[Discontinuation of tyrosine kinase inhibitors before epiphyseal closure leading to improved short stature in pediatric chronic myelogenous leukemia].

A 3-year-old boy was referred to our hospital with splenomegaly. Blood tests revealed hyperleukocytosis and bone marrow examination showed major BCR::ABL1 fusion, leading to the diagnosis of chronic myelogenous leukemia (CML). Due to intolerance, the tyrosine kinase inhibitor (TKI) was changed from imatinib to dasatinib to nilotinib. The patient achieved molecular remission but became markedly short in stature, measuring 129.3 cm (height standard deviation score [SDS] -3.3) at the age of 12. TKI therapy was discontinued at age 12 years and 10 months, which was 9 years and 8 months after the start of TKI and 1 year and 6 months after achievement of MR4.0, as discontinuation before epiphyseal closure would not improve short stature. At 2 years and 6 months after discontinuation, the patient's height improved to 156.1 cm (SDS-2.0) without relapse. Growth suppression by TKIs is a problem in the management of pediatric CML. This case illustrates how improvement in severe short stature can be achieved by discontinuing TKI therapy before epiphyseal closure.

Mitochondrial uncoupler and retinoic acid synergistically induce differentiation and inhibit proliferation in neuroblastoma.

Neuroblastoma is a leading cause of death in childhood cancer cases. Unlike adult malignancies, which typically develop from aged cells through accumulated damage and mutagenesis, neuroblastoma originates from neural crest cells with disrupted differentiation. This distinct feature provides novel therapeutic opportunities beyond conventional cytotoxic methods. Previously, we reported that the mitochondrial uncoupler NEN (niclosamide ethanolamine) activated mitochondria respiration to reprogram the epigenome, promoting neuronal differentiation. In the current study, we further combine NEN with retinoic acid (RA) to promote neural differentiation both in vitro and in vivo. The treatment increased the expression of RA signaling and neuron differentiation-related genes, resulting in a global shift in the transcriptome towards a more favorable prognosis. Overall, these results suggest that the combination of a mitochondrial uncoupler and the differentiation agent RA is a promising therapeutic strategy for neuroblastoma.

Association between dietary diversity and chronic kidney disease in community-dwelling older adults.

OBJECTIVE: The present study examined whether dietary diversity is associated with chronic kidney disease (CKD) in community-dwelling older Japanese adults. METHODS: Participants comprised 8,195 older adults (mean age was 74.0 ± 5.6 years; 42.7% were men) in this cross-sectional study. In this study, CKD was defined as estimated Glomerular Filtration Rate (eGFR) < 45 mL/min/1.73 m2. Diet variety was assessed using the Food Frequency Score (FFS) (maximum, 30 points). The FFS assessed the one-week consumption frequency of ten foods (meat, fish/shellfish, eggs, milk, soybean products, green & yellow vegetables, potatoes, fruits, seafood, and fats & oil). Participants with an FFS of 16 or fewer points were defined as having low dietary diversity. RESULTS: The prevalence of CKD was 376 (4.6%), and the low dietary diversity group had higher prevalence (5.6%) compared with the high and low dietary diversity group (4.3%). Multiple logistic regression analysis revealed low dietary diversity was associated with CKD in older adults (OR 1.30, 95%CI 1.01-1.68). Stratified analysis showed that low dietary diversity was independently associated with CKD (OR 1.43, 95% CI 1.07-1.91) in older adults with hypertension, but not in adults without hypertension (OR 0.94, 95% CI 0.54-1.64). CONCLUSIONS AND IMPLICATIONS: This cross-sectional study revealed that low dietary diversity was associated with CKD among older adults. Furthermore, low dietary diversity was associated with CKD among older adults with hypertension.

Visualization of the structural transformation of NiO/YSZ/BZY nanocomposite particles using in situ gas environmental transmission electron microscopy.

This study focused on investigating the dynamic structural transformations of spherical NiO/YSZ/BZY triple-phase nanocomposite particles, commonly employed for cermet anodes, during the hydrogen reduction reaction. We utilized both spherical aberration (Cs) corrected transmission electron microscopy (TEM) and high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) observation modes under a controlled gaseous environment. The environmental gas pressure was set to 1 atm (760 Torr), mirroring real-world conditions. To elucidate pre- and post-hydrogen reduction compositional alterations, we conducted elemental mapping using energy-dispersive X-ray spectroscopy (EDS). Our findings indicated that NiO nanoparticles underwent reduction to Ni particles upon heat treatments in an environment containing H2 gas. Significantly, this reduction of NiO led to the migration of Ni along the external surface of each composite particle, ultimately resulting in the agglomeration at the interparticle spaces among the three NiO/YSZ/BZY nanocomposite particles.

