Aortic rupture following acute aortitis in a patient with head and neck carcinoma treated with nivolumab: a rare but severe immune-related adverse event.

INTRODUCTION: Immune-related adverse events (irAEs) due to immune checkpoint inhibitors may lead to discontinuation and treatment-related death. Acute aortitis is a rare but severe irAE. CASE PRESENTATION: A 67-year-old man with recurrent lower gingival carcinoma received nivolumab therapy. Twenty-three months later, he experienced chest compression, which resulted in syncope. Following a whole-body computed tomography (CT) scanning, which revealed diffuse thickening of the aorta, and systemic assessments of the causes of aortitis, he was diagnosed with acute aortitis due to irAE. Nivolumab discontinuation and oral steroids improved CT findings. However, 11 months after nivolumab discontinuation, he developed an aortic aneurysmal rupture. Endovascular aortic repair rescued him. A durable anti-cancer response was still observed 4 months after the aortic rupture. CONCLUSION: Although severe irAE, such as acute aortitis, occurred, the patient may still achieve a durable response. A broad examination and prompt treatment of irAE can help improve the patient's survival.

Immobilization of Thermoplasma acidophilum Glucose Dehydrogenase and Isocitrate Dehydrogenase Through Enzyme-Inorganic Hybrid Nanocrystal Formation.

The development of green catalysts, specifically biocatalysts, is crucial for building a sustainable society. To enhance the versatility of biocatalysts, the immobilization of enzymes plays a vital role as it improves their recyclability and robustness. As target enzymes to immobilize, glucose dehydrogenases and carboxylases are particularly important among various kinds of enzymes due to their involvement in two significant reactions: regeneration of the reduced form of coenzyme required for various reactions, and carboxylation reactions utilizing CO2 as a substrate, respectively. In this study, we immobilized Thermoplasma acidophilum glucose dehydrogenase (TaGDH) and T. acidophilum isocitrate dehydrogenase (TaIDH) using a previously reported method involving the formation of enzyme-inorganic hybrid nanocrystals, in the course of our continuing study focusing on carboxylation catalyzed by the free form of TaGDH and TaIDH. Subsequently, we investigated the properties of the resulting immobilized enzymes. Our results indicate the successful immobilization of TaGDH and TaIDH through the formation of hybrid nanocrystals utilizing Mn2+. The immobilization process enhanced TaIDH activity, up to 211%, while TaGDH retained 71% of its original activity. Notably, the immobilized TaGDH exhibited higher activity at temperatures exceeding 87 °C than the free TaGDH. Moreover, these immobilized enzymes could be recycled. Finally, we successfully utilized the immobilized enzymes for the carboxylation of 2-ketoglutaric acid under 1 MPa CO2. In conclusion, this study represents the first immobilization of TaGDH and TaIDH using the hybrid nanocrystal forming method. Furthermore, we achieved significant activity enhancement of TaIDH through immobilization and demonstrated the recyclability of the immobilized enzymes.