Efficacy of off-the-shelf bone marrow mesenchymal stem cells for pediatric steroid-refractory acute graft-versus-host disease.

Introduction: Temcell is a mesenchymal stem cell (MSC) product approved for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in Japan. However, reports regarding Temcell's efficacy in pediatric patients have been scarce, and the appropriate use of MSC therapy against pediatric SR-aGVHD also remains to be determined. Patients and Methods: We retrospectively assessed a cohort of pediatric patients treated with Temcell for SR-aGVHD following allogeneic hematopoietic transplantation. MSCs were infused intravenously at a dose of 2 × 106 cells/kg according to the manufacturer's instructions. Results: Twelve patients received eighteen cycles of MSC therapy (median age, 10.3 [1.7-17.8] years), with four receiving additional cycles (one cycle: n = 3, three cycles: n = 1). The severity of aGVHD before MSC therapy was grade I-II in three patients and grade III-IV in nine patients (gut stage 3-4, n= 7; liver stage 3-4; n =2). The median number of immunosuppressive therapy regimens received prior to MSC administration was two (range: 1-5). The first MSC cycle displayed the best overall response rate of 83%, including six patients with a complete response (CR) and with a 49% reduction in the mean daily dose of prednisone after eight weeks. The median time to first response was 3.5 days (range: 2-15 days). Two of the four patients who were re-administered MSCs for recurrent or persistent GVHD achieved a CR. The three-year overall survival rate was 69.4%, while the three-year failure free survival (FFS) rate was 22.2%, with a median FFS of 4.9 months. There were no observable side effects of MSC therapy. Conclusions: MSC therapy appears to be an effective and safe treatment for pediatric SR-aGVHD, with a steroid-sparing effect and satisfactory efficacy upon re-administration. Further studies are needed to determine its appropriate combination with additional treatments and the optimal use of re-administration of MSCs.

Nelarabine-containing salvage therapy and conditioning regimen in transplants for pediatric T-cell acute lymphoblastic leukemia and lymphoma.

Therapy for relapsed or refractory (r/r) T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) in children is challenging, and new treatment methods are needed. We retrospectively analyzed eight patients with r/r T-ALL (five patients) and T-LBL (three patients) who were treated with nelarabine (NEL) plus etoposide, cyclophosphamide, and intrathecal therapy, administered 3 days apart. Five patients achieved a complete response, and the other three achieved a partial response (PR). All patients underwent hematopoietic stem cell transplantation (HSCT) after two cycles of treatment, except for one patient who received one cycle. Three patients who had previously received HSCT were treated with reduced-intensity conditioning regimens, including fludarabine, melphalan, and NEL; one survived for over 5 years after the second HSCT. Grade 2 neuropathy occurred in one patient, but other severe toxicities commonly associated with NEL were not observed during NEL administration in combination with chemotherapy. The 2-year overall survival and event-free survival rates were 60.0% and 36.5%, respectively. The addition of NEL to reinduction chemotherapy was useful in achieving remission and did not lead to excessive toxicity. In addition, a conditioning regimen, including NEL, appeared to be effective in patients who had previously undergone HSCT.

Rare TCF3 variants associated with pediatric B cell acute lymphoblastic leukemia.

Germline genetic variants influence development of pediatric B cell acute lymphoblastic leukemia (B-ALL). Genome-wide association studies (GWAS) have identified several pediatric B-ALL susceptibility loci. IKZF1 and PAX5, transcription factors involved in B cell development, have been reported as susceptibility genes for B-ALL development. Therefore, we hypothesized that rare variants of genes involved in B cell development would be candidate susceptibility loci for pediatric B-ALL. Thus, we sequenced TCF3, a key transcription factor gene involving in B cell development. Saliva DNA from 527 pediatric patients with pediatric B-ALL in remission who were registered with the Tokyo Children's Cancer Study Group (TCCSG) were examined. As a TCF3 gene-based evaluation, the numbers of rare deleterious germline TCF3 sequence variants in patients with pediatric B-ALL were compared with those in cancer-free individuals using data in public databases. As a TCF3 single-variant evaluation, the frequencies of rare deleterious germline TCF3 sequence variants in patients with pediatric B-ALL were also compared with those in control data. TCF3 gene-based analysis revealed significant associations between rare deleterious variants and pediatric B-ALL development. In addition, TCF3 variant-based analysis showed particularly strong association between variant rs372168347 (three in 521 TCCSG and three in the 15780 gnomAD whole genome analysis cohort, p = 0.0006) and pediatric B-ALL development. TCF3 variants are known to influence B cell maturation and may increase the risk of preleukemic clone emergence.

