Transient Worsening of Pain After Administration of Immune Checkpoint Inhibitors - A Case Series.

BACKGROUND/AIM: Transient pain enhancement or flare pain, is observed following the administration of immune checkpoint inhibitors (ICIs). However, the detailed mechanism of this phenomenon remains unclear. In this report, we present our experience of documenting the course of flare pain following ICI administration in six cases. PATIENTS AND METHODS: Six patients with advanced solid tumors received ICI monotherapy between July 2017 and November 2019. Their pain increased within hours of ICI administration despite being stable before ICI administration. We evaluated the changes in the numerical rating scale (NRS) score over 72 h after ICI administration. RESULTS: Four non-small cell lung cancer patients, one gastric cancer patient, and one renal cell cancer patient were included. Four patients experienced an increase in NRS, as evidenced by scores on two or more scales compared to the day before administration, whereas two patients showed an increase only on one scale. The NRS score decreased to almost the same level as that on the day before administration. Flare pain is observed in the same area as the primary site. Most of the pain was alleviated without the need for rescue analgesics, although one patient experienced a 4-point increase in the NRS scale. CONCLUSION: Flare pain may occur following ICI administration. Healthcare providers should be aware of these events and provide patients with suitable information and coping techniques.

[Urine Protein/Creatinine Ratio Measurement Is Useful to Continue Anti-Angiogenic Agent Treatment].

BACKGROUND: Aside effect of anti-angiogenic agent treatment is proteinuria. Evaluation of the severity of adverse effects and the decision to discontinue treatment is based on the qualitative analysis of urinary proteins. However, a qualitative analysis result may not be indicative of the actual amounts of protein excreted. In this study, we evaluated the possibility of using the urine protein/creatinine ratio(UPCR), instead of a qualitative urine analysis, to monitor patients treated with antiangiogenic agents. METHODS: Urinalysis data of patients receiving anti-angiogenic agents-bevacizumab, ramucirumab, or aflibercept-were retrospectively analyzed from clinical records. Acorrelation between the urine protein content(qualitative and quantitative analyses)and continuity of anti-angiogenic agent treatment was evaluated. RESULTS: Atotal of 24 patients (age, 70.83±7.45 years)who received treatment for colorectal cancer(n=17), lung cancer(n=4), gastric cancer(n=2), and breast cancer(n=1)were included. One hundred and sixty-five urinalysis results were collected. Alinear correlation between the qualitative urinalysis results(1+to 3+)and UPCR(r=0.746, p<0.01)was obtained. In patients with a urine protein content of 2+(qualitative analysis), the UPCR was <2.0 for 25 patients and ≥2.0 but <3.5 for 4 patients. Similarly, in patients with a urine protein content of 3+, the UPCR was <2.0 for 3 patients and ≥2.0 but <3.5 for 1 patient. Seventeen patients with a urine protein content of 2+ and 3 patients with a urine protein content of 3+ discontinued treatment with anti-angiogenic agents before estimation of the UPCR could be performed. These figures were reduced to 4 patients and 2 patients, respectively, following UPCR assessment. CONCLUSIONS: Switching the estimation of proteinuria from a qualitative analysis to UPCR might lead to better safety monitoring and prevent unnecessary discontinuation of anti-angio- genic agent treatment.

Juvenile hormone (JH) esterase activity but not JH epoxide hydrolase activity is downregulated in larval Adoxophyes honmai following nucleopolyhedroviruses infection.

Juvenile hormones (JHs) and ecdysteroids are critical insect developmental hormones. JH esterase (JHE) and JH epoxide hydrolase (JHEH) are JH-selective enzymes that metabolize JH and thus regulate the titer of JH. Baculoviruses are known to alter host endocrine regulation. The nucleopolyhedroviruses, AdhoNPV and AdorNPV, are known to have slow and fast killing activity against Adoxophyes honmai (Lepidoptera: Tortricidae), respectively. Here we found that when penultimate (4th) instar A. honmai are inoculated with AdhoNPV or AdorNPV, the mean survival time is 9.7 and 8.2 days, respectively. The larvae molted once but did not pupate. The AdhoNPV- or AdorNPV-infected larvae did not show a dramatic increase in JHE activity as was found in mock-infected larvae, instead they showed a marked decrease in JHE activity. In contrast, both viral infections had no effect on JHEH activity. In order to further characterize the JHE activity, the JHE-coding sequence of A. honmai (ahjhe) was cloned and confirmed to encode a biologically active JHE. Quantitative real-time PCR analysis of ahjhe expression in 4th and 5th instar A. honmai revealed that AdhoNPV and AdorNPV are able to reduce ahjhe expression levels.

Field efficacy and transmission of fast- and slow-killing nucleopolyhedroviruses that are infectious to Adoxophyes honmai (Lepidoptera: Tortricidae).

The smaller tea tortrix, Adoxophyes honmai (Lepidoptera: Tortricidae), is an economically important pest of tea in Japan. Previous work showed that a fast-killing nucleopolyhedrovirus (NPV) isolated from A. orana (AdorNPV) and a slow-killing NPV isolated from A. honmai (AdhoNPV) are both infectious to A. honmai larvae. Field application of these different NPVs was conducted against an A. honmai larval population in tea plants, and the control efficacy and transmission rate of the two NPVs were compared. The slow-killing AdhoNPV showed lower field efficacy, in terms of preventing damage caused by A. honmai larvae against the tea plants, than the fast-killing AdorNPV. However, AdhoNPV had a significantly higher horizontal transmission rate than AdorNPV. These results show that AdorNPV is suitable as an inundative agent, while AdhoNPV is an appropriate inoculative agent.