Three-dimensional fusion imaging to assess apposition of low-profile visualized intraluminal support stent for intracranial aneurysm coiling.

Objective: To investigate on three-dimensional (3D) fusion images the apposition of low-profile visualized intraluminal support (LVIS) stents in intracranial aneurysms after treatment and assess inter-rater reliability. Materials and methods: Records of all patients with unruptured intracranial aneurysms who were treated with the LVIS stent were retrospectively accessed and included in this study. Two neurosurgeons evaluated the presence of malapposition between the vessel walls and the stent trunk (crescent sign) and the vessel wall and the stent edges (edge malappostion) on 3D fusion images. These images were high-resolution cone-beam computed tomography images of the LVIS stent fused with 3D-digital subtraction angiography images of the vessels. Associations between malapposition and aneurysm location were assessed by Fisher's exact test, and inter-rater agreement was estimated using Cohen's kappa statistic. Results: Forty consecutive patients were included. In all patients, 3D fusion imaging successfully visualized the tantalum helical strands and the closed-cell structure of the nitinol material of the low-profile visualized intraluminal support. A crescent sign was observed in 27.5 % and edge malapposition in 47.5 % of the patients. Malapposition was not significantly associated with location (p = 0.23 crescent sign, p = 0.07 edge malapposition). Almost perfect (κ = 0.88) and substantial (κ = 0.76) agreements between the two raters were found for the detection of crescent signs and edge appositions, respectively. Conclusions: 3D fusion imaging provided clear visualization of the LVIS stent and parent arteries, and could detect malapposition with excellent inter-rater reliability. This technique may provide valuable guidance for surgeons in determining postoperative management.

Association of polydoctoring and mortality among very old persons with multimorbidity: a prospective cohort study in Japan.

BACKGROUND: Polydoctoring is a crucial aspect of care fragmentation among patients with multimorbidity, but its impact on health outcomes remains unclear. AIM: To determine the effects of polydoctoring, as measured by the Regularly Visited Facility (RVF) indicator, on patient outcomes among older individuals with multimorbidity. DESIGN & SETTING: Data from the ongoing prospective cohort study, Kawasaki Aging and Wellbeing Project (KAWP), was utilized in this study. Among the 1,026 KAWP participants aged 85-89 years, those with two or more chronic conditions were enrolled in this study. METHOD: Care fragmentation or polydoctoring, was evaluated using the RVF, a new indicator that measures the number of medical facilities consistently involved in a patient's care. Based on RVF, mortality was analysed using the Cox-hazards model, with adjustments for age, sex, frailty, and number of comorbidities. RESULTS: A significant reduction in mortality rates was observed in participants with an RVF of ≥3 and 2-4 comorbidities (hazard ratio [HR] 0.46, 95% confidence interval [CI]: 0.18-0.99). However, no significant difference in mortality based on RVF was observed for those with ≥5 comorbidities. Notably, individuals with ≥5 comorbidities and an RVF of 0 had a significantly higher HR for death (HR 2.68, 95% CI 1.05-6.84). CONCLUSIONS: In older patients with multimorbidity, polydoctoring reduces mortality in patients with ≤4 coexisting conditions, but it does not significantly impact mortality in those with ≥5 conditions. These findings provide insights for healthcare decision-making in managing older patients with multimorbidity.

Plasma Angiogenic Factors as Predictors of the Efficacy of Second-line Chemotherapy Combined with Angiogenesis Inhibitors in Metastatic Colorectal Cancer: Results From the GI-SCREEN CRC-Ukit Study.

