OUTO trial
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer, Abdominal Aortic Aneurysm
PROVIDER: 20031 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:Interventions: For an optimal period of 5 weeks prior to surgery, physical health, nutritional health status, factors of frailty and haemoglobin levels will be optimised
Primary outcome(s): Incidence of delirium
Study Design: Non-randomized controlled trial, Open (masking not used), Active, Other
| 19960 | ecrin-mdr-crc
Project description:Frailty affects the physical, cognitive, and social domains exposing older adults to an increased risk of cardiovascular disease (CVD) and death. The mechanisms linking frailty and cardiovascular outcomes are mostly unknown. Here, we studied the association of abundance (flow cytometry) and gene expression profile (RNAseq) of stem/progenitor cells (HSPCs) and molecular markers of inflammaging (ELISA) with the cardiorespiratory phenotype and prospective adverse events of individuals classified according to levels of frailty. Two cohorts of older adults were enrolled in the study. In a cohort of pre-frail 35 individuals (average age: 75 years), a physical frailty score above the median identified subjects with initial alterations in cardiorespiratory function. RNA sequencing revealed S100A8/A9 upregulation in HSPCs from the bone marrow (>10-fold) and peripheral blood (>200-fold) of individuals with greater physical frailty. Moreover higher frailty was associated with increased alarmins S100A8/A9 and inflammatory cytokines in peripheral blood. We then studied a cohort of 104 more frail individuals (average age: 81 years) with multi-domain health deficits. Reduced levels of circulating HSPCs and increased S100A8/A9 concentrations were independently associated with the frailty index. Remarkably, low HSPCs and high S100A8/A9 simultaneously predicted major adverse cardiovascular events at 1-year follow-up after adjustment for age and frailty index. In conclusion, inflammaging characterized by alarmin and pro-inflammatory cytokines in pre-frail individuals is mirrored by the pauperization of HSPCs in frail older people with comorbidities. S100A8/A9 is upregulated within HSPCs, identifying a phenotype that associates with poor cardiovascular outcomes.
2022-03-23 | GSE190446 | GEO
Project description:Frailty in aging is driven by the dysregulation of multiple biological pathways. Protectin DX (PDX) is a docosahexaenoic acid (DHA)-derived molecule that alleviates many chronic inflammatory disorders, but its potential effects on frailty remain unknown. Our goal is to identify age-related impairments in metabolic systems and to evaluate the therapeutic potential of PDX on frailty, physical performance, and health parameters. A set of 22-month-old C57BL/6 male and female mice were assigned to vehicle (Old) or PDX daily gavage treatment for 8 weeks, whereas 6-monthold (Adult) mice received only vehicle. Forelimb and hindlimb strength, endurance, voluntary wheel activity and walking speed determined physical performance and were combined with a frailty index score and body weight loss to determine frailty status. Our data shows that old vehicle-treated mice from both sexes had body weight loss paralleling visceromegaly, and old females also had impaired insulin clearance as compared to the Adult group. Aging was associated with physical performance decline together with higher odds of frailty development. There was also age-driven mesangial expansion and glomerular hypertrophy as well as bone mineral density loss. All of the in vivo and in vitro impairments observed with aging co-occurred with upregulation of inflammatory pathways and Myc signaling as well as downregulation of genes related to adipogenesis and oxidative phosphorylation in liver. PDX attenuated the age-driven physical performance (strength, exhaustion, walking speed) decline, promoted robustness, prevented bone losses and partially reversed changes in hepatic expression of Myc targets and metabolic genes. In conclusion, our data provides evidence of the beneficial therapeutic effect of PDX against features of frailty in mice. Further studies are warranted to investigate the mechanisms of action and the potential for human translation.
