Clinical outcomes in patients with non-small cell lung cancer harboring EGFR Exon20 in-frame insertions in the near-loop and far-loop: Results from LC-SCRUM-Asia.

OBJECTIVES: In this study, we explored the clinical outcomes of non-small cell lung cancer (NSCLC) patients with EGFR Exon20 in-frame insertions (Exon20ins), and the impact of the location of Exon20ins on these clinical outcomes. MATERIALS AND METHODS: The efficacies of current systemic therapies in NSCLC patients harboring Exon20ins were investigated using a large-scale clinico-genomic database of LC-SCRUM-Asia, and compared with that of amivantamab in the CHRYSALIS trial. RESULTS: Of the 11,397 patients enrolled in LC-SCRUM-Asia, Exon20ins were detected in 189 patients (1.7 %). Treatment with classical EGFR tyrosine-kinase inhibitors (classical TKIs) was associated with a significantly shorter progression-free survival (PFS) in NSCLC patients with Exon20ins as compared with Exon19 deletions and L858R. Post platinum-based chemotherapy, classical TKIs and immune checkpoint inhibitors (ICIs) were associated with a shorter PFS than with docetaxel in patients with Exon20ins (HR [95 % CI]; TKIs vs docetaxel, 2.16 [1.35-3.46]; ICIs vs docetaxel, 1.49 [1.21-1.84]). Patients treated with amivantamab in the CHRYSALIS trial showed a risk reduction in PFS and overall survival as compared with LC-SCRUM-Asia patients treated with docetaxel, classical TKIs, or ICIs. Among the 189 patients, Exon20ins were classified as near-loop or far-loop insertions in 115 (61 %) and 56 (30 %) patients, respectively. Treatment with osimertinib was associated with a longer PFS in patients with Exon20ins in near-loop as compared with far-loop (median, 5.6 vs. 2.0 months; HR [95 % CI], 0.22 [0.07-0.64]). CONCLUSIONS: After platinum-based chemotherapy, classical TKIs and ICIs are less effective in NSCLC patients with Exon20ins, and amivantamab may be a promising targeted therapy. There is a possibility that the location of Exon20ins has an impact on the efficacy of TKIs.

Motivational decline and proactive response under thermal environmental stress are related to emotion- and problem-focused coping, respectively: Questionnaire construction and fMRI study.

Despite the diversity of human behavioral and psychological responses to environmental thermal stress, the major dimensions of these responses have not been formulated. Accordingly, the relevance of these responses to a framework of coping with stress (i.e., emotion- and problem-focused) and the neural correlates are unexplored. In this study, we first developed a multidimensional inventory for such responses using social surveys and a factor analysis, and then examined the neural correlates of each dimension using a functional magnetic resonance imaging; we manipulated the ambient temperature between uncomfortably hot and cold, and the correlations between the inventory factor scores and discomfort-related neural responses were examined. We identified three factors to construct the inventory: motivational decline, proactive response, and an active behavior, which appeared to reflect inefficient emotion-focused coping, efficient problem-focused coping, and positive appreciation of extreme environmental temperatures, respectively, under environmental thermal stress. Motivational decline score was positively associated with common neural response to thermal stress in the frontal and temporoparietal regions, implicated in emotion regulation, while proactive response score negatively with the neural responses related to subjective discomfort in the medial and lateral parietal cortices, implicated in problem-solving. We thus demonstrated that two of three major dimensions of individual variation in response to and coping with environmental thermal stress conform to an influential two-dimensional framework of stress coping. The current three-dimensional model may expand the frontiers of meteorological human science in both basic and application domains.

Weekly nanoparticle albumin-bound paclitaxel and paclitaxel for relapsed small cell lung cancer: A retrospective observational study.

ABSTRACT: In addition to advanced non-small cell lung cancer, nanoparticle albumin-bound paclitaxel (nab-PTX) may also harbor potential benefit for patients with relapsed small cell lung cancer (SCLC), since weekly paclitaxel (PTX) shows modest activity for relapsed SCLC. We evaluated the efficacy and safety of both weekly nab-PTX and PTX for relapsed SCLC.We retrospectively reviewed 52 consecutive relapsed SCLC patients who were treated with weekly nab-PTX or PTX at our hospital.The response rate, median progression-free survival and overall survival with nab-PTX and PTX were 5.6 vs 8.8%, 3.2 vs 1.7 months, and 5.4 vs 4.5 months, respectively. No statistically significant differences were observed. There was no statistical difference between the 2 groups for ≥Grade 3 adverse events.Weekly nab-PTX and PTX showed similar activity for relapsed SCLC. The toxicity profile of nab-PTX was equally tolerable to that of PTX.