Early chemotherapeutic intervention to avoid thyroidectomy in pediatric Langerhans cell histiocytosis with thyroid involvement accompanying tracheal stenosis: a report of two cases.

Thyroid involvement is rare in pediatric Langerhans cell histiocytosis (LCH). It may cause airway narrowing, leading to acute-onset respiratory distress. Severe cases may require emergent surgical interventions such as thyroidectomy, which should be avoided in children due to higher rates of complication, particularly in infancy. There is currently no consensus on the indications for surgical treatment in LCH with thyroid involvement. In this report, we describe the cases of two children who presented with tracheal stenosis caused by thyroid LCH, both of which were successfully treated by early induction of chemotherapy, and one of which was also treated for a shorter duration. Mutation analysis detected in-frame deletions of BRAF exon 12 in both cases. These cases suggest that timely diagnosis and administration of chemotherapy may alleviate severe airway obstruction and reduce the need for thyroidectomy in pediatric patients with thyroid LCH.

[Development and validation of the University of Tokyo Occupational Mental Health leadership checklist among occupational health specialists].

OBJECTIVES: Recently, occupational health specialists (OHS) are expected to exert leadership to develop high-quality occupational health activities. This study aimed to develop and investigate the reliability and validity of a scale to measure leadership preparation among OHS (The University of Tokyo Occupational Mental Health [TOMH] Leadership Checklist; TLC). METHODS: Based on literature reviews and interviews among OHS, we created potential items consisting of 54 items with six factors (10 items for self-awareness, 10 items for situational awareness, 9 items for vision, 12 items for mindset, 3 items for performance of one's duties, and 10 items for relationship-building). An online survey was conducted with 300 OHS in Japan to verify the scale's reliability and validity. RESULTS: Consequent to the exploratory factor analysis, using the principal factor method and promax rotation, 51 items across the following five factors were identified; "self-awareness", "situational awareness", "vision", "mindset", and "performance of one's duties". The confirmatory factor analysis showed good fit indices; CFI = 0.877, SRMR = 0.050, and RMSEA = 0.072. Cronbach's α ranged from 0.93-0.96. Additionally, the scores of the TLC were significantly positively correlated with work engagement, job satisfaction, and self-efficacy; contrastingly, they were significantly negatively correlated with psychological distress (p < .05). Furthermore, the participants who had experience leadership without authority indicated significantly higher scores of the TLC and its subscales than those who did not (p < .001). DISCUSSION AND CONCLUSIONS: The newly developed TLC appeared to have acceptable levels of reliability and validity. It would be beneficial for OHS to show good leadership.

Reduced-intensity allogenic transplantation for children and adolescents with Philadelphia chromosome-positive acute lymphoblastic leukemia.

Survival rates of patients with Philadelphia chromosome-positive ALL (Ph+ALL) have improved considerably with the introduction of tyrosine kinase inhibitors (TKI); however, hematopoietic stem cell transplantation (HSCT) continues to play an important role. Reduced-intensity conditioning (RIC) regimens have been widely applied particularly for older patients, but their validity for children and adolescents with Ph+ALL has not been investigated. In this study, data from patients receiving HSCT for de novo Ph+ALL in first or second remission at ages younger than 25 years and with a history of pre-HSCT TKI therapy were retrospectively collected through the nationwide registry in Japan. In 265 patients who received myeloablative conditioning (MAC) and 33 patients receiving RIC, 5-year leukemia-free survival (LFS) rates were 67.3% and 79.8%, respectively (p = 0.142). Multivariate analysis of LFS, focusing on patients with good performance status, identified RIC as a significant prognostic factor for LFS (hazard ratio 0.32, p = 0.032), as well as older age, higher leukocyte count at diagnosis, and disease with additional chromosomal abnormalities. These trends were similar when we focused on patients who received prophylactic post-HSCT TKI treatment, as 5-year LFS was 81.0% for MAC and 84.4% for RIC (p = 0.748). In summary, HSCT with RIC regimen showed at least comparable LFS to HSCT with MAC regimen, and RIC was an independent favorable prognostic factor on multivariate analysis adjusting potential prognostic factors. While patient numbers were limited, our data suggest that RIC may be safely applied in this group, particularly combined with prophylactic post-HSCT TKI maintenance therapy.