2023-04-05 | GSE228901 | GEO
Project description:This work describes for the first time a different circular RNA (circRNAs) expression pattern between frail and robust individuals. Moreover, the level of some circRNAs is modulated after a physical intervention. These results suggest that they could be used as minimally invasive biomarkers of frailty. Frailty is an intermediate and reversible geriatric syndrome that often precedes dependency. Therefore, its identification is essential to prevent dependency. Diverse molecules have been proposed as biomarkers of frailty, but none of them has reached clinical practice. Recently, circular RNAs have emerged as new non-coding RNAs. Their regulatory role together with their high stability in biofluids makes them good candidates as biomarkers for several processes, but, to date, no studies have characterized circRNA expression in frailty. We studied RNA from leukocytes of 35 frail and 35 robust individuals. After RNA-Sequencing, circRNA detection was performed by CIRI2 and Circexplorer2 and differential expression analysis by DESeq2. Validation was performed by Quantitative-PCR. A Linear Discriminant Analysis was performed to determine the best circRNA combination to discriminate frails from robusts. Besides, CircRNA candidates were studied in 13 additional elder donors before and after a 3-month physical intervention. We found 89 differentially expressed circRNAs (p-value<0.05, FC>|1.5|) with frailty. The upregulation of hsa_circ_0007817, hsa_circ_0101802 and hsa_circ_0060527 in frail individuals was validated. The combination of hsa_circ_0079284, hsa_circ_0007817 and hsa_circ_0075737 levels showed a great biomarker value with a 95.9% probability of correctly classifying frail and robust individuals. Moreover, hsa_circ_0079284 levels decreased after physical intervention in concordance with an improvement in frailty scores.
2023-01-31 | GSE206762 | GEO
Project description:Sarcopenia is an age-related condition characterized by progressive decline in muscle mass, strength, and physical performance, contributing to frailty and adverse health outcomes. Despite increasing interest in molecular biomarkers, longitudinal data with external validation are limited. This study utilized high-throughput proteomic analysis to identify and validate biomarkers associated with progression of sarcopenia in prospective cohorts.
2026-03-09 | PXD072647 | Pride
Project description:AbstractBackground: A decreased intramuscular carnitine status with aging may contribute to frailty and fatigue, but studies are often confounded by sex-heterogeneity and lack of control groups. We hypothesize that muscle carnitine deficiency is associated with (pre-)frailty, diminished physical performance and altered mitochondrial function, possibly in a sex-dependent manner. This was tested in well-matched age groups, allowing gender-specific analyses. Methods: A cross-sectional study was performed in well-matched fit (n = 15) and (pre-)frail (n = 13) old males as well as in fit (n = 15) and (pre-)frail (n = 11) old females, using young males (n = 13) and females (n = 13) as healthy controls. In the elderly, frailty was assessed according to the Fried criteria and physical performance was determined by 400-m walk test, short physical performance battery and handgrip strength. Acylcarnitine status was assessed in muscle biopsies and blood plasma using liquid chromatography-tandem mass spectrometry. Muscle mitochondrial gene expression was analyzed. Results: Intramuscular total carnitine levels and short chain acylcarnitine levels were lower in (pre-)frail old females compared to fit old females and young females, whereas no differences were observed in males. Intramuscular short chain acylcarnitine levels were associated with low physical performance in females, even after correction for muscle mass (%), whereas in males no such association was found. The decline in short chain acylcarnitine levels in (pre-)frail old females was associated with low expression of genes involved in mitochondrial energy production and mitochondrial functionality. Conclusions: In (pre-)frail old females, intramuscular total carnitine levels and short chain acylcarnitine levels are decreased and this decrease is accompanied by reduced physical performance and low expression of a wide range of genes involved in mitochondrial function.
