Associations of baseline frailty, cancer and their interaction with EQ-5D score at baseline and follow-up.

<p>Associations of baseline frailty, cancer and their interaction with EQ-5D score at baseline and follow-up.</p

Heat map presenting the proportions of frailty deficits in frail* respondents with versus without cancer.

<p>The proportions in frailty deficits per item among older frail people with and without cancer were graphically represented as colors. The higher the proportion, the higher the color intensity. In addition, percentages of participants with the deficit endorsed were also shown. * Cut-off point for frail people: TOPICS-FI38 ≥ 0.25.</p

Frailty and quality of life among older people with and without a cancer diagnosis: Findings from TOPICS-MDS

<div><p>Background</p><p>The number of older cancer patients is rising. Especially in older people, treatment considerations should balance the impact of disease and treatment on quality of life (QOL) and survival. How a cancer diagnosis in older people interacts with concomitant frailty to impact on QOL is largely unknown. We aimed to determine the association between frailty and QOL among community-dwelling older people aged 65 years or above with and without a cancer diagnosis cross-sectionally and at 12 months follow-up.</p><p>Methods</p><p>Data were derived from the TOPICS-MDS database. Frailty was quantified by a frailty index (FI). QOL was measured with the subjective Cantril’s Self Anchoring Ladder (CSAL, range: 0–10) and the health-related EuroQol-5D (EQ-5D, range:-0.33–1.00) at baseline and after 12 months. To determine associations, linear mixed models were used.</p><p>Results</p><p>7493 older people (78.6±6.4 years, 58.4% female) were included. Dealing with a cancer diagnosis (n = 751) was associated with worse QOL both at baseline (CSAL:-0.25 (95%-CI:-0.36;-0.14), EQ-5D:-0.03 (95%-CI:-0.05;-0.02)) and at follow-up (CSAL:-0.13 (95%-CI:-0.24;-0.02), EQ-5D:-0.02 (95%-CI:-0.03;-0.00)). A ten percent increase in frailty was also associated with a decrease in QOL at baseline (CSAL:-0.35 (95%-CI:-0.38;-0.32), EQ-5D:-0.12 (95%-CI:-0.12;-0.11)) and follow-up (CSAL:-0.27 (95%-CI:-0.30;-0.24), EQ-5D:-0.07 (95%-CI:-0.07;-0.06)). When mutually adjusting for frailty and a cancer diagnosis, associations between a cancer diagnosis and QOL only remained significant for CSAL at baseline (-0.14 (95%-CI:-0.25;-0.03)), whereas associations between frailty and QOL remained significant for all QOL outcomes at baseline and follow-up. No statistical interactions between cancer and frailty in their combined impact on QOL were found.</p><p>Conclusions</p><p>Cancer diagnosis and frailty were associated with worse health-related and self-perceived QOL both at baseline and at follow-up. Differences in QOL between older people with and without a cancer diagnosis were explained to a large extent by differences in frailty levels. This stresses the importance to take into account frailty in routine oncologic care.</p></div

Sample characteristics of the respondents with versus without cancer.

<p>Sample characteristics of the respondents with versus without cancer.</p

Intra- and extracellular quenching of H₂O₂ by STS.

<p>(A) SOD activity was rescued by STS treatment upon 24 hours of oxalate-exposure to LLC-PK1 cells. (B) Oxalate-exposure of LLC-PK1 cells leads to the intracellular generation and accumulation of H₂O₂. While STS-treatment reduced the amount of H₂O₂ released from the cells after 72 hours, SC- and SS-treatment did not. (C) 72 hours of oxalate-exposure of LLC-PK1 cells leads to a significant decrease in cell viability (measured by sulforhodamine), which was maintained by STS in a dose dependent manner. (D) STS directly quenches H₂O₂ in aqueous solution, providing evidence for a direct interaction between STS and the non-radical oxidant H₂O₂. SC and SS in contrast did not lead to the consumption of H₂O₂. The changes and significance levels are with reference to the Ox group. The data are means ± SD from 8 values per group. *p< 0.05, **p < 0.01, ***p < 0.001.</p

Oxidant-antioxidant status.

<p>The activities of the two antioxidant enzymes (A) Superoxide dismutase (SOD), and (B) Catalase (CAT) were determined in renal tissue at time point 4 weeks in the control, EG, EG+STS, EG+SC and EG+SS animal group. SOD activity was preserved with STS treatment; (C) Urinary 8-Isoprostaglandin levels were elevated in the EG-exposed animals and maintained in the normal range only in STS-treated animals. The changes and significance levels are with reference to the EG group. The data are means ± SD from 7–8 animals per group. *p< 0.05, **p < 0.01, ***p < 0.001.</p

Interrelations between cancer, frailty, adverse outcomes and quality of life.

<p>Interrelations between cancer, frailty, adverse outcomes and quality of life.</p

Flowchart included TOPICS-MDS studies.

<p>FU = Follow-up.</p

α-SMA stain of kidney tissue.

<p>The groups are (A) control, (B) EG-exposed, (C) EG+STS-exposed, (D) EG+SC-exposed, (E) EG+SS-exposed animals. The α -SMA stain was markedly increased in EG-exposed animals but decreased in all treatment groups. The significance levels are with reference to the EG group. The data are means ± SD from 7–8 animals per group. *p< 0.05, **p < 0.01, ***p < 0.001.</p

STS reduces intracellular oxidative stress.

<p>Oxidative stress was induced by exposure of proximal tubular LLC-PK1 cells towards 1 mM oxalate, and detected using the fluorescence dye H₂DFFDA. (A) Fluorescence changes in untreated LLC-PK1 cells (Control), oxalate (Ox)-exposed LLC-PK1 cells (1 mM), and Ox+STS, Ox+SC and Ox+SS-exposed LLC-PK1 cells. STS largely protects LLC-PK1 cells against oxalate-induced oxidative stress. (B) Dose-dependent protection by STS against oxalate-induced ROS in LLC-PK1 cells. Data were analyzed by one-way analysis of variance (ANOVA) with Bonferroni’s multiple comparison. Asterisks (*) indicate statistically significant differences (<i>p <</i> 0.05) with respect to oxalate-exposed cells. (C) H₂DFFDA- and DAPI-fluorescence imaging of LLC-PK1 cells. The absence of green fluorescence in oxalate-exposed, STS-treated LLC-PK1 cells indicates the quenching of intracellular oxidative stress by STS. Control = 100% in (A) and (B). Significance levels are with reference to oxalate (Ox) group. The data are means ± SD from 8 values per group. *p< 0.05, **p < 0.01, ***p < 0.001.</p