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Background The association between the development of checkpoint inhibitor pneumonitis (CIP) with tumor response and survival has remained unclear so far. The aim of the present study was to evaluate the association between CIP and the clinical efficacy of anti‐programmed cell death‐1 antibody in patients with advanced non‐small cell lung cancer (NSCLC). Methods Between January 2016 and August 2019, 203 advanced NSCLC patients were administered with nivolumab or pembrolizumab. Comparisons were made between patients with and without CIP. We evaluated the time‐to‐treatment failure (TTF), progression‐free survival (PFS), and overall survival (OS). Results CIP was observed in 28 (14%) patients. CIP was associated with a longer PFS (18.9 months [95% confidence interval, CI: 8.7 months–not reached] vs. 3.9 months [95% CI: 3.4–5.1 months, p, This study aimed to evaluate the association between checkpoint inhibitor pneumonitis (CIP) and the clinical efficacy of anti‐programmed cell death‐1 monotherapy in patients with advanced non‐small cell lung cancer (NSCLC). CIP was associated with a longer PFS (18.9 months vs. 3.9 months, p

To the best of the authors’ knowledge, we present the first-ever demonstration of the two-dimensional linear optical sampling of fiber spatial modes. The images of the fiber cross sections excited by the LP01 or LP11 modes are directly projected onto a two-dimensional photodetector array and coherently sampled by local pulses with a uniform spatial distribution. Consequently, the spatiotemporal complex amplitude of the fiber mode is observed with a time resolution of a few picoseconds by using electronics with a bandwidth of only a few MHz. Such ultrafast and direct observation of vector spatial modes enables the characterization of the space-division multiplexing fiber itself with high time accuracy and wide bandwidth.

Background: Programmed cell death-ligand 1 (PD-L1) inhibitor durvalumab has been found to improve disease control in patients with unresectable stage III non-small cell lung cancer (NSCLC) treated with definitive concurrent chemoradiation therapy (dCCRT), but approximately a half of patients eventually experience disease progression within one year after the start of durvalumab. The mechanism of this resistance at such an early timing is poorly identified. Therefore, we conducted a prospective biomarker study to explore the resistance mechanisms to durvalumab after CCRT (Trial Identifier: UMIN000035916). Methods: A total of 139 patients with unresectable stage III NSCLC enrolled into this study after dCCRT were treated with durvalumab for up to 1 year. 135 patients who fulfilled the predetermined selection criteria were included for this primary biomarker analysis. Archival tumor tissues collected before the treatment were analyzed by immunohistochemistry for several key biomarkers such as PD-L1, CD8, and CD73, DNA sequencing for tumor-mutation burden (TMB) and genomic profile, as well as gene expression profiling (GEP). Peripheral blood mononuclear cells (PBMC) were also collected before and after durvalumab for flow-cytometry (FCM) analysis where available. Progression-free survival (PFS) was compared based on these biomarkers. Results: Median follow-up time was 14.4 months. Median PFS was 14.9 months (95% confidence interval [CI], 11.3-not reached), and 1-year PFS rate was 56.3% (95% CI, 47.3-64.3). CD8+ tumor-infiltrating lymphocytes (TILs), PD-L1 tumor proportion score (TPS), TMB, and CD73 on tumor cells were associated with PFS (hazard ratios [HRs], 0.40 [95% CI, 0.22-0.73] for CD8+TILs; 0.67 [95% CI, 0.40-1.11] for PD-L1-TPS ≥1%; 0.59 [95% CI, 0.34-1.02] for high TMB; 1.45 [95% CI, 0.86-2.43] for high CD73). Common pathogenic gene alterations such as EGFR, KRAS, and TP53 were not associated with PFS. Multivariable analysis including key clinical factors as covariables indicated that CD8+TILs and the CD73-expressing tumor cells were independently associated with durvalumab outcome (HRs, 0.26 [95% CI, 0.08-0.89] for CD8+TILs; 5.83 [95% CI, 1.33-25.62] for CD73). The significance of CD73-expressing tumor cells as a resistance factor was more obvious in patients with high CD8+TILs (HR, 2.35 [95% CI, 1.14-4.86]). GEP of tumor tissue and FCM of PBMC suggested that CD73-expressing tumor cells prevented effective reinvigoration of antigen-reactive CD8+ T cells by durvalumab due to the immunosuppressive activity. Conclusions: Low preexisting CD8+TILs or high CD73-expressing tumor cells were suggested to be primary resistance mechanism to durvalumab after CCRT in stage III NSCLC. Further development of next treatment approach will be prompted based on these findings. Citation Format: Koji Haratani, Atsushi Nakamura, Nobuaki Mamesaya, Kenji Sawa, Yasuto Yoneshima, Ryota Saito, Tomohiro Ozaki, Kenjiro Tsuruoka, Akito Hata, Kosuke Tsuruno, Tomohiro Sakamoto, Shunsuke Teraoka, Masahide Oki, Hiroshi Watanabe, Tomoyuki Otani, Kazuko Sakai, Shuta Tomida, Yasutaka Chiba, Akihiko Ito, Kazuto Nishio, Nobuyuki Yamamoto, Kazuhiko Nakagawa, Hidetoshi Hayashi. A multi-institutional prospective biomarker study of durvalumab after concurrent chemoradiation therapy in patients with unresectable stage III non-small cell lung cancer (WJOG11518L/SUBMARINE) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2173.