A COMPARATIVE STUDY OF MEDIUM-SIZED MACULAR HOLE SURGERY WITH INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE VERSUS CONVENTIONAL PEELING.

PURPOSE: To investigate surgical results for medium-sized (251-400 µ m) macular holes (MHs). METHODS: This retrospective observational study involved 266 eyes of 262 consecutive patients who underwent internal limiting membrane (ILM) peeling (147 eyes in the ILM peeling group) or inverted ILM flap cover technique (119 eyes in the inverted flap group) for primary medium-sized full-thickness MHs. Macular hole associated with retinal detachment, recurrent MH, and traumatic MH were excluded. RESULTS: The primary closure rate for overall medium-sized MHs was 100% (119 of 119 eyes) in the inverted flap group, which was significantly higher than that (94.6% [139/147 eyes]; P = 0.010) in the ILM peeling group. Notably, even after adjusting for the minimum MH diameter, presence of high myopia, or preexisting posterior vitreous detachment, the primary closure rate was significantly better in the inverted flap group than in the ILM peeling group (Cochran-Mantel-Haenszel test, overall adjusted P = 0.006, 0.009, 0.005, respectively). The preoperative and postoperative restoration of the outer retinal layers and visual acuity were comparable between the inverted ILM flap and ILM peeling techniques. CONCLUSION: Primary closure for medium-sized MHs was significantly superior in the inverted flap group than in the ILM peeling group.

The long-term efficacy and safety of nilotinib in pediatric patients with CML: a 5-year update of the DIALOG study.

The efficacy and safety of nilotinib in pediatric patients with imatinib/dasatinib resistant/intolerant (R/I) or newly diagnosed (ND) Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP) was demonstrated in the phase 2, open-label DIALOG study. In this final analysis, long-term efficacy and safety are presented for patients who completed 66 cycles (of 28 days) of treatment with nilotinib (230 mg/m2 twice daily) or discontinued early. Overall, 59 patients were enrolled and 58 were treated (R/I, n = 33; ND, n = 25; median time on treatment: 60.5 and 51.9 months, respectively). In the R/I cohort, the cumulative major molecular response (MMR; BCR::ABL1 international scale [IS] ≤ 0.1%) rate was 60.6%, and no patients had a confirmed loss of MMR. Among ND patients, the best overall MMR rate was 76.0%; 3 patients had a confirmed loss of MMR. The cumulative molecular response MR4 (BCR::ABL1IS ≤ 0.01%) and MR4.5 (BCR::ABL1IS ≤ 0.0032%) rates by 66 cycles were 27.3% and 12.1% in the R/I cohort, and 56.0% and 44.0% in the ND cohort, respectively. The safety profile of nilotinib was consistent with those of earlier reports. No on-treatment deaths occurred. These long-term (up to ∼5 years) data support the efficacy and safety of nilotinib in pediatric patients with Ph+ CML-CP. This trial was registered at www.clinicaltrials.gov.uk as #NCT01844765.

Pneumocystis jirovecii pneumonia after CD4+ T-cell recovery subsequent to CD19-targeted chimeric antigen receptor T-cell therapy: A case report and brief review of literature.

