Postmortem normothermic regional perfusion (NRP) is a rising preservation strategy in controlled donation after circulatory determination of death (cDCD). Herein, we present results for cDCD liver transplants performed in Spain 2012–2019, with outcomes evaluated through December 31, 2020. Results were analyzed retrospectively and according to recovery technique (abdominal NRP [A‐NRP] or standard rapid recovery [SRR]). During the study period, 545 cDCD liver transplants were performed with A‐NRP and 258 with SRR. Median donor age was 59 years (interquartile range 49–67 years). Adjusted risk estimates were improved with A‐NRP for overall biliary complications (OR 0.300, 95% CI 0.197–0.459, p < .001), ischemic type biliary lesions (OR 0.112, 95% CI 0.042–0.299, p < .001), graft loss (HR 0.371, 95% CI 0.267–0.516, p < .001), and patient death (HR 0.540, 95% CI 0.373–0.781, p = .001). Cold ischemia time (HR 1.004, 95% CI 1.001–1.007, p = .021) and re‐transplantation indication (HR 9.552, 95% CI 3.519–25.930, p < .001) were significant independent predictors for graft loss among cDCD livers with A‐NRP. While use of A‐NRP helps overcome traditional limitations in cDCD liver transplantation, opportunity for improvement remains for cases with prolonged cold ischemia and/or technically complex recipients, indicating a potential role for complimentary ex situ perfusion preservation techniques.
Leukocytes and endothelial cells frequently cooperate to resolve inflammatory events. In most cases, these interactions are transient in nature and triggered by immunological insults. Here, we report that, in areas of disturbed blood flow, aortic endothelial cells permanently and intimately associate with a population of specialized macrophages. These macrophages are recruited at birth from the closing ductus arteriosus and share the luminal surface with the endothelium, becoming interwoven in the tunica intima. Anatomical changes that affect hemodynamics, such as in patent ductus arteriosus, alter macrophage seeding to coincide with regions of disturbed flow. Aortic resident macrophages expand in situ via direct cell renewal. Induced depletion of intimal macrophages leads to thrombin-mediated endothelial cell contraction, progressive fibrin accumulation and formation of microthrombi that, once dislodged, cause blockade of vessels in several organs. Together the findings reveal that intravascular resident macrophages are essential to regulate thrombin activity and clear fibrin deposits in regions of disturbed blood flow.
Evolutionarily conserved, “natural” (n)IgM is broadly reactive to both self and foreign antigens. Its selective deficiency leads to increases in autoimmune diseases and infections. In mice, nIgM is secreted independent of microbial exposure to bone marrow (BM) and spleen B-1 cell–derived plasma cells (B-1PC), generating the majority of nIgM, or by B-1 cells that remain non-terminally differentiated (B-1sec). Thus, it has been assumed that the nIgM repertoire is broadly reflective of the repertoire of body cavity B-1 cells. Studies here reveal, however, that B-1PC generate a distinct, oligoclonal nIgM repertoire, characterized by short CDR3 variable immunoglobulin heavy chain regions, 7–8 amino acids in length, some public, many arising from convergent rearrangements, while specificities previously associated with nIgM were generated by a population of IgM-secreting B-1 (B-1sec). BM, but not spleen B-1PC, or B-1sec also required the presence of TCRαβ CD4 T cells for their development from fetal precursors. Together, the studies identify important previously unknown characteristics of the nIgM pool.
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