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Purpose: Lenvatinib and pembrolizumab (LEN+PEMBRO) demonstrated clinically meaningful and statistically significant improvements in efficacy versus treatment of physician's choice (TPC) in patients with advanced endometrial cancer (aEC) in the phase 3 Study 309/KEYNOTE-775. Health-related quality-of-life (HRQoL) is reported. Patients and Methods: Patients were randomly assigned to receive LEN+PEMBRO (n = 411; LEN 20 mg/day; PEMBRO 200 mg Q3W) or TPC (n = 416; doxorubicin 60 mg/m2 Q3W or paclitaxel 80 mg/m2 [weekly, 3 weeks on/1 week off]). Impact of treatment on HRQoL assessed by the global health status/quality of life (GHS/QoL) score of the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) was a secondary objective; other scales of the Quality-of-Life Questionnaire (QLQ-C30), EORTC QLQ-Endometrial, 24 questions (EORTC QLQ-EN24), and EuroQoL 5 dimensions, 5 levels (EQ-5D-5L) were exploratory objectives. HRQoL was assessed on day 1 of each cycle. Completion/compliance, change from baseline, time to first and definitive deterioration were assessed. No multiplicity adjustments were applied for HRQoL endpoints. Results: The latest timepoint at which the predefined rates of completion (≥60%) and compliance (≥80%) were met was week 12. HRQoL at week 12 between treatment groups was generally similar. Time to first deterioration symptom scales favoured LEN+PEMBRO for QLQ-C30 dyspnoea, and QLQ-EN24 for poor body image, tingling/numbness, and hair loss; and TPC was favoured for QLQ-C30 pain, appetite loss, and diarrhoea, and QLQ-EN24 muscular pain. While the QLQ-C30 physical functional scale favoured TPC, other functional scales were generally similar between arms. Time to definitive deterioration favoured LEN+PEMBRO on most scales. Conclusion: HRQoL data from Study 309/KEYNOTE-775, with previously published efficacy and safety results, indicate that LEN+PEMBRO has an overall favourable benefit/risk profile versus TPC for the treatment of patients with aEC.

A 73-year-old woman in complete remission from localized small-cell lung cancer associated with Lambert-Eaton myasthenic syndrome (LEMS) 22 years earlier was referred to our hospital and diagnosed with non-small-cell lung cancer. After three courses of pembrolizumab, an immune checkpoint inhibitor, the patient complained of muscle weakness, fatigue, ptosis, and dysarthria. The anti-voltage-gated calcium channel antibody level was elevated, and waxing was observed on a high-frequency repetitive stimulation test using an electromyogram. We diagnosed her with recurrence of LEMS as an immune-related adverse event (irAE) induced by pembrolizumab. After intravenous immunoglobulin therapy, the patient's symptoms improved, and she was discharged.

We observed a stellar occultation by (3200) Phaethon, which occurred in western Japan on 2021 October 3 (UTC). This observation was requested by the DESTINY+ mission team, which plans to conduct a flyby of asteroid Phaethon in 2028. Overall, this research effort contributes towards a large-scale observation campaign with a total of 72 observers observing from western Japan to southern Korea. 36 stations were established, and stellar occultation by the asteroid Phaethon was detected in 18 of them. This is the first time that this many multiple chord observations have been made for such a small asteroid (it has a diameter of 5–6 km). Observational reductions show that the apparent cross-section of Phaethon at the time of the occultation could be approximated using an ellipse with a major diameter of 6.12 ± 0.07 km and a minor diameter of 4.14 ± 0.07 km, and a position angle of 117.°4 ± 1.°5. As can be seen from the small error bars of the fitted ellipse, we have succeeded in estimating the shape and size of the asteroid with an extremely high degree of accuracy. Our observation results, together with other observations, will be used to create a 3D model of Phaethon and to improve its orbit. The instruments that we used for this observation are commonly used by many amateur astronomers in Japan for occultation observations and are not difficult to obtain. This paper describes the method and results of our observations using a CMOS camera and a GPS module, so that many people can participate in occultation observations in the future.