BACKGROUND: CD19-targeted chimeric antigen receptor (CAR)-T cell therapy involves administration of patient-derived T cells that target B cells, resulting in B-cell depletion and aplasia. In immunity against Pneumocystis jirovecii (Pj), CD4+ T cells and, more recently, B cells, are generally considered important. Antigen presentation by B cells to CD4+ T cells is particularly important. Trimethoprim-sulfamethoxazole (TMP/SMX) for Pj pneumonia (PJP) prophylaxis is generally discontinued when the CD4+ T-cell count is >200/µL. Here we report the first case, to our knowledge, of PJP in a patient with a CD4+ T cell count of >200/µL after CAR-T cell therapy. CASE: A 14-year-old girl developed hemophagocytic lymphohistiocytosis (HLH) after cord blood transplantation (CBT) for relapsed precursor B-cell acute lymphoblastic leukemia (B-ALL). Twenty-one months after CBT, she was diagnosed with combined second relapse in the bone marrow and central nervous system. The patient was treated with CD19-targeted CAR-T cell therapy for the relapse. After CAR-T cell therapy, the patient remained in remission and continued to receive TMP/SMX for PJP prophylaxis. Seven months after CAR-T cell therapy, CD4+ T cells recovered and TMP/SMX was discontinued. The B-cell aplasia persisted. Ten months after CAR-T cell therapy, the patient developed PJP. The patient was also considered to have macrophage hyperactivation at the onset of PJP. Treatment with immunoglobulin, TMP/SMX, and prednisolone was initiated, and the patient's symptoms rapidly ameliorated. CONCLUSION: The patient in the present case developed PJP despite a CD4+ T-cell count of >200/µL after CAR-T cell therapy, probably because of inadequate CD4+ T-cell activation caused by B-cell depletion after CAR-T cell therapy and repeated abnormal macrophage immune responses after CBT. It is important to determine the duration of TMP/SMX for prophylaxis after CAR-T cell therapy according to each case, as well as the CD4+ T-cell count.

Refractory Burkitt Lymphoma With False-positive and False-negative Mass Detected on Positron Emission Tomography-computed Tomography After Chemotherapy.

A 4-year-old boy with an abdominal mass extending from the spleen to the lower umbilicus was diagnosed with Burkitt lymphoma stage III. Because the fluorodeoxyglucose uptake on positron emission tomography (PET)-computed tomography of the residual splenic tumor remained elevated, splenectomy was performed. The PET-positive area was composed of inflammatory infiltrates, whereas the PET-negative area was composed of a viable tumor surrounded by necrotic or dying tumor cells. The residual tumor may have been false-negative for PET because of its poor proliferative potential. In this case, the comparison of PET-computed tomography and pathologic findings demonstrates the simultaneous presence of a false-positive inflammatory lesion and a false-negative residual tumor.

Concurrent application of interferon-gamma and vincristine inhibits tumor growth in an orthotopic neuroblastoma mouse model.

PURPOSE: Tumor-associated macrophages are present within neuroblastoma, and interferon-gamma (IFN-γ) can polarize macrophages into cancer-inhibiting M1 type. We hypothesize that treating neuroblastoma with interferon-gamma (IFN-γ) can suppress tumor growth, and the concurrent treatment with IFN-γ and vincristine can lead to enhanced tumor killing as compared to vincristine alone. METHODS: We loaded IFN-γ or vincristine into silk biomaterials and recorded the amount released over time. Orthotopic, syngeneic neuroblastoma xenografts were generated by injecting 9464D cells into adrenal gland of C57BL/6 mice, and IFN-γ-loaded and/or vincristine-loaded silk biomaterials were implanted into the tumor once the tumors reached 100 mm3. Drug release at different timepoints was measured and tumor growth after different treatments were compared. RESULTS: 1-2% of IFN-γ and 70% of vincristine were released from the biomaterials by the fifth day. Combining IFN-γ and vincristine significantly slowed tumor growth as compared to the controls (12.2 ± 2.7 days to reach 800 mm3 versus 5.7 ± 1.2 days, p = 0.01), and IFN-γ alone also delayed tumor growth as compared to the controls (10.9 ± 1.5 days versus 5.7 ± 1.2 days, p = 0.001). Hematoxylin and eosin staining demonstrated tumor necrosis adjacent to the drug-loaded silk biomaterials. CONCLUSION: Local delivery of sustained release IFN-γ can inhibit neuroblastoma tumor growth by itself and in combination with vincristine.

Difference in employment status and onset of disability among Japanese community-dwelling older adults: a prospective cohort study.

OBJECTIVE: This prospective cohort study investigates the relationship between the onset of disability and employment status. METHODS: We investigated 3,741 community-dwelling adults aged 70 or older, who participated in a population-based cohort study in Japan. Their onset of disability was monitored monthly using the long-term care insurance certification registration system, for five years from baseline. Based on an employment status questionnaire, we categorized participants into three groups: (1) employee, (2) self-employed, and (3) not working. Covariates included demographic information, medical history, number of medications, educational level, living alone, social group engagement, smoking status, walking speed, instrumental activities of daily living, global cognitive function, and depressive symptoms. Missing values were managed using multiple imputation. Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for incident disability risk by employment status. RESULTS: The disability incidence rates were 15.3/1,000 (95% CIs: 10.7-22.0) person-years among employees, and 33.0/1000 (95% CIs: 24.4-44.6) and 39.6/1000 (95% CIs: 36.5-43.0) person-years among self-employed and non-working participants, respectively. The adjusted HRs for the onset of disability among non-working and self-employed participants were 1.69 (95% CIs: 1.16-2.46, p = 0.007) and 1.63 (95% CIs: 1.01-2.62, p = 0.044) compared with employees, respectively. Similar results were found among men. Among women, disability onset was not associated with employment status. CONCLUSIONS: Older adults' risk of disability onset differed according to their employment status. Older employees had a lower risk of disability onset than those not working or self-employed.

