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Background: Transfers of nursing home (NH) residents to the emergency department (ED) is frequent. Our main objective was to assess the cost of care pathways 6 months before and after the transfer to the emergency department among NH residents, according to the type of transfer (i.e. appropriate or inappropriate). Methods: This was a part of an observational, multicenter, case-control study: the Factors associated with INappropriate transfer to the Emergency department among nursing home residents (FINE) study. Sixteen public hospitals of the former Midi-Pyrénées region participated in recruitment, in 2016. During the inclusion period, all NH residents arriving at the ED were included. A pluri-disciplinary team categorized each transfer to the ED into 2 groups: appropriate or inappropriate. Direct medical and nonmedical costs were assessed from the French Health Insurance (FHI) perspective. Healthcare resources were retrospectively gathered from the FHI database and valued using the tariffs reimbursed by the FHI. Costs were recorded over a 6-month period before and after transfer to the ED. Other variables were used for analysis: sex, age, Charlson score, season, death and presence inside the NH of a coordinating physician or a geriatric nursing assistant. Results: Among the 1037 patients initially included in the FINE study, 616 who were listed in the FHI database were included in this economic study. Among them, 132 (21.4%) had an inappropriate transfer to the ED. In the 6 months before ED transfer, total direct costs on average amounted to 8,145€ vs. 6,493€ in the inappropriate and appropriate transfer groups, respectively. In the 6 months after ED transfer, they amounted on average to 9,050€ vs. 12,094€. Conclusions: Total costs on average are higher after transfer to the ED, but there is no significant increase in healthcare expenditure with inappropriate ED transfer. Support for NH staff and better pathways of care could be necessary to reduce healthcare expenditures in NH residents. Trial registration: clinicaltrials.gov, NCT02677272. [ABSTRACT FROM AUTHOR]

We derive a three‐dimensional shear‐wave velocity model of the Ligurian‐Provence back‐arc basin (Northwestern Mediterranean Sea) using ocean‐bottom seismometers (AlpArray OBSs) and land stations from permanent and temporary seismic networks. The quality of OBS continuous records is enhanced by a specific processing that reduces instrumental and seabed‐induced noises (transients, tilt, compliance). To further improve the resolution of ambient‐noise tomography in the offshore area, we compute the Rayleigh‐wave part of the Green functions for OBS‐OBS pairs by using onshore stations as virtual sources. 2‐D group‐velocity maps and their uncertainties are computed in the 4–150 s period range by a transdimensional inversion of Rayleigh‐wave travel times. The dispersion data and their uncertainties are inverted for a probabilistic 3‐D shear‐wave velocity model that includes probability densities for Vs and for the depth of layer interfaces. The probabilistic model is refined by a linearized inversion that accounts for the water layer in the Ligurian Sea. Our S‐wave velocity and layer boundary probability models correspond well to a recent, high‐resolution P‐wave velocity cross‐section derived from controlled‐source seismic profiling along the Ligurian‐Provence basin axis. A joint interpretation of the P‐ and S‐wave velocity sections along this profile reveals a thin, anomalous oceanic crust of low P‐wave velocities but high S‐wave velocities, intruded by a gabbroic body. The illuminated part of the upper mantle appears to be devoid of serpentinization. Plain Language Summary: The Ligurian‐Provence basin (Northwestern Mediterranean Sea) is one of the Miocene‐Pliocene back‐arc basins that resulted from the retreat of the Adria subduction in the plate reorganization due to Africa‐Europe convergence. The crustal structure of the basin is still debated, even though it has been probed by active seismic profiling. We compute a high‐resolution shear‐wave velocity model of the Ligurian‐Provence basin and its margins by making optimal use of ambient‐noise recordings of seafloor broadband seismometers. In particular, we improve the usually low quality of surface‐wave signals in noise correlations between seafloor stations by involving correlations with land stations. The joint interpretation of our S‐wave velocity model with a P‐wave velocity section obtained in the basin axis by controlled‐source seismic profiling provides compelling evidence for the presence of a thick sediment pile above a thin, ∼4.5 km‐thick oceanic crust, intruded by gabbroic bodies emplaced at the crust‐mantle transition. These results show the potential of a joint interpretation of P‐ and S‐wave velocity models since they provide reliable answers to a number of debated questions on the petrological nature of the crust and uppermost mantle, in particular in the Ligurian‐Provence basin. Key Points: Efficient processing scheme to remove transients and reduce tilt and compliance from continuous ambient noise recorded by ocean‐bottom seismometers (OBSs)Computation of iterative correlations between OBSs based on a virtual reconstruction of the Rayleigh wavesThin, anomalous oceanic crust with gabbroic intrusions evidenced in the basin axis from a joint interpretation of Vs and Vp models [ABSTRACT FROM AUTHOR]

