Impact of fat to muscle ratio with risk of disability on community-dwelling Japanese older adults: A 5-year longitudinal study.

PURPOSE: Sarcopenic obesity is a combination of sarcopenia and obesity, which is associated with the onset of disability. Fat to muscle ratio (FMR) is a screening measure that assesses the ratio of muscle mass to fat mass. However, the relationship between the FMR and disability has not been investigated. METHODS: This study included 11,427 community-dwelling older adults aged ≥65 years enrolled in NCGG-SGS (National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes), a national cohort study in Japan. FMR was measured by the bioelectrical impedance analysis and calculated by dividing fat mass by muscle mass. Cox proportional hazard regression analysis adjusted for covariates was used to investigate the association between FMR and the risk of developing new care needs at 5 years. FMR was divided by about quintile, with quintile 5 as the high. RESULTS: The high FMR group had the highest incidence of disability at 20.8 % for women and 20.1 % for men. In women, the association between FMR and disability was significantly different for the FMR (hazard risk [HR]: 1.43, 95 % confidence interval [CI]: 1.16-1.75). There was no association between FMR and disability in men (HR: 0.98, 95 %CI: 0.76-1.25). Lagged analyses accounting for reverse causality did not change the relationship. CONCLUSIONS: FMR is associated with increased risk of disability in women community-dwelling older adults but not among men. Because the rate of decreased muscle strength is faster in men than in women, early decreased muscle strength may affect men's risk of disability more than muscle mass or fat mass.

Diversity in productive activities enhances life satisfaction among Japanese community-dwelling older adults: A cross-sectional study.

Few studies have reported an association between diversity in productive activities and life satisfaction; hence, this cross-sectional study conducted in Japan aimed to clarify this association. We assessed the life satisfaction of 4,498 Japanese community-dwelling older adults engaged in productive activities (e.g., paid work, volunteering, taking care of children, and supporting others) using the Life Satisfaction Scale. We took the sum of the number of engaging productive activities as the diversity in productive activities score. A dose-response relationship was observed for each additional productive activity on life satisfaction. Participants who engaged in one, two, three, or four productive activities were more likely to have higher life satisfaction than those who did not engage; the odds ratios (95 % confidence intervals) were 1.19 (1.02-1.39), 1.19 (1.00-1.42), 1.71 (1.37-2.13), and 2.27 (1.58-3.27), respectively. Diversity in productive activities may enhance higher life satisfaction likelihood among Japanese community-dwelling older adults.

Association between Hearing Aid Use and Cognitive Function in Persons with Hearing Impairment Stratified by Cardiovascular Risk.

The purpose of this study was to conduct a cross-sectional analysis of the association between hearing aid use and cognitive decline in community-dwelling older adults with hearing impairment, stratified by cardiovascular risk level. This cross-sectional study covers 1857 hearing-impaired individuals selected among 10,674 community-dwelling older adults (≥65 years of age) in Japan. We investigate the association between hearing aid use and cognitive decline stratified by cardiovascular risk level, by assessing self-reported hearing impairment and hearing aid use, absolute cardiovascular risk, cognitive function, and potential confounding factors. The association between hearing impairment severity and increased cardiovascular risk, and the benefit of hearing aid use in preventing cognitive decline, were examined in a binomial logistic regression analysis, with the presence of cognitive decline as the objective variable. In the low cardiovascular risk group, hearing aid users had a lower odds ratio for decline in executive function than non-users (odds ratio = 0.61, 95% confidence interval: 0.39-0.98). However, there was no significant association between hearing aid use and cognitive decline in the high cardiovascular risk group (p > 0.05). Among older adults with hearing impairment, hearing aid use was associated with the maintenance of executive function in individuals of low cardiovascular risk.

Association between perceived value of adopting new behaviors and incident disability among Japanese community-dwelling older adults.

