Triggering receptor expressed on myeloid cells-like (TREM-like) transcript-1 (TLT-1), a type 1 single Ig domain orphan receptor specific to platelet and megakaryocyte α-granules, relocates to the platelet surface upon platelet stimulation. We found here that patients diagnosed with sepsis, in contrast to healthy individuals, had substantial levels of soluble TLT-1 (sTLT-1) in their plasma that correlated with the presence of disseminated intravascular coagulation. sTLT-1 bound to fibrinogen and augmented platelet aggregation in vitro. Furthermore, the cytoplasmic domain of TLT-1 could also bind ezrin/radixin/moesin family proteins, suggesting its ability to link fibrinogen to the platelet cytoskeleton. Accordingly, platelets of Treml1 -/-mice failed to aggregate efficiently, extending tail-bleeding times. Lipopolysaccharide-treated Treml1 -/-mice developed higher plasma levels of TNF and D-dimers than wild-type mice and were more likely to succumb during challenge. Finally, Treml1 -/-mice were predisposed to hemorrhage associated with localized inflammatory lesions. Taken together, our findings suggest that TLT-1 plays a protective role during inflammation by dampening the inflammatory response and facilitating platelet aggregation at sites of vascular injury. Therefore, therapeutic modulation of TLT-1-mediated effects may provide clinical benefit to patients with hypercoagulatory conditions, including those associated with inflammation.
Objective: to conduct a comparative analysis of the effectiveness of two methods - endoscopic band ligation (EBL) alone and in combination with nonselective beta blockers (NSBB) - used for prevention of variceal bleeding (VB); to evaluate their impact on patient survival in severe ascites during long-term stay on the liver transplant waiting list (LTWL).Materials and methods. A retrospective comparative study of two groups of patients with decompensated liver disease, ascites and varices included in the LTWL, who received EBL (n = 41, group 1) and EBL + NSBB (n = 45, group 2).Results. The groups being compared did not differ in demographics, clinical parameters, MELD and Child-Turcotte-Pugh scores. There were no significant differences in the incidence of severe ascites, particularly diuretic-resistant ascites. The study groups did not differ in the incidence of medium-and large-sized varices. Incidence of bleeding did not differ in both groups. Overall mortality was significantly higher in the EBL + NSBB group than in the EBL group. Patient survival was lower, while mortality was higher in the EBL + NSBB group. The combined therapy group had a significantly higher number of acute kidney injury (AKI) than the EBL group.Conclusion. The compared methods are equivalently effective in preventing VB in patients with decompensated cirrhosis with a prolonged stay on the waiting list. Survival rate is significantly lower, while mortality is significantly higher in the EBL + NSBB group than in the EBL group.
Objective: to determine the threshold MELD scores when prioritizing for liver transplantation. Materials and methods. We conducted a cohort study of 350 patients who were waitlisted for liver transplantation between 2015 and 2020. Results. A logistic regression model was used to identify the independent predictors of liver transplantation waitlist mortality. MELD scores and serum albumin at the time of listing were significant predictors of mortality (p = 0.001 and p = 0.004, respectively). Their predictive values were confirmed using ROC (Receiver Operating Characteristic) analysis. The area under the ROC curve (AUC) was 0.883 [95% confidence interval (CI) 0.828–0.939; p < 0.001] for MELD, and 0.841 [95% CI 0.775–0.907; p < 0.001] for serum albumin. Mortality odds ratio was 3.7778, 95% CI (1.619–7.765) provided that the listing MELD score was ≥25. Mortality odds ratio was 2.979 (95% CI 1.63–5.95) provided that the listing serum albumin concentration was ≤30.1 g/L. With a threshold MELD score of 25, there were significant differences between patient survival when comparing patient cohorts with MELD ≥25 and with MELD ≤25 (Log-rank, p < 0.0001). Conclusion. The MELD model has a high predictive ability in prioritization of waitlisted candidates for liver transplantation. The threshold MELD score and mortality predictors were determined. There were significant differences between patient survival among patient cohorts with MELD ≥25 and with MELD ≤25.
The clinical case of liver revascularization in a recipient using the technique of selective thrombolysis of the hepatic artery and its stenting at the arterial anastomosis site has been reported. The applied technique allowed a quick elimination of thrombosis and stenosis of the arterial anastomosis, providing a long-term effect, preventing more severe consequences for the recipient, and saving the liver graft. The presented case showed that the combined technique of endovascular intervention might be a good alternative to the reconstruction of arterial anastomosis by re-exploration and by liver retransplantation.
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