BACKGROUND: The significance of angiogenic factors as predictors of second-line (2L) chemotherapy efficacy when combined with angiogenesis inhibitors for metastatic colorectal cancer (mCRC) remains unestablished. PATIENTS AND METHODS: In this multicenter prospective observational study, 17 angiogenic factors were analyzed in plasma samples collected at pretreatment and progression stages using a Luminex multiplex assay. Patients who received chemotherapy plus bevacizumab (BEV group), FOLFIRI plus ramucirumab (RAM group), or FOLFIRI plus aflibercept (AFL group) as the 2L treatment were included. Interactions between pretreatment and treatment groups for progression-free survival (PFS), overall survival (OS), and response rate (RR) were assessed using the propensity-score weighted Cox proportional hazards model. RESULTS: From February 2018 to September 2020, 283 patients were analyzed in the 2L cohort. A strong interaction was observed for PFS between BEV and RAM with HGF, sNeuropilin-1, sVEGFR-1, and sVEGFR-3. Interactions for RR between the BEV and RAM groups were observed for sNeuropilin-1 and sVEGFR-1. Contrarily, OS, PlGF, sVEGFR-1, and sVEGFR-3 differentiated the treatment effect between BEV and AFL. Plasma samples were evaluable for dynamic analysis in 203 patients. At progression, VEGF-A levels significantly decreased in the BEV group and increased in the RAM and AFL groups. CONCLUSION: The pretreatment plasma sVEGFR-1 and sVEGFR-3 levels could be predictive biomarkers for distinguishing BEV and RAM when combined with chemotherapy in 2L mCRC treatment. Based on the VEGF-A dynamics at progression, selecting RAM or AFL for patients with significantly elevated VEGF-A levels may be a 2L treatment strategy, with BEV considered for the third-line treatment. CLINICAL TRIAL NUMBER: UMIN000028616.

Measurement of polydoctoring as a crucial component of fragmentation of care among patients with multimorbidity: Cross-sectional study in Japan.

Background: Care fragmentation, characterized by the uncoordinated involvement of multiple healthcare providers, leads to inefficient and ineffective healthcare, posing a significant challenge in managing patients with multimorbidity. In this context, "polydoctoring," where patients see multiple specialists, emerges as a crucial aspect of care fragmentation. This study seeks to develop an indicator to assess polydoctoring, which can subsequently enhance the management of multimorbidity. Methods: Baseline survey data from the Kawasaki Aging and Wellbeing Project (KAWP) involving independent community-dwelling older adults aged 85-89 were utilized in this cross-sectional study. Polydoctoring measure was defined as the number of regularly visited facilities (RVFs). The association of RVF with the Fragmentation of Care Index (FCI) and the outcome measures of polypharmacy and ambulatory care costs were examined as indicators of care fragmentation. Results: The analysis comprised 968 participants, with an average of 4.70 comorbid chronic conditions; 65.3% of the participants had two or more RVFs, indicating polydoctoring. A significant correlation between RVF and FCI was observed. Modified Poisson regression analyses revealed associations between higher RVF and increased prevalence ratio of polypharmacy. Likewise, a higher RVF was associated with higher outpatient medical costs. Conclusions: RVF was significantly correlated with FCI, polypharmacy, and higher outpatient medical costs. Unlike complex indices, RVF is simple and intuitively comprehensible. Further research is needed to evaluate the impact of care fragmentation on patient outcomes, considering factors such as RVF thresholds, patient multimorbidity, and social support. Understanding the influence of polydoctoring can enhance care quality and efficiency for patients with multimorbidity.

Virtual coil images can optimize the visualization of the neckline of intracranial aneurysms during coil embolization: A technical note.

Background: During coil embolization of intracranial aneurysms, the aneurysmal neck needs to be evaluated because coil protrusion into the parent artery may lead to ischemic complications. However, the neck cannot always be clearly visualized due to the limitation of the angiography system and due to the structure of the aneurysm. As a visual aid, we propose a color-coded fusion imaging method that generates "virtual coil" images using preoperative three-dimensional digital subtraction angiography (3D-DSA) images. Case Description: Coil embolization for intracranial aneurysms was performed using the working angles determined from the preoperative 3D-DSA. The aneurysms were located at the middle cerebral artery, anterior communicating artery (A-com), and posterior communicating artery (P-com). The A-com and P-com aneurysms were recurrent. During the later phase of the procedure, physicians could not judge whether coils protruded into the parent artery on two-dimensional digital subtraction angiography (2D-DSA) images because an optimal working angle could not be realized. Virtual coil images were displayed on the angiography system's monitor to show the expected completed embolization, which could be compared to the current 2D-DSA images as a visual aid. Conclusion: Virtual coil images can provide visual aid to the treating physician during aneurysm coil embolization, which is useful when an accurate working angle cannot be reached.

Status and physiological significance of circulating adiponectin in the very old and centenarians: an observational study.