Assessing the Usefulness of Ultrasonography for the Diagnosis and Evaluation of Intra-Orbital Lesions in Pediatric Patients: A Retrospective Analysis.

OBJECTIVES: To assess the usefulness of ultrasonography in the diagnosis and evaluation of extraocular intra-orbital lesions in pediatric patients. METHODS: Twenty-three pediatric patients with intra-orbital lesions who underwent both ultrasound and computed tomography/magnetic resonance imaging (CT/MRI) were included. The following parameters were evaluated using ultrasound: 1) lesion detection rate (presence or absence of lesions), 2) lesion characteristics, 3) lesion location (extraconal or intraconal), and 4) the lesion longest linear dimensions, and these were compared using Fisher's exact test and Mann-Whitney U test. RESULTS: Two lesions could not be detected using ultrasound; in the other 21 cases, the lesion characteristics diagnosed by ultrasound were correct. Diagnostic accuracy of detection and characteristics assessment using ultrasound were 91.3% and 91.3%, respectively. The lesion location was not significantly different between the two groups (intraconal/extraconal in those detected using ultrasound versus those in the absence on ultrasound = 7/14 versus 0/2, P > .999); however, in two cases that were not detected on ultrasound, the lesions were located at extraconal. Lesions that were small in longest linear dimensions on CT/MRI were not detected using ultrasound (the longest linear dimensions in lesions detected using ultrasound versus that in the absence of ultrasound: 29.5 ± 8.2 [range, 13-46] versus 10 and 11 mm, P = .043). CONCLUSIONS: Ultrasonography proved to be useful for visualizing and evaluating intra-orbital lesions except for lesions that were relatively small in size. Therefore, although ultrasound could not detect lesions located behind bone and bone invasion, it could be used for diagnosing and selecting treatment strategies for intra-orbital lesions.

Exploring the Impact of Intermolecular Interactions on the Glassy Phase Formation of Twist-Bend Liquid Crystal Dimers: Insights from Dielectric Studies.

The formation of the nematic to twist-bend nematic (NTB) phase has emerged as a fascinating phenomenon in the field of supramolecular chemistry, based on complex intermolecular interactions. Through a careful analysis of molecular structures and dynamics, we elucidate how these intermolecular interactions drive the complex twist-bend modulation observed in the NTB. The study employs broadband dielectric spectroscopy spanning frequencies from 10 to 2 × 109 Hz to investigate the molecular orientational dynamics within the glass-forming thioether-linked cyanobiphenyl liquid crystal dimers, namely, CBSC7SCB and CBSC7OCB. The experimental findings align with theoretical expectations, revealing the presence of two distinct relaxation processes contributing to the dielectric permittivity of these dimers. The low-frequency relaxation mode is attributed to an "end-over-end rotation" of the dipolar groups parallel to the director. The high-frequency relaxation mode is associated with precessional motions of the dipolar groups about the director. Various models are employed to describe the temperature-dependent behavior of the relaxation times for both modes. Particularly, the critical-like description via the dynamic scaling model seems to give not only quite good numerical fittings, but also provides a consistent physical picture of the orientational dynamics in accordance with findings from infrared (IR) spectroscopy. Here, as the longitudinal correlations of dipoles intensify, the m1 mode experiences a sudden upsurge in enthalpy, while the m2 mode undergoes continuous changes, displaying critical mode coupling behavior. Interestingly, both types of molecular motion exhibit a strong cooperative interplay within the lower temperature range of the NTB phase, evolving in tandem as the material's temperature approaches the glass transition point. Consequently, both molecular motions converge to determine the glassy dynamics, characterized by a shared glass transition temperature, Tg.

Emergency department activities at the Athletes' Village during the Tokyo 2020 Olympic and Paralympic Games.

Aim: More than 15,000 elite athletes participated in the Tokyo 2020 Olympic and Paralympic Games. Providing adequate medical services to these elite athletes was a priority. Hence, a polyclinic was established in the Athletes' Village. Visitors were triaged at the emergency department of the polyclinic to enable early treatment of critical illnesses or injuries in the emergency room (ER) and to identify patients suspected of having coronavirus disease as early as possible. No reports of emergency department activities at large sporting events in the pandemic era are available. Here, we aim to summarize the activities at the emergency department of the polyclinic. Methods: Data were collected using an electronic medical record system, nursing records, and questionnaires administered during triage from July 13 to September 8, 2021. Polyclinic data involving accredited athletes and team members were summarized. Results: During the Olympic Games, 12,318 triage cases were reported, of which 75 were treated in the ER. During the Paralympic Games, 8398 triage cases were reported, of which 94 were treated in the ER. During the Olympic Games, musculoskeletal issues (26 patients) were the most common. During the Paralympic Games, ear, nose, and throat issues were the most common (21 patients). Two patients experienced cardiopulmonary arrest in the Athletes' Village and were transported to the hospital postresuscitation. Conclusion: During the study period, many critically ill patients were triaged and treated at the emergency department. Our data can be used to improve medical care and infection prevention at future international sporting events.