Introduction Despite the extensive use of the combination of cytotoxic chemotherapy and programmed cell death protein 1/programmed death-ligand 1 checkpoint inhibitors for cancer treatment, the incidence and characteristics of pneumonitis caused by this combination therapy have not been examined in clinical settings. Methods We conducted a 36-centre, retrospective cohort study in patients with chemo-naive advanced non-squamous non-small cell lung cancer who received a combination of platinum, pemetrexed and pembrolizumab between December 2018 and June 2019. Results The study comprised 299 patients. The most frequent grade ≥3 non-hematologic adverse event was pneumonitis. There were 37 patients (12.4%, 95% CI 8.9–16.7) with all-grade pneumonitis and 10 (3.3%, 95% CI 1.6–6.1) with grade ≥3 pneumonitis. Of these, 21 (7.0%, 95% CI 4.4–10.5) and 9 patients (3.0%, 95% CI 1.4–5.6) developed all-grade and grade ≥3 pneumonitis within 90 days after initiating the combination therapy, respectively. The median time to treatment failure and progression-free survival was 5.9 (95% CI 5.0–6.8) and 7.5 (95% CI 6.5–8.7) months, respectively. In the survival analysis after adjusting for immortal time bias, pneumonitis was independently associated with shorter progression-free survival (HR 1.99, 95% CI 1.07–3.69, P = 0.03) and overall survival (HR 3.03, 95% CI 1.12–8.20, P = 0.03). Conclusions Treatment-related pneumonitis occurred at a higher rate in the real-world population than that reported previously; it led to worse survival outcomes. Pneumonitis requires more attention. Additional studies are required to improve the safety of this combination therapy. Trial registration number UMIN000038084

We fabricated unique ceramics matrix composites (CMCs) called natto-structured oxides using metal-ethylenediaminetetraacetic acid (EDTA) solution. The natto-structured oxide in this study is a combination of micron-sized oxide particles and oxide with nanoscale fibrous microstructures. The natto-structures were fabricated on Si substrates by spin-coating Er-EDTA solutions with hollow (Y2O3:Eu3+, SiO2) particles followed by atmospheric sintering. We investigated the effects of filler concentrations, rotation speeds, and filler diameters on the formation of natto-structured oxides. The results indicate that the rotating centrifugal force in the spin coating process is the dominant factor affecting the formation of natto-structured oxides.

