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Immune effector cell-associated neurotoxicity syndrome usually occurs within the first four weeks of chimeric antigen receptor (CAR)-T cell therapy. In addition, prolonged cytopenia is a long-term adverse effect following the use of CAR T-cell therapies. Here, we present a case of prolonged severe cytopenia followed by fatal CAR T-cell-mediated encephalitis. A 22-year-old male patient was referred to our hospital for a second relapse of B-cell precursor acute lymphoblastic leukemia (ALL), which was diagnosed 22 months after hematopoietic stem cell transplantation from an unrelated donor. CAR T-cells (tisagenlecleucel) were infused during the third cycle of complete remission after chemotherapy. The patient developed grade 2 cytokine release syndrome requiring a single dose of tocilizumab. Cytopenia was profound from day 30 onward, but no other serious complications were observed. On day 50, the patient developed sensory impairment, disturbing behavior, and confusion. Brain magnetic resonance imaging (MRI) scan and cerebrospinal fluid (CSF) analysis revealed no pathological findings. Severe neutropenia persisted despite G-CSF treatment, and the patient's neurological symptoms rapidly progressed from day 65. Brain MRI revealed hydrocephalus. The CSF showed elevated xanthochromia, mononuclear cell counts, and protein levels. A therapeutic attempt with prednisolone for encephalitis was ineffective, and the patient died on day 77 owing to neurological toxicity. Late-onset CAR T-cell-mediated encephalitis was suspected, although the CSF was not assessed for CAR T-cells. In addition, the patient developed prolonged and severe cytopenia. To the best of our knowledge, this is the first report of prolonged severe cytopenia followed by late-onset CAR T-cell-mediated encephalitis. These unexpected long-term adverse effects may occur and should also be considered., Competing Interests: The authors declare no conflict of interest. Disclosure forms provided by the authors are available on the website., (Copyright Ⓒ2024 Asia-Pacific Blood and Marrow Transplantation Group (APBMT).)

The prognosis of patients with osteosarcoma who experience recurrence or progression (R/P) is extremely poor, and more effective and less toxic therapies are needed. In the current study, the clinical data of osteosarcoma patients who experienced R/P were retrospectively analyzed to verify the reliability of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression or MGMT promoter methylation for predicting the response to off-label temozolomide (TMZ)-containing chemotherapy. Of the 30 evaluable patients, 9 (30%) showed no/low MGMT protein expression, whereas all 16 evaluable patients had unmethylated MGMT promoter irrespective of MGMT protein expression levels. Twenty-three patients received TMZ-containing chemotherapy for measurable lesions (n = 14) or as adjuvant therapy following resection of recurrent lesions (n = 9). Among 14 patients with radiologically measurable lesions, the objective response rate was higher in the MGMT no/low-expression group (50.0%) than in the MGMT intermediate/high-expression group with borderline significance (0%, p = 0.066). The 6-month progression-free survival (PFS) rate in patients with radiologically measurable lesions was significantly higher in the MGMT no/low-expression group (50.0%) than in the MGMT intermediate/high-expression group (0%, p = 0.036). In the multivariate analysis of the 23 patients receiving TMZ-containing chemotherapy, MGMT expression and disease status before TMZ-containing chemotherapy were significantly associated with PFS. No severe adverse effects were observed during TMZ-containing chemotherapy. MGMT protein expression, but not MGMT promoter methylation, could predict a favorable outcome in patients receiving TMZ-containing chemotherapy., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Coronavirus disease 2019 (COVID-19) is characterized by high interleukin-6 levels. Clinical data supporting tocilizumab, a monoclonal antibody that targets interleukin-6 receptor-alpha, for treating Japanese patients with severe COVID-19 pneumonia are needed., Methods: This single-arm phase 3 study investigated tocilizumab (8 mg/kg) plus standard of care (SOC) in Japanese patients hospitalized with severe COVID-19 pneumonia. Clinical status was assessed using a 7-category ordinal scale on day 28 (primary endpoint) and day 14 (secondary endpoint). Other secondary endpoints were time to improvement (≥2 category improvement) and time to hospital discharge. Safety was assessed as the incidence of adverse events (AEs)., Results: Among 48 patients enrolled, 44 (91.7 %) scored ≥3 on the 7-category ordinal scale at baseline. At day 28, 35 patients (72.9 %) scored 1 and 5 (10.4 %) scored 7 on the 7-category ordinal scale; 36 (75.0 %, 95 % confidence interval [CI]: 60.40 %-86.36 %) and 39 (81.3 %, 95 % CI: 67.37 %-91.05 %) patients achieved ≥2- and ≥1-category improvement, respectively; 6 patients (12.5 %, 95 % CI: 4.73 %-25.25 %) demonstrated ≥1-category worsening. At day 14, 25 (52.1 %, 95 % CI: 37.19 %-66.71 %) and 33 patients (68.8 %, 95 % CI: 53.75 %-81.34 %) achieved ≥2- and ≥1-category improvement, respectively; 5 patients (10.4 %, 95 % CI: 3.47 %-22.66 %) demonstrated ≥1-category worsening. Median times (95 % CI) to improvement and hospital discharge were 11 (9-15) and 15 (11-18) days, respectively. Forty patients (83.3 %) experienced AEs; the incidence of ≥grade 3 AEs was 25 %., Conclusion: Tocilizumab plus SOC may provide improved clinical status in Japanese patients with severe COVID-19 pneumonia; no new safety signals were identified., Competing Interests: Declaration of competing interest AH discloses consulting fees from Chugai Pharmaceutical Co. Ltd and Kowa Company Ltd. MY, NO, YK, and NM disclose research grants from Chugai Pharmaceutical Co. Ltd. MY and YK provided honoraria lectures for Chugai Pharmaceutical Co. Ltd. NM provided honoraria lectures for MSD, Shionogi Inc., Asahi Kasei Pharma, and Zeria Pharmaceutical Co., Ltd. NK, RS, and RO are employees of Chugai Pharmaceutical Co. Ltd. TN discloses consulting fees from Chugai Pharmaceutical Co. Ltd and research grants from Chugai Pharmaceutical Co. Ltd, Eli Lilly Japan K.K., and Shionogi & Co., Ltd, and provided honoraria lectures for Chugai Pharmaceutical Co. Ltd, Eli Lilly Japan K.K., AstraZeneca K.K., GlaxoSmithKline Plc, and Pfizer Japan Inc., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