Label-free mid-infrared photothermal live-cell imaging beyond video rate.

Advancement in mid-infrared (MIR) technology has led to promising biomedical applications of MIR spectroscopy, such as liquid biopsy or breath diagnosis. On the contrary, MIR microscopy has been rarely used for live biological samples in an aqueous environment due to the lack of spatial resolution and the large water absorption background. Recently, mid-infrared photothermal (MIP) imaging has proven to be applicable to 2D and 3D single-cell imaging with high spatial resolution inherited from visible light. However, the maximum measurement rate has been limited to several frames s-1, limiting its range of use. Here, we develop a significantly improved wide-field MIP quantitative phase microscope with two orders-of-magnitude higher signal-to-noise ratio than previous MIP imaging techniques and demonstrate live-cell imaging beyond video rate. We first derive optimal system design by numerically simulating thermal conduction following the photothermal effect. Then, we develop the designed system with a homemade nanosecond MIR optical parametric oscillator and a high full-well-capacity image sensor. Our high-speed and high-spatial-resolution MIR microscope has great potential to become a new tool for life science, in particular for live-cell analysis.

Effects of Daily Consumption of Soy Products on Basic/Instrumental Activities of Daily Living in Community-Dwelling Japanese Women Aged 75 Years and Older: A 4-Year Cohort Study.

Introduction: Since soy isoflavones compensate for age-related estrogen reduction, adequate intake of soy products may prevent the decline in activities of daily living (ADL) due to estrogen reduction in women. However, it is unclear whether regular soy product intake prevents ADL decline. This study examined the effects of soy product consumption on basic/instrumental ADL (BADL/IADL) in Japanese women 75 years or older for 4 years. Materials and Methods: The subject population consisted of 1289 women aged 75 years or older living in Tokyo who underwent private health examinations in 2008. For 1114 (or 1042) participants without baseline BADL (or IADL) disability, we examined the association between baseline soy product consumption frequency and the BADL (or IADL) disabilities 4 years later using logistic regression analyses. The models were adjusted for baseline age, or further for dietary variety for food groups other than soy products, exercise and sport participation, smoking, pre-existing disease number, and body mass index. Results: Regardless of adjustment for potential confounding factors, less frequent soy product consumption was associated with higher BADL or IADL disability incidence. In the fully adjusted models, the trend toward a higher incidence of disabilities with less frequent soy product consumption was statistically significant for both BADL (p = 0.001) and IADL (p = 0.007). Conclusions: Those who consumed soy products more frequently at baseline were less likely to develop BADL and IADL disabilities after 4 years than those who did not. The results show that daily soy product consumption may prevent functional ADL decline in older Japanese women.

A 15-Year-Old Boy with Primary Maxillary Bone Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma Relapsed with Rib Metastasis after Spontaneous Remission of a Maxillary Bone Lesion: A Case Report and Literature Review.

Anaplastic large cell lymphoma (ALCL) is a rare form of non-Hodgkin's lymphoma (NHL) in children, accounting for 10-15% of all NHL cases. ALCL is currently classified as follows: systemic anaplastic lymphoma kinase (ALK)-positive, systemic ALK-negative, primary cutaneous, and breast implant-associated ALCL. In children, systemic ALK-positive ALCL is the most common, and patients often present with extranodal involvement. We report a rare case of systemic ALK-positive ALCL with primary bone involvement in a 15-year-old male patient. Primary bone lymphoma is most commonly observed in diffuse large B-cell lymphoma and is extremely rare in systemic ALCL. Therefore, the clinical features and prognosis of primary bone ALCL remain unclear. Our patient had spontaneous remission of primary maxillary bone ALCL after gingival scraping but relapsed 12 months later with rib metastasis. Spontaneous remission of ALCL has been reported frequently in primary cutaneous ALCL and rarely in systemic ALCL. Our case demonstrates for the first time that systemic ALCL can also present as solitary bone involvement that can spontaneously remit. Because systemic ALCL is aggressive and has a risk of relapse, as in our case, it is important to consider ALCL in the differential diagnosis of primary bone lesions and to make a precise pathological diagnosis.