A full understanding of the dynamics of mountain ranges such as the Alps requires the integration of available geological and geophysical knowledge into a lithospheric-scale 3-D geological model. As a first stage in the construction of this geo-model, we derive a new 3-D shear wave velocity model of the Alpine region, with a spatial resolution of a few tens of kilometres, making it possible to compare with geological maps. We use four years of continuous vertical-component seismic noise records to compute noise correlations between more than 950 permanent broad-band stations complemented by ∼600 temporary stations from the AlpArray sea-land seismic network and the Cifalps and EASI linear arrays. A specific pre-processing is applied to records of ocean–bottom seismometers in the Liguro-Provençal basin to clean them from instrumental and oceanic noises. We first perform a 2-D transdimensional inversion of the traveltimes of Rayleigh waves to compute group-velocity maps from 4 to |$150\, \mathrm{ s}$|⁠. The data noise level treated as an unknown parameter is determined with a Hierarchical Bayes method. A Fast Marching Eikonal solver is used to update ray path geometries during the inversion. We use next the group-velocity maps and their uncertainties to derive a 3-D probabilistic Vs model. The probability distributions of Vs at depth and the probability of presence of an interface are estimated at each location by exploring a set of 130 million synthetic four-layer 1-D Vs models. The obtained probabilistic model is refined using a linearized inversion. Throughout the inversion for Vs , we include the water column where necessary. Our Vs model highlights strong along-strike changes of the lithospheric structure, particularly in the subduction complex between the European and Adriatic plates. In the South-Western Alps, our model confirms the existence of a low-velocity structure at |$50-80\, \mathrm{ km}$| depth in the continuation of the European continental crust beneath the subduction wedge. This deep low-velocity anomaly progressively disappears towards the North-Western and Central Alps. The European crust includes lower crustal low-velocity zones and a Moho jump of |$\sim \, 8-12$| km beneath the western boundary of the External Crystalline Massifs of the North-Western Alps. The striking fit between our Vs model and the receiver function migrated depth section along the Cifalps profile documents the reliability of the Vs model. In light of this reliability and with the aim to building a 3-D geological model, we re-examine the geological structures highlighted along the Cifalps profile. [ABSTRACT FROM AUTHOR]

The Integrated Care for Older People (ICOPE) program is a healthcare pathway that uses a screening test for intrinsic capacity (IC) as its entry point. However, real-life data informing on how IC domains cluster and change over time, as well as their clinical utility, are lacking. Using primary healthcare screening data from more than 20,000 French adults 60 years of age or older, this study identified four clusters of IC impairment: 'Low impairment' (most prevalent), 'Cognition+Locomotion+Hearing+Vision', 'All IC impaired' and 'Psychology+Vitality+Vision'. Compared to individuals with 'Low impairment', those in the other clusters had higher likelihood of having frailty and limitations in both activities of daily living (ADL) and instrumental activities of daily living (IADL), with the strongest associations being observed for 'All IC impaired'. This study found that ICOPE screening might be a useful tool for patient risk stratification in clinical practice, with a higher number of IC domains impaired at screening indicating a higher probability of functional decline., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Aging is characterized by several major changes, including altered body composition, which is associated with numerous negative clinical consequences such as sarcopenia, osteoporosis, and frailty. The study is to evaluate body composition parameters depending on age and sex in a population ranging from the young adult to the very old, and to identify break points in the association between body composition and age. In this cross-sectional study, we included the enrolment population of the French INSPIRE-T prospective cohort, accounting for 915 subjects (62% female). Age ranged from 20 to 93 years, median age (years) was 63 (IQR 27). Body composition (lean mass, fat mass, and bone mineral content) was assessed with dual-X-ray absorptiometry (DXA). Different break points in the relationship between age and body composition variables in males and females were identified using a segmented regression analysis adjusted on physical activity, nutritional status, educational level, and comorbidities. Lean mass decreased from the age of 55 years for males (CI 95% 44-66) and 31 years for females (CI 95% 23-39). For fat mass, we observed a trend towards an increase with age for males. For females, we observed an increase with age up to age 75 (CI 95% 62-86), followed by a decreasing trend. In this study, we described the relationship between body composition and age as a function of sex, establishing a foundation for further studies on predictive biomarkers of age-related body composition alteration., (© 2024. The Author(s).)

