BACKGROUND: Motion sickness is a common transportation issue worldwide. Vestibular dysfunction has been reported to be a key etiology of motion sickness. However, there are limited technologies for alleviating motion sickness. METHODS: The most appropriate frequency (Hz) and level (dBZ) of pure tone for modulation of vestibular function were determined by an ex vivo study using murine utricle explants. The preventive effects of the selected pure tone on motion sickness were then confirmed by using a beam balance test in mice. The alleviating effects of pure tone on motion sickness induced by a swing, driving simulator or real car were objectively assessed by using posturography and electrocardiography (ECG) and were subjectively assessed by using the Motion Sickness Assessment Questionnaire (MSAQ) in humans. RESULTS: The effect of short-term (≤5 min) exposure to a pure tone of 80-85 dBZ (= 60.9-65.9 dBA) at 100 Hz on motion sickness was investigated in mice and humans. A mouse study showed a long-lasting (≥120 min) alleviative effect on shaking-mediated exacerbated beam test scores by 5-min exposure to a pure tone of 85 dBZ at 100 Hz, which was ex vivo determined as a sound activating vestibular function, before shaking. Human studies further showed that 1-min exposure to a pure tone of 80-85 dBZ (= 60.9-65.9 dBA) at 100 Hz before shaking improved the increased envelope areas in posturography caused by the shakings of a swing, a driving simulator and a vehicle. Driving simulator-mediated activation of sympathetic nerves assessed by the heart rate variable (HRV) and vehicle-mediated increased scores of the MSAQ were improved by pure tone exposure before the shaking. CONCLUSION: Since the exacerbated results of posturography and HRV reflect shaking-mediated imbalance and autonomic dysfunction, respectively, the results suggest that the imbalance and autonomic dysregulation in motion sickness could be improved by just 1-min exposure to a pure tone with daily exposable sound pressure levels. TRIAL REGISTRATION Registration number: UMIN000022413 (2016/05/23-2023/04/19) and UMIN000053735 (2024/02/29-present).
Motion Sickness/therapy* ; Animals ; Mice ; Humans ; Male ; Adult ; Female ; Sound ; Middle Aged ; Young Adult ; Mice, Inbred C57BL

Objective: In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression. Methods: Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events. Results: Between February 2018 and September 2020, 99 patients were enrolled; of these, 82patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase). Conclusion The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE.Trial Registration: JRCT Identifier: jRCTs031180124

Objective: In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression. Methods: Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events. Results: Between February 2018 and September 2020, 99 patients were enrolled; of these, 82patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase). Conclusion The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE.Trial Registration: JRCT Identifier: jRCTs031180124

Objective: In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression. Methods: Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events. Results: Between February 2018 and September 2020, 99 patients were enrolled; of these, 82patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase). Conclusion The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE.Trial Registration: JRCT Identifier: jRCTs031180124

Background: The anti-programmed death 1 (PD-1) antibody has led to durable clinical responses in a wide variety of human tumors. We have previously developed the caninized anti-canine PD-1 antibody (ca-4F12-E6) and evaluated its therapeutic properties in dogs with advance-staged oral malignant melanoma (OMM), however, their therapeutic effects on other types of canine tumors remain unclear. Objective: The present clinical study was carried out to evaluate the safety profile and clinical efficacy of ca-4F12-E6 in dogs with advanced solid tumors except for OMM. Methods: Thirty-eight dogs with non-OMM solid tumors were enrolled prospectively and treated with ca-4F12-E6 at 3 mg/kg every 2 weeks of each 10-week treatment cycle. Adverse events (AEs) and treatment efficacy were graded based on the criteria established by the Veterinary Cooperative Oncology Group. Results: One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca-4F12-E6. Treatment-related AEs of any grade occurred in 13 out of 37 cases (35.1%).Two dogs with sterile nodular panniculitis and one with myasthenia gravis and hypothyroidism were suspected of immune-related AEs. In 30 out of 37 dogs that had target tumor lesions, the overall response and clinical benefit rates were 6.9% and 27.6%, respectively. The median progression-free survival and overall survival time were 70 days and 215 days, respectively. Conclusions The present study demonstrated that ca-4F12-E6 was well-tolerated in nonOMM dogs, with a small number of cases showing objective responses. This provides evidence supporting large-scale clinical trials of anti-PD-1 antibody therapy in dogs.