OBJECTIVES: This longitudinal observational cohort study aimed to clarify the relationship between perceived value (PV) to adopt new behaviors and incident disability in community-dwelling older adults. METHOD: Participants were 5073 community-dwelling older adults aged ≥65 years in Japan (Mage = 74.0 ± 5.6 years; female = 55.1%). The mean follow-up time was 34.5 months. Baseline data were collected during health checkups in a prospective cohort study. Measurements included engagement in physical activity (PA), cognitive activity (CA), and social activity (SA), PV, health and physical conditions, and demographic characteristics. PV was assessed by asking whether participants thought it was valuable to adopt new behaviors related to PA, CA, and SA. Participants were classified as having higher/lower PV, PA, CA, and SA. Cox proportional hazard models were used to analyze the association between PV and incident disability. PV was examined both as an independent variable and in combination as follows: higher PV and higher PA/CA/SA (high/high); lower PV and higher PA/CA/SA (low/high); higher PV and lower PA/CA/SA (high/low); and lower PV and lower PA/CA/SA (low/low). RESULTS: Higher PV was significantly associated with a lower hazard ratio (HR) for incident disability. The low/high, high/low, and low/low significantly increased the HR compared to high/high in the analyses of PV & PA and CA. The analysis of PV & SA showed that only low/low increased the HR compared to high/high. CONCLUSION: Having both higher PV and higher activity engagement may contribute to preventing disability development. Both support for activities and value education in older adults may be needed.

Estimating the Effect of Engagement in Community-Based Going-Out Program on Incidence Disability in Older Adults.

OBJECTIVES: Although going out has been reported to be associated with the incidence of disability, few studies have investigated the effect of community-based programs to promote going out on the incidence of disability. This study aimed to estimate the effects of a program fostering going-out on the incidence of disability in community-dwelling older adults. DESIGN: Longitudinal, observational study. SETTING AND PARTICIPANTS: Nonengaged (n = 1086) and engaged older adults (n = 1086) enrolled in the National Center for Geriatrics and Gerontology Study of Geriatric Syndrome by using a one-to-one nearest neighbor propensity score-matching scheme. METHODS: After the baseline assessments, participants in the community-based going-out program received a specialized physical activity tracker, monitored their daily physical activity, and received personalized feedback on going out to community facilities with a system for reading the device for 12 months. Disability onset was defined as a new case of long-term care under the public insurance certification in Japan within 48 months of program completion. The absolute risk reduction and the number needed to treat for the incidence of disability were calculated for the nonengaged and engaged groups. Cox proportional hazard regression analysis, using inverse probability weighting was used to obtain the hazard ratio. RESULTS: Disabilities occurred in 112 individuals in the matched nonengaged group and 51 individuals in the engaged group. The absolute risk reduction was 5.67% (95% CI 3.46%-7.88%). The number needed to treat was 18 (95% CI 13-29). The hazard ratio, with the nonengaged group as the reference, was 0.49 (95% CI 0.36-0.67). CONCLUSIONS AND IMPLICATIONS: This longitudinal observational study suggested that a community-based program could prevent 1 disability in every 18 participants. This program does not require a professional instructor, only the distribution of devices and system installation, and it could be beneficial as a population-based approach to preventing disabilities.

Social participation in the neighborhood community prevents onset of disability in community-dwelling older adults whose life space with activities is limited: A 2-year prospective cohort study.

AIMS: For older adults with limited life space and activity, social participation in the neighborhood community is essential to ensure social interaction and activity levels. This study examined the association between social participation in the neighborhood community and the onset of disability in older adults with different life spaces and activities. METHODS: The participants were 9513 older adults from a cohort study conducted at the National Center for Geriatrics and Gerontology Study of Geriatric Syndromes (NCGG-SGS). Social participation in the neighborhood community was assessed by participating in the community meetings. Life space with activities was evaluated using the Activity Mobility Index (AMI) developed in the NCGG-SGS, with higher scores indicating better mobility and movement. The participants were divided into four groups based on the quartiles of their AMI scores (Q1-Q4). Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for disability incidence by social participation in each quartile. RESULTS: Over the 2-year follow-up period, disability occurred in 4.3% of the participants (n = 409). In the Q1 group, participants who participated in the neighborhood community had a significantly lower risk of developing a disability than those who did not (HR, 0.47; 95% CI, 0.28-0.76). There were no significant differences in onset of disability between the presence and absence of social participation for groups Q2, Q3, and Q4. CONCLUSIONS: Social participation in the neighborhood community was associated with the onset of disability in the lowest life space group. Social participation within a limited life space with activities may prevent disability onset. Geriatr Gerontol Int 2024; 24: 609-618.

