Medicine (RMH) - Research Publications

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    Assessment of cell cycle regulators in human peripheral blood cells as markers of cellular senescence
    Guan, L ; Crasta, KC ; Maier, AB (ELSEVIER IRELAND LTD, 2022-06)
    Cellular senescence has gained increasing interest during recent years, particularly due to causal involvement in the aging process corroborated by multiple experimental findings. Indeed, cellular senescence considered to be one of the hallmarks of aging, is defined as a stable growth arrest predominantly mediated by cell cycle regulators p53, p21 and p16. Senescent cells have frequently been studied in the peripheral blood of humans due to its accessibility. This review summarizes ex vivo studies describing cell cycle regulators as markers of senescence in human peripheral blood cells, along with detection methodologies and associative studies examining demographic and clinical characteristics. The utility of techniques such as the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), microarray, RNA sequencing and nCounter technologies for detection at the transcriptional level, along with Western blotting, enzyme-linked immunosorbent assay and flow cytometry at the translational level, will be brought up at salient points throughout this review. Notably, housekeeping genes or proteins serving as controls such as GAPDH and β-Actin, were found not to be stably expressed in some contexts. As such, optimization and validation of such genes during experimental design were recommended. In addition, the expression of cell cycle regulators was found to vary not only between different types of blood cells such as T cells and B cells but also between stages of cellular differentiation such as naïve T cells and highly differentiated T cells. On the other hand, the associations of the presence of cell cycle regulators with demographics (age, gender, ethnicity, and socioeconomic status), clinical characteristics (body mass index, specific diseases, disease-related parameters) and lifestyle vary in groups of participants. One envisions that increased understanding and insights into the assessment of cell cycle regulators as markers of senescence in human peripheral blood cells will help inform prognostication and clinical intervention in elderly individuals.
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    Association of a modified laboratory frailty index with adverse outcomes in geriatric rehabilitation inpatients: RESORT
    Guan, L ; Soh, CH ; Reijnierse, EM ; Lim, WK ; Maier, AB (ELSEVIER IRELAND LTD, 2022-04)
    A higher number of laboratory measurements is associated with mortality in patients admitted to hospital, but is not part of the frailty index based on laboratory tests (FILab). This study aimed to modify the FI-Lab (mFI-Lab) by accounting for the number of laboratory measurements and compare its validity to predict institutionalization and mortality at three-month post-discharge with the clinical frailty scale (CFS) in geriatric rehabilitation inpatients. In 1819 patients (median age 83.3 [77.6-88.3], 56.6% female), a higher FI-Lab was not associated with institutionalization but a higher risk of mortality. A higher mFI-Lab was associated with lower odds of institutionalization but a higher risk of mortality. A higher CFS was associated with institutionalization and higher mortality. The Akaike information criterion value was lowest for the CFS, followed by the mFI-Lab and the FI-Lab. The CFS is better than the mFI-Lab predicting short-term adverse outcomes in geriatric rehabilitation inpatients. When using laboratory data to estimate frailty, the mFI-Lab rather than the FI-Lab should be used.
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    Unresolved inflammation during hospitalization is associated with post-discharge institutionalization and mortality in geriatric rehabilitation inpatients: The RESORT cohort
    Guan, L ; Tuttle, CSL ; Reijnierse, EM ; Lim, WK ; Maier, AB (PERGAMON-ELSEVIER SCIENCE LTD, 2021-12)
    BACKGROUND: Inflammation contributes to adverse health outcomes in community-dwelling populations. Little is known about inflammation in hospitalized older adults and its association with adverse outcomes. This study aimed to evaluate the association of the inflammatory markers C-reactive protein (CRP) and albumin measured during acute and geriatric rehabilitation hospitalization with institutionalization and mortality in geriatric rehabilitation inpatients. METHODS: Within the REStORing health of acutely unwell adulTs (RESORT) cohort, CRP and albumin were measured as part of usual care during acute and geriatric rehabilitation hospitalization. Inflammatory markers are presented as median, peak (CRP: maximum; albumin: minimum), variation (interquartile range) and direction of change (increased CRP or decreased albumin: positive or negative difference between last measurement and median of preceding measurements). Logistic regression was used to determine the associations between inflammatory markers and institutionalization at three-month and all-cause mortality at three- and twelve-month post-discharge. RESULTS: Geriatric rehabilitation inpatients (n = 1846) with a median age of 83.3 years (interquartile range 77.6-88.3) and 56.6% of female were included. Increased CRP during geriatric rehabilitation was associated with institutionalization. Higher median, peak and increased levels of CRP during geriatric rehabilitation but not during acute hospitalization were associated with higher mortality. Lower CRP variation during acute hospitalization but higher CRP variation during geriatric rehabilitation was associated with higher mortality. Lower median level of albumin during both hospitalizations were associated with higher mortality. CONCLUSIONS: Inflammation characterized by lower albumin during acute hospitalization and, higher CRP and lower albumin during geriatric rehabilitation was associated with mortality in geriatric rehabilitation inpatients. Increased CRP during geriatric rehabilitation was associated with institutionalization. Unresolved inflammation in geriatric rehabilitation might indicate ongoing disease activity leading to adverse outcomes.