Circulating Syndecan-1 Levels Are Associated with Chronological Coagulofibrinolytic Responses and the Development of Disseminated Intravascular Coagulation (DIC) after Trauma: A Retrospective Observational Study.

BACKGROUND: The purpose of this study was to evaluate the association between endotheliopathy represented by high levels of circulating syndecan-1 (SDC-1) and coagulofibrinolytic responses due to trauma, which can lead to disseminated intravascular coagulation (DIC). METHODS: We retrospectively evaluated 48 eligible trauma patients immediately admitted to our hospital and assessed SDC-1 and coagulofibrinolytic parameters for 7 days after admission. We compared the longitudinal changes of coagulofibrinolytic parameters and SDC-1 levels between two groups (high and low SDC-1) according to median SDC-1 value on admission. RESULTS: The median circulating SDC-1 level was 99.6 (61.1-214.3) ng/mL on admission, and levels remained high until 7 days after admission. Coagulofibrinolytic responses assessed by biomarkers immediately after trauma were correlated with SDC-1 elevation (thrombin-antithrombin complex, TAT: r = 0.352, p = 0.001; antithrombin, AT: r = -0.301, p < 0.001; plasmin-α2-plasmin inhibitor complex, PIC: r = 0.503, p = 0.035; tissue plasminogen activator, tPA: r = 0.630, p < 0.001). Sustained SDC-1 elevation was associated with intense and prolonged coagulation activation, impairment of anticoagulation, and fibrinolytic activation followed by inhibition of fibrinolysis, which are the primary responses associated with development of DIC in the acute phase of trauma. Elevation of circulating SDC-1 level was also associated with consumption coagulopathy and the need for transfusion, which revealed a significant association between high SDC-1 levels and the development of DIC after trauma (area under the curve, AUC = 0.845, cut-off value = 130.38 ng/mL, p = 0.001). CONCLUSIONS: High circulating levels of syndecan-1 were associated with intense and prolonged coagulation activation, impairment of anticoagulation, fibrinolytic activation, and consumption coagulopathy after trauma. Endotheliopathy represented by SDC-1 elevation was associated with trauma induced coagulopathy, which can lead to the development of DIC.

Cricotracheostomy for patients with severe COVID-19: A case control study.

Background: Tracheostomy is an important procedure for the treatment of severe coronavirus disease-2019 (COVID-19). Older age and obesity have been reported to be associated with the risk of severe COVID-19 and prolonged intubation, and anticoagulants are often administered in patients with severe COVID-19; these factors are also related to a higher risk of tracheostomy. Cricotracheostomy, a modified procedure for opening the airway through intentional partial cricoid cartilage resection, was recently reported to be useful in cases with low-lying larynx, obesity, stiff neck, and bleeding tendency. Here, we investigated the usefulness and safety of cricotracheostomy for severe COVID-19 patients. Materials and methods: Fifteen patients with severe COVID-19 who underwent cricotracheostomy between January 2021 and April 2022 with a follow-up period of ≥ 14 days were included in this study. Forty patients with respiratory failure not related to COVID-19 who underwent traditional tracheostomy between January 2015 and April 2022 comprised the control group. Data were collected from medical records and comprised age, sex, body mass index, interval from intubation to tracheostomy, use of anticoagulants, complications of tracheostomy, and decannulation. Results: Age, sex, and days from intubation to tracheostomy were not significantly different between the COVID-19/cricotracheostomy and control/traditional tracheostomy groups. Body mass index was significantly higher in the COVID-19 group than that in the control group (P = 0.02). The rate of use of anticoagulants was significantly higher in the COVID-19 group compared with the control group (P < 0.01). Peri-operative bleeding, subcutaneous emphysema, and stomal infection rates were not different between the groups, while stomal granulation was significantly less in the COVID-19 group (P = 0.04). Conclusions: These results suggest that cricotracheostomy is a safe procedure in patients with severe COVID-19.

Dynamic coagulofibrinolytic responses under long-term VV-ECMO management without anticoagulation in a COVID-19-ARDS patient: A case report.

RATIONALE: Venovenous extracorporeal membrane oxygenation (ECMO) is recommended for the treatment of critically ill patients with acute respiratory distress syndrome due to coronavirus disease 2019 (COVID-19). However, ECMO management can cause both bleeding and thrombotic complications. There are insufficient coagulofibrinolytic data for appropriate ECMO management in patients with COVID-19. PATIENT CONCERNS: A 48-year-old man with severe COVID-19-acute respiratory distress syndrome underwent long-term venovenous ECMO management for 48 days. Refractory oronasal bleeding developed on day 13, so the administration of unfractionated heparin was ceased for 29 days. DIAGNOSIS: The patient showed dynamic coagulofibrinolytic responses associated with ECMO management, as shown by fibrin/fibrinogen degradation products, soluble fibrin, thrombin-antithrombin complex, and plasmin-α2-plasmin inhibitor complex elevations, suggesting the development of ECMO-induced coagulopathy. INTERVENTIONS: We assessed coagulofibrinolytic markers to decide the appropriate timing for controlling excessive activation of coagulation by exchanging ECMO circuits. Moreover, viscoelastic hemostatic assays were used for adequate transfusion of blood products. OUTCOMES: Safe long-term ECMO management was completed, which was withdrawn on day 48. The patient was weaned off mechanical ventilation on day 57 and was transferred to another hospital for rehabilitation. LESSONS: Monitoring the coagulofibrinolytic status using markers and viscoelastic hemostatic assays may be effective for safe long-term ECMO management even without anticoagulant therapy.