Background and clinical significance of biomarker-based patient enrichment in non-small-cell lung cancer drug development.

Pharmaceutical companies have adopted biomarker-based enrichment (personalized) strategies to improve research and development productivity. We explored the background in which personalized strategies are adopted and examined whether their adoption is linked to improved efficacy of new drugs approved for non-small cell lung cancer (NSCLC) by US Food and Drug Administration (FDA). We extracted data from the first labels of drugs approved for NSCLC between May 2003 and February 2021, and performed a qualitative comparative analysis and meta-analysis. Personalized strategies were adopted in more than half of the trials (16/27) and were often used in trials aimed at obtaining first-line indications and in drugs that were not first-in-class. The meta-analysis showed that personalized trials had significantly improved progression-free survival (PFS) hazard ratio (HR) than trials without personalization but not for relative response rate ratio (RRR) or overall survival (OS) HR. Trials in which PFS HR was the primary endpoint tended to have improved PFS HR, and trials in which OS HR was the primary endpoint had worse PFS HR. The efficacy endpoints that are substantially affected by personalized strategies appear to differ, especially for new drugs with novel mechanism of action (MOA), because trial designs are employed to validate drug-specific advantages.

Elevated Risk of Dementia Diagnosis in Older Adults with Low Frequencies and Durations of Social Conversation.

Background: Social networks and social participation have protective effects on cognitive function maintenance and Alzheimer's disease and general dementia development. Objective: We aimed to investigate the association between conversations and dementia incidence in older adults. Methods: This longitudinal prospective cohort study used population data from the National Center for Geriatric and Gerontology-Study of Geriatric Syndromes (NCGG-SGS) from September 2015 to February 2017. The database included 4,167 individuals in Japan aged ≥60 years who were generally healthy and without major cognitive impairment. Participants were classified into two groups according to six daily conversation measures at baseline. The conversation index was calculated as a composite score for these measures. Participants were tracked monthly over 60 months for new-onset dementia. Results: Data from 2,531 participants were analyzed (72.7±6.7 years; range: 60-96 years). Dementia incidence per 1,000 person-years was 15.7 (95% confidence interval, 13.6-18.1). The Youden index determined the cut-off point for dementia incidence, with a conversation index of 16/17 points. The low conversation group included more participants with new-onset dementia. Cox proportional hazards regression crude models showed remarkable relationships between dementia onset and specific conversation measurements, including conversation index. According to the Cox regression adjusted model, the cut-off point of the conversation index showed only a remarkable relationship with dementia onset. Conclusions: Dementia risk was extensively associated with low daily conversation statuses. The assessment of conversational factors may be useful as a risk indicator for the development of Alzheimer's disease and general dementia.

Association between the perceived value of adopting new behaviors and depressive symptoms among older adults.

Early preventive measures against depression have become important with unprecedented global aging. Increase in one's perceived value (PV) may correspond to better mental health outcomes. This cross-sectional observation study aimed to clarify whether the PV of adopting new behaviors is associated with depressive symptoms. The participants were 5266 community-dwelling older adults aged ≥ 65 years. We developed a questionnaire to measure the PV of adopting new behaviors, specifically activities beneficial for preventing depressive symptoms (physical, cognitive, and social activities) in older adults. The questionnaire asked whether adopting the ten selected behaviors was valuable. The scores were added, and the total score ranged from - 20 to 20. The odds ratios (OR) of depressive symptoms were calculated using binomial logistic regression according to the PV score quartiles. Depressive symptoms were reported by 595 (11.3%) participants. After adjusting for potential confounders, higher quartiles of PV scores were significantly associated with lower prevalence of depressive symptoms: vs Q1; Q2 OR 0.76 (95% confidence interval: 0.59-0.97); Q3 0.67 (0.51-0.87); Q4 0.54 (0.40-0.73) (P for trend < .001). Having a higher PV of adopting new behaviors may prevent depressive symptoms among older adults. Healthcare professionals need to pay attention to poor value orientation among older adults.