Orthogonal and twisted dimers of pyrrole-fused pentaazapolycyclic hydrocarbons (pentaazacoronene analogs) were synthesized, linked either directly or by phenylenes. Although the dimers and the reference monomer did not have any substituents at the [Formula: see text]-positions of the terminal pyrroles, two reversible oxidation waves were observed in the cyclic voltammograms. ESR measurements of the chemically generated dications of the dimers showed typical radical cation signals, indicating successful accumulation of the redox activity of the pentaazacoronene analog.

BACKGROUND: The systematic characteristics of force generation and relaxation have been investigated using a graded isometric task for several target levels and magnitudes in the upper and lower limb. However, whether a relaxation modality affects the accuracy or speed of grading remains unclear. In addition, speed characteristics are still unclear in both force generation and relaxation modalities. OBJECTIVE: To investigate the effect of force adjustment modalities on force generation and relaxation characteristics. METHODS: Participants were instructed to match a target force level as quickly and as accurately as possible under peak and keep adjustment modalities. The force generation task was increased from 10% to 30%, 50%, and 70% of the maximum voluntary force (MVF). The force relaxation task was decreased from 70% to 50%, 30%, and 10% MVF. The recorded force was analyzed. Errors in reproduction were computed in both modalities and target levels of force. RESULTS: The errors of the peak adjustment modality were greater than those of the keep adjustment modality in both tasks. The reaction time was longer with the peak adjustment modality than with the keep adjustment modality in both tasks. CONCLUSION: Speed was affected by the choice of adjustment modality.

A small collection of chirostyloid squat lobsters was studied, collected from seamounts on the Nishi-Shichito, West Mariana, and Central Mariana ridges, which have been collectively designated as marine protected areas (MPAs) of Japan. Specimens were collected using a remotely operated vehicle (ROV). Four species belonging to three families were identified, of which two are new to science: Uroptychus medius n. sp. (Chirostylidae), Eumunida smithii Henderson, 1885, E. treguieri de Saint Laurent & Poupin, 1996 (Eumunididae), and Sternostylus spiniger n. sp. (Sternostylidae). Identities of those species were assessed using an integrative approach based on morphological comparison and genetic analysis of two mitochondrial markers (COI and 16S rRNA genes). The two species of Eumunida represent the first records from Japanese waters.

Introduction Three randomized controlled trials have resulted in extremely extensive application of the strategy of using neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) for patients with advanced epithelial ovarian cancer in Japan. This study aimed to evaluate the status and effectiveness of treatment strategies using NAC followed by IDS in Japanese clinical practice. Patients and methods We conducted a multi-institutional observational study of 940 women with Federation of Gynecology and Obstetrics (FIGO) stages III–IV epithelial ovarian cancer treated at one of nine centers between 2010 and 2015. Progression-free survival (PFS) and overall survival (OS) were compared between 486 propensity-score matched participants who underwent NAC followed by IDS and primary debulking surgery (PDS) followed by adjuvant chemotherapy. Results Patients with FIGO stage IIIC receiving NAC had a shorter OS (median OS: 48.1 vs. 68.2 months, hazard ratio [HR]: 1.34; 95% confidence interval [CI] 0.99–1.82, p = 0.06) but not PFS (median PFS: 19.7 vs. 19.4 months, HR: 1.02; 95% CI: 0.80–1.31, p = 0.88). However, patients with FIGO stage IV receiving NAC and PDS had comparable PFS (median PFS: 16.6 vs. 14.7 months, HR: 1.07 95% CI: 0.74–1.53, p = 0.73) and OS (median PFS: 45.2 vs. 35.7 months, HR: 0.98; 95% CI: 0.65–1.47, p = 0.93). Conclusions NAC followed by IDS did not improve survival. In patients with FIGO stage IIIC, NAC may be associated with a shorter OS.

