Frequently used LAs at traditional concentrations are toxic to and can injure the peripheral nerve. Any combination of motor and/or sensory sequelae may result due to the varying fascicular topography of a nerve.
Significance
Intravital imaging, oxidative lipidomics, and a transplant model were used to define mechanisms that regulate neutrophil recruitment into lungs during ischemia reperfusion injury, a clinically relevant form of sterile inflammation. We found that early neutrophil-mediated damage is largely confined to the subpleural vasculature, a process that is orchestrated by a spatially restricted distribution of nonclassical monocytes that produce chemokines following necroptosis of pulmonary cells. Neutrophils disrupt the integrity of subpleural capillaries, which is associated with impaired lung function. Neutrophil-mediated vascular leakage is dependent on TLR4 expression on vascular endothelium, NOX4 signaling, and formation of neutrophil extracellular traps. Our research provides insights into mechanisms that regulate neutrophil recruitment during sterile lung inflammation and lays the foundation for developing new therapies.
Antibody-mediated rejection (AMR) has been identified as a significant form of acute allograft dysfunction in lung transplantation. The development of consensus diagnostic criteria has created a uniform definition of AMR; however, significant limitations of these criteria have been identified. Treatment modalities for AMR have been adapted from other areas of medicine and data on the effectiveness of these therapies in AMR are limited. AMR is often refractory to these therapies, and graft failure and death are common. AMR is associated with increased rates of chronic lung allograft dysfunction (CLAD) and poor long-term survival. In this review, we discuss the history of AMR and describe known mechanisms, application of the consensus diagnostic criteria, data for current treatment strategies, and long-term outcomes. In addition, we highlight current gaps in knowledge, ongoing research, and future directions to address these gaps. Promising diagnostic techniques are actively being investigated that may allow for early detection and treatment of AMR. We conclude that further investigation is required to identify and define chronic and subclinical AMR, and head-to-head comparisons of currently used treatment protocols are necessary to identify an optimal treatment approach. Gaps in knowledge regarding the epidemiology, mechanisms, diagnosis, and treatment of AMR continue to exist and future research should focus on these aspects.
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