Background: The effectiveness of the body physiological regulatory mechanisms declines in late life, and increased Blood Pressure Variability (BPV) may represent an alteration in cardiovascular homeostatic patterns. Intrinsic Capacity (IC) has been proposed by the World Health Organization as a marker of healthy aging, based on individual's functional abilities and intended at preserving successful aging. We aimed to investigate the association of visit-to-visit BPV with IC decline in a population of community-dwelling older adults., Methods: The study population consisted of 1407 community-dwelling participants aged ≥70 years from the MAPT study evaluated during the 5-year follow-up. Systolic BPV (SBPV) and diastolic BPV (DBPV) were determined through six indicators. Cognition, psychology, locomotion and vitality constituted the four IC domains assessed. Total IC Z-score resulted from the sum of the four domains Z-scores divided by 4. The incidence of domain impairment over time was also assessed., Results: Higher SBPV was significantly associated with poorer IC Z-scores in all linear mixed models [1-SD increase of CV%: β(SE)=-0.010(0.001), p < 0.01]. Similar results were observed for DBPV [1-SD increase of CV%: β(SE)=-0.003(0.001), p = 0.02]. Incident IC impairment was significantly higher in participants with greater SBPV, [HR=1.16 (95 % CI, 1.01-1.33), p = 0.03], while greater DBPV did not show a higher risk of incident IC impairment., Conclusions: Greater BPV is associated with IC decline over time. Our findings support BP instability as a presumable index of altered cardiovascular homeostatic mechanism, suggesting that BPV might be a clinical marker of aging and addressable risk factor for promoting healthy aging., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2024. Published by Elsevier B.V.)

Background: The way physical activity (PA) and sedentary behaviour (SB) independently and interactively modify the age-related decline in physical capacity remains poorly understood. This cross-sectional study investigated the independent and interactive associations of PA and SB with physical function and performance throughout the adult life course., Methods: Data from 499 community-dwelling adults (63% female) aged 20-92 years, involved in the INSPIRE Human Translational Cohort, were used in this cross-sectional study. Daily time spent on moderate-to-vigorous PA (MVPA, min/day) and SB (h/day) was measured with activPAL triaxial accelerometers. Physical function and performance were assessed through the measurement of the 4-m usual gait speed (m/s), handgrip strength (kg), lower-limb strength (isokinetic knee extension torque, N·m), estimated lower-limb power (five-time chair-rise test performance, s) and cardiorespiratory fitness (V̇O 2 max, mL/kg/min). Confounder-adjusted multiple linear and curvilinear regressions were performed to investigate how MVPA, SB and their interactions were associated with the physical outcomes (all square root-transformed except gait speed) throughout the adulthood spectrum., Results: Interaction analyses revealed that the combination of higher levels of MVPA with lower levels of SB favourably reshaped the negative relationship between handgrip strength and age (age 2  × SB × MVPA: B = -7E-08, SE = 3E-08, P < 0.05). In addition, higher levels of MVPA were independently associated with an improved age-related profile in gait speed (age 2  × MVPA: B = 3E-06, SE = 1E-06, P < 0.05), chair-rise performance (age × MVPA: B = -9E-05, SE = 4E-05, P < 0.05) and V̇O 2 max (MVPA at 21 years: B = 3E-02, SE = 7E-03, P < 0.05; age × MVPA: B = -5E-04, SE = 2E-04, P < 0.05). Conversely, the detrimental association of age with lower-limb muscle strength (age × SB: B = -1E-04, SE = 6E-05, P < 0.05) and chair-rise performance (age × SB: B = 1E-05, SE = 7E-06, P < 0.05) was exacerbated with increasing duration of SB, independently of MVPA. Supplementary analyses further revealed that some of these associations were age and sex specific., Conclusions: This cross-sectional study demonstrated that reduced sedentary time and increased activity duration were independently and synergistically associated with an attenuated age-related loss in physical capacity. These findings need to be confirmed with longitudinal data but encourage both adopting an active lifestyle and reducing sedentary time as preventive measures against physical aging., (© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