Objective: The consumption of various foods is internationally recommended in healthy diet although the association between dietary variety and incident dementia is unknown. We aimed to examine the association between dietary variety and the incidence of disabling dementia in older Japanese adults. Design: We conducted a prospective cohort study. Dietary variety was assessed based on the Dietary Variety Score (DVS). DVS was assessed by counting the number of ten food components (meat, fish/shellfish, eggs, milk, soyabean products, green/yellow vegetables, potatoes, fruit, seaweed and fats/oils) that were consumed almost daily using a FFQ. Participants were categorised into low (0–2 points), middle (3–4 points) and high (5–10 points) groups based on the DVS. Data on newly diagnosed disabling dementia were retrieved from the public long-term care insurance database. Cox proportional hazards regression was used to estimate hazard ratios (HR) with 95 % CI. Setting: Yabu cohort study, Japan. Participants: A total of 4972 community-dwelling adults aged 65 years or older. Results: During the median follow-up of 6·8 years, 884 participants were newly diagnosed with disabling dementia. After adjusting for confounders, the multivariable-adjusted HR for incident disabling dementia was 0·82 (95 % CI, 0·69, 0·97) for participants in the highest DVS category compared with those in the lowest DVS category (Pfor trend = 0·019). Conclusions: A higher dietary variety is associated with a reduced risk of disabling dementia in older Japanese adults. These results have potential implications for the development of effective public nutritional approaches to prevent dementia in older adults.

The introduction of tyrosine kinase inhibitors has revolutionized treatment strategies for metastatic renal cell carcinoma (RCC) and has improved survival rates. The number of patients with bone metastases from RCC requiring surgery will increase as survival rates improve. However, there is insufficient evidence to standardize the treatment of bone metastases after the introduction of targeted therapy for metastatic RCC. We aimed to determine the outcomes of palliative surgical treatment of bone metastases in the extremities of patients with metastatic RCC.We retrospectively reviewed 26 lesions from 17 patients who underwent surgery for extremity and acetabular bone metastases and were treated with targeted therapies for advanced RCC between 2008 and 2020. The median follow-up duration was 19 months (range, 4-76). We assessed the patients' activities of daily living, quality of life, and pain and analyzed their postoperative values relative to preoperative values. Postoperative overall survival (OS), local progression-free survival (LPFS), and the factors affecting them were evaluated using the Kaplan-Meier method and log-rank test.The 5-year OS and LPFS rates were 39.5% and 65.6%, respectively. The factors affecting OS were sex, Katagiri score, visceral metastases, and preoperative targeted therapy, while the factors affecting LPFS were pathologic fractures and surgical technique.In this study, the postoperative outcomes of palliative surgery for bone metastases from metastatic RCC were good. We suggest that systemic treatment should be prioritized over local control for advanced bone metastasis in RCC and surgery before pathological fracture should be performed for local control.

Study Design: A retrospective cohort study.Purpose: We aimed to investigate the surgical results of foramen magnum decompression (FMD) to identify the potential factors associated with syrinx reduction in Chiari malformation type I (CMI).Overview of Literature: The predictive value of preoperative factors for syrinx reduction in patients with CMI remains debatable.Methods: We enrolled patients who underwent microscopic FMD with outer dural layer resection for CMI. The distance from the tip of the cerebellar tonsil to the C2 vertebral endplate on sagittal magnetic resonance imaging (MRI) was defined as the tonsillar distance (TD). Patients who showed a >20% syrinx diameter reduction on the 1-year follow-up MRI were defined as the syrinx reduction group while the others were categorized in the syrinx nonreduction group. Patients with syringomyelia were categorized into the clinically improved and unimproved groups using the Chicago Chiari Outcome Scale. The imaging and clinical parameters were evaluated pre- and postoperatively.Results: This study included 25 patients of whom 19 (76.0%) had syringomyelia. At the 1-year follow-up, the syrinx diameter had decreased in 11 patients (57.8%). The increased TD significantly differed between the syrinx reduction and nonreduction groups. At the 1-year follow-up, 12 and seven patients with syringomyelia were categorized into the clinically improved and unimproved groups, respectively. The clinically improved and unimproved groups showed significant differences in the mean age and increased TD.Conclusions: Postoperative syrinx reduction was significantly correlated with the upward shifting of the cerebellar tonsil in patients with CMI. Our quantitative evaluation of the alterations in hindbrain position after FMD was easily performed and reflects the clinical outcomes.

