Flying under the radar: treatment of refractory hyperglycemia.

UNLABELLED: Clinicians are often presented with the scenario of what to do when one medication in a drug class has failed a therapeutic trial on a patient. We encountered a patient who developed profound resistance to glargine, aspart and regular insulin, but had a rapid and sustained response to detemir. The mechanism of the increased sensitivity to detemir is unclear, but may be related to an additional carbon chain on detemir shielding it from an antibody response. This case highlights the profound impact that subtle differences in molecular structure can have on biological activity and thus patient outcomes. LEARNING POINTS: Subtle differences in molecular structure can have a profound impact on biological activity, and thus patient outcomes.Poor outcomes with one medication in a drug class should not be used to rule out the efficacy of all related medications.Detemir has been shown to be less immunogenic than other insulins, and should be considered in patients with insulin resistance.

Normothermic acellular ex vivo liver perfusion reduces liver and bile duct injury of pig livers retrieved after cardiac death.

We compared cold static with acellular normothermic ex vivo liver perfusion (NEVLP) as a novel preservation technique in a pig model of DCD liver injury. DCD livers (60 min warm ischemia) were cold stored for 4 h, or treated with 4 h cold storage plus 8 h NEVLP. First, the livers were reperfused with diluted blood as a model of transplantation. Liver injury was determined by ALT, oxygen extraction, histology, bile content analysis and hepatic artery (HA) angiography. Second, AST levels and bile production were assessed after DCD liver transplantation. Cold stored versus NEVLP grafts had higher ALT levels (350 ± 125 vs. 55 ± 35 U/L; p < 0.0001), decreased oxygen extraction (250 ± 65 mmHg vs. 410 ± 58 mmHg, p < 0.01) and increased hepatocyte necrosis (45% vs. 10%, p = 0.01). Levels of bilirubin, phospholipids and bile salts were fivefold decreased, while LDH was sixfold higher in cold stored versus NEVLP grafts. HA perfusion was decreased (twofold), and bile duct necrosis was increased (100% vs. 5%, p < 0.0001) in cold stored versus NEVLP livers. Following transplantation, mean serum AST level was higher in the cold stored versus NEVLP group (1809 ± 205 U/L vs. 524 ± 187 U/L, p < 0.05), with similar bile production (2.5 ± 1.2 cc/h vs. 2.8 ± 1.4 cc/h; p = 0.2). NEVLP improved HA perfusion and decreased markers of liver duct injury in DCD grafts.