Dielectric Study of Liquid Crystal Dimers: Probing the Orientational Order and Molecular Interactions in Nematic and Twist-Bend Nematic Phases.

Dielectric spectroscopy in frequencies that range from 10 Hz to 1 GHz has been used to study the molecular orientational dynamics of the two types of dimers that form the twist-bend nematic phase over a wide range of temperatures for both nematic and twist-bend nematic phases. The symmetrical and asymmetrical liquid crystal dimers with the cyanobiphenyl mesogenic groups were investigated. The results were analyzed within the framework of the molecular theory of dielectric permittivity for nematogens. The two molecular processes can be assigned to the reorientation of the monomeric unit: the high frequency one to the precessional rotation of the longitudinal components of the cyanobiphenyl groups (CN) and the second (low frequency) to the end-over-end rotation of the CN dipole around the short molecular axis. The precession mode, which is determined by the local order and is almost unaffected by the phase transition from the nematic to the twist-bend phase, while the end-over-end rotation clearly slowed down at the transition, as it is affected by the growth of the intermolecular interactions. The latter corresponds well to the fact revealed by IR spectroscopy about the longitudinal correlation of the molecular dipoles.

Useful sonographic findings for diagnosing dermal metastases of rhabdomyosarcoma.

Rhabdomyosarcoma developing in deep locations, such as the genitourinary tract, and perianal and perineal regions, symptoms may be obscure. Dermal rhabdomyosarcoma metastases may be first symptom of that and those arise in the subcutaneous fat tissue, presenting as a high echoic area surrounded by a low echoic area, accompanied by a high echoic peripheral area. These sonographic findings might indicate an aggressive malignant disease, and that would be useful to differentiate from other dermal lesions.

Married women's decision to delay childbearing, and loneliness, severe psychological distress, and suicidal ideation under crisis: online survey data analysis from 2020 to 2021.

BACKGROUND: The COVID-19 pandemic has affected every aspect of our lives, including the decision to become pregnant. Existing literature suggests that infertility and the decision to delay childbearing at a younger age are associated with a lower level of well-being and regrets when women start to desire a baby. Thus, the decision to delay childbearing due to the pandemic could negatively affect the well-being of women. This study focuses on how pregnancy decisions affect the well-being of women during the COVID-19 pandemic. METHODS: From the Japan COVID-19 and Society Internet Survey, a nationally representative web-based survey, 768 observations of married women aged 18 to 50 years who had the intention of getting pregnant during the pre-pandemic period (conducted in 2020 and 2021) were used. Loneliness, severe psychological distress, and suicidal ideation were used as well-being indicators. For pooled data, a generalised estimated equation (GEE) model was used to estimate how pregnancy decision related to well-being indicators. For a sub-analysis, the sample was divided by the survey year and a Poisson regression model was used. RESULTS: The GEE analysis showed an association between delaying childbearing and severe psychological distress, with the prevalence ratio (PR) being 2.06 [95% CI (1.40-3.03)]. Furthermore, loneliness and suicidal ideation that occurred after the beginning of the pandemic were significantly related to the decision to delay childbearing-1.55 [95% CI (1.03,2.34)] and 2.55 [95% CI (1.45-4.51)], respectively. Moreover, these PRs were larger for 2021 compared to 2020. CONCLUSION: During the COVID-19 pandemic, approximately one-fifth of married women who had childbearing intentions before the pandemic decided to postpone pregnancy. They exhibited a deteriorated mental health state. Furthermore, the negative associations were larger in 2021 compared to 2020. Loneliness has negative consequences for both mental and physical health, as well as elevated severe psychological distress and suicidal ideation among those who decided to postpone pregnancy. Therefore, the current results should not be overlooked by society.

Remote Communication and Loneliness During the COVID-19 Pandemic: Cross-Sectional Study.

