The effect of normothermic machine perfusion (NMP) on post-reperfusion hemodynamics and extrahepatic biliary duct histology of donors after cardiac death (DCD) livers after transplantation has not been addressed thoroughly and represented the object of this study. Ten livers (n=5/group) with 60’ of warm ischemia were preserved by cold storage (CS) or sanguineous NMP for 10 hours, and then reperfused for 24 hours with whole blood in an isolated perfusion system to simulate transplantation. In our experiment, arterial and portal venous flows were stable in NMP group during the entire simulated reperfusion, while decreased dramatically in CS group after 16 hours post-reperfusion (P<.05), findings consistent with severe parenchymal injury. Similarly, significant differences existed between CS and NMP group on hepatocellular enzyme release, bile volume produced, and enzyme released into bile (P<.05). On histology CS livers presented with diffuse hepatocyte congestion, necrosis, intraparenchymal hemorrhage, denudated biliary epithelium and submucosal bile duct necrosis, while NMP liver showed very mild injury in liver parenchyma and biliary architecture. Most importantly, Ki67 staining in extrahepatic bile duct showed biliary epithelial regeneration. Our findings advance the knowledge of post-reperfusion events that characterize DCD livers and propose NMP as a beneficial preservation modality able to improve biliary regeneration after a major ischemic event, which may prevent in clinical transplantation the development of ischemic cholangiopathy.
Background
Oral food challenge (OFC) is the criterion standard to assess peanut allergy (PA), but it involves a risk of allergic reactions of unpredictable severity.
Objective
Our aim was to identify biomarkers for risk of severe reactions or low dose threshold during OFC to peanut.
Methods
We assessed Learning Early about Peanut Allergy study, Persistance of Oral Tolerance to Peanut study, and Peanut Allergy Sensitization study participants by administering the basophil activation test (BAT) and the skin prick test (SPT) and measuring the levels of peanut-specific IgE,
Arachis hypogaea
2–specific IgE, and peanut-specific IgG4, and we analyzed the utility of the different biomarkers in relation to PA status, severity, and threshold dose of allergic reactions to peanut during OFC.
Results
When a previously defined optimal cutoff was used, the BAT diagnosed PA with 98% specificity and 75% sensitivity. The BAT identified severe reactions with 97% specificity and 100% sensitivity. The SPT, level of
Arachis hypogaea
2–specific IgE, level of peanut-specific IgE, and IgG4/IgE ratio also had 100% sensitivity but slightly lower specificity (92%, 93%, 90%, and 88%, respectively) to predict severity. Participants with lower thresholds of reactivity had higher basophil activation to peanut
in vitro
. The SPT and the BAT were the best individual predictors of threshold. Multivariate models were superior to individual biomarkers and were used to generate nomograms to calculate the probability of serious adverse events during OFC for individual patients.
Conclusions
The BAT diagnosed PA with high specificity and identified severe reactors and low threshold with high specificity and high sensitivity. The BAT was the best biomarker for severity, surpassed only by the SPT in predicting threshold. Nomograms can help estimate the likelihood of severe reactions and reactions to a low dose of allergen in individual patients with PA.
The utilization of normothermic machine perfusion (NMP) may be an effective strategy to resuscitate livers from donation after circulatory death (DCD). There is no consensus regarding the efficacy of different perfusates on graft and bile duct viability. The aim of this study was to compare, in an NMP porcine DCD model, the preservation potential of three different perfusates. Twenty porcine livers with 60 min of warm ischemia were separated into four preservation groups: cold storage (CS), NMP with Steen solution (Steen; XVIVO Perfusion Inc., Denver, CO), Steen plus red blood cells (RBCs), or whole blood (WB). All livers were preserved for 10 h and reperfused to simulate transplantation for 24 h. During preservation, the NMP with Steen group presented the highest hepatocellular injury. At reperfusion, the CS group had the lowest bile production and the worst hepatocellular injury compared with all other groups, followed by NMP with Steen; the Steen plus RBC and WB groups presented the best functional and hepatocellular injury outcomes, with WB livers showing lower aspartate aminotransferase release and a trend toward better results for most parameters. Based on our results, a perfusate that contains an oxygen carrier is most effective in a model of NMP porcine DCD livers compared with Steen solution. Specifically, WB-perfused livers showed a trend toward better outcomes compared with Steen plus RBCs.
Chronic suppression with oral antibiotics increased the infection-free prosthetic survival rate following surgical treatment for periprosthetic joint infection. Patients who underwent irrigation and debridement with polyethylene exchange and those who had a Staphylococcus aureus infection had the greatest benefit.
There was no clinically significant difference between the pediatric and adult IKDC form scores in adolescents aged 13 to 17 years. This result allows use of whichever form is most practical for long-term tracking of patients. A simple linear equation can convert one form into the other. If the adult questionnaire is used at this age, it can be consistently used during follow-up.
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