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- Trevisan, Caterina, et al.
(author)
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Twelve-year sarcopenia trajectories in older adults : results from a population-based study
- 2022
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In: Journal of Cachexia, Sarcopenia and Muscle. - : Wiley. - 2190-5991 .- 2190-6009. ; 13:1, s. 254-263
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Journal article (peer-reviewed)abstract
- Background The dynamic nature of sarcopenia, including possible transitions between its different stages, is currently unknown. We aimed to explore 12 year transitions through sarcopenia stages and identify factors associated with different sarcopenia trajectories in older adults.Methods We included 3219 participants (aged >= 60 years, 35.8% men, 96.4% community-dwelling) from the SNAC-K study. No sarcopenia (normal muscle strength and mass), probable sarcopenia (low muscle strength and normal muscle mass), and sarcopenia (low muscle strength and mass) were assessed at baseline and up to 12 years. Such conditions were defined based on a modified version of the EWGSOP2 criteria with muscle strength evaluated through handgrip or chair stand tests, and muscle mass from calf circumference. We estimated 1, 5, and 10 year transition probabilities through continuous-time multistage Markov modelling. Sociodemographic, lifestyle, and medical factors associated with the likelihood of different transitions were evaluated with proportional intensity models, and the associations' strength was expressed as hazard ratio (HR) and 95% confidence interval (CI).Results Participants with no sarcopenia had 10-year probabilities of 17.1% and 5.1% to develop probable sarcopenia and sarcopenia, and a 40.4% chance of not transitioning. Those with probable sarcopenia had similar 5-year chances of developing sarcopenia (10.3%) and reverting to no sarcopenia (10.7%). Participants with sarcopenia had chances to revert to probable sarcopenia ranging from 8.2% (at 5 years) to 4.7% (at 10 years), and a 70.9% chance of dying after 10 years. Older age (HR = 1.11, 95% CI: 1.07-1.14), male sex (HR = 1.84, 95% CI: 1.16-2.91), current smoking (HR = 1.84, 95% CI: 1.16-2.91), and higher number of chronic diseases (HR = 1.07, 95% CI: 1.00-1.14) were associated with sarcopenia development, while higher levels of physical activity (HR = 1.84, 95% CI: 1.19-2.84) and cognitive function (HR = 1.17, 95% CI: 1.05-1.31 per each 1-point increase in the Mini-Mental State Examination) were associated with subsequent higher reversion rates from probable sarcopenia to no sarcopenia (P < 0.05 for all). None of the explored characteristics were associated with sarcopenia reversion to healthier stages.Conclusions Sarcopenia appears to be a dynamic condition with possible two-way transitions between different sarcopenia stages, especially the earliest ones. Timely interventions to improve physical and cognitive function and better control individuals' chronic conditions could help counteract sarcopenia progression.
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| 2. |
- Picca, Anna, et al.
(author)
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Biomarkers shared by frailty and sarcopenia in older adults : A systematic review and meta-analysis
- 2022
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In: Ageing Research Reviews. - : Elsevier BV. - 1568-1637 .- 1872-9649. ; 73
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Research review (peer-reviewed)abstract
- Background: Physical frailty and sarcopenia show extensive clinical similarities. Whether biomarkers exist that are shared by the two conditions is presently unclear.Methods: We conducted a systematic review and meta-analysis of cross-sectional and longitudinal studies that investigated the association of frailty and/or sarcopenia with biomarkers as a primary or secondary outcome in adults aged 60 years and older. Only studies published in English that defined frailty using a validated scale and/ or questionnaire and diagnosed sarcopenia according to the presence of muscle atrophy plus dynapenia or low physical function were included. Studies were identified from a systematic search of MEDLINE and SCOPUS databases from inception through August 2020. The quality of reporting of each study was assessed by using the Quality Assessment Tool for Observational Cohort, Cross-Sectional and Case-Control studies of the National Institute of Health. A meta-analysis was conducted when at least three studies investigated the same biomarker in both frailty and sarcopenia. Pooled effect size was calculated based on standard mean differences and randomeffect models. Sensitivity analysis was performed based on age and the setting where the study was conducted.Results: Eighty studies (58 on frailty and 22 on sarcopenia) met the inclusion criteria and were included in the qualitative analysis. Studies on frailty included 33,160 community-dwellers, hospitalized, or institutionalized older adults (60-88 years) from 21 countries. Studies on sarcopenia involved 4904 community-living and institutionalized older adults (68-87.6 years) from 9 countries. Several metabolic, inflammatory, and hematologic markers were found to be shared between the two conditions. Albumin and hemoglobin were negatively associated with both frailty and sarcopenia. Interleukin 6 was associated with frailty and sarcopenia only in people aged < 75. Community-dwelling older adults with frailty and sarcopenia had higher levels of tumor necrosis factor alpha compared with their robust and non-sarcopenic counterparts.Conclusions: A set of metabolic, hematologic, and inflammatory biomarkers was found to be shared by frailty and sarcopenia. These findings fill a knowledge gap in the quest of biomarkers for these conditions and provide a rationale for biomarker selection in studies on frailty and sarcopenia.
