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Cohort profile: the Dutch oral cavity cancer cohort

Purpose

The Dutch Head and Neck Audit–Oral Cavity (DHNA-OC) cohort was collected to study the quality of care, current treatment and survival for oral cavity cancer (OCC) across all hospitals treating head and neck cancer (HNC) in the Netherlands.

Patients

The DHNA-OC is a registry-based national cohort of 2545 first primary OCC patients treated with curative intent between 2018 and 2021. All 14 HNC hospitals in the Netherlands contributed, guaranteeing national coverage. The DHNA-OC cohort is an elaborate dataset including variables on patient and tumour characteristics, treatment, complications, recurrence rates and survival.

Findings to date

The median age at diagnosis was 67 years and most tumours were early stage (cT1 in 32% and cT2 in 31%). Tongue tumours were most common, and surgery was performed in 91.3% of the patients. The number of included patients per hospital varied from 82 to 367. The proportion of advanced tumour stage varied significantly between hospitals. Substantial data completeness was acquired with only two variables exceeding 10% missing (comorbidities and performance score).

Future plans

The DHNA-OC cohort will be used to study benchmarking of and current knowledge gaps in OCC care. Collaboration with other institutions or national/regional databases is highly encouraged. Some examples of planned studies are the assessment of hospital variation in outcome indicators for surgery and population-based treatment effects. The results of these studies will be used to identify best practices and continue improving the quality of care. Longitudinal cohort follow-up and enrolment will continue prospectively.

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.

Investigating the effects of home-based rehabilitation after intensive inpatient rehabilitation on motor function, activities of daily living, and caregiver burden

by Kenji Sato, Eri Otaka, Kenichi Ozaki, Kenta Shiramoto, Rie Narukawa, Takeshi Kamiya, Masaki Kamiya, Daiki Shimotori, Chiaki Kamizato, Naoki Itoh, Hitoshi Kagaya, Izumi Kondo

Background

Home-based rehabilitation involves professional rehabilitation care and guidance offered by physical, occupational, and speech therapists to patients in their homes to help them recuperate in a familiar living environment. The effects on the patient’s motor function and activities of daily living (ADLs), and caregiver burden for community-dwelling patients are well-documented; however, little is known about the immediate benefits in patients discharged from the hospital. Therefore, we examined the effects of continuous home-based rehabilitation immediately after discharge to patients who received intensive rehabilitation during hospitalization.

Methods

We retrospectively reviewed 150 patients [mean (standard deviation, SD) = 81 (9) years] discharged from the convalescent rehabilitation and community-based integrated care wards undergoing tailored home-based rehabilitation for 6 months (provided by physical or occupational therapists: 1–2 sessions of 40–60 min each per week). The outcome measures at baseline and after 3 and 6 months were compared.

Results

The participants included in this study had orthopedic (n = 76), cerebrovascular (n = 50), neuromuscular (n = 11), cardiovascular (n = 5), respiratory (n = 3), cancer (n = 3) and other diseases (n = 2). The mean (SD) time from discharge to the start of rehabilitation was 4 (4) days. One-way analysis of variance and post-hoc comparisons showed significant improvements at 3 months from baseline in grip strength (p = 0.002), 5-repetition sit-to-stand test (p Conclusions

Home-based rehabilitation improves motor function, ADLs, and instrumental ADLs even after intensive inpatient rehabilitation and decreases the burden of the caregiver in the long term. Hence, tailored home-based rehabilitation should be continuously implemented after the completion of intensive inpatient rehabilitation.

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.

Exploiting mechanisms for hierarchical branching structure of lung airway

by Hisako Takigawa-Imamura, Katsumi Fumoto, Hiroaki Takesue, Takashi Miura

The lung airways exhibit distinct features with long, wide proximal branches and short, thin distal branches, crucial for optimal respiratory function. In this study, we investigated the mechanism behind this hierarchical structure through experiments and modeling, focusing on the regulation of branch length and width during the pseudoglandular stage. To evaluate the response of mouse lung epithelium to fibroblast growth factor 10 (FGF10), we monitored the activity of extracellular signal-regulated kinase (ERK). ERK activity exhibited an increase dependent on the curvature of the epithelial tissue, which gradually decreased with the progression of development. We then constructed a computational model that incorporates curvature-dependent growth to predict its impact on branch formation. It was demonstrated that branch length is determined by the curvature dependence of growth. Next, in exploring branch width regulation, we considered the effect of apical constriction, a mechanism we had previously proposed to be regulated by Wnt signaling. Analysis of a mathematical model representing apical constriction showed that branch width is determined by cell shape. Finally, we constructed an integrated computational model that includes curvature-dependent growth and cell shape controls, confirming their coordination in regulating branch formation. This study proposed that changes in the autonomous property of the epithelium may be responsible for the progressive branch morphology.
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