Mesalazine-induced lung injury with severe respiratory failure successfully treated with steroids and non-invasive positive pressure ventilation.

Drug-induced lung injury (DLI) has become more common because of the increasing number of therapeutic agents in use. Mesalazine, also known as 5-aminosalicylic acid (5-ASA), is one of the key drugs for the treatment of ulcerative colitis (UC). Although mesalazine-induced lung injury has been previously reported, few cases have included severe respiratory failure. In this report, we present a case of mesalazine-induced lung injury with severe respiratory failure, which was improved by discontinuation of mesalazine and introduction of corticosteroid therapy and ventilation support with non-invasive positive pressure ventilation (NPPV). We also review the previous literature on mesalazine-induced lung injury.

Neural correlates of ambient thermal sensation: An fMRI study.

An increasing number of biometeorological and psychological studies have demonstrated the importance and complexity of the processes involved in environmental thermal perception in humans. However, extant functional imaging data on thermal perception have yet to fully reveal the neural mechanisms underlying these processes because most studies were performed using local thermal stimulation and did not dissociate thermal sensation from comfort. Thus, for the first time, the present study employed functional magnetic resonance imaging (fMRI) and manipulated ambient temperature during brain measurement to independently explore the neural correlates of thermal sensation and comfort. There were significant correlations between the sensation of a lower temperature and activation in the left dorsal posterior insula, putamen, amygdala, and bilateral retrosplenial cortices but no significant correlations were observed between brain activation and thermal comfort. The dorsal posterior insula corresponds to the phylogenetically new thermosensory cortex whereas the limbic structures (i.e., amygdala and retrosplenial cortex) and dorsal striatum may be associated with supramodal emotional representations and the behavioral motivation to obtain heat, respectively. The co-involvement of these phylogenetically new and old systems may explain the psychological processes underlying the flexible psychological and behavioral thermo-environmental adaptations that are unique to humans.

Effects of heated seats in vehicles on thermal comfort during the initial warm-up period.

Eight subjects participated in a subjective experiment of eight conditions to investigate the effects of heated seats in vehicles on skin temperature, thermal sensation and thermal comfort during the initial warm-up period. The experimental conditions were designed as a combination of air temperature in the test room (5, 10, 15, or 20 °C) and heated seat (on/off). The heated seat was effective for improving thermal comfort during the initial warm-up period when air temperature was lower than 15 °C. Use of heated seats prevented decreases in or increased toe skin temperature. Heated seats also increased foot thermal sensation at 15 and 20 °C. Optimal thermal sensation in contact with the seat was higher when air temperature was lower. Optimal skin temperature in contact with the seat back was higher than that with the seat cushion. Moreover, these optimal skin temperatures were higher when air temperature was lower.

Effects of heated seat and foot heater on thermal comfort and heater energy consumption in vehicle.

Subjective experiments involving 12 different conditions were conducted to investigate the effects of heated seats and foot heaters in vehicles on thermal sensation and thermal comfort. The experimental conditions involved various combinations of the operative temperature in the test room (10 or 20°C), a heated seat (on/off) and a foot heater (room operative temperature +10 or +20°C). The heated seat and foot heater improved the occupant's thermal sensation and comfort in cool environments. The room operative temperature at which the occupants felt a 'neutral' overall thermal sensation was decreased by about 3°C by using the heated seat or foot heater and by about 6°C when both devices were used. Moreover, the effects of these devices on vehicle heater energy consumption were investigated using simulations. As a result, it was revealed that heated seats and foot heaters can reduce the total heater energy consumption of vehicles. Statement of Relevance: Subjective experiments were conducted to investigate the effects of heated seats and foot heaters in vehicles on thermal comfort. The heated seat and foot heater improved the occupant's thermal sensation and comfort in cool environments. These devices can reduce the total heater energy consumption in vehicles.