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| 3. |
- Picca, Anna, et al.
(author)
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Circulating extracellular vesicles : friends and foes in neurodegeneration
- 2022
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In: Neural Regeneration Research. - : Medknow. - 1673-5374 .- 1876-7958. ; 17:3, s. 534-542
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Research review (peer-reviewed)abstract
- Extracellular vesicles have been identified as pivotal mediators of intercellular communication with critical roles in physiological and pathological conditions. Via this route, several molecules (e.g., nucleic acids, proteins, metabolites) can be transferred to proximal and distant targets to convey specific information. Extracellular vesicle-associated cargo molecules have been proposed as markers of several disease conditions for their potential of tracking down the generating cell. Indeed, circulating extracellular vesicles may represent biomarkers of dysfunctional cellular quality control systems especially in conditions characterized by the accrual of intracellular misfolded proteins. Furthermore, the identification of extracellular vesicles as tools for the delivery of nucleic acids or other cargo molecules to diseased tissues makes these circulating shuttles possible targets for therapeutic development. The increasing interest in the study of extracellular vesicles as biomarkers resides mainly in the fact that the identification of peripheral levels of extracellular vesicle-associated proteins might reflect molecular events occurring in hardly accessible tissues, such as the brain, thereby serving as a “brain liquid biopsy”. The exploitation of extracellular vesicles for diagnostic and therapeutic purposed might offer unprecedented opportunities to develop personalized approaches. Here, we discuss the bright and dark sides of extracellular vesicles in the setting of two main neurodegenerative diseases (i.e., Parkinson’s and Alzheimer’s diseases). A special focus will be placed on the possibility of using extracellular vesicles as biomarkers for the two conditions to enable disease tracking and treatment monitoring.
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| 4. |
- Ponziani, Francesca Romana, et al.
(author)
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Gut Dysbiosis and Fecal Calprotectin Predict Response to Immune Checkpoint Inhibitors in Patients With Hepatocellular Carcinoma
- 2022
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In: Hepatology Communications. - : Ovid Technologies (Wolters Kluwer Health). - 2471-254X. ; 6:6, s. 1492-1501
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Journal article (peer-reviewed)abstract
- The gut microbiota is a well-known prognostic factor and a modulator of treatment sensitivity in patients with cancers treated with immune checkpoint inhibitors. However, data on hepatocellular carcinoma (HCC) are lacking. This study aimed to evaluate the prognostic role of the gut microbiota and changes produced by immunotherapy on the intestinal environment in patients with cirrhosis and HCC. Eleven patients treated with Tremelimumab and/or Durvalumab were included in the analysis. All study participants underwent gut microbiota profiling, quantification of fecal calprotectin, serum levels of zonulin-1, lipopolysaccharide binding protein (LBP), and programmed death-ligand 1 (PD-L1) at baseline and at each treatment cycle until the third cycle, then every three cycles until treatment discontinuation or last visit. The 6 patients who achieved disease control (DC) showed lower pretreatment fecal calprotectin (median, 12.5; interquartile range [IQR], 5-29 vs. median, 116; IQR, 59-129 µg/g; P = 0.047) and PD-L1 serum levels (median, 0.08; IQR, 0.07-0.09 vs. median, 1.04; IQR, 0.17-1.95 ng/mL; P = 0.02) than nonresponders. The relative abundance of Akkermansia (log2 fold change [FC], 2.72; adjusted P [Padj] = 0.012) was increased, whereas that of Enterobacteriaceae (log2 FC, −2.34; Padj = 0.04) was reduced in the DC group. During treatment, fecal calprotectin showed a temporal evolution opposite to the Akkermansia to Enterobacteriaceae ratio and gut microbiota alpha diversity, but similar to zonulin-1 and LBP. Bifidobacterium had a stable behavior in patients with a long follow-up, while Akkermansia was more variable. Akkermansia and Bifidobacterium showed similar temporal patterns and causative relationships with Prevotella, Veillonella, Ruminococcus, Roseburia, Lachnospira, Faecalibacterium, and Clostridium. Conclusion: A favorable composition of the gut microbiota and low intestinal inflammation are associated with achieving DC. The intestinal environment changes dynamically during therapy.
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