RESUMEN
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.
Asunto(s)
Enfermedades del Sistema Inmune , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neutrófilos , Factores de RiesgoRESUMEN
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.
Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Antiinflamatorios/administración & dosificación , Anticolesterolemiantes/administración & dosificación , Enfermedades de las Arterias Carótidas/tratamiento farmacológico , Ezetimiba/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Placa Aterosclerótica , Rosuvastatina Cálcica/administración & dosificación , Síndrome Coronario Agudo/diagnóstico por imagen , Anciano , Antiinflamatorios/efectos adversos , Anticolesterolemiantes/efectos adversos , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Combinación de Medicamentos , Ezetimiba/efectos adversos , Femenino , Fluorodesoxiglucosa F18/administración & dosificación , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Estudios Prospectivos , Radiofármacos/administración & dosificación , Rosuvastatina Cálcica/efectos adversos , Seúl , Factores de Tiempo , Resultado del TratamientoRESUMEN
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.