Background: High levels of circulating adiponectin are associated with increased insulin sensitivity, low prevalence of diabetes, and low body mass index (BMI); however, high levels of circulating adiponectin are also associated with increased mortality in the 60-70 age group. In this study, we aimed to clarify factors associated with circulating high-molecular-weight (cHMW) adiponectin levels and their association with mortality in the very old (85-89 years of age) and centenarians. Methods: The study included 812 (women: 84.4%) for centenarians and 1498 (women: 51.7%) for the very old. The genomic DNA sequence data were obtained by whole-genome sequencing or DNA microarray-imputation methods. Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate regression analyses were used to evaluate cHMW adiponectin characteristics and associated factors. All-cause mortality was analyzed in three quantile groups of cHMW adiponectin levels using Cox regression. Results: The cHMW adiponectin levels were increased significantly beyond 100 years of age, were negatively associated with diabetes prevalence, and were associated with SNVs in CDH13 (p=2.21 × 10-22) and ADIPOQ (p=5.72 × 10-7). Multivariate regression analysis revealed that genetic variants, BMI, and high-density lipoprotein cholesterol (HDLC) were the main factors associated with cHMW adiponectin levels in the very old, whereas the BMI showed no association in centenarians. The hazard ratios for all-cause mortality in the intermediate and high cHMW adiponectin groups in very old men were significantly higher rather than those for all-cause mortality in the low-level cHMW adiponectin group, even after adjustment with BMI. In contrast, the hazard ratios for all-cause mortality were significantly higher for high cHMW adiponectin groups in very old women, but were not significant after adjustment with BMI. Conclusions: cHMW adiponectin levels increased with age until centenarians, and the contribution of known major factors associated with cHMW adiponectin levels, including BMI and HDLC, varies with age, suggesting that its physiological significance also varies with age in the oldest old. Funding: This study was supported by grants from the Ministry of Health, Welfare, and Labour for the Scientific Research Projects for Longevity; a Grant-in-Aid for Scientific Research (No 21590775, 24590898, 15KT0009, 18H03055, 20K20409, 20K07792, 23H03337) from the Japan Society for the Promotion of Science; Keio University Global Research Institute (KGRI), Kanagawa Institute of Industrial Science and Technology (KISTEC), Japan Science and Technology Agency (JST) Research Complex Program "Tonomachi Research Complex" Wellbeing Research Campus: Creating new values through technological and social innovation (JP15667051), the Program for an Integrated Database of Clinical and Genomic Information from the Japan Agency for Medical Research and Development (No. 16kk0205009h001, 17jm0210051h0001, 19dk0207045h0001); the medical-welfare-food-agriculture collaborative consortium project from the Japan Ministry of Agriculture, Forestry, and Fisheries; and the Biobank Japan Program from the Ministry of Education, Culture, Sports, and Technology.

Dietary protein intake and all-cause mortality: results from The Kawasaki Aging and Wellbeing Project.

BACKGROUND: Increased protein intake has been recommended to prevent sarcopenia/frailty, reports on the quantity and quality of protein intake needed and the associated prognosis, particularly in the aging population of Asia, are limited. In this study, we aimed to investigate the relationship between protein intake and mortality in Japanese individuals, aged 85 years and older. METHODS: The data were obtained from The Kawasaki Aging and Wellbeing Project, which is a prospective cohort study of older adults aged between 85 and 89 years with no physical disability at baseline. Of the 1,026 adults in the cohort, 833 were included in the analysis, after excluding those who had not completed a brief, self-administered diet history questionnaire or those who scored less than 24 on the Mini-Mental State Examination. The participants were grouped into quartiles based on protein intake: Q1 (protein < 14.7, %Energy), Q2 (14.7 ≤ protein < 16.7, %Energy), Q3 (16.7 ≤ protein < 19.1, %Energy), and Q4 (≥ 19.1, %Energy). Multivariate Cox proportional hazards models were utilized to evaluate the association between protein intake and all-cause mortality. Kaplan-Meier survival curves were employed to investigate the relationship between protein intake and all-cause mortality. RESULTS: The mean protein intake of our study population was 17.0% of total energy. Animal protein intake, particularly fish intake, increased significantly along with total protein intake. The study had an average observation period of 1,218 days and recorded 89 deaths. After adjusting for age, sex, skeletal muscle mass index, cardiovascular disease, cancer, education, and serum albumin levels, a lower risk of all-cause mortality was observed in the highest protein intake (Q4) group than in the lowest protein intake (Q1) group (hazard ratio: 0.44, 95% confidence interval: 0.22-0.90, p-value: 0.020). CONCLUSION: Protein intake is associated with a reduced risk of all-cause mortality in older adults (aged ≥ 85 years) who engage in independent activities of daily living. This association may impact all-cause mortality independent of muscle mass.