BACKGROUND: Although remote communication technologies have been widely used to maintain connections with others against interpersonal contact restrictions and exacerbated loneliness during the COVID-19 pandemic, it is unclear whether and what types of remote communication technologies are effective in mitigating loneliness. OBJECTIVE: This study aimed to investigate the association between remote communication and loneliness when face-to-face meetings with others were strongly prohibited and whether this association varied across types of communication tools, age, and gender. METHODS: We used cross-sectional data from the Japan COVID-19 and Society Internet Survey conducted from August to September 2020. From registered panelists of the research agency, 28,000 randomly sampled participants completed the survey on the website. We created 2 study cohorts who stopped meeting with family members living apart and friends during the pandemic. We categorized whether participants had technology-based remote communication (voice calling, text messaging, and video calling) with family and friends. Loneliness was assessed using the 3-item University of California, Los Angeles Loneliness Scale. We used a modified Poisson regression model to investigate the association between loneliness and remote communication with family members living apart or friends. We also conducted subgroup analyses based on age and gender. RESULTS: A total of 4483 participants stopped meeting with family members living apart, and 6783 participants stopped meeting with friends during the COVID-19 pandemic. Remote communication with family members living apart did not show an association with loneliness, whereas remote communication with friends was associated with a low prevalence of loneliness (family: adjusted prevalence ratio [aPR]=0.89, 95% CI 0.74-1.08; P=.24 and friends: aPR=0.82, 95% CI 0.73-0.91; P<.001). From analyses by tools, voice calling was associated with low loneliness (family: aPR=0.88, 95% CI 0.78-0.98; P=.03 and friends: aPR=0.87, 95% CI 0.80-0.95; P=.003). Similarly, text messaging was associated with low loneliness (family: aPR=0.82, 95% CI 0.69-0.97; P=.02 and friends: aPR=0.81, 95% CI 0.73-0.89; P<.001). However, we did not find an association between video calling and loneliness (family: aPR=0.88, 95% CI 0.75-1.02; P=.09 and friends: aPR=0.94, 95% CI 0.85-1.04; P=.25). Text messaging with friends was associated with low loneliness regardless of age, whereas voice calling with family or friends was associated with low loneliness only among participants aged ≥65 years. An association between remote communication with friends and low loneliness was found regardless of the type of remote communication tool among men, whereas it was found only for text messaging with friends among women. CONCLUSIONS: In this cross-sectional study of adults in Japan, remote communication, especially via voice calling and text messaging, was associated with low loneliness. Promoting remote communication may reduce loneliness when face-to-face contact is restricted, which should be the subject of future research.

Acute monocytic leukemia with KMT2A::LASP1 developed 9 months after diagnosis of acute megakaryoblastic leukemia in a 2-year-old boy.

Acute myeloid leukemia (AML) is known as one of the subsequent malignant neoplasms that can develop after cancer treatment, but it is difficult to distinguish from relapse when the preceding cancer is leukemia. We report a 2-year-old boy who developed acute megakaryoblastic leukemia (AMKL, French-American-British classification [FAB]: M7) at 18 months of age and achieved complete remission with multi-agent chemotherapy without hematopoietic stem cell transplantation. Nine months after diagnosis and 4 months after completing treatment for AMKL, he developed acute monocytic leukemia (AMoL) with the KMT2A::LASP1 chimeric gene (FAB: M5b). The second complete remission was achieved using multi-agent chemotherapy and he underwent cord blood transplantation 4 months after AMoL was diagnosed. He is currently alive and disease free at 39 and 48 months since his AMoL and AMKL diagnoses, respectively. Retrospective analysis revealed that the KMT2A::LASP1 chimeric gene was detected 4 months after diagnosis of AMKL. Common somatic mutations were not detected in AMKL or AMoL and no germline pathogenic variants were detected. Since the patient's AMoL was different from his primary leukemia of AMKL in terms of morphological, genomic, and molecular analysis, we concluded that he developed a subsequent leukemia rather than a relapse of his primary leukemia.

Effectiveness of mHealth consultation services for preventing postpartum depressive symptoms: a randomized clinical trial.