Study Design: This is a single-center retrospective cohort study with a university hospital setting.Purpose: This study aims to evaluate the short-term course of physical function and walking ability after intramedullary spinal cord tumor (ISCT) resection and predict walking independence 1 year after surgery.Overview of Literature: Although several reports have shown the postoperative functional prognosis of spinal intramedullary tumors with long-term follow-up, no reports have identified the predictors associated with the functional outcome at an early stage. Methods: A total of 79 individuals who underwent ISCT resection at our institute between 2014 and 2019 were enrolled in the study, whose preoperative walking state was independent ambulator regardless of cane support with the Functional Independence Measure Locomotor Scale (FIM-L) score of ≥6. The FIM-L, the American Spinal Injury Association (ASIA) motor and sensory scores in the lower extremities, and the Walking Index for Spinal Cord Injury II (WISCI II) were assessed for walking independence, lower-limb function, and walking ability, respectively. These evaluations were performed at 4 time points: preoperatively, 1 week (1W), 2 weeks (2W), and 1 year after surgery.Results: In the early phase after surgery, 71% and 43% of the participants were nonindependent ambulators at 1W and 2W, respectively. Histopathology indicated that patients with solid tumors (ependymoma, astrocytoma, or lipoma) showed significantly lower indices at 1W and 2W than those with vascular tumors (hemangioblastoma or cavernous hemangioma). Regarding tumor location, thoracic cases exhibited poorer lower-limb function at 1W and 2W and poorer walking ability at 2W than cervical cases. According to the receiver operating characteristic (ROC) analysis, 2 WISCI II points at 2W had the highest sensitivity (100%) and specificity (92.2%) in predicting the level of walking independence at 1 year postoperatively (the area under the ROC curve was 0.99 (95% confidence interval, 0.93–1.00).Conclusions: The higher the lower-limb function scores in the early phase, the better the improvement in walking ability is predicted 1 year after ISCT resection.

Nasogastric tube syndrome (NGTS) induced by a nasointestinal ileus tube is an uncommon but potentially life-threatening complication. NGTS often becomes serious and progresses to acute upper airway obstruction caused by bilateral vocal cord paralysis or laryngeal infection. Early detection and proper treatment of NGTS are necessary. We describe the case of a 78-year-old patient with this syndrome induced by a nasointestinal ileus tube. At administration, ileus was suspected based on physical examination and thoracoabdominal X-ray findings. A nasointestinal ileus tube was placed through the left nasal cavity. Three days after tube placement, hoarseness and wheezing were found during nutrition support team rounds. Upper airway obstruction was suspected and evaluated immediately with flexible laryngoscopy by an otolaryngologist. The nasointestinal ileus tube was removed. The symptoms decreased with prompt proper management. Immediate removal of the tube and early recognition of symptoms are the first steps in the treatment for this syndrome, in addition to the initiation of steroid, proton pump inhibitor, and antibiotic therapy. The cause of NGTS is thought to be continuous pressure on the hypopharynx and cervical esophagus. NGTS should be considered in patients with either nasogastric or nasointestinal ileus tubes. Early diagnosis and proper management of NGTS are important.

At present, the combination of immune checkpoint inhibitors (ICIs) or an ICI and a tyrosine kinase inhibitor (TKI) are the main treatment options as first-line therapy for metastatic renal cell cancer (mRCC). Among them, pembrolizumab plus lenvatinib was recently launched in Japanese clinical practice. In this review, the efficacies and safety profiles of pembrolizumab plus lenvatinib for mRCC between Japanese and global populations are compared. In addition, lenvatinib is currently available for the treatment of not only mRCC but also of endometrial, thyroid, thymic, and hepatocellular cancers. We briefly summarized the characteristics of pembrolizumab plus lenvatinib or lenvatinib monotherapy for these malignancies. Finally, the characteristics of pembrolizumab plus lenvatinib for mRCC in the Japanese population are briefly elucidated. In order to develop optimal personalized treatment for mRCC patients, it is necessary for physicians who treat mRCC patients to possess in-depth knowledge of not only the efficacy and safety profile of the respective therapies but also of the interpatient heterogeneities between Japanese and global populations.