The dosimetry evaluation for the selective internal radiation therapy is currently performed assuming a uniform activity distribution, which is in contrast with literature findings. A 2D microscopic model of the perfused liver was developed to evaluate the effect of two different 90 Y microspheres distributions: i) homogeneous partitioning with the microspheres equally distributed in the perfused liver, and ii) tumor-clustered partitioning where the microspheres distribution is inferred from the patient specific images., Methods: Two subjects diagnosed with liver cancer were included in this study. For each subject, abdominal CT scans acquired prior to the SIRT and post-treatment 90 Y positron emission tomography were considered. Two microspheres partitionings were simulated namely homogeneous and tumor-clustered partitioning. The homogeneous and tumor-clustered partitionings were derived starting from CT images. The microspheres radiation is simulated by means of Russell's law., Results: In homogenous simulations, the dose delivery is uniform in the whole liver while in the tumor-clustered simulations a heterogeneous distribution of the delivered dose is visible with higher values in the tumor regions. In addition, in the tumor-clustered simulation, the delivered dose is higher in the viable tumor than in the necrotic tumor, for all patients. In the tumor-clustered case, the dose delivered in the non-tumoral tissue (NTT) was considerably lower than in the perfused liver., Conclusions: The model proposed here represents a proof-of-concept for personalized dosimetry assessment based on preoperative CT images., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Born out of the COVID crisis, an innovative disposal called "Geriatric Team Healthcare Pathways" (GTHPs) has been implemented in the Occitania area in the south of France. GTHPs can be considered as geriatric "hotlines" providing expertise and knowledge to long-term care facility (LTCF) professionals, pursuing the general objective to promote a simplified, direct, and fair access to geriatric care for residents. This article highlights the history of their creation and their current use cases and operating modes for the year 2023, which includes a "quality of care approach" on good practices at a regional level (820 LTCFs), on topics such as the prevention of malnutrition and falls., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Adenosine triphosphatase inhibitory factor 1 (IF1) is a key protein involved in energy metabolism. IF1 has been linked to various age-related diseases, although its relationship with physical activity (PA) remains unclear. Additionally, the apolipoprotein A-I (apoA-I), a PA-modulated lipoprotein, could play a role in this relationship because it shares a binding site with IF1 on the cell-surface ATP synthase. We examined here the associations between chronic PA and plasma IF1 concentrations among older adults, and we investigated whether apoA-I mediated these associations., Methods: In the present work, 1096 healthy adults (63.8% females) aged 70 years and over who were involved in the Multidomain Alzheimer Prevention Trial study were included. IF1 plasma concentrations (square root of ng/mL) were measured at the 1-year visit of the Multidomain Alzheimer Prevention Trial, while PA levels (square root of metabolic equivalent task min/week) were assessed using questionnaires administered each year from baseline to the 3-year visit. Multiple linear regressions were performed to investigate the associations between the first-year mean PA levels and IF1 concentrations. Mediation analyses were conducted to examine whether apoA-I mediated these associations. Mixed-effect linear regressions were carried out to investigate whether the 1-year visit IF1 concentrations predicted subsequent changes in PA., Results: Multiple linear regressions indicated that first-year mean PA levels were positively associated with IF1 concentrations (B = 0.021; SE = 0.010; p = 0.043). Mediation analyses revealed that about 37.7% of this relationship was mediated by apoA-I (B ab  = 0.008; SE = 0.004; p = 0.023). Longitudinal investigations demonstrated that higher concentrations of IF1 at the 1-year visit predicted a faster decline in PA levels over the subsequent 2 years (time × IF1: B = -0.148; SE = 0.066; p = 0.025)., Conclusion: This study demonstrates that regular PA is associated with plasma IF1 concentrations, and it suggests that apoA-I partly mediates this association. Additionally, this study finds that baseline concentrations of IF1 can predict future changes in PA. However, further research is needed to fully understand the mechanisms underlying these observations., (Copyright © 2023. Production and hosting by Elsevier B.V.)

