We herein report the cytokine expression at different stages for three patients who developed cardiac complications after immune checkpoint inhibitor (ICI) therapy. Case 1 with biopsy-proven myocarditis showed increased levels of interleukin (IL)-8, monocyte chemotactic and activating factor, and granulocyte macrophage colony-stimulating factor (GM-CSF) when he developed Takotsubo cardiomyopathy. Case 2 with subclinical myocarditis showed predominant activation of IL-8 during the progressive clinical course. Case 3 with cytokine-releasing syndrome showed substantial activations of IL-6, IL-8, GM-CSF, and interferon-γ. Our data suggest the development of unique cytokine activation in individual patients with cardiac complications after ICI therapy.
Brand advertising is a type of advertising that aims at increasing the awareness of companies or products. This type of advertising is well studied in economic, marketing, and psychological literature; however, there are no studies in the area of computational advertising because the effect of such advertising is difficult to observe.
In this study, we consider a real-time biding strategy for brand advertising. Here, our objective to maximizes the total number of users who remember the advertisement, averaged over the time. For this objective, we first introduce a new objective function that captures the cognitive psychological properties of memory retention, and can be optimized efficiently in the online setting (i.e., it is a monotone submodular function). Then, we propose an algorithm for the bid optimization problem with the proposed objective function under the second price mechanism by reducing the problem to the online knapsack constrained monotone submodular maximization problem. We evaluated the proposed objective function and the algorithm in a real-world data collected from our system and a questionnaire survey.
We observed that our objective function is reasonable in real-world setting, and the proposed algorithm outperformed the baseline online algorithms.
We describe the case of a patient with neuroendocrine ethmoid sinus carcinoma, who exhibited markedly elevated levels of serum cardiac troponin-T and creatine kinase (CK)-MB isoenzyme without any symptom after the administration of nivolumab, immune checkpoint inhibitor. The repeated 12-leads-electrocardiogram did not show any changes in the ST-T segments or arrhythmias. The echocardiogram showed normal ranges of left ventricular contraction in the clinical course. Cardiac magnetic resonance imaging showed minimal myocardial edema and inflammation. Blood clots in the metastatic lesion of bone marrow aspirates exhibited positive staining for cardiac troponin-T and CK-MB in the cytoplasm and nucleoplasm of neoplastic cells. Although we did not perform a second cardiac magnetic resonance imaging and autopsy, we postulate that the attack of the neoplastic cells by the immune checkpoint inhibitor or the secretion from neoplastic cell-derived extracellular vesicles may have exacerbated the increase in concentrations of these molecules in the blood. Our case should warrant consideration a false-positive value of cardiac troponin-T and CK-MB can be obtained in cases with malignancy.
A 51-year-old man with nasopharyngeal carcinoma underwent chemoradiotherapy with cisplatin and 5-fluorouracil, followed by a left cervical lymphadenectomy. Distant metastatic disease was excluded using fluoro-deoxyglucose positron emission tomography. Seven months later, bone marrow metastasis and disseminated intravascular coagulation were diagnosed. The patient received weekly paclitaxel therapy and maintained a good performance status for seven months. During the treatment period, the patient developed no severe organ toxicity except for neutropenia. Weekly paclitaxel may therefore be considered as the treatment of choice in patients with advanced or recurrent nasopharyngeal carcinoma with bone marrow metastasis.
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