[Purpose] In Japan, one measure against the novel coronavirus disease-2019 infection involves the public use of surgical masks. Research indicates that exercising while wearing a mask increases the physical burden, particularly affecting young people during high-intensity exercise. This study examined the effects of wearing masks while running in male university students. [Participants and Methods] The participants were 20 healthy male university students (21.6 ± 1.6 years). The participants underwent cardiopulmonary exercise tests with the masks on and off on different days until exhaustion. The following parameters were measured: exercise duration, Borg Scale rating (respiratory or lower extremities), surface temperature around the mouth, time to sweat onset, metabolic reaction, pulmonary ventilation, and cardiovascular reaction parameters. [Results] The results showed that VO 2 max remained consistent between the mask-on and mask-off conditions. However, minute ventilation, respiratory rate, and heart rate decreased in the mask-on condition, which correlated with a reduction in exercise duration. Furthermore, running with the mask significantly decreased the VE/VO 2 , VE/ VO 2 , Borg Scale rating of the lower extremities, and the time to sweat onset. [Conclusion] Running with a surgical mask affected respiratory function and decreased exercise duration in healthy male university students. However, it did not induce any changes in VO 2 max., Competing Interests: The authors declare no conflict of interest., (2024©by the Society of Physical Therapy Science. Published by IPEC Inc.)

A new technique for ex situ solid-state nuclear magnetic resonance imaging of polymeric films has been developed. This method uses the static magnetic field gradient generated by a water-cooled copper electromagnet. The imaging process involves scanning the sample in the plane of the film under a static magnetic field gradient. Two-dimensional (2D) 19F MRI measurements are attempted, where the fast Fourier transform (FFT) spectra of the second half of a Hahn echo peak is used for the depth (X-axis) direction, and the sample film is mechanically moved for the Y-axis, which is in-plane with respect to the film surface and normal to the inter-magnetic-pole line (Z-axis). The sample is a poly(tetrafluoroethylene) [PTFE] film with carved stripes on its surface. Furthermore, three-dimensional (3D) measurements of the film surface and thickness orientations were also performed for an analogous PTFE film. For 2D profiling on the film surface, 2D sample-moving was used. For depth profiling, FFT spectrum analysis was undertaken for each voxel situated at a specific (Y, Z) coordinate within the film. As a result, a 3D image of the sample and its corresponding geometry were obtained, although the scanning area was restricted to a part of the sample. Finally, numerical simulations of the spatial distribution of the static magnetic field were performed to confirm the validity of the present method., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Introduction: The current study investigated the relationship between the characteristics of a darts game, including the throwing motion toward a target, and mild cognitive impairment (MCI). To this end, we examined the associations between cognitive function and mental health, and the shift in center of gravity while throwing darts. In a preliminary investigation, a 1-month dart game intervention was conducted among older individuals living in the community. The participants were divided into the non-MCI and MCI groups, and the relationship between center of gravity movement during throwing and the presence of dementia was examined., Methods: The intervention lasted for 1 month and was tested on healthy older individuals (aged ≥ 65 years) recruited from the community. The Japanese version of the Montreal Cognitive Assessment and the Trail Making Test was used to assess cognitive function. Mental health was evaluated using the Kessler Psychological Distress Scale and the Subjective Well-being Inventory. The center of pressure was analyzed to determine the center of gravity shift during dart throwing., Results: The analysis of factors influencing the determination of the MCI score during the intervention revealed a tendency for the center of gravity shift to be associated as a protective factor in the non-MCI group, although this association did not reach statistical significance (odds ratio = 0.942, p  = 0.084). In the MCI group, a significant effect of age was observed in the MCI score (odds ratio = 1.539, p  = 0.007)., Conclusion: The current findings suggest that conducting center of gravity shift testing could potentially provide a helpful tool for predicting early decline in cognitive function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Kawabata, Iida, Kunishige, Fukuda, Miyaguchi and Harada.)