Alzheimer's disease is strongly linked to metabolic abnormalities. We aimed to distinguish amyloid-positive people who progressed to cognitive decline from those who remained cognitively intact. We performed untargeted metabolomics of blood samples from amyloid-positive individuals, before any sign of cognitive decline, to distinguish individuals who progressed to cognitive decline from those who remained cognitively intact. A plasma-derived metabolite signature was developed from Supercritical Fluid chromatography coupled with high-resolution mass spectrometry (SFC-HRMS) and nuclear magnetic resonance (NMR) metabolomics. The 2 metabolomics data sets were analyzed by Data Integration Analysis for Biomarker discovery using Latent approaches for Omics studies (DIABLO), to identify a minimum set of metabolites that could describe cognitive decline status. NMR or SFC-HRMS data alone cannot predict cognitive decline. However, among the 320 metabolites identified, a statistical method that integrated the 2 data sets enabled the identification of a minimal signature of 9 metabolites (3-hydroxybutyrate, citrate, succinate, acetone, methionine, glucose, serine, sphingomyelin d18:1/C26:0 and triglyceride C48:3) with a statistically significant ability to predict cognitive decline more than 3 years before decline. This metabolic fingerprint obtained during this exploratory study may help to predict amyloid-positive individuals who will develop cognitive decline. Due to the high prevalence of brain amyloid-positivity in older adults, identifying adults who will have cognitive decline will enable the development of personalized and early interventions., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Objectives: To assess the prevalence of potentially avoidable transfers (PAT) and identify factors associated with these transfers to emergency departments (EDs) among nursing home (NH) residents., Design: This is a secondary outcome analysis of the FINE study, a multicenter observational study collecting data on NH residents, NH settings, and contextual factors of ED transfers., Settings and Participants: NHs in the former Midi-Pyrénées region of the southwest of France (n = 312); a total of 1037 NH residents who experienced ED transfers (n = 1017) between January 2016 and December 2016., Methods: The analysis included resident baseline characteristics and NH and transfer decision-making characteristics. An expert group categorized the transfer status as either PAT or unavoidable. Multivariable analysis using a mixed logistic model, accounting for intra-NH correlation, was conducted to assess factors independently associated with PAT., Results: Among 1017 included transfers, 87.02% (n = 885) were identified as PAT and 12.98% (n = 132) unavoidable transfers. Multivariable analysis revealed that the following patient-related factors were associated with a likely high rate of PAT: usual behavior disturbances before transfer, including productive trouble (OR 2.04, 95% CI 1.25-3.33; P = .0044) and unusual symptom of falling during the week preceding the transfer (OR 4.55, 95% CI 1.76-11.82; P = .0019). On the other hand, distance between ED and NH (OR 0.98, 95% CI 0.97-0.998; P = .0231), NH staff trained in palliative care in the last 3 years (OR 0.52, 95% CI 0.29-0.95; P = .0324), the impossibility of direct hospitalization to an appropriate unit (OR 0.54, 95% CI 