Laryngeal complications after endotracheal intubation and prone positioning in patients with coronavirus disease 2019.

Objectives: Laryngeal complications have been reported after endotracheal intubation and prone positioning in patients with critical coronavirus disease 2019 (COVID-19), but their association is unclear. In this study, we investigated the rate of laryngeal complications in patients with COVID-19 compared to an alternative condition (control group). Methods: We retrospectively analyzed the data of 40 patients who underwent endotracheal intubation for either COVID-19 or an alternative condition (control group). Data on age, sex, body mass index (BMI), cardiovascular disease (CVD) risk factors, use of prone therapy, duration of endotracheal intubation, and duration from extubation/tracheostomy to laryngeal evaluation were collected from medical records. Results: There were no significant differences in BMI, frequency of CVD risk factors, duration of endotracheal intubation, or duration from extubation/tracheostomy to laryngeal evaluation between the two groups. In the COVID-19 group, all patients adopted the prone position. In comparison, only one patient in the control group adopted the prone position. Significant differences were observed between the two groups regarding the incidence of vocal fold immobility and laryngeal granuloma. Conclusion: Laryngeal complications were more common in the COVID-19 group than in the control group. Prone positioning may be a risk factor for these complications. Level of Evidence: 4.

Differential expression of the ghrelin-related mRNAs GHS-R1a, GHS-R1b, and MBOAT4 in Japanese patients with schizophrenia.

OBJECTIVES: Ghrelin regulates appetite and also plays important roles in cognition and may be involved in vulnerability to SCZ. METHODS: In this study, we measured mRNA expression of the ghrelin-related molecules, growth hormone secretagogue receptor 1a (GHS-R1a) and 1b (GHS-R1b), and the ghrelin activator, membrane bound O-acyltransferase 4 (MBOAT4). Peripheral leukocytes from Japanese patients with SCZ (n = 49; 23 males, 26 females; age = 61.8 ±â€¯13.3 years) and controls (n = 50; 25 males, 25 females; age = 62.0 ±â€¯14.3 years) were recruited according to their clinical information. We also studied the DNA methylation rates of these genes in DNA from leukocytes. RESULTS: The mRNA expression of GHS-R1a was significantly decreased in SCZ (SCZ vs. control: 0.35 ±â€¯0.081 vs. 1.00 ±â€¯0.059, respectively, p = 0.007), but expression levels of GHS-R1b and MBOAT4 were significantly increased in SCZ (SCZ vs. control: 2.02 ±â€¯0.91 vs. 1.00 ±â€¯0.32, p = 0.023, 1.37 ±â€¯0.21 vs. 1.00 ±â€¯0.11, respectively, p = 0.014). No differences in methylation rates for any genes were found. CONCLUSION: We conclude that opposite expression of GHS-R1a and GHS-R1b, and elevated MBOAT4 mRNA expression may reflect the mechanisms of SCZ.

Elevated mRNA expression of CASPR3 in patients with schizophrenia.

BACKGROUND: Recently, it was reported that antipsychotic treatment reverted Contactin Associated Protein-Like 3 (CASPR3, same as CNTNAP3) mRNA expressions in leukocytes of schizophrenia (SCZ) subjects to the same levels as healthy controls. CASPR3 was expressed in various regions of the mice brain (cortex, frontal lobes, corpus callosum, hippocampus, etc.). Thus, this study evaluated CASPR3 mRNA expression in SCZ subjects to find a new clue of schizophrenia pathogenesis. METHODS: One hundred SCZ subjects and 100 age-matched controls were compared. Levels of CASPR3 mRNA in leukocytes were analysed with a quantitative real-time PCR method using TaqMan probes. RESULTS: CASPR3 mRNA expression was significantly higher in leukocytes of SCZ subjects than controls. However, there were no significant correlations between expression level and any clinical parameters in 50 SCZ subjects. CONCLUSION: Considering that CASPR3 is involved in building the brain neural network and autophagy in circulating leukocytes, abnormal CASPR3 expression in SCZ subjects may be associated with the pathogenesis of SCZ.

Association Study and Meta-Analysis of Polymorphisms, Methylation Profiles, and Peripheral mRNA Expression of the Serotonin Transporter Gene in Patients with Alzheimer's Disease.

BACKGROUND/AIM: The aim of this study was to elucidate the relationship between Alzheimer's disease (AD) and the serotonin transporter gene (SLC6A4). METHODS: AD subjects (n = 43) and controls (n = 47) were recruited and evaluated. In leukocytes, we evaluated two polymorphisms in SLC6A4, the serotonin transporter length polymorphic region (5-HTT-LPR) and rs25531, as well as methylation rates of the SLC6A4 promoter region and the SLC6A4 mRNA expression level. We also performed a meta-analysis to examine the relationship between the frequency of the L allele and the risk of AD. RESULTS: The distributions of 5-HTT-LPR and rs25531 polymorphisms in AD subjects were not different from those of controls. Although the methylation rates in AD subjects were not significantly different from those of controls, the expression level in AD subjects was significantly higher than in controls. Additionally, the expression level in AD subjects was significantly correlated with apathy. Meta-analysis revealed that the L/L genotype significantly reduced the risk of AD, but only in the Caucasian population. CONCLUSION: Higher SLC6A4 mRNA expression in leukocytes in AD was associated with apathy regardless of SLC6A4 genotypes and methylation rates of the promoter region. The L/L genotype may reduce the risk of AD in the Caucasian population.