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Summary: Psoriasis is a chronic inflammatory skin disease, which affects approximately 2% of the population. Severe psoriasis is often treated by inhibition of a molecule which plays a role in psoriasis, called tumour necrosis factor, by the drug infliximab. Recently, a much cheaper variant (a biosimilar) of infliximab, CT‐P13, produced by a different company, has been introduced. This study from the University of Bergen, Norway, aimed to compare activation of white blood cells from infliximab‐treated patients and healthy controls, and to investigate if switching from original infliximab to biosimilar CT‐P13 affected disease activity and activation of white blood cells (which is linked to psoriasis). Blood samples were collected at three time points from 25 patients who had been diagnosed with severe psoriasis. When taking the first blood sample, all patients were already treated with original infliximab. Then, patients either continued this treatment or switched to CT‐P13. 19 age‐, gender‐ and BMI matched healthy controls were also included. The activation level of selected molecules inside the cells was measured and was found to be higher in psoriasis patients than in healthy controls. This was despite the fact that the psoriasis patients at that time had little skin rash. However, the activation inside the cells declined during continued treatment. No clear differences were detected between the patient groups (original infliximab or CT‐P13) after 12 months. These findings suggest that people with severe psoriasis have on‐going inflammation in the blood, despite having resolved the skin rash by treatment with infliximab. This may be associated with an increased risk of cardiovascular disease. This study also supports that switching from original infliximab to CT‐P13 is safe. [ABSTRACT FROM AUTHOR]

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A letter to the editor in response to an article on platelet factor V levels in moderate to severe congenital factor V deficiency, is presented.

Although treatment for multiple sclerosis (MS) has undergone a revolution in the last decades, at least two important barriers remain: alleviation of innate inflammation driving disease progression and promotion of remyelination and neural regeneration. Mesenchymal stem cells (MSCs) possess immunomodulatory properties and promote remyelination in murine MS models. The main therapeutic mechanism has, however, been attributed to their potent paracrine capacity, and not to in vivo tissue implantation. Studies have demonstrated that exosomes released as part of the cells' secretome effectively encapsulate the beneficial properties of MSCs. These membrane-enclosed nanoparticles contain a variety of proteins and nucleic acids and serve as mediators of intercellular communication. In vitro studies have demonstrated that exosomes from MSCs modulate activated microglia from an inflammatory to an anti-inflammatory phenotype and thereby dampen the innate inflammation. Rodent studies have also demonstrated potent immunomodulation and remyelination with improved outcomes following exosome administration. Thus, exosomes from MSCs may represent a potential cell-free treatment modality to prevent disease progression and promote remyelination in MS. In this narrative review, we summarize the current knowledge of exosomes from MSCs as a potential treatment for MS and discuss the remaining issues before successful translation into clinical trials.