Role of plasma angiogenesis factors in the efficacy of first-line chemotherapy combined with biologics in RAS wild-type metastatic colorectal cancer: Results from the GI-SCREEN CRC-Ukit study.

BACKGROUND: Several biomarkers have been established for metastatic colorectal cancer (mCRC). We investigated whether plasma angiogenesis factors could predict the efficacy of biologics combined with chemotherapy in first-line (1L) treatment in patients with RAS wild-type mCRC and the dynamics of plasma angiogenesis factors at progression during 1L treatment. METHODS: In this multicenter prospective observational study, serial plasma samples were prospectively collected at pretreatment and progression stages; 17 plasma angiogenesis factors were analyzed using the multiplex assay with Luminex® technology. Interactions between the pretreatment measurements and treatment groups on progression-free survival (PFS) and overall survival (OS) in patients with RAS wild-type were assessed using the propensity-score weighted Cox proportional hazards model. RESULTS: From February 2018 to September 2020, 202 patients were enrolled in the 1L cohort; 133 patients had RAS wild-type (chemotherapy plus bevacizumab [BEV group, n = 33] and plus anti-epidermal growth factor receptor monoclonal antibodies [aEGFR group, n = 100]). A trend of strong interaction on PFS was observed for interleukin-8 (IL-8) (p = 0.0752) and soluble vascular cell adhesion molecule-1 (sVCAM-1) (p = 0.0156). Regarding OS, IL-8 (p = 0.0283), soluble vascular endothelial growth factor-receptor-1 (sVEGFR-1) (p = 0.0777) and sVCAM-1 (p = 0.0011) tended to differentiate the treatment effect. In 112 patients, plasma samples were evaluable for dynamic analysis (57 and 55 from the BEV and aEGFR groups, respectively). In the BEV group, six factors significantly increased during progression, whereas two decreased. In the aEGFR group, three factors significantly increased, and six decreased. CONCLUSION: Pretreatment plasma IL-8 and sVCAM-1 levels could be predictive biomarkers to distinguish BEV and anti-EGFR mAbs when combined with chemotherapy in the 1L treatment of RAS wild-type mCRC. Several plasma angiogenesis factors showed significant change at progression in 1L chemotherapy plus biologics for RAS wild-type mCRC, which are potential biomarkers for selecting an optimal angiogenesis inhibitor in second-line treatment.

Three-dimensional fusion images from digital subtraction angiography for the treatment of direct carotid-cavernous fistulas: illustrative case.

BACKGROUND: Direct carotid-cavernous fistulas (dCCFs) are often treated endovascularly. However, because the dCCF is usually a high-flow shunt, it is often difficult to obtain an accurate vascular structure using conventional digital subtraction angiography (DSA). Here, the authors report a case of successfully treated dCCF using three-dimensional (3D) fused DSA images. OBSERVATIONS: The patient presented with tinnitus, followed by oculomotor palsy, prompting magnetic resonance imaging that indicated a dural arteriovenous fistula of the cavernous sinus. DSA was performed before treatment, and a diagnosis of dCCF due to a ruptured aneurysm was made. In this case, the 3D fused simulation images enabled the authors to obtain an accurate vascular structure, resulting in successful coil embolization. LESSONS: Three-dimensional fusion images from DSA provide detailed anatomical information and are useful for treating high-flow dCCFs.

Plasma amino acid signature for sarcopenic phenotypes in community-dwelling octogenarians: Results from the Kawasaki Aging Wellbeing Project.