To understand the workload of house cleanup and related workforce shortage after a disaster, the actual work situation in disaster-stricken areas is accounted for by disaster volunteer work management data created by the Disaster Volunteer Center of Joso City in Ibaraki Prefecture at the time of the Kanto–Tohoku Heavy Rain Disaster in September 2015. Using the classification of inundation depth, judged from ground elevation, the weekly workload of house cleanup according to the work content is recorded to clarify the characteristics of each area. Comparing this with the inundated areas without destructions by water flow, near the bank break with house destructions, in the urban area, and around the farmland along the old road, a model to estimate the workload is constructed. It was observed that indoor work to recommence living in urban areas continued for a long time, while the work was completed in a relatively short time in the area along the old road. The area near the bank break, with a small number of houses, witnessed very few house destructions. Hence, it is not necessary to separately calculate the workload caused by house destructions. The appropriateness of the estimated results was verified by using a method to estimate the workload based on the amount of disaster waste. As a result, the total workload estimated by disaster volunteers and victims for the busy period of two months was a million people. In the case of the Joso City flood, very few houses were completely destroyed, therefore, regular living could be resumed swiftly and people settled there after the disaster due to its proximity to the metropolitan area. Hence, the population decreased by the flood was recovered in two years.

Naoyuki Akashi,1 Tomio Umemoto,1 Hodaka Yamada,2 Takayuki Fujiwara,3 Kei Yamamoto,1 Yousuke Taniguchi,1 Kenichi Sakakura,1 Hiroshi Wada,1 Shin-ichi Momomura,1 Hideo Fujita1 1Division of Cardiovascular Medicine, Jichi Medical University Saitama Medical Center, Saitama, Japan; 2Division of Endocrinology and Metabolism, Jichi Medical University Saitama Medical Center, Saitama, Japan; 3Department of Cardiovascular Medicine, The University of Tokyo Hospital, Tokyo, JapanCorrespondence: Tomio Umemoto, Division of Cardiovascular Medicine, Jichi Medical University Saitama Medical Center, 1-847 Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan, Tel +81-48-647-2111, Fax +81-48-648-5188, Email to-ume@omiya.jichi.ac.jpPurpose: Dipeptidyl peptidase-4 (DPP-4) inhibitors increase endothelial progenitor cells (EPCs) in peripheral blood circulation. However, the underlying mechanisms and effects on vascular endothelial function remain unclear. We evaluated whether the DPP-4 inhibitor teneligliptin increases circulating EPCs by inhibiting stromal-derived factor-1α (SDF-1α) and improves flow-mediated vascular dilatation (FMD) in type 2 diabetes mellitus patients with acute coronary syndrome (ACS) or its risk factors.Patients and Methods: This single-center, open-label, prospective, randomized controlled trial evaluated 17 patients (hemoglobin A1c ≤ 7.5% and peak creatinine phosphokinase < 2000 IU/mL) with ACS or a history of ACS or multiple cardiovascular risk factors. Metabolic variables of glucose and lipids, circulating EPCs, plasma DPP-4 activity, and SDF-1α levels, and FMD were evaluated at baseline and 28 ± 4 weeks after enrollment. Patients were randomly assigned to either the teneligliptin (n = 8) or control (n = 9) groups.Results: The DPP-4 activity (∆− 509.5 ± 105.7 vs ∆32.8 ± 53.4 μU/mL) and SDF-1α levels (∆− 695.6 ± 443.2 vs ∆11.1 ± 193.7 pg/mL) were significantly decreased after 28 weeks in the teneligliptin group than those in the control group. The number of EPCs showed an increasing trend in the teneligliptin treated group; albeit this did not reach statistical significance. Glucose and lipid levels were not significantly different between the groups before and after 28 weeks. However, FMD was significantly improved in the teneligliptin group when compared to the control group (∆3.8% ± 2.1% vs ∆− 0.3% ± 2.9%, P=0.006).Conclusion: Teneligliptin improved FMD through a mechanism other than increasing the number of circulating EPCs.Keywords: endothelial progenitor cell, teneligliptin, DPP-4 inhibitor, flow-mediated dilation, type 2 diabetes mellitus