Background: Reticulated platelets (RePLT) are emergency circulating platelets released to contrast peripheral platelet destruction., Aim: We conducted a prospective study to [a] characterize RePLT in cirrhosis; [b] evaluate the association between RePLT and hepatic decompensation/death., Methods: Cirrhosis patients without hepatocellular carcinoma were prospectively recruited and underwent assessment of RePLT and thrombopoietin (TPO). RePLT were evaluated by cytofluorimetry and immuno-fluorescence microscopy. Twenty healthy subjects were included as controls. Patients were followed for 6 months for hepatic decompensation and further decompensation/ACLF., Results: Forty-five patients were included (Child-Pugh [CP] A/B/C 18/11/16). Compared to controls, RePLT in cirrhosis were significantly increased (0.82% vs. 0.05%; p < 0.001) and hyperactivated (4.35% vs. 0.17%; p = 0.004). No correlation was observed between RePLT and CP, platelet count, TPO, MELD score, and C-reactive protein. TPO was lower in cirrhosis than controls (28 pg/mL vs. 52 pg/mL; p = 0.005), decreasing significantly with CP stage. In CP B/C patients (n = 27), RePLT were significantly higher in those who progressed towards further decompensation/ACLF (2.11 [0.56-2.95] vs. 0.69 [0.02-1.22]; p < 0.01). A proportion of RePLT >2% accurately identified high-risk patients (AUROC 0.818; 95%CI: 0.639-0.997; sensitivity 94%, specificity 73%)., Conclusion: RePLT in cirrhosis are increased and hyper-activated. In decompensated patients, higher RePLT appear to be associated with worse outcomes., Competing Interests: Conflict of interest None declared., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Extracellular vesicles (EVs) modulate inflammation, coagulation and vascular homeostasis in decompensated cirrhosis., Aim: To characterize the profile of plasmatic EVs in patients with decompensated cirrhosis and bacterial infections and evaluate the association between EVs and the development of hemostatic complications., Methods: We measured the levels of EVs using high-sensitivity flow cytometry and phospholipid-dependent clotting time (PPL) in a prospective cohort of hospitalized patients with acutely decompensated cirrhosis with versus without bacterial infections. A separate cohort of patients with bacterial infections without cirrhosis was also enrolled. We measured endothelium-, tissue factor (TF)-bearing, platelet- and leukocyte-derived EVs. In patients with infections, EVs were reassessed upon resolution of infection. Bleeding and thrombotic complications were recorded during 1-year follow-up., Results: Eighty patients with decompensated cirrhosis were recruited (40 each with and without bacterial infections). Electron microscopy confirmed the presence of plasma EVs. Despite no difference in total EVs and PPL, patients with cirrhosis and infection had significantly higher TF + EVs, P-Selectin + EVs (activated platelet-derived), CD14 + EVs (monocyte/macrophages derived) and CD14 + TF + EVs versus those with cirrhosis without infection. Upon infection resolution, levels of these EVs returned to those without infection. Patients with infections showed a significant association between reduced P-Selectin + EVs and bleeding complications (HR 8.0 [95%CI 1.3-48.1]), whereas high levels of leukocyte-derived EVs (CD45 + ) and CD14 + EVs were significantly associated with thrombotic complications (HR 16.4 [95%CI 1.7-160] and 10.9 [95%CI 1.13-106], respectively). Results were confirmed in a validation cohort., Conclusion: Bacterial infections are associated with particular alterations of plasma EVs profile in decompensated cirrhosis. Bacterial infections trigger the release of EVs originating from various cell types, which may tip the precarious hemostatic balance of patients with acutely decompensated cirrhosis towards hyper- or hypocoagulability., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Mass cytometry by time-of-flight (CyTOF) is an emerging technology allowing for in-depth characterization of cellular heterogeneity in cancer and other diseases. Unfortunately, high-dimensional analyses of CyTOF data remain quite demanding. Here, we deploy a bioinformatics framework that tackles two fundamental problems in CyTOF analyses namely (1) automated annotation of cell populations guided by a reference dataset and (2) systematic utilization of single-cell data for effective patient stratification. By applying this framework on several publicly available datasets, we demonstrate that the Scaffold approach achieves good trade-off between sensitivity and specificity for automated cell type annotation. Additionally, a case study focusing on a cohort of 43 leukemia patients reported salient interactions between signaling proteins that are sufficient to predict short-term survival at time of diagnosis using the XGBoost algorithm. Our work introduces an automated and versatile analysis framework for CyTOF data with many applications in future precision medicine projects., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Introduction: Factor XI (FXI) is associated with thrombosis in patients without liver disease, but it alterations and prognostic value in cirrhosis are uncertain., Patients and Methods: We studied a prospective cohort of cirrhosis patients determining FXI and its association with portal vein thrombosis (PVT), bleeding, and hepatic decompensation/ACLF during 1-year follow-up. Odds ratios (OR) and 95 % CIs were calculated using logistic regression., Results: We included 183 patients (Child-Pugh [CP] A/B/C 57/59/57). FXI was reduced in cirrhosis, decreasing with CP stage (78 % [66-94] vs. 58 % [44-78] vs. 41 % [30-52] in CP A, B, and C, respectively; p < 0.001). FXI was correlated with MELD score (rho: -0.6, p < 0.001), INR (rho: -0.6, p < 0.001), and platelet count (rho: 0.4, p < 0.001). Sixteen patients (8.7 %) experienced PVT, which only predictor was baseline platelet count (OR: 0.94; CI95 %: 0.91-0.97, p < 0.001). Bleeding occurred in 7 patients (3.8 %). Cirrhosis severity, platelet count, fibrinogen, and FXI (60% vs. 78 %; p = 0.2) were comparable between bleeding and non-bleeding individuals. Finally, no association was found between FXI and hepatic decompensation/ACLF, which were predicted by lower albumin and platelet count, respectively., Conclusion: FXI seems not to be responsible for thrombosis and cirrhosis progression. The lack of association between low FXI and bleeding events, however, indirectly opens to future studies evaluating FXI inhibitors in cirrhosis., Competing Interests: Declaration of competing interest We don't have any conflict of interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)