Challenge and Outcome for the Prostate Squamous Cell Carcinoma Which Developed 8 Years after Low-Dose-Rate Brachytherapy Approached by a Combined Multimodal Treatment with High-Dose-Rate Interstitial Brachytherapy, External Beam Radiation Therapy, and Chemotherapy

Prostate squamous cell carcinoma (pSCC) rarely develops as a secondary cancer after treatment with low-dose-rate brachytherapy (LDR-BT). There is no established effective treatment for the disease condition. Herein, we present a 78-year-old man who developed pSCC 8 years after LDR-BT. He was subsequently selected to receive a combined multimodal treatment with high-dose-rate interstitial brachytherapy (HDR-ISBT), external beam radiation therapy, and chemotherapy for his pSCC. Eleven months later, he displayed no biochemical failure nor clinical radiographic recurrence. However, MRI detected a newly developed prostatic-rectal fistula (grade 4), and a colostomy was performed to relieve pain and inflammation. To our knowledge, this is the first report to perform a combined multimodal treatment with HDR-ISBT for pSCC suspected as a secondary cancer due to LDR-BT

Potential application of measuring serum infliximab levels in rheumatoid arthritis management: A retrospective study based on KURAMA cohort data

Infliximab (IFX) therapy has considerably improved the treatment of rheumatoid arthritis (RA). However, some patients still do not respond adequately to IFX therapy, or the efficacy of the treatment diminishes over time. Although previous studies have reported a relationship between serum IFX levels and therapeutic efficacy, the potential applications of IFX therapeutic drug monitoring (TDM) in clinical practice remain unclear. The purpose of this study was to investigate the potential applications of IFX TDM by analyzing a Japanese cohort database. Data were collected retrospectively from the Kyoto University Rheumatoid Arthritis Management Alliance cohort between January 1, 2011, and December 31, 2018. Serum IFX levels were measured using a liquid chromatography-tandem mass spectrometer. Out of the 311 RA patients that used IFX, 41 were eligible for the analysis. Serum IFX levels were significantly higher in responders than in non-responders. An optimal cut-off value was determined to be 0.32 μg/mL based on a receiver operating characteristic curve. At the IFX measurement point, a better therapeutic response was observed in the high IFX group (n = 32) than in the low IFX group (n = 9). Conversely, at the maximum effect point, when DAS28-ESR was the lowest between IFX introduction and measurement points, there were no differences in responder proportions between the low and high IFX groups. IFX primary ineffectiveness could be avoided with appropriate dose escalation without blood concentration measurement in clinical practice. In conclusion, IFX TDM could facilitate the identification of secondary non-responders and in turn, proper IFX use

Infliximab Treatment Persistence among Japanese Patients with Chronic Inflammatory Diseases: A Retrospective Japanese Claims Data Study

Infliximab (IFX) has contributed to the treatment of several chronic inflammatory diseases, including Crohn's disease (CD), ulcerative colitis (UC), psoriasis (Pso), and rheumatoid arthritis (RA). However, the loss of response in some patients with long-term IFX therapy has been a major problem. Randomized controlled trials (RCTs) are limited in their short duration and lack of generalizability to the real-world population. We aimed to describe the persistence rates of IFX therapy to estimate its long-term effectiveness in clinical practice. Claims data from the Japan Medical Data Center database from January 2005 to June 2017 were used. The study population was identified based on the International Classification of Diseases, 10th Revision and the Anatomical Therapeutic Chemical Classification System. The 5-year persistence rates of IFX therapy were estimated using the Kaplan-Meier method. Overall, 281, 235, 41, and 222 patients with CD, UC, Pso, and RA, respectively, were selected. The 5-year persistence rates for IFX claims were 62.9, 38.9, 22.1, and 28.1% in patients with CD, UC, Pso, and RA, respectively. Patients with CD and UC administered IFX beyond the median dose had higher persistence rates. In patients with RA, female sex and no prior use of other biologics were associated with longer persistence. In conclusion, IFX persistence rates differed across chronic inflammatory diseases, which did not correspond to the results of the major RCTs. Factors associated with longer IFX persistence were identified in each disease group. Our findings may provide useful information to facilitate the proper use of IFX

The Limits of Words: Expanding a Word-Based Emotion Analysis System with Multiple Emotion Dictionaries and the Automatic Extraction of Emotive Expressions

Wide adoption of social media has caused an explosion of information stored online, with the majority of that information containing subjective, opinionated, and emotional content produced daily by users. The field of emotion analysis has helped effectively process such human emotional expressions expressed in daily social media posts. Unfortunately, one of the greatest limitations of popular word-based emotion analysis systems has been the limited emotion vocabulary. This paper presents an attempt to extensively expand one such word-based emotion analysis system by integrating multiple emotion dictionaries and implementing an automatic extraction mechanism for emotive expressions. We first leverage diverse emotive expression dictionaries to expand the emotion lexicon of the system. To do that, we solve numerous problems with the integration of various dictionaries collected using different standards. We demonstrate the performance improvement of the system with improved accuracy and granularity of emotion classification. Furthermore, our automatic extraction mechanism facilitates the identification of novel emotive expressions in an emotion dataset, thereby enriching the depth and breadth of emotion analysis capabilities. In particular, the automatic extraction method shows promising results for applicability in further expansion of the dictionary base in the future, thus advancing the field of emotion analysis and offering new avenues for research in sentiment analysis, affective computing, and human–computer interaction

Concentration and Glycoform of Rituximab in Plasma of Patients with B Cell Non-Hodgkin’s Lymphoma

Purpose: Therapeutic antibodies have heterogeneities in their structures, although its structural alteration in the body is unclear. Here, we analyzed the change of amino acid modifications and carbohydrate chains of rituximab after administration to patients. Methods: Twenty B cell non-Hodgkin’s lymphoma patients who were treated with rituximab for the first time or after more than one year’s abstinence were recruited. Structural analysis of rituximab was carried out at 1 h after administration and at the trough by using liquid chromatography/time-of-flight-mass spectrometry. Plasma rituximab concentration and pharmacodynamic markers were also determined. Results: Of recruited twenty, 3 patients exhibited rapid rituximab clearance. Nine types of carbohydrate chains were detected in rituximab isolated from the blood. The composition ratios in some glycoforms were significantly different between at 1 h after administration and at the trough, although consisted amino acids remained unchanged. The patients with high clearance showed extensive alterations of glycoform composition ratios. However, pharmacodynamics makers were not different. Conclusion: Inter-individual variations in plasma concentrations of rituximab were found in some B-NHL patients. We could analyze a change in glycoforms of rituximab in the patients, and this finding may affect the pharmacokinetics of rituximab