Sarcopenia is one of the primary risk factors for various adverse health events in later life. However, its pathophysiology in the very old population remains unclear. Hence, this study aimed to examine whether plasma free amino acids (PFAAs) correlate with major sarcopenic phenotypes (i.e., muscle mass, muscle strength, and physical performance) in community-dwelling adults aged 85-89 years living in Japan. Cross-sectional data from the Kawasaki Aging Well-being Project were used. We included 133 adults aged 85-89 years. In this study, fasting blood was collected to measure 20 plasma PFAAs. Measures for the three major sarcopenic phenotypes included appendicular lean mass assessed by multifrequency bioimpedance, isometric handgrip strength, and gait speed from a 5 m walk at a usual pace. Furthermore, we used phenotype-specific elastic net regression models adjusted for age centered at 85 years, sex, body mass index, education level, smoking status, and drinking habit to identify significant PFAAs for each sarcopenic phenotype. Higher histidine and lower alanine levels were associated with poor gait speed, but no PFAAs correlated with muscle strength or mass. In conclusion, PFAAs such as plasma histidine and alanine are novel blood biomarkers associated with physical performance in community-dwelling adults aged 85 years or older.

The Role of a Composite Fitness Score in the Association Between Low-Density Cholesterol and All-Cause Mortality in Older Adults: An Individual Patient Data Meta-Analysis.

BACKGROUND: In the general population, an increase in low-density lipoprotein cholesterol (LDL-C) predicts higher cardiovascular disease risk, and lowering LDL-C can prevent cardiovascular disease and reduces mortality risk. Interestingly, in cohort studies that include very old populations, no or inverse associations between LDL-C and mortality have been observed. This study aims to investigate whether the association between LDL-C and mortality in the very old is modified by a composite fitness score. METHODS: A 2-stage meta-analysis of individual participant data from the 5 observational cohort studies. The composite fitness score was operationalized by performance on a combination of 4 markers: functional ability, cognitive function, grip strength, and morbidity. We pooled hazard ratios (HR) from Cox proportional-hazards models for 5-year mortality risk for a 1 mmol/L increase in LDL-C. Models were stratified by high/low composite fitness score. RESULTS: Composite fitness scores were calculated for 2 317 participants (median 85 years, 60% females participants), of which 994 (42.9%) had a high composite fitness score, and 694 (30.0%) had a low-composite fitness score. There was an inverse association between LDL-C and 5-year mortality risk (HR 0.87 [95% CI: 0.80-0.94]; p < .01), most pronounced in participants with a low-composite fitness score (HR 0.85 [95% CI: 0.75-0.96]; p = .01), compared to those with a high composite fitness score (HR = 0.98 [95% CI: 0.83-1.15]; p = .78), the test for subgroups differences was not significant. CONCLUSIONS: In this very old population, there was an inverse association between LDL-C and all-cause mortality, which was most pronounced in participants with a low-composite fitness scores.

Regulation of MEK inhibitor selumetinib sensitivity by AKT phosphorylation in the novel BRAF L525R mutant.

BACKGROUND: Oncogenic mutations in BRAF genes are found in approximately 5-10% of colorectal cancers. The majority of BRAF mutations are located within exons 11-15 of the catalytic kinase domains, with BRAF V600E accounting for more than 80% of the observed BRAF mutations. Sensitivity to BRAF- and mitogen-activated protein kinase (MEK) inhibitors varies depending on BRAF mutations and tumor cell types. Previously, we newly identified, BRAF L525R-mutation, in the activation segment of the kinase in colorectal cancer patient. Here, we characterized the function of the BRAF L525R mutation. METHODS: HEK293 cells harboring a BRAF mutation (V600E or L525R) were first characterized and then treated with cetuximab, dabrafenib, and selumetinib. Cell viability was measured using WST-1 assay and the expression of proteins involved in the extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) signaling pathways was evaluated using western blot analysis. RESULTS: The MEK inhibitor selumetinib effectively inhibited cell proliferation and ERK phosphorylation in BRAF L525R cells but not in BRAF V600E cells. Further studies revealed that AKT phosphorylation was reduced by selumetinib in BRAF L525R cells but not in BRAF V600E cells or selumetinib-resistant BRAF L525R cells. Moreover, the AKT inhibitor overcame the selumetinib resistance. CONCLUSIONS: We established a model system harboring BRAF L525R using HEK293 cells. BRAF L525R constitutively activated ERK. AKT phosphorylation caused sensitivity and resistance to selumetinib. Our results suggest that a comprehensive network analysis may provide insights to identify effective therapies.

