Pyrimidine depletion enhances targeted and immune therapy combinations in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a fatal disease characterized by the accumulation of undifferentiated myeloblasts, and agents that promote differentiation have been effective in this disease but are not curative. Dihydroorotate dehydrogenase inhibitors (DHODHi) have the ability to promote AML differentiation and target aberrant malignant myelopoiesis. We introduce HOSU-53, a DHODHi with significant monotherapy activity, which is further enhanced when combined with other standard-of-care therapeutics. We further discovered that DHODHi modulated surface expression of CD38 and CD47, prompting the evaluation of HOSU-53 combined with anti-CD38 and anti-CD47 therapies, where we identified a compelling curative potential in an aggressive AML model with CD47 targeting. Finally, we explored using plasma dihydroorotate (DHO) levels to monitor HOSU-53 safety and found that the level of DHO accumulation could predict HOSU-53 intolerability, suggesting the clinical use of plasma DHO to determine safe DHODHi doses. Collectively, our data support the clinical translation of HOSU-53 in AML, particularly to augment immune therapies. Potent DHODHi to date have been limited by their therapeutic index; however, we introduce pharmacodynamic monitoring to predict tolerability while preserving antitumor activity. We additionally suggest that DHODHi is effective at lower doses with select immune therapies, widening the therapeutic index.

Corticosteroid-Induced Psychosis: A Report of Three Cases.

Corticosteroids are commonly used for pain management and inflammatory conditions but can cause neuropsychiatric complications ranging from anxiety to severe mood and psychotic symptoms. These complications can occur shortly after steroid treatment begins or at any point during therapy, and even after treatment has stopped. We present three cases of corticosteroid-induced psychosis in patients being treated for pain. The mechanism behind these complications is not fully understood, but stress on the hypothalamic-pituitary-adrenal (HPA) axis is thought to play a role. Clinicians should be cautious and regularly evaluate patients to minimize the risk of complications. More research is needed to understand the underlying pathophysiology.

Management of Psychosis Associated with Graves' Disease: A Rare Case Report.

Graves' disease is an autoimmune disease in which patients can rarely present with psychiatric symptoms. In these patients, detailed history with psychiatric evaluation using a mental status examination is crucial for the early identification of psychiatric manifestations. Early intervention with medical and surgical therapy can help effectively treat the condition and prevent adverse outcomes such as catatonia. We reported the case of a 25-year-old African American female with Graves' disease who had significant stressors and presented with auditory hallucinations. She was diagnosed with psychosis secondary to Graves' disease and was managed medically using antithyroid drugs and beta-blockers. On failure of medical therapy, a surgical approach was employed. The patient was managed successfully, and her condition improved. Our case highlights that the importance of early intervention in these cases can lead to successful outcomes in patients with Graves' disease-induced psychosis.