Allogeneic stem cell transplantation for children and adolescents/young adults with de novo blastic phase chronic myeloid leukemia in the tyrosine kinase inhibitor era.

The analysis of 165 children and adolescents/young adults with de novo blastic phase chronic myeloid leukemia showed disease status at hematopoietic stem cell transplantation was a strong prognostic factor and clearly separated the patient outcomes.

The capture of extracellular vesicles endogenously released by xenotransplanted tumours induces an inflammatory reaction in the premetastatic niche.

The capture of tumour-derived extracellular vesicles (TEVs) by cells in the tumour microenvironment (TME) contributes to metastasis and notably to the formation of the pre-metastatic niche (PMN). However, due to the challenges associated with modelling release of small EVs in vivo, the kinetics of PMN formation in response to endogenously released TEVs have not been examined. Here, we have studied the endogenous release of TEVs in mice orthotopically implanted with metastatic human melanoma (MEL) and neuroblastoma (NB) cells releasing GFP-tagged EVs (GFTEVs) and their capture by host cells to demonstrate the active contribution of TEVs to metastasis. Human GFTEVs captured by mouse macrophages in vitro resulted in transfer of GFP vesicles and the human exosomal miR-1246. Mice orthotopically implanted with MEL or NB cells showed the presence of TEVs in the blood between 5 and 28 days after implantation. Moreover, kinetic analysis of TEV capture by resident cells relative to the arrival and outgrowth of TEV-producing tumour cells in metastatic organs demonstrated that the capture of TEVs by lung and liver cells precedes the homing of metastatic tumour cells, consistent with the critical roles of TEVs in PMN formation. Importantly, TEV capture at future sites of metastasis was associated with the transfer of miR-1246 to lung macrophages, liver macrophages, and stellate cells. This is the first demonstration that the capture of endogenously released TEVs is organotropic as demonstrated by the presence of TEV-capturing cells only in metastatic organs and their absence in non-metastatic organs. The capture of TEVs in the PMN induced dynamic changes in inflammatory gene expression which evolved to a pro-tumorigenic reaction as the niche progressed to the metastatic state. Thus, our work describes a novel approach to TEV tracking in vivo that provides additional insights into their role in the earliest stages of metastatic progression.

Lorlatinib with or without chemotherapy in ALK-driven refractory/relapsed neuroblastoma: phase 1 trial results.

Neuroblastomas harbor ALK aberrations clinically resistant to crizotinib yet sensitive pre-clinically to the third-generation ALK inhibitor lorlatinib. We conducted a first-in-child study evaluating lorlatinib with and without chemotherapy in children and adults with relapsed or refractory ALK-driven neuroblastoma. The trial is ongoing, and we report here on three cohorts that have met pre-specified primary endpoints: lorlatinib as a single agent in children (12 months to <18 years); lorlatinib as a single agent in adults (≥18 years); and lorlatinib in combination with topotecan/cyclophosphamide in children (<18 years). Primary endpoints were safety, pharmacokinetics and recommended phase 2 dose (RP2D). Secondary endpoints were response rate and 123I-metaiodobenzylguanidine (MIBG) response. Lorlatinib was evaluated at 45-115 mg/m2/dose in children and 100-150 mg in adults. Common adverse events (AEs) were hypertriglyceridemia (90%), hypercholesterolemia (79%) and weight gain (87%). Neurobehavioral AEs occurred mainly in adults and resolved with dose hold/reduction. The RP2D of lorlatinib with and without chemotherapy in children was 115 mg/m2. The single-agent adult RP2D was 150 mg. The single-agent response rate (complete/partial/minor) for <18 years was 30%; for ≥18 years, 67%; and for chemotherapy combination in <18 years, 63%; and 13 of 27 (48%) responders achieved MIBG complete responses, supporting lorlatinib's rapid translation into active phase 3 trials for patients with newly diagnosed high-risk, ALK-driven neuroblastoma. ClinicalTrials.gov registration: NCT03107988 .

Association of Loneliness With the Incidence of Disability in Older Adults With Hearing Impairment in Japan.

