Integrative analysis of risk factors for immune-related adverse events of checkpoint blockade therapy in cancer.

Immune-related adverse events (irAEs) induced by checkpoint inhibitors involve a multitude of different risk factors. Here, to interrogate the multifaceted underlying mechanisms, we compiled germline exomes and blood transcriptomes with clinical data, before and after checkpoint inhibitor treatment, from 672 patients with cancer. Overall, irAE samples showed a substantially lower contribution of neutrophils in terms of baseline and on-therapy cell counts and gene expression markers related to neutrophil function. Allelic variation of HLA-B correlated with overall irAE risk. Analysis of germline coding variants identified a nonsense mutation in an immunoglobulin superfamily protein, TMEM162. In our cohort and the Cancer Genome Atlas (TCGA) data, TMEM162 alteration was associated with higher peripheral and tumor-infiltrating B cell counts and suppression of regulatory T cells in response to therapy. We developed machine learning models for irAE prediction, validated using additional data from 169 patients. Our results provide valuable insights into risk factors of irAE and their clinical utility.

Comparison of High-Dose Rosuvastatin Versus Low-Dose Rosuvastatin Plus Ezetimibe on Carotid Atherosclerotic Plaque Inflammation in Patients with Acute Coronary Syndrome.

We compared the effects of ezetimibe/rosuvastatin 10/5 mg versus rosuvastatin 20 mg on carotid atherosclerotic plaque inflammation measured by 18FDG PET/CT. Fifty patients with acute coronary syndrome (ACS) were randomly assigned to the ezetimibe/rosuvastatin 10/5 mg and rosuvastatin 20 mg groups. The primary outcome was the percent change in the target-to-background ratio (TBR) of the index vessel in the most diseased segment (MDS), as assessed by 18FDG PET/CT at baseline and at 6 months. Forty-eight patients completed follow-up PET/CT. MDS TBR was - 6.2 ± 13.9% for patients in the ezetimibe/rosuvastatin group and - 10.8 ± 17.7% for those in the rosuvastatin group (difference, 4.6 percentage points; upper limitation of one-sided confidence interval = 13.8; p = 0.60 for noninferiority). In conclusion, combination therapy with ezetimibe 10 mg and rosuvastatin 5 mg compared with rosuvastatin 20 mg did not meet the criterion for non-inferiority for primary outcome, and the present study was not conclusive on whether the former was non-inferior to the latter. Graphical Abstract.

Altered Biodistribution of 99mTc-DPD on Bone Scan After Intravenous Iron Supplement.

We report a case with altered biodistribution of 99mTc-dicarboxypropane diphosphonate (99mTc-DPD) on whole body bone scan after intravenous iron supplement therapy. A 47-year-old male patient who had recently been detected with a hepatic mass suggestive of hepatocellular carcinoma underwent bone scan as staging work-up before surgery. Bone scan images at 3 h after injection of 99mTc-DPD demonstrated unusually increased blood pool activities in the heart, liver, and spleen with usual skeletal uptakes. The patient had been treated for severe anemia from hemorrhoid with two intravenous administration of ferric hydroxide carboxymaltose complex at approximately 22 h and 2 h prior to the 99mTc-DPD injection, which we consider as the most probable cause of altered biodistribution of 99mTc-DPD.