Immune checkpoint inhibitor-related haemophagocytic lymphohistiocytosis in a patient with non-small cell lung carcinoma.

Hemophagocytic lymphohistiocytosis (HLH) has been reported as a rare complication of immune checkpoint inhibitors (ICI); however, ICI-related HLH is a life-threatening and comparatively late adverse event. Early diagnosis is critical, and it should be included in the differential diagnosis especially in patients with cytopenia with fever and hyperferritinaemia.

Epigenetic profile of Japanese supercentenarians: a cross-sectional study.

BACKGROUND: Centenarians and supercentenarians with exceptional longevity are excellent models for research towards improvements of healthy life expectancy. Extensive research regarding the maintenance and reduction of epigenetic age has provided insights into increasing healthy longevity. To this end, we explored the epigenetic signatures reflecting hallmarks of exceptional healthy longevity, including avoidance of age-related diseases and cognitive functional decline. METHODS: In this cross-sectional study, we enrolled Japanese non-centenarians (eligible participants aged 20-80 years) from the Tohoku Medical Megabank Community-Based Cohort Study and centenarians and supercentenarians (aged 101-115 years) from the Tokyo Centenarian Study and the Japanese Semi-supercentenarian Study. We assessed participants' whole-blood DNA methylation profiles and then developed sex-specific and non-specific first-generation epigenetic clocks by elastic net regression, calculated individuals' epigenetic ages, and assessed their age acceleration. We also screened for age-related CpG sites in non-centenarians by epigenome-wide linear regression analyses and ANOVA. We subsequently investigated which CpG sites in centenarians and supercentenarians had DNA methylation patterns following the age-related findings obtained from non-centenarians and which did not. We further characterised CpG sites with hypermethylation or hypomethylation in the centenarians and supercentenarians using enrichment and protein-protein interaction network analyses. FINDINGS: We enrolled 421 non-centenarians (231 [55%] women and 190 [45%] men; age range 20-78 years), recruited between May 20, 2013, and March 31, 2016, and 94 centenarians and supercentenarians (66 women [70%] and 28 [30%] men; age range 101-115 years), recruited between Jan 20, 2001, and April 17, 2018. Non-sex-specific epigenetic clock showed the highest accuracy (r=0·96) based on which centenarians and supercentenarians had negative epigenetic age acceleration. Epigenome-wide association analyses further showed that centenarians and supercentenarians had younger-than-expected epigenetic states (DNA methylation profiles similar to those of non-centenarians) for 557 CpG sites enriched in cancer-related and neuropsychiatric-related genes, whereas these individuals had advanced (or older) epigenetic states for 163 CpG sites represented by genes related to TGF-ß signalling, which is involved in anti-inflammatory responses and known to contribute to healthy ageing. INTERPRETATION: These results indicate that exceptionally healthy longevity depends not only on maintaining young epigenetic states but also on advanced states of specific epigenetic regions. FUNDING: The Japan Agency for Medical Research and Development, KDDI Research, and Keio University. TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.

Relationship between dietary patterns and physical performance in the very old population: a cross-sectional study from the Kawasaki Aging and Wellbeing Project.

OBJECTIVES: As the world's population is ageing, improving the physical performance (PP) of the older population is becoming important. Although diets are fundamental to maintaining and improving PP, few studies have addressed the role of these factors in adults aged ≥ 85 years, and none have been conducted in Asia. This study aimed to determine the dietary patterns (DP) and examine their relationship with PP in this population. DESIGN: This cross-sectional study (Kawasaki Aging and Wellbeing Project) estimated food consumption using a brief-type self-administered diet history questionnaire. The results were adjusted for energy after aggregating into thirty-three groups, excluding possible over- or underestimation. Principal component analysis was used to identify DP, and outcomes included hand grip strength (HGS), timed up-and-go test, and usual walking speed. SETTING: This study was set throughout several hospitals in Kawasaki city. PARTICIPANTS: In total, 1026 community-dwelling older adults (85-89 years) were enrolled. RESULTS: Data of 1000 participants (median age: 86·9 years, men: 49·9 %) were included in the analysis. Three major DP (DP1: various foods, DP2: red meats and coffee, DP3: bread and processed meats) were identified. The results of multiple regression analysis showed that the trend of DP2 was negatively associated with HGS (B, 95 % CI -0·35, -0·64, -0·06). CONCLUSIONS: This study suggests a negative association between HGS and DP characterised by red meats and coffee in older adults aged ≥ 85 years in Japan.