2023-02-04 | GSE144304 | GEO
Project description:Delirium is a common postoperative complication among older patients with many adverse outcomes. Due to lack of validated biomarkers, prediction and monitoring of delirium by biological testing is not currently feasible. Circulating proteins in cerebrospinal fluid (CSF) may reflect biological processes causing delirium. Our goal was to discover and investigate candidate protein biomarkers in preoperative CSF that were associated with development of postoperative delirium in older surgical patients. We employed a nested case–control study design coupled with high multiplex affinity proteomics analysis to measure 1305 proteins in preoperative CSF. Twenty-four matched delirium cases and non-delirium controls were selected from the Healthier Postoperative Recovery (HiPOR) cohort and the associations between preoperative protein levels and postoperative delirium were assessed using t-test statistics with further analysis by systems biology to elucidate delirium pathophysiology. Proteomics analysis identified 32 proteins in preoperative CSF that significantly associate with delirium (t-test p<0.05). Due to the limited sample size these proteins did not remain significant by multiple hypothesis testing using the Benjamini-Hochberg correction and q-value method. Three algorithms were applied to separate delirium cases from non-delirium controls. Hierarchical clustering classified 40/48 case-control samples correctly, principal components analysis separated 43/48. The receiver operating characteristic curve yielded an area under the curve [95% confidence interval] of 0.91 [0.80-0.97]. Systems biology analysis identified several key pathways associated with risk of delirium: inflammation, immune cell migration, apoptosis, angiogenesis, synaptic depression and neuronal cell death. Proteomics analysis of preoperative CSF identifies 32 proteins that might discriminate individuals who subsequently develop postoperative delirium from matched control samples. These proteins are potential candidate biomarkers for delirium and may play a role in its pathophysiology.
2023-09-09 | GSE242736 | GEO
Project description:Sarcopenia is an age-related condition characterized by progressive decline in muscle mass, strength, and physical performance, contributing to frailty and adverse health outcomes. Despite increasing interest in molecular biomarkers, longitudinal data with external validation are limited. This study utilized high-throughput proteomic analysis to identify and validate biomarkers associated with progression of sarcopenia in two independent prospective cohorts. The OsteoSarc cohort (n=93) was followed up for two years. Plasma proteomic profiling was conducted using data-independent acquisition (DIA) mass spectrometry. Statistical analyses included multivariable regression, principal component analysis, and pathway enrichment.
2026-03-09 | PXD070542 | Pride
Project description:Physical frailty's impact on hemagglutination inhibition antibody titers (HAI) and peripheral blood mononuclear cell (PBMC) transcriptional responses after influenza vaccination is unclear. Physical frailty was assessed using the 5-item Fried frailty phenotype in 168 community- and assisted-living adults ≥55 years of age during an observational study. Blood was drawn before, 3, 7, and 28 days post-vaccination with the 2017-2018 inactivated influenza vaccine. HAI response to the A/H1N1 strain was measured at Days 0 and 28 using seropositivity, seroconversion, log2 HAI titers, and fold-rise in log2 HAI titers. RNA sequencing of PBMCs from Days 0, 3 and 7 was measured in 28 participants and compared using pathway analyses. Frailty was not significantly associated with any HAI outcome in multivariable models. Compared with non-frail participants, frail participants expressed decreased cell proliferation, metabolism, antibody production, and interferon signaling genes. Conversely, frail participants showed elevated gene expression in IL-8 signaling, T-cell exhaustion, and oxidative stress pathways compared with non-frail participants. These results suggest that reduced effectiveness of influenza vaccine among older, frail individuals may be attributed to immunosenescence-related changes in PBMCs that are not reflected in antibody levels.
2022-02-16 | GSE196793 | GEO
Project description:This an interventional, non-pharmacologic study. Prehabilitation is a multidisciplinary preoperative intervention aimed at preventing or reducing functional decline related to surgery and improving perioperative outcomes. The current study is aimed at standardizing a prehabilitation pathway, evaluating its feasibility within the AUSL Romagna in collaboration with the PRIME Centre and the multiple professions that populate the two institutes in the spirit of confirming the beneficial effect of an integrated prehabilitation programme on surgical outcomes.
Patients will follow an intensive prehabilitation course before surgery:
* Colon cancer patients will do 4 weeks of prehabilitation before surgery.
* Rectal cancer patients will do 12 weeks of prehabilitation after neoadjuvant therapy and before surgery.
The prehabilitation course is structured around the following aspects:
* Frailty assessment and identification of optimisation fields
* Optimisation of modifiable factors (anaemia, polypharmacotherapy, smoking, alcoholism, diabetes)
* Assessment by an integrative medicine specialist
* Nutritional pre-qualification
* Cardiovascular, respiratory, motor prehabilitation
* Emotional and psychological prehabilitation
| 59501 | ecrin-mdr-crc