0.34-0.87; P = .0117), and the resident Charlson Comorbidity Index (OR 0.90, 95% CI 0.82-0.99; P = .0369) were associated with a lower probability of PAT., Conclusion and Implications: Transfers from NHs to hospital EDs were frequently potentially avoidable, meaning that there are still significant opportunities to reduce PAT. Our findings may help to specifically identify interventions that should be targeted at both NH and resident levels., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Transcatheter Aortic Valve Implantation has become the preferred method of aortic valve replacement in the elderly. Preoperative standardized geriatric assessment (SGA) helps guide the decision to proceed, taking into account geriatric parameters not targeted by surgical risk scores. This is a descriptive, retrospective study of patients who underwent EGS at the Toulouse University Hospital, analyzing their length of stay and postoperative care pathway., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Interim analysis of the DOSISPHERE-01 study demonstrated a strong improvement in response and overall survival (OS) on using 90 Y-loaded glass microspheres with personalized dosimetry compared with standard dosimetry in patients with nonoperable locally advanced hepatocellular carcinoma. This report sought to provide a long-term analysis of OS. Methods: In this phase II study (ClinicalTrials.gov identifier NCT02582034), treatment was randomly assigned (1:1) with the goal to deliver either at least 205 Gy (if possible >250-300 Gy) to the index lesion in the personalized dosimetry approach (PDA) or 120 ± 20 Gy to the treated volume in the standard dosimetry approach (SDA). The 3-mo response of the index lesion was the primary endpoint, with OS being one of the secondary endpoints. This report is a post hoc long-term analysis of OS. Results: Overall, 60 hepatocellular carcinoma patients with at least 1 lesion larger than 7 cm and more than 30% of hepatic reserve were randomized (intent-to-treat population: PDA, n = 31; SDA, n = 29), with 56 actually treated (modified intent-to-treat population: n = 28 in each arm). The median follow-up for long-term analysis was 65.8 mo (range, 2.1-73.1 mo). Median OS was 24.8 mo and 10.7 mo (hazard ratio [HR], 0.51; 95% CI, 0.29-0.9; P = 0.02) for PDA and SDA, respectively, in the modified intent-to-treat population. Median OS was 22.9 mo for patients with a tumor dose of at least 205 Gy, versus 10.3 mo for those with a tumor dose of less than 205 Gy (HR, 0.42; 95% CI, 0.22-0.81; P = 0.0095), and was 22.9 mo for patients with a perfused liver dose of 150 Gy or higher, versus 10.3 mo for those with a perfused liver dose of less than 150 Gy (HR, 0.42; 95% CI, 0.23-0.75; P = 0.0033). Lastly, median OS was not reached in patients who were secondarily resected ( n = 11, 10 in the PDA group and 1 in the SDA group), versus 10.8 mo in those without secondary resection ( n = 45) (HR, 0.17; 95% CI, 0.065-0.43; P = 0.0002). Only resected patients displayed favorable long-term OS rates, meaning an OS of more than 50% at 5 y. Conclusion: After longer follow-up, personalized dosimetry sustained a meaningful improvement in OS, which was dramatically improved for patients who were accurately downstaged toward resection, including most portal vein thrombosis patients., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Competing Interests: None.