Relation between number of teeth, malnutrition, and 3-year mortality in elderly individuals ≥85 years.

OBJECTIVE: The number of teeth has been shown to affect mortality. However, it is unclear why the number of teeth is associated with mortality. We focused on the number of teeth and malnutrition and examined whether these differences affect 3-year all-cause mortality among very elderly individuals. METHODS: This analysis was conducted using data from the Tokyo Oldest Old Survey on Total Health study. Altogether 513 participants ≥85 years were categorized based on remaining teeth (0, 1-7, 8-18, ≥19). All-cause mortality was determined by calculating the cumulative 3-year survival rate according to the remaining number of teeth and the presence/absence of malnutrition. Further, hazard ratios (HRs) were analyzed using Cox regression analyses. RESULTS: No difference was observed according to the number of teeth (p = 0.638), but the presence/absence of malnutrition was significantly associated with mortality (p < 0.001). Malnutrition was independently associated with higher HRs, even after adjusting for confounding factors associated with mortality. (HR: 2.315, 95% CI: 1.431-3.746). Additionally, adjusting for the number of teeth, HR remained significant (HR: 2.365, 95% CI: 1.449-3.853). CONCLUSION: In the very elderly, malnutrition-but not the number of teeth-was independently associated with 3-year all-cause mortality after adjusting for various health issues.

Association between dietary patterns and subjective and objective measures of physical activity among Japanese adults aged 85 years and older: a cross-sectional study.

A healthy diet and regular physical activity (PA) are delineated as healthy behaviours. Their implementation is associated with better health outcomes and improved quality of life. There is less evidence of a relationship between dietary patterns (DP) and PA, especially in adults aged ≥ 85. Hence, this cross-sectional study investigates the association between DP and PA in people of this age group, using the data from The Kawasaki Aging and Well-Being Project. Brief-type self-administered diet history questionnaire was used to estimate the intake of fifty-eight types of food. After energy adjustment, principal component analysis was performed to identify DP. PA was measured objectively using an accelerometer and subjectively using a questionnaire validated for this age group. Thousand participants (median age: 86·9 years, men: 49·9 %) were included in the analysis. Three major DP (DP1 'various foods', DP2 'red meats and coffee', DP3 'bread and processed meats') were identified. DP1 'various foods' was similar to DP previously named 'healthy' or 'prudent' and showed a positive association with PA time (PAT) as measured by accelerometer (B, 6·25; 95 % CI 0·13, 12·37) and relatively shorter sedentary behaviour (SB) time. DP2 'red meats and coffee' and DP3 'bread and processed meats' were negatively associated with PAT and positively associated with SB time. This study observed the relationship between diet and PA behaviours in adults aged ≥ 85, with healthier and more food-diverse DP associated with longer PAT and relatively unhealthy DP with shorter PAT.

Osteoporosis and sarcopenia are associated with each other and reduced IGF1 levels are a risk for both diseases in the very old elderly.

It is mandatory to manage musculoskeletal disorders in the elderly to prevent their becoming bed-ridden or requiring long-term care. However, the prevalence of musculoskeletal disorders such as osteoporosis and sarcopenia in otherwise healthy people over 85 years old is not completely known. Here we enrolled 1026 healthy subjects between 85 and 89 years old and evaluated them for the presence of osteoporosis, sarcopenia and fragility fracture(s), and how those conditions were related. We also evaluated biomarkers such as serum levels of insulin-like growth factor 1 (IGF1) and vitamin D status. The prevalence of osteoporosis, sarcopenia or fragility fracture(s) in these subjects was 22.4, 10.2 or 15.0 %, respectively. Serum IGF1 and 25(OH)D were significantly and negatively correlated with osteoporosis or sarcopenia. Osteoporosis and either sarcopenia or fragility fracture(s) were significantly related and shown to be risk factors for each other, even after adjustment for gender and BMI, while sarcopenia and fragility fracture(s) were not associated. Our data may provide a health platform for the very elderly and suggest strategies to prevent musculoskeletal disorders in this population.