Lifetime Physical Activity and Late-Life Mild Cognitive Impairment in Community-Dwelling Older Adults.

OBJECTIVES: Regular physical activity throughout life is generally recommended to prevent dementia; however, there is little evidence regarding the association between lifetime physical activity and mild cognitive impairment (MCI), which often precedes dementia. This study aimed to examine the association of lifetime physical activity and their transitions with late-life MCI. DESIGN: A population-based case-control study. SETTING AND PARTICIPANTS: A total of 2968 Japanese community-dwelling older adults aged ≥70 years without dementia. METHODS: We evaluated the participants' early-, mid-, and late-life physical activity habits and categorized their transitions across life stages. Cognitive functions in late life were assessed for memory, attention, executive function, and processing speed; functional impairment in one or more cognitive domains was defined as MCI. RESULTS: Regular physical activity in early life was not significantly associated with late-life MCI [odds ratio (OR), 0.80; 95% CI, 0.63-1.02], although those in mid-life (OR, 0.64; 95% CI, 0.51-0.81) and late-life (OR, 0.74; 95% CI, 0.59-0.91) were associated with lower odds of late-life MCI. Compared with nonexercisers, participants who acquired new habits of physical activity during mid- or late-life (OR, 0.71; 95% CI, 0.55-0.91) and those who maintained physical activity throughout their life span (OR, 0.61; 95% CI, 0.42-0.87) had lower odds of late-life MCI; those who stopped regular activity during mid- or late-life did not (OR, 0.79; 95% CI, 0.58-1.06). CONCLUSIONS AND IMPLICATIONS: While physical activity throughout the life span is associated with the lowest odds of MCI, starting regular physical activity, even later in life, confers a benefit and should be encouraged as a "lifelong approach" to MCI risk reduction.

Association of objectively measured physical activity with incidence disability in older adults with/without social isolation.

PURPOSE: This study aimed to investigate association between objectively measured physical activities with incidence disability in older adults with and without social isolation. METHODS: This 5-year longitudinal observational study used a population-based study from a sub-cohort of the National Center for Geriatrics and Gerontology Study of Geriatric Syndrome. In Japan, Incident disability is defined as a new case of public insurance certification for long-term care. As participants, we enrolled 5,257 community-dwelling older adults aged ≥ 70 years. The Participants on whom incomplete baseline physical activity assessments were performed; who required long-term care; had a history of dementia, Parkinson's disease, stroke, or depression; who lacked independence in basic ADL; who had Mini-Mental State Examination scores; or who had missing measurements; were excluded. Thus, 2,071 participants were included. RESULTS: Of the participants, 1,183 non-socially isolated participants had 151 (4.3%) cases of disability, while socially isolated participants had 150 (13%) cases. Cox proportional-hazards regression analysis presented the adjusted hazard ratio (HR) and 95% confidence interval (95%CI) of daily steps and low-intensity and moderate-to-vigorous physical activities-0.62(0.43-0.89), 0.84(0.60-1.18), 0.62(0.43-0.89) in participants with social isolation, and 0.58(0.40-0.85), 0.86(0.60-1.24), 0.70(0.49-1.01) in those with social isolation. CONCLUSIONS: Daily steps were significantly associated with a decreased risk of incidence disability, regardless of social isolation. These results suggest the greater importance of daily physical activity than its specific intensity in socially isolated older adults.

Combined impact of physical frailty and social isolation on use of long-term care insurance in Japan: A longitudinal observational study.

