatment strategies.

Effects of evidence-based ICU care on long-term outcomes of patients with sepsis or septic shock (ILOSS): protocol for a multicentre prospective observational cohort study in Japan.

INTRODUCTION: Sepsis is not only the leading cause of death in the intensive care unit (ICU) but also a major risk factor for physical and cognitive impairment and mental disorders, known as postintensive care syndrome (PICS), reduced health-related quality of life (HRQoL) and even mental health disorders in patient families (PICS-family; PICS-F). The ABCDEF bundle is strongly recommended to overcome them, while the association between implementing the bundle and the long-term outcomes is also unknown. METHODS AND ANALYSIS: This is a multicentre prospective observational study at 26 ICUs. All consecutive patients between 1 November 2020 and 30 April 2022, who are 18 years old or older and expected to stay in an ICU for more than 48 hours due to sepsis or septic shock, are enrolled. Follow-up to evaluate survival and PICS/ PICS-F will be performed at 3, 6 and 12 months and additionally every 6 months up to 5 years after hospital discharge. Primary outcomes include survival at 12 months, which is the primary outcome, and the incidence of PICS defined as the presence of any physical impairment, cognitive impairment or mental disorders. PICS assessment scores, HRQoL and employment status are evaluated. The association between the implementation rate for the ABCDEF bundle and for each of the individual elements and long-term outcomes will be evaluated. The PICS-F, defined as the presence of mental disorders, and HRQoL of the family is also assessed. Additional analyses with data up to 5 years follow-up are planned. ETHICS AND DISSEMINATION: This study received ethics approvals from Saiseikai Utsunomiya Hospital (2020-42) and all other participating institutions and was registered in the University Hospital Medical Information Network Clinical Trials Registry. Informed consent will be obtained from all patients. The findings will be published in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION NUMBER: UMIN000041433.

Early recognition of sepsis-induced coagulopathy using the C2PAC index: a ratio of soluble type C lectin-like receptor 2 (sCLEC-2) level and platelet count.

C-type lectin-like receptor 2 (CLEC-2) is a platelet-activated receptor expressed on the surface of platelet membranes. Soluble CLEC-2 (sCLEC-2) has been receiving attention as a predictive marker for thrombotic predisposition. The present study examined the relationship between sCLEC-2 level and degree of coagulation disorder in septic patients. Seventy septic patients were divided into the sepsis-induced disseminated intravascular coagulation (DIC) (SID) group (n = 44) and non-SID group (n = 26). The sCLEC-2 levels were compared between the two groups. Because we suspected that the sCLEC-2 level was affected by the platelet count, we calculated the sCLEC-2/platelet count ratio (C2PAC index). We further divided septic patients into four groups using the Japanese Association for Acute Medicine (JAAM) DIC scoring system (DIC scores: 0-1, 2-3, 4-5, and 6-8). The C2PAC index was significantly higher in the SID group (2.6 ± 1.7) compared with the non-SID group (1.2 ± 0.5) (P < .001). The C2PAC indexes in the four JAAM DIC score groups were 0.9 ± 0.3, 1.1 ± 0.3, 1.7 ± 0.7, and 3.6 ± 1.0, respectively, and this index increased significantly as the DIC score increased (P < .001). According to the receiver-operating curve analysis, the area under the curve (AUC) and optimal cutoff value for the diagnosis of SID were 0.8051 and 1.4 (sensitivity, 75.0%; specificity, 76.9%), respectively. When the C2PAC index and D-dimer level, one of the main fibrinolytic markers, were selected as predictive markers for SID diagnosis in stepwise multiple logistic regression analysis, it was possible to diagnose SID with a high probability (AUC, 0.9528; sensitivity, 0.9545; specificity, 0.8846). The C2PAC index is a useful predictor of SID progression and diagnosis in septic patients.

Relationship between serum zinc level and sepsis-induced coagulopathy.

BACKGROUND: We investigated whether a decrease in the serum zinc level (SZL) among patients with sepsis admitted to the intensive care unit (ICU) was related to sepsis-induced coagulopathy. METHODS: All patients (≥20 years) with a diagnosis of sepsis defined by Sepsis-3 criteria, presenting to the ICU between June 2016 and July 2017, were enrolled. Demographic characteristics and the Sequential Organ Failure Assessment (SOFA) and Japanese Association of Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) scores were recorded. Blood samples were collected upon admission and analyzed for SZL. RESULTS: One hundred patients with sepsis (median age, 70 years) were enrolled. Patients with SOFA scores ≥8 had a significantly lower SZL compared to those with SOFA scores <8 (p < 0.001). The SZL in the DIC group (JAAM DIC score ≥4) was significantly lower than that in the non-DIC group (JAAM DIC score <4) (p < 0.001). Analysis of receiver operating characteristic (ROC) curves for prediction of sepsis-induced DIC based on SZL in patients with sepsis showed a cut-off value of 25 µg/dL for zinc level and a sensitivity of 63% and a specificity of 72% with AUC of 0.7 (p = 0.0065). CONCLUSION: We observed that SZL reflects organ failure, particularly coagulopathy, in patients with sepsis.

Oral Health of COVID-19 Patients Using Extracorporeal Membrane Oxygenation: A Clinical Study of 19 Cases.

The oral health of coronavirus disease 2019 (COVID-19) patients in the intensive care unit (ICU) is an important issue in treatment of respiratory failure. We retrospectively investigated the oral health history of severe COVID-19 patients who received extracorporeal membrane oxygenation (ECMO) from April 2020 to December 2020 using the oral assessment guide from Fukuoka University (OAG-F). Nineteen consecutive patients (median age: 62 years) were divided into two groups according to survival (survivors, n = 12; non-survivors, n = 7). A univariate analysis revealed no significant differences between the groups in sex, age, body mass index (BMI), or the number of remaining teeth, whereas the ECMO assistance of non-survivors (median: 34 days) was prolonged in comparison to survivors (median: 8 days; p < 0.05). Among the factors of OAG-F, significant differences were observed between the groups in the conditions of the saliva, mucous membrane, and gingiva. The total scores in non-survivors (median: 19) were significantly higher in comparison to survivors (Median: 15.5), suggesting that the frequency of oral health deterioration was higher in non-survivors (p < 0.05). Taken together, these findings suggest that poor oral health is associated with mortality in COVID-19 patients receiving ECMO in the ICU.