Short sleep duration is a significant risk factor of obesity: A multicenter observational study of healthy adults in Japan

by Mami Takahashi, Takeshi Shimamoto, Lumine Matsumoto, Yusuke Mitsui, Yukari Masuda, Hirotaka Matsuzaki, Eriko Hasumi, Chie Bujo, Keiko Niimi, Takako Nishikawa, Ryoichi Wada, Nobutake Yamamichi

This multicenter study aimed to elucidate the association between sleep duration and various lifestyle-related disorders in healthy adults in Japan. A total of 62,056 healthy participants (age: 49.4 ±  10.9 years) who received medical checkups from 2010 to 2020 were analyzed cross-sectionally and longitudinally. The mean sleep duration was 6.2 ±  1.0 h in men and 6.1 ±  1.0 h in women. The distribution of sleep duration showed that older people tended to sleep longer, which was clearly observed in men but not in women. Univariate analyses showed that older age, lower body mass index (BMI), habitual drinking, and habitual exercise were significantly associated with longer sleep duration. Multivariate analyses in men showed that sleep duration was positively associated with age, habitual exercise, serum triglyceride (TG), systolic blood pressure (SBP), and habitual drinking and negatively associated with BMI and hemoglobin A1c (HbA1c). Alternatively, in women, sleep duration was positively associated with habitual exercise and TG and negatively associated with BMI, high-density lipoprotein-cholesterol, HbA1c, and current smoking. During the follow-up period, 3,360 of 31,004 individuals (10.8%) developed obesity. The Cox proportional hazards model showed that shorter sleep duration was a significantly higher risk of obesity, and longer sleep duration might be a lower risk of obesity. On the other hand, 1,732 of 39,048 participants (4.4%) developed impaired glucose tolerance, and 6,405 of 33,537 participants (19.1%) developed hypertriglyceridemia. However, the Cox proportional hazards model did not show significant association between sleep duration and impaired glucose tolerance or hypertriglyceridemia. In conclusion, our large-scale cross-sectional study showed that sleep duration was positively associated with habitual exercise and TG and negatively associated with BMI and HbA1c, regardless of sex. Longitudinal analysis revealed that shorter sleep duration is a significant risk factor for obesity.

Deep generative abnormal lesion emphasization validated by nine radiologists and 1000 chest X-rays with lung nodules

by Shouhei Hanaoka, Yukihiro Nomura, Naoto Hayashi, Issei Sato, Soichiro Miki, Takeharu Yoshikawa, Hisaichi Shibata, Takahiro Nakao, Tomomi Takenaga, Hiroaki Koyama, Shinichi Cho, Noriko Kanemaru, Kotaro Fujimoto, Naoya Sakamoto, Tomoya Nishiyama, Hirotaka Matsuzaki, Nobutake Yamamichi, Osamu Abe

A general-purpose method of emphasizing abnormal lesions in chest radiographs, named EGGPALE (Extrapolative, Generative and General-Purpose Abnormal Lesion Emphasizer), is presented. The proposed EGGPALE method is composed of a flow-based generative model and L-infinity-distance-based extrapolation in a latent space. The flow-based model is trained using only normal chest radiographs, and an invertible mapping function from the image space to the latent space is determined. In the latent space, a given unseen image is extrapolated so that the image point moves away from the normal chest X-ray hyperplane. Finally, the moved point is mapped back to the image space and the corresponding emphasized image is created. The proposed method was evaluated by an image interpretation experiment with nine radiologists and 1,000 chest radiographs, of which positive suspected lung cancer cases and negative cases were validated by computed tomography examinations. The sensitivity of EGGPALE-processed images showed +0.0559 average improvement compared with that of the original images, with -0.0192 deterioration of average specificity. The area under the receiver operating characteristic curve of the ensemble of nine radiologists showed a statistically significant improvement. From these results, the feasibility of EGGPALE for enhancing abnormal lesions was validated. Our code is available at https://github.com/utrad-ical/Eggpale.

Effect of immortal time bias on the association between immune-related adverse events and oncological outcomes following immune checkpoint inhibitors therapy for head and neck squamous cell carcinoma

by Koichi Tamura, Yukinori Takenaka, Kiyohito Hosokawa, Takashi Sato, Takeshi Tsuda, Hirotaka Eguchi, Masami Suzuki, Takahito Fukusumi, Motoyuki Suzuki, Hidenori Inohara

Immune checkpoint inhibitors (ICIs) are pharmacological agents indicated for recurrent and metastatic head and neck squamous cell carcinoma (HNCSCC). Immune-related adverse events (irAEs) have been reported as predictors of therapeutic response to ICIs. However, previous studies have not adequately addressed the immortal time bias. Therefore, we aimed to investigate the association between the onset of irAEs and oncological outcomes, accounting for immortal time bias. We conducted a retrospective study involving 130 patients with HNSCC who were treated with ICIs. The objective response, progression-free survival (PFS), and overall survival (OS) were assessed using logistic regression analysis, the Kaplan–Meier method, and the Cox proportional hazard (PH) model. The immortal time bias was considered using a landmark analysis and an extended Cox (EC) model. The odds ratios for response and disease control were smaller in the landmark than in the naïve analyses. In the landmark analysis, the 1-year PFS rates were 47.6% and 27.2% for irAE+ and irAE- patients, respectively (p = 0.049), and the 1-year OS rates were 85.7% and 66.5%, respectively (p = 0.006). Regarding PFS, the adjusted HRs for irAEs were 0.49 (95% confidence interval (CI) 0.28–0.85) in the PH analysis and 0.75 (95% CI 0.40–1.40) in the EC analysis. As for OS, the adjusted HRs for irAEs were 0.36 (95% CI 0.19–0.66) in the PH analysis and 0.51 (95% CI 0.27–0.95) in the EC analysis. IrAEs were an independent prognostic factor for OS but not PFS. Without considering the immortal time bias, the association between irAEs and oncologic outcomes in patients with HNSCC treated with ICIs was overestimated. Therefore, the balance between the benefits and risks of ICI therapy must be carefully weighed in clinical settings.