Importance: Loneliness is suggested to negatively affect physical and mental health and influence the development of disability; however, a consensus on the relationship between loneliness and disability has not been reached. Age-related hearing impairment worsens the daily-life activities of older adults, and the association between loneliness and the incidence of disability may be influenced by hearing impairment. Objective: To examine the association between loneliness and the incidence of disability among older adults stratified by hearing impairment. Design, Setting, and Participants: This prospective observational cohort study included 5563 community-dwelling adults 65 years or older who participated in functional health examinations in Tokai City, Aichi Prefecture, Japan, between September 2017 and June 2018. Data analysis was conducted from August 2022 to February 2023. Main Outcomes and Measures: Cox proportional hazards regression models were used to examine the association between loneliness and the incidence of disability stratified by hearing impairment. Results: Among the 4739 participants who met the inclusion criteria (mean [SD] age, 73.8 [5.5] years; 2622 [55.3%] female), 3792 (80.0%) were without hearing impairment and 947 (20.0%) were with hearing impairment. Of those who reported experiencing loneliness, 1215 (32.0%) were without hearing impairment, and 441 (46.6%) were with hearing impairment. After 2 years, the number of individuals with disabilities was 172 (4.5%) without hearing impairment and 79 (8.3%) with hearing impairment. Cox proportional hazards regression analysis showed no statistically significant association between loneliness and the incidence of disability in a model adjusted for potential confounding factors among community-dwelling older adults without hearing impairment (hazard ratio, 1.10; 95% CI, 0.80-1.52). Among community-dwelling older adults with hearing impairment, a model adjusted for potential confounding factors showed a statistically significant association between loneliness and the incidence of disability (hazard ratio, 1.71; 95% CI, 1.04-2.81). Conclusions and Relevance: This cohort study found that the association between loneliness and the incidence of disability was moderated by the presence or absence of hearing impairment. Hearing impairment is the most common symptom of geriatric syndromes, showing that among the various risk factors, loneliness may require special attention in the prevention of disability in people with hearing impairment.

Impact of osteosarcopenia on disability and mortality among Japanese older adults.

BACKGROUND: In clinical settings, muscle mass and bone mineral density assessments are usually performed using dual-energy X-ray absorptiometry (DXA), the clinical standard technique. However, DXA is often unavailable in community settings. This study aimed to determine whether osteoporosis, osteopenia (OP) and sarcopenia (SP) identified by simplified instruments are associated with the future incidence of disability and mortality and evaluate the validity of these instruments as community screening tools. We also examined osteosarcopenia (OS), defined as the coexistence of OP and SP, as a new indicator of geriatric syndromes to determine whether it has an additive effect on adverse outcome incidence compared with OP and SP alone. METHODS: In total, 8995 older adults participated in the study (women: 51.7%, average age: 73.5 ± 5.4 years). Data were extracted from the Japanese national cohort study, National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes. We determined OP based on T-scores generated based on the speed of sound, which is the time taken for ultrasound waves to go through a determined distance in the calcaneus bone. Skeletal muscle mass was evaluated using a bioimpedance analysis device. Handgrip strength and walking speed were measured as physical performance indicators. Incidences of disability and mortality were prospectively determined for 5 years. RESULTS: The prevalence of OP, SP and OS was 45.5%, 3.9% and 7.4%, respectively. The incidence of disability in the nonOP/nonSP, OP, SP and OS groups was 6.5%, 14.9%, 20.5% and 33.5%, respectively. The incidence of mortality in the nonOP/nonSP, OP, SP and OS groups was 4.0%, 4.9%, 10.3% and 10.2%, respectively. Participants with OP (hazard ratio [HR]: 1.45, 95% confidence interval [CI]: 1.25-1.68), SP (HR: 1.38, 95% CI: 1.08-1.76) and OS (HR: 1.73, 95% CI: 1.43-2.09) had a higher risk of disability than nonOP/nonSP participants. Participants with OP (HR: 1.31, 95% CI: 1.04-1.64) and OS (HR: 1.45, 95% CI: 1.05-2.00) had a higher risk of mortality than nonOP/nonSP participants. SP was not significantly related to mortality (HR: 1.14, 95% CI: 0.90-1.45). There was no statistical interaction between OP and SP in incident disability and mortality. CONCLUSIONS: Among older adults, OS identified by bioimpedance and quantitative ultrasound assessments was associated with an increased risk of disability and mortality. Further research is needed to implement these findings in community health activities, such as setting precise cut-off values and constructing accurate disability and mortality prediction models.