The morphology and microstructure of splats impact the comprehensive capability of a new coating methodology called chelate flame spraying (CFS). This study addresses the quantitative characterization of the spread morphologies of flame sprayed Er2O3 splats directly deposited under different spray conditions on aluminum alloy substrates with a mirror finish. The influence of the in-flight particle temperature and velocity, carrier gas type, and carrier gas ratio on the solidification mechanism of molten droplets was investigated. Image analysis methods were employed to identify single splats from the morphology observed with field-emission scanning electron microscopy (FE-SEM). In addition, Er2O3 films were synthesized on an Al–Mg alloy (A5052) substrate using N2 or O2 as the carrier gas. When O2 was used as the carrier gas, 109-μm-thick films were deposited on the A5052 substrate. The cross-sectional porosity of the films was 3.8%. In contrast, films with 101-μm thickness were synthesized on the A5052 substrate when N2 was used as the carrier gas. The cross-sectional porosity of these films was 13.8%. The results showed that the carrier gas type (N2) and carrier gas ratio had a significant effect on the flattening behavior of the molten droplets. A spraying method combined with multidimensional modes is proposed to control the morphology of the splats.

Objective The severity of Clostridioides difficile infection (CDI) is an important prognostic factor. The "MN criteria," proposed in Japan in 2017, attempted to remedy the shortfalls in the reported guidelines proposed globally to determine CDI severity. We therefore assessed the accuracy of the MN criteria and validated the important factors associated with predicting CDI severity. Methods Sixty-six CDI cases were investigated retrospectively at a Japanese University Hospital from January 2015 to December 2018. The fulminant cases were screened out, and the non-fulminant cases were classified according to their severity stages using the nine variables included in the MN criteria. Clinical events, such as death within 28 days, colectomy, and admission to the intensive-care unit, were evaluated. First, the sensitivity and specificity of the MN criteria for predicting clinical events were determined. The relationships between clinical events and the explanatory variables were then evaluated through univariate and multivariate analyses. Results The screening of the fulminant cases and classification of the non-fulminant cases into mild/moderate and severe/super severe cases resulted in a sensitivity of 1.00 and a specificity of 0.89. Univariate and multivariate analyses revealed a significant association of the serum albumin level (Alb) as well as white blood cell count (WBC) with clinical events. Conclusion The findings provide evidence supporting the accuracy of the MN criteria in predicting CDI severity and show that the Alb and WBC are important variables in predicting CDI severity.

Older adults with subjective memory complaints (SMC) may experience very minor difficulties in daily activities. Although caregivers and occupational therapists who support community-dwelling older adults are aware of the existence of characteristic behaviours related to refrigerator management, no specific studies have been conducted. This study aimed to examine the implications of refrigerator management for older adults with SMC.A self-administered questionnaire was sent to 3000 randomly selected members of Consumer's Co-operative Kagoshima. Of the returned responses, a total of 282 older adults were analyzed. Analyzed subjects were divided into two groups: SMC (+) group (n = 74) and SMC (-) group (n = 192). A questionnaire was created by four occupational therapists and used to assess the characteristics of analyzed subjects and their abilities to manage the refrigerator. The observation list for early signs of dementia was also utilised. A multiple logistic analysis was performed to examine the association between SMC and refrigerator management.The SMC (+) group had a significantly higher number of refrigerator management errors than the SMC (-) group (P = 0.008). The SMC (+) group had more errors than the SMC (-) group in the following four items regarding refrigerator management; the refrigerator has a lot of the same foods / expired food, the person does not know what's in the refrigerator, the person cannot find what he/she needs in the refrigerator. Moreover, SMC was associated with the item 'the person does not know what is in the refrigerator' (odds ratio 7.44, 95% CI 1.51-43.8, P = 0.02).Our results showed that older adults with SMC had several problems regarding refrigerator management. Evaluating refrigerator management among older adults with SMC may help consider multifaceted support.