OBJECTIVES: The combined effect of physical frailty and social isolation on the need to make use of long-term care insurance (LTCI) among older adults remains unknown. Thus this study investigates the association between physical frailty, social isolation, and the use of LTCI among older adults in Japan. STUDY DESIGN: This is a prospective observational study. MAIN OUTCOME MEASURES: Physical frailty is defined as limitations in strength, mobility, and physical activity, as well as exhaustion and weight loss. People with one or two indicators were categorized as pre-frail. Participants with a score of 1 point or more on the social isolation scale were defined as being socially isolated. Participants were followed up monthly for two years to check whether incident certification of care had been required. RESULTS: Data on 4576 community-dwelling independent older adults (mean age, 73.9 ± 5.5 years, 2032 men, 2544 women) were analyzed. A time-dependent Cox proportional hazards regression model showed that individuals with pre-frailty without social isolation (hazard ratio [HR] 2.02, 95 % confidence interval [CI] 1.40-2.91), pre-frailty with social isolation (HR 2.36, 95 % CI 1.62-3.43), frailty without social isolation (HR 2.98, 95 % CI 1.83-4.85), and frailty with social isolation (HR 3.19, 95 % CI 2.07-4.91) had significantly higher risks of needing to make use of LTCI than those with no frailty and without social isolation. This higher risk was non-significant among individuals with no frailty and social isolation (HR 1.28, 95 % CI 0.78-2.10). CONCLUSION: Combined frailty and social isolation among older adults should be addressed to prevent adverse health outcomes, including use of LTCI.

Physical frailty and survival time after the onset of functional disability: Is there a sex difference?

BACKGROUND: Physical frailty accelerates the timing of both subsequent disability and death; however, evidence regarding the impact of frailty on the period from disability onset to death and sex differences of this impact is lacking. The aim of this study was to examine the relationship among physical frailty, disability, death, and sex differences. METHODS: This Japanese cohort study included 10,524 community-dwelling people aged ≥65 years. Physical frailty was operationalized by key phenotypes as per Fried's criteria (slowness, weakness, exhaustion, weight loss, and low activity) at baseline. We calculated hazard ratios (HRs) with 95% confidence intervals (CIs) for disability onset and post-disability survival according to the frailty status. RESULTS: During a 5-year follow-up, the risk of disability onset for pre-frailty (HR: 1.74, 95% CI: 1.51-2.00) and frailty (HR: 3.27, 95% CI: 2.77-3.87) were significantly higher than that for robust people. Furthermore, among participants who developed disabilities within 5 years (n = 1481), the risk of post-disability death for pre-frailty was not different from that for robust (HR: 1.49, 95% CI: 0.99-2.24), but frailty showed a higher risk of post-disability death than did robust people. (HR: 1.75, 95% CI: 1.13-2.72). In the sex-stratified analysis, although the female group showed no association between frailty status and post-disability death (HR: 1.21, 95% CI: 0.63-2.33 in pre-frailty; HR: 1.24, 95% CI: 0.60-2.57 in frailty), the male group showed higher risk of post-disability death in both pre-frailty (HR: 1.74, 95% CI: 1.03-2.96) and frailty (HR: 2.32, 95% CI: 1.32-4.09). CONCLUSIONS: Physical frailty shortens the period from disability onset to death. Additionally, the impact of frailty on post-disability death is greater for males than for females. Our findings suggest that physical frailty is an important clinical indicator distinct from disability and that interventions to prevent and address frailty in men need further investigation.

Cross-sectional associations between sedentary time with cognitive engagement and brain volume among community-dwelling vulnerable older adults.

