Potential application of mesenchymal stromal cells as a new therapeutic approach in acute respiratory distress syndrome and pulmonary fibrosis.

While the COVID-19 outbreak and its complications are still under investigation, post-inflammatory pulmonary fibrosis (PF) has already been described as a long-term sequela of acute respiratory distress syndrome (ARDS) secondary to SARS-CoV2 infection. However, therapeutical strategies for patients with ARDS and PF are still limited and do not significantly extend lifespan. So far, lung transplantation remains the only definitive treatment for end-stage PF. Over the last years, numerous preclinical and clinical studies have shown that allogeneic mesenchymal stromal cells (MSCs) might represent a promising therapeutical approach in several lung disorders, and their potential for ARDS treatment and PF prevention has been investigated during the COVID-19 pandemic. From April 2020 to April 2022, we treated six adult patients with moderate COVID-19-related ARDS in a late proliferative stage with up to two same-dose infusions of third-party allogeneic bone marrow-derived MSCs (BM-MSCs), administered intravenously 15 days apart. No major adverse events were registered. Four patients completed the treatment and reached ICU discharge, while two received only one dose of MSCs due to multiorgan dysfunction syndrome (MODS) and subsequent death. All four survivors showed improved gas exchanges (PaO2/FiO2 ratio > 200), contrary to the others. Furthermore, LDH trends after MSCs significantly differed between survivors and the deceased. Although further investigations and shared protocols are still needed, the safety of MSC therapy has been recurrently shown, and its potential in treating ARDS and preventing PF might represent a new therapeutic strategy.

Left atrium veno-arterial extra corporeal membrane oxygenation as temporary mechanical support for cardiogenic shock: A case report.

BACKGROUND: Veno-arterial extra corporeal membrane oxygenation (VA-ECMO) support is commonly complicated with left ventricle (LV) distension in patients with cardiogenic shock. We resolved this problem by transeptally converting VA-ECMO to left atrium veno-arterial (LAVA)-ECMO that functioned as a temporary paracorporeal left ventricular assist device to resolve LV distension. In our case LAVA-ECMO was also functioning as a bridge-to-transplant device, a technique that has been scarcely reported in the literature. CASE SUMMARY: A 65 year-old man suffered from acute myocardial injury that required percutaneous stents. Less than two weeks later, noncompliance to antiplatelet therapy led to stent thrombosis, cardiogenic shock, and cardiac arrest. Femoro-femoral VA-ECMO support was started, and the patient underwent a second coronary angiography with re-stenting and intra-aortic balloon pump placement. The VA-ECMO support was complicated by left ventricular distension which we resolved via LAVA-ECMO. Unfortunately, episodes of bleeding and sepsis complicated the clinical picture and the patient passed away 27 d after initiating VA-ECMO. CONCLUSION: This clinical case demonstrates that LAVA-ECMO is a viable strategy to unload the LV without another invasive percutaneous or surgical procedure. We also demonstrate that LAVA-ECMO can also be weaned to a left ventricular assist device system. A benefit of this technique is that the procedure is potentially reversible, should the patient require VA-ECMO support again. A transeptal LV venting approach like LAVA-ECMO may be indicated over ImpellaTM in cases where less LV unloading is required and where a restrictive myocardium could cause LV suctioning. Left ventricular over-distention is a well-known complication of peripheral VA-ECMO in cardiogenic shock and LAVA ECMO through transeptal cannulation offers a novel and safe approach for treating LV overloading, without the need of an additional percutaneous access.

Blood Coagulation and Beyond: Position Paper from the Fourth Maastricht Consensus Conference on Thrombosis.

The Fourth Maastricht Consensus Conference on Thrombosis included the following themes. Theme 1: The "coagulome" as a critical driver of cardiovascular disease. Blood coagulation proteins also play divergent roles in biology and pathophysiology, related to specific organs, including brain, heart, bone marrow, and kidney. Four investigators shared their views on these organ-specific topics. Theme 2: Novel mechanisms of thrombosis. Mechanisms linking factor XII to fibrin, including their structural and physical properties, contribute to thrombosis, which is also affected by variation in microbiome status. Virus infection-associated coagulopathies perturb the hemostatic balance resulting in thrombosis and/or bleeding. Theme 3: How to limit bleeding risks: insights from translational studies. This theme included state-of-the-art methodology for exploring the contribution of genetic determinants of a bleeding diathesis; determination of polymorphisms in genes that control the rate of metabolism by the liver of P2Y12 inhibitors, to improve safety of antithrombotic therapy. Novel reversal agents for direct oral anticoagulants are discussed. Theme 4: Hemostasis in extracorporeal systems: the value and limitations of ex vivo models. Perfusion flow chamber and nanotechnology developments are developed for studying bleeding and thrombosis tendencies. Vascularized organoids are utilized for disease modeling and drug development studies. Strategies for tackling extracorporeal membrane oxygenation-associated coagulopathy are discussed. Theme 5: Clinical dilemmas in thrombosis and antithrombotic management. Plenary presentations addressed controversial areas, i.e., thrombophilia testing, thrombosis risk assessment in hemophilia, novel antiplatelet strategies, and clinically tested factor XI(a) inhibitors, both possibly with reduced bleeding risk. Finally, COVID-19-associated coagulopathy is revisited.

A retrospective analysis of the hemolysis occurrence during extracorporeal membrane oxygenation in a single center.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO)-associated hemolysis still represents a serious complication. The present study aimed to investigate those predictive factors, such as flow rates, the use of anticoagulants, and circuit connected dialysis, that might play a pivotal role in hemolysis in adult patients. METHODS: This is a retrospective single-center case series of 35 consecutive adult patients undergoing veno-venous ECMO support at our center between April 2014 and February 2020. Daily plasma-free hemoglobin (pfHb) and haptoglobin (Hpt) levels were chosen as hemolysis markers and they were analyzed along with patients' characteristics, daily laboratory findings, and corresponding ECMO system variables, as well as continuous renal replacement therapy (CRRT) when administered, looking for factors influencing their trends over time. RESULTS: Among the many settings related to the ECMO support, the presence of CRRT connected to the ECMO circuit has been found associated with both higher daily pfHb levels and lower Hpt levels. After correction for potential confounders, hemolysis was ascribable to circuit-related variables, in particular the membrane oxygenation dead space was associated with an Hpt reduction (B = -215.307, p = 0.004). Moreover, a reduction of ECMO blood flow by 1 L/min has been associated with a daily Hpt consumption of 93.371 mg/dL (p = 0.001). CONCLUSIONS: Technical-induced hemolysis during ECMO should be monitored not only when suspected but also during quotidian management and check-ups. While considering the clinical complexity of patients on ECMO support, clinicians should not only be aware of and anticipate possible circuitry malfunctions or inadequate flow settings, but they should also take into account the effects of an ECMO circuit-connected CRRT, as an equally important key factor triggering hemolysis.