Developments in Transfusion Medicine: Pulmonary Transfusion Reactions and Novel Blood Cell Labeling Techniques.

Staying updated on advancements in transfusion medicine is crucial, especially in critical care and perioperative setting, where timely and accurate transfusions can be lifesaving therapeutic interventions. This narrative review explores the landscape of transfusion-related adverse events, focusing on pulmonary transfusion reactions such as transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI). TACO and TRALI are the leading causes of transfusion-related morbidity and mortality; however, specific treatments are lacking. Understanding the current incidence, diagnostic criteria, pathogenesis, treatment, and prevention strategies can equip clinicians to help reduce the incidence of these life-threatening complications. The review discusses emerging pathogenic mechanisms, including the possible role of inflammation in TACO and the mechanisms of reverse TRALI and therapeutic targets for TACO and TRALI, emphasizing the need for further research to uncover preventive and treatment modalities. Despite advancements, significant gaps remain in our understanding of what occurs during transfusions, highlighting the necessity for improved monitoring methods. To address this, the review also presents novel blood cell labeling techniques in transfusion medicine used for improving monitoring, quality assessment, and as a consequence, potentially reducing transfusion-related complications. This article aims to provide an update for anesthesiologists, critical care specialists, and transfusion medicine professionals regarding recent advancements and developments in the field of transfusion medicine.

Aging-regulated PNUTS maintains endothelial barrier function via SEMA3B suppression.

Age-related diseases pose great challenges to health care systems worldwide. During aging, endothelial senescence increases the risk for cardiovascular disease. Recently, it was described that Phosphatase 1 Nuclear Targeting Subunit (PNUTS) has a central role in cardiomyocyte aging and homeostasis. Here, we determine the role of PNUTS in endothelial cell aging. We confirm that PNUTS is repressed in senescent endothelial cells (ECs). Moreover, PNUTS silencing elicits several of the hallmarks of endothelial aging: senescence, reduced angiogenesis and loss of barrier function. Findings are validate in vivo using endothelial-specific inducible PNUTS-deficient mice (Cdh5-CreERT2;PNUTSfl/fl), termed PNUTSEC-KO. Two weeks after PNUTS deletion, PNUTSEC-KO mice present severe multiorgan failure and vascular leakage. Transcriptomic analysis of PNUTS-silenced HUVECs and lungs of PNUTSEC-KO mice reveal that the PNUTS-PP1 axis tightly regulates the expression of semaphorin 3B (SEMA3B). Indeed, silencing of SEMA3B completely restores barrier function after PNUTS loss-of-function. These results reveal a pivotal role for PNUTS in endothelial homeostasis through a SEMA3B downstream pathway that provides a potential target against the effects of aging in ECs.

Cardioprotecive Properties of Known Agents in Rat Ischemia-Reperfusion Model Under Clinically Relevant Conditions: Only the NAD Precursor Nicotinamide Riboside Reduces Infarct Size in Presence of Fentanyl, Midazolam and Cangrelor, but Not Propofol.

Background: Cardioprotective strategies against ischemia-reperfusion injury (IRI) that remain effective in the clinical arena need to be developed. Therefore, maintained efficacy of cardioprotective strategies in the presence of drugs routinely used clinically (e.g., opiates, benzodiazepines, P2Y12 antagonist, propofol) need to be identified in preclinical models. Methods: Here, we examined the efficacy of promising cardioprotective compounds [fingolimod (Fingo), empagliflozin (Empa), melatonin (Mela) and nicotinamide riboside (NR)] administered i.v. as bolus before start ischemia. Infarct size as percentage of the area of risk (IS%) was determined following 25 min of left ascending coronary (LAD) ischemia and 2 h of reperfusion in a fentanyl-midazolam anesthetized IRI rat model. Plasma lactate dehydrogenase (LDH) activity at 30 min reperfusion was determined as secondary outcome parameter. Following pilot dose-response experiments of each compound (3 dosages, n = 4-6 animals per dosage), potential cardioprotective drugs at the optimal observed dosage were subsequently tested alone or in combination (n = 6-8 animals per group). The effective treatment was subsequently tested in the presence of a P2Y12 antagonist (cangrelor; n = 6/7) or propofol aesthesia (n = 6 both groups). Results: Pilot studies suggested potential cardioprotective effects for 50 mg/kg NR (p = 0.005) and 500 µg/kg melatonin (p = 0.12), but not for Empa or Fingo. Protection was subsequently tested in a new series of experiments for solvents, NR, Mela and NR+Mela. Results demonstrated that only singular NR was able to reduce IS% (30 ± 14 vs. 60 ± 16%, P = 0.009 vs. control). Mela (63 ± 18%) and NR+Mela (47 ± 15%) were unable to significantly decrease IS%. NR still reduced IS in the presence of cangrelor (51 ± 18 vs. 71 ± 4%, P = 0.016 vs. control), but lost protection in the presence of propofol anesthesia (62 ± 16 vs. 60 ± 14%, P = 0.839 vs. control). LDH activity measurements supported all IS% results. Conclusion: This observational study suggests that NR is a promising cardioprotective agent to target cardiac ischemia-reperfusion injury in clinical conditions employing opioid agonists, benzodiazepines and platelet P2Y12 inhibitors, but not propofol.