Backgound and Aims: In advanced, liver-only intrahepatic cholangiocarcinoma (iCCA), selective internal radiation therapy (SIRT) has been suggested as promising in nonrandomized studies. We aimed to compare data from patients with advanced, liver-only iCCA treated in the first line in clinical trials with either chemotherapy alone or the combination with SIRT., Approach and Results: We collected individual patients' data from the ABC-01, ABC-02, ABC-03, BINGO, AMEBICA, and MISPHEC prospective trials. Data from patients with liver-only iCCA treated in chemotherapy-only arms of the first 5 trials were compared with data from patients treated with SIRT and chemotherapy in MISPHEC. Emulated target trial paradigm and Inverse Probability of Treatment Weighting (IPTW methods) using the propensity score were used to minimize biases. We compared 41 patients treated with the combination with 73 patients treated with chemotherapy alone, the main analysis being in 43 patients treated with cisplatin-gemcitabine or gemcitabine-oxaliplatin. After weighting, overall survival was significantly higher in patients treated with SIRT: median 21.7 months (95% CI: 14.1; not reached) versus 15.9 months(95% CI: 9.8; 18.9), HR = 0.59 (95% CI: 0.34; 0.99), p = 0.049. Progression-free survival was significantly improved: median 14.3 months (95% CI: 7.8; not reached) versus 8.4 months (95% CI: 5.9; 12.1), HR = 0.52 (95% CI: 0.31; 0.89), p < 0.001. Results were confirmed in most sensitivity analyses., Conclusions: This analysis derived from prospective clinical trials suggests that SIRT combined with chemotherapy might improve outcomes over chemotherapy alone in patients with advanced, liver-only iCCA. Randomized controlled evidence is needed to confirm these findings., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Background: Weight and appetite regulation have been associated with the expression and secretion of ATPase inhibitory factor 1 (IF1) and growth differentiation factor-15 (GDF-15), 2 potential biomarkers for age-related mitochondrial dysfunction. The aim was to explore the associations between these biomarkers and nutritional variables in the Multidomain Alzheimer Preventive Trial study., Methods: IF1 and GDF-15 plasma levels were quantified at 1-year follow-up. The nutritional status was measured using the Mini Nutritional Assessment (MNA) score variation between baseline and 1- and 2-year visits; appetite loss was extracted from the MNA. Bodyweight was measured every 6 months until the third year and then yearly until the fifth year of follow-up, and weight loss was established if the loss was greater than 5% or 10% within the past 6 or 12 months, respectively. Bidirectional associations of IF1 and GDF-15 levels with malnutrition, appetite, and weight loss were examined. The interactions between individual IF1 and GDF-15 with sex were explored., Results: Four hundred and forty-eight participants had MNA data and 1 045 had weight loss data. All the associations between IF1 levels and the MNA score, appetite loss, and weight loss were nonsignificant. Higher GDF-15 levels were cross-sectionally associated with appetite loss at the first year of follow-up, and the GDF-15 highest quartile was associated with nearly 80% higher risks of weight loss over 4 years. Interactions between IF1 and GDF-15 levels, and between these 2 markers and sex were not significantly associated with the outcomes., Conclusions: GDF-15 plasma levels were related to key malnutrition criteria., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Intrinsic capacity (IC) is a concept related to functionality that reflects healthy aging. ATPase inhibitory factor 1 (IF1) is a multifaceted protein that regulates mitochondrial oxidative phosphorylation (OXPHOS), and may be involved in IC. The objective of this study is to investigate the association between plasma levels of IF1 and IC changes in community-dwelling older adults., Methods: Community-dwelling older adults from the Multidomain Alzheimer Preventive Trial (MAPT Study) were enrolled in this study. A composite IC score was calculated based on 4 IC domains: locomotion, psychological dimension, cognition, and vitality (with data available annually over 4 years of follow-up). Secondary analyses were conducted on the sensory domain (with data available only for 1 year of follow-up). Mixed-model linear regression adjusted for confounders was conducted., Results: A total of 1 090 participants with usable IF1 values were included in the study (75.3 ± 4.4 years; 64% females). Compared to the lowest quartile, both the low- and high-intermediate IF1 quartiles were found to be cross-sectionally associated with greater composite IC scores across 4 domains (βlow-intermediate, 1.33; 95% confidence interval [CI] 0.06-2.60 and βhigh-intermediate, 1.78; 95% CI 0.49-3.06). In the secondary analyses, the highest quartile was found to be associated with a slower decline in composite IC scores across 5 domains over 1 year (βhigh 1.60; 95% CI 0.06-3.15). The low- and high-intermediate IF1 quartiles were also found to be cross-sectionally associated with greater locomotion (βlow-intermediate, 2.72; 95% CI 0.36-5.08) and vitality scores (βhigh-intermediate, 1.59; 95% CI 0.06-3.12), respectively., Conclusions: This study is the first to demonstrate that levels of circulating IF1, a mitochondrial-related biomarker, are associated with IC composite scores in both cross-sectional and prospective analyses among community-dwelling older adults. However, further research is needed to confirm these findings and elucidate the potential underlying mechanisms that may explain these associations., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)