AIMS: Vulnerable older adults tend to decrease physical activity (PA) and increase sedentary time (ST). Previous research on the associations between ST and brain volume have yielded inconsistent findings, without considering the impact of cognitive engagement (CE) on cognitive function. We aimed to examine the association between ST with CE and brain volume. METHODS: A structural magnetic resonance imaging survey was conducted among community-dwelling vulnerable older adults. Brain volumetric measurements were obtained using 3T magnetic resonance imaging and pre-processed using FreeSurfer. ST with low or high CE was assessed using a 12-item questionnaire. PA was assessed by the frequency of light and moderate levels of physical exercise according to the Japanese version of the Cardiovascular Health Study criteria. Participants were categorized into a low PA group and a moderate-to-high PA group. RESULTS: Among 91 participants (83.1 ± 5.2 years old, 61.5% female), 26 were low PA. The overall sample and moderate-to-high PA group did not show significant positive associations with brain volume for ST with high CE. In the low PA group, isotemporal substitution models showed that replacing ST with low CE by ST with high CE was significantly associated with increased brain volume in some areas, including the rostral and caudal anterior cingulate (ß = 0.486-0.618, all P < 0.05, adjusted R2 = 0.344-0.663). CONCLUSIONS: Our findings suggest that replacing ST with low CE by ST with high CE is positively associated with brain volume in vulnerable older adults with low PA. Geriatr Gerontol Int 2024; 24: 82-89.

Neurophysiological markers in community-dwelling older adults with mild cognitive impairment: an EEG study.

BACKGROUND: Neurodegeneration and structural changes in the brain due to amyloid deposition have been observed even in individuals with mild cognitive impairment (MCI). EEG measurement is considered an effective tool because it is noninvasive, has few restrictions on the measurement environment, and is simple and easy to use. In this study, we investigated the neurophysiological characteristics of community-dwelling older adults with MCI using EEG. METHODS: Demographic characteristics, cognitive function, physical function, resting-state MRI and electroencephalogram (rs-EEG), event-related potentials (ERPs) during Simon tasks, and task proportion of correct responses and reaction times (RTs) were obtained from 402 healthy controls (HC) and 47 MCI participants. We introduced exact low-resolution brain electromagnetic tomography-independent component analysis (eLORETA-ICA) to assess the rs-EEG network in community-dwelling older adults with MCI. RESULTS: A lower proportion of correct responses to the Simon task and slower RTs were observed in the MCI group (p < 0.01). Despite no difference in brain volume between the HC and MCI groups, significant decreases in dorsal attention network (DAN) activity (p < 0.05) and N2 amplitude of ERP (p < 0.001) were observed in the MCI group. Moreover, DAN activity demonstrated a correlation with education (Rs = 0.32, p = 0.027), global cognitive function (Rs = 0.32, p = 0.030), and processing speed (Rs = 0.37, p = 0.010) in the MCI group. The discrimination accuracy for MCI with the addition of the eLORETA-ICA network ranged from 0.7817 to 0.7929, and the area under the curve ranged from 0.8492 to 0.8495. CONCLUSIONS: The eLORETA-ICA approach of rs-EEG using noninvasive and relatively inexpensive EEG demonstrates specific changes in elders with MCI. It may provide a simple and valid assessment method with few restrictions on the measurement environment and may be useful for early detection of MCI in community-dwelling older adults.

Subjective Cognitive Decline and Frailty Trajectories and Influencing Factors in Japanese Community-Dwelling Older Adults: A Longitudinal Study.

We studied frailty and subjective cognitive decline (SCD) trajectories in older Japanese adults and evaluated the influence of various factors on these trajectories. We analyzed data from 1157 non-demented adults aged 70 and above from 2013 to 2019. Frailty was assessed using the self-administered Kihon Checklist (KCL), a Japanese frailty index. SCD was evaluated using the questionnaire of the Subjective Memory Complaints scale. Through group-based joint trajectory models, we discerned three frailty trajectories: non-progressive (n = 775), moderate progressive (n = 312), and rapid progressive (n = 70); and three SCD trajectories: non-progressive (n = 302), moderate progressive (n = 625), and rapid progressive (n = 230). Individuals in the rapid progressive SCD trajectory had a 32.2% probability of also being in the rapid progressive frailty trajectory. In contrast, those in the non-progressive SCD trajectory had zero probability of being in the rapid progressive frailty trajectory. Both the rapid progressive frailty and SCD groups combined had a higher incidence of depressive symptoms and slow gait speed. Our results have found that frailty and SCD share a similar trajectory in Japanese older adults. Additionally, rapid progressive frailty and SCD were associated with the highest risk of depressive symptoms and slow gait speed. Thus, interventions targeting both frailty and cognitive decline should prioritize mental health enhancement and gait speed improvement.