We describe a rare case of sacral epidural arteriovenous fistulas (edAVFs) with atypical clinical course of treatment. A 78-year-old man with a history of spinal surgery presented progressive gait disturbance and urinary incontinence. Spinal angiography demonstrated a sacral spinal AVF fed by bilateral lateral sacral arteries, draining to the venous pouch with subdural drainage. The first treatment by direct interruption of a subdural drainer was incompletely finished. Postoperative reassessment by 3D imaging analysis led to the diagnosis of sacral edAVF and 3D understanding of its angioarchitecture. The second treatment by transarterial embolization (TAE) resulted in complete occlusion of a sacral edAVF. However, spinal venous congestion didn’t improve, because the recruitment of occult edAVFs at the multiple lumbar levels and complex-shaped sacral ventral epidural venous plexus (VEP) were involved in the remnant of prior subdural drainage. The third treatment was performed by TAE for three occult edAVFs and the VEP compartment connecting between a patent edAVF and subdural drainage, which resulted in complete disappearance of spinal cord edema. Endovascular embolization of VEP compartment connecting to subdural drainage in addition to fistulous occlusion may be one of the treatment options for several edAVFs at the multiple spinal levels.

The patient was an 80-year-old man who was diagnosed with cStage IIIB non-small cell lung cancer (NSCLC) and early gastric cancer. The advanced lung cancer was treated with chemotherapy while the gastric cancer was monitored. Immune checkpoint inhibitors were effective against the lung cancer for a long period, but new gastric cancer appeared and progressed to an advanced stage, necessitating total gastrectomy 5 years after the diagnosis of NSCLC. The patient is currently being treated with a molecular targeted agent for progression of the lung cancer after gastrectomy. In the future, the number of cases with multiple primary cancers will increase alongside aging of the population and advances in cancer treatment, and a system for tumor-agnostic treatment selection and medical treatment will be necessary.

Although the descriptions of shigyakukachotanto in “Waitaimiyaofang” and tsumyakushigyakukachotanjuto in “Songban Shanghanlun” are quite similar to each other, the specifications of the dosages of crude drugs and the water volume in the books were considerably different. Focused on the specified water volume to decoct these formulas, each reasonable decocting period was estimated, then the decoctions were prepared using hard water that was common in mainland China. The dosages of aconite root were 2­-fold different between these two formulas, but the contents of aconitine-­type diester alkaloids (ADA) in both decoctions were found in the range of 1.2—1.4­-fold. It was suggested that in order to control the efficacy and the safety of aconite, the decocting period was well regulated by the specification of water volume for decocting at this ancient era. Moreover, the dosages of aconite root and glycyrrhiza in bukuryoshigyakuto (BSGT) formula of “Songban Shanghanlun” are equal to those of shigyakuto (SGT) but the specified water volume to begin decocting is as about twice as that of SGT. When prepared using hard water, BSGT resulted to make the contents of ADA lower and those of non-­ester alkaloids higher compared with those of SGT decoction. It was suggested the spe­cific water volume for each formula prescribed in classical Chinese medicine had considerable significance to determine the dosages of chemical ingredients in the decoctions especially in the circumstances using hard water to prepare them.

To decide the policy to promote palliative care properly, a new questionnaire has been added to Patient’s behavior survey to assess Quality of Life (QOL) of inpatients and outpatients in Japan. The aim of this study was to survey QOL score of general population in Japan by using a questionnaire of patient’s behavior survey. A large nationwide postal survey was conducted from January through February 2013 in Japan. A total of 2400 subjects were selected randomly from among members of the general population who were 20 to 79 years of age and lived in Japan. A total of 978 (41.1%) questionnaires were analyzed, and reference data of QOL score weighted by the national standard value of sex-age group population were calculated. Correlation coefficients were calculated between QOL score and SF-8TM, Patient Health Questionnaire-9 (PHQ-9), Eastern Cooperative Oncology Group Performance Status (ECOG), Memorial Symptom Assessment Scale (MSAS) score. In addition, sociodemographic factors related to QOL score were evaluated. From the perspectives of public health and administrative policy, the results of this survey will provide important basic data to evaluate patient’s behavior survey broadly and continuously with the goal of establishing a palliative care system in Japan.