BACKGROUND: Although many conventional healthcare services to prevent postpartum depression are provided face-to-face, physical and psychosocial barriers remain. These barriers may be overcome by using mobile health services (mHealth). To examine the effectiveness of mHealth professional consultation services in preventing postpartum depressive symptoms in real-world settings, we conducted this randomized controlled trial in Japan, where universal free face-to-face perinatal care is available. METHODS: This study included 734 pregnant women living in Yokohama city who could communicate in Japanese, recruited at public offices and childcare support facilities. The participants were randomized to the mHealth group (intervention, n = 365), where they could use a free app-based mHealth consultation service with gynecologists/obstetricians, pediatricians, and midwives whenever and as many times as they wanted between 6 p.m. and 10 p.m. on weekdays throughout their pregnancy and postpartum periods (funded by the City of Yokohama government) or the usual care group (control, n = 369). The primary outcome was the risk of elevated postpartum depressive symptoms, defined as Edinburgh Postnatal Depression Scale score ≥ 9. Secondary outcomes were self-efficacy, loneliness, perceived barriers to healthcare access, number of clinic visits, and ambulance usage. All outcomes were collected three months post-delivery. We also conducted subgroup analyses assessing the differences in the treatment effect by sociodemographic status. RESULTS: Most women completed all questionnaires (n = 639 of 734, response rate: 87%). The mean baseline age was 32.9 ± 4.2 years, and 62% were primipara. Three months post-delivery, women in the mHealth group had a lower risk of elevated postpartum depressive symptoms (47/310 [15.2%]) compared to the usual care group (75/329 [22.8%], risk ratio: 0.67 [95% confidence interval: 0.48-0.93]). Compared with the usual care group, women in the mHealth group had higher self-efficacy, less loneliness, and fewer perceived barriers to healthcare access. No differences were observed in the frequency of clinic visits or ambulance usage. Furthermore, in the subgroup analyses, we did not find differences in the treatment effect by sociodemographic status. CONCLUSIONS: Local government-funded mHealth consultation services have a preventive effect on postpartum depressive symptoms, removing physical and psychological barriers to healthcare access in real-world settings. TRIAL REGISTRATION: UMIN-CTR identifier: UMIN000041611. Registered 31 August 2021.

Prevalence of pathogenic variants in cancer-predisposing genes in second cancer after childhood solid cancers.

BACKGROUND: Second malignant neoplasms (SMNs) are one of the most severe late complications after pediatric cancer treatment. However, the effect of genetic variation on SMNs remains unclear. In this study, we revealed germline genetic factors that contribute to the development of SMNs after treatment of pediatric solid tumors. METHODS: We performed whole-exome sequencing in 14 pediatric patients with SMNs, including three brain tumors. RESULTS: Our analysis revealed that five of 14 (35.7%) patients had pathogenic germline variants in cancer-predisposing genes (CPGs), which was significantly higher than in the control cohort (p < 0.01). The identified genes with variants were TP53 (n = 2), DICER1 (n = 1), PMS2 (n = 1), and PTCH1 (n = 1). In terms of the type of subsequent cancer, leukemia and multiple episodes of SMN had an exceptionally high rate of CPG pathogenic variants. None of the patients with germline variants had a family history of SMN development. Mutational signature analysis showed that platinum drugs contributed to the development of SMN in three cases, which suggests the role of platinum agents in SMN development. CONCLUSIONS: We highlight that overlapping effects of genetic background and primary cancer treatment contribute to the development of second cancers after treatment of pediatric solid tumors. A comprehensive analysis of germline and tumor samples may be useful to predict the risk of secondary cancers.

Social isolation, loneliness, and their correlates in older Japanese adults.

BACKGROUND: Loneliness and social isolation are elevated in older adults and associated with a range of detrimental outcomes. Despite this, there has been little research on these phenomena or on similarities and differences in their occurrence or combination in older Japanese adults. The current study aims to (i) determine what factors are associated with social isolation and loneliness among older adults in Japan; and (ii) describe the characteristics of individuals who are socially isolated but not lonely, as well as those who feel lonely but are not socially isolated. METHODS: Data were analysed from 13 766 adults aged ≥65 years who participated in the 2019 wave of the Japan Gerontological Evaluation Study. Poisson regression analysis was used to examine associations. RESULTS: Among older Japanese adults, the attributes of higher age, male gender, lower socioeconomic status, being a welfare recipient, and having depressive symptoms were associated with social isolation, while lower socioeconomic status, unemployment, welfare receipt, and poor physical and mental health were associated with loneliness. In addition, better educated, and mentally and physically healthy people were less likely to feel lonely even when socially isolated, while people who were not working and who had mental or physical health problems were more likely to feel lonely even if they were not socially isolated. DISCUSSION: Our results indicate that in order to reduce unwanted social isolation and loneliness among older Japanese adults, in the first instance the focus should be on those individuals who are socioeconomically disadvantaged and unhealthy.