Common clinicopathological and immunological features of sarcomatoid carcinoma across organs: A histomorphology-based cross-organ study.

Sarcomatoid carcinoma (SC), which can occur in any organ, is a rare disease. To elucidate common characteristics of SC beyond organs, we evaluated clinicopathological and immunological features of SC defined by the single histological criterion beyond organs compared to randomly matched conventional carcinoma (non-SC) adjusted for the disease stage. Immunological features were assessed by multiplex immunohistochemistry, comparing immune cell density in tumor tissues and tumor programmed death-ligand 1 (PD-L1) expression. A total of 101 patients with SC or non-SC (31 lung, 19 esophagus, 22 pancreas, 15 liver, 4 bile duct, 6 kidney, 2 uterus and 2 ovary) were identified among 7197 patients who underwent surgery at our institute (1997-2020). SC was significantly associated with worse survival (HR: 1.571; 95% CI: 1.084-2.277; P = .017). The frequency of postoperative progression within 6 months was significantly higher for SC patients (54% vs 28%; P = .002). The immune profiling revealed the densities of CD8+ T cells (130 vs 72 cells/mm2 ; P = .004) and tumor-associated macrophages (566 vs 413 cells/mm2 ; P < .0001) and the tumor PD-L1 expression score (40% vs 5%; P < .0001) were significantly higher in SCs than in non-SCs. Among 73 SC patients with postoperative progression, multivariate Cox regression analysis showed that immunotherapy tended to be associated with favorable survival (HR: 0.256; 95% CI: 0.062-1.057; P = .060). Collectively, SCs shared clinicopathological and immunological features across organs. Our study can initiate to standardize the pathological definition of SC and provide a rationale for the investigation and development for this rare disease in a cross-organ manner.

Cardiac Reversibility and Survival After Transcatheter Aortic Valve Implantation in Patients With Low-Gradient Aortic Stenosis.

Background Prognostic implications of transcatheter aortic valve implantation (TAVI) in low-gradient (LG) aortic stenosis (AS) remain controversial. The authors hypothesized that differences in cardiac functional recovery may solve this ongoing controversy. The aim was to evaluate clinical outcomes and the response of left ventricular (LV) function following TAVI in patients with LG AS. Methods and Results This multicenter retrospective study included 1742 patients with severe AS undergoing TAVI between January 2015 and March 2019. Patients were subdivided into low-flow (LF) LG, normal-flow (NF) LG, LF high-gradient, and NF high-gradient AS groups according to the mean gradient of the aortic valve (LG <40 mm Hg) and LV stroke volume index (LF <35 mL/m2). Outcomes and changes in echocardiographic parameters after TAVI were compared between the groups. A total of 227 patients (13%) had reduced ejection fraction, and 486 patients (28%) had LG AS (LF-LG 143 [8%]; NF-LG 343 [20%]). During a median follow-up period of 747 days, 301 patients experienced a composite end point of cardiovascular death and rehospitalization for cardiovascular events, which was higher in the LF-LG and NF-LG groups than in the high-gradient groups. LG AS was independently associated with the primary outcome (hazard ratio, 1.69; P<0.001). Among 1239 patients with follow-up echocardiography, LG AS showed less improvement in the LV mass index and LV end-diastolic volume compared with high-gradient AS after 1 year, while LV recovery was similar between the LF AS and NF AS groups. Conclusions LG AS was associated with poorer outcomes and LV recovery, regardless of flow status after TAVI. Careful evaluation of AS severity may be required in LG AS to provide TAVI within the appropriate time and advanced care afterward.