Real-world sequential treatment patterns and clinical outcomes among patients with advanced urothelial carcinoma in Japan.

OBJECTIVES: Immune checkpoint inhibitors and enfortumab vedotin have opened new avenues for sequential treatment strategies for locally advanced/metastatic urothelial carcinoma (la/mUC). In the pre-enfortumab vedotin era, many patients could not receive third-line treatment owing to rapid disease progression and poor general status. This study aimed to analyze real-world sequential treatment practices for la/mUC in Japan, with a focus on patients who do not receive third-line treatment. METHODS: We analyzed data for 1023 la/mUC patients diagnosed between January 2020 and December 2021 at 54 institutions from a Japanese nationwide cohort. RESULTS: At the median follow-up of 28.5 months, the median overall survival from first-line initiation for 905 patients who received systemic anticancer treatment was 19.1 months. Among them, 81% and 32% received second- and third-line treatment. Notably, 52% had their treatment terminated before the opportunity for third-line treatment. Multivariate logistic regression analysis revealed that low performance status (≥1), elevated neutrophil-to-lymphocyte ratio (≥3), and low body mass index (<21 kg/m2) at the start of first-line treatment were independent risk factors for not proceeding to third-line treatment (p = 0.0024, 0.0069, and 0.0058, respectively). In this cohort, 33% had one of these factors, 36% had two, and 15% had all three. CONCLUSIONS: This study highlights the high frequency of factors associated with poor tolerance to anticancer treatment in la/mUC patients. The findings suggest the need to establish optimal sequential treatment strategies, maximizing efficacy within time and tolerance constraints, while concurrently providing strong supportive care, considering immunological and nutritional aspects.

Associations Among Hypersensitivity, Vagal Tone, and Mood State in Adults.

Although many previous studies have reported the relationship between hypersensitivity and vagal function in children, the relationship in adults is unclear. This study investigates the relationship between hypersensitivity and vagal function, discomfort to sensory stimuli, and daily mood states in healthy adults. Using a questionnaire, 39 healthy adults were divided into hypersensitivity and control groups. We compared the baseline respiratory sinus arrhythmia (RSA), reflecting vagal tone and reactivity, subjective discomfort to sensory stimuli, and daily mood status between groups. Those in the hypersensitivity group had significantly lower baseline RSA and were more likely to experience greater RSA variability and discomfort during exposure to sensory stimuli than the control group. We found no significant difference between groups in daily mood status. These findings suggest that vagal function is an important marker of hypersensitivity in healthy adults.

Relationships Among Hypersensitivity, Parasympathetic Function, and Mood States in AdultsPrevious studies in children have reported many associations between sensory characteristics, such as hypersensitivity to sensory stimuli, and parasympathetic function, but the association in adults is not clear. This study divided 39 healthy adults into a hypersensitivity group and a control group and compared their parasympathetic function, discomfort to sensory stimuli, and daily mood. We found that the hypersensitivity group had significantly lower baseline parasympathetic function and tended to experience greater fluctuations in parasympathetic activity and discomfort during sensory stimulation than the control group. However, we found no significant difference in daily mood between the groups. This suggests that parasympathetic function is an important marker of hypersensitivity in healthy adults. This may help therapists support those with hypersensitivity. Future research is needed in clinical practice.

Capture of emotional responses under a simulated earthquake experience using near-infrared spectroscopy and virtual reality.

AIM: In a previous study, we reported that watching two-dimensional videos of earthquakes significantly reduced sympathetic nerve activity in healthy young adults. In the present study, we aimed to investigate the emotional responses to earthquakes using immersive virtual reality (VR), which can provide a more realistic experience. METHODS: In total, 24 healthy young adults (12 males, 21.4 ± 0.2 years old) participated. Participants were required to watch earthquake and neutral videos while wearing a head-mounted display and near-infrared spectroscopy (NIRS), during which physiological signals, including pulse rate and cerebral blood flow (CBF) in the dorsolateral prefrontal cortex, were measured. We also analyzed changes in sympathetic and parasympathetic indices and obtained seven emotion ratings: valence, arousal, dominance, fear, astonishment, anxiety, and panic. RESULTS: The VR earthquake videos evoked negative subjective emotions, and the pulse rate significantly decreased. Sympathetic nerve activity tended to decrease, whereas CBF in the left prefrontal cortex showed a slight increase, although this was not significant. CONCLUSIONS: This study showed that measurements combined with NIRS and immersive VR have the potential to capture emotional responses to different stimuli.