Older adults are at risk of multiple chronic diseases, most of which could be prevented by engaging in regular physical activity. Frailty is a state of increased vulnerability to diseases. Worsening ...symptoms of frailty, such as decrease in physical functionality, can compromise health-related quality of life (HR-QOL). Previous findings suggest that frailty moderates the relationship between physical activity and HR-QOL, yet intervention findings are limited, particularly in dose-response analyses. Hence, this study was conducted to test if lower-dose physical activity (120 minutes/week) would provide the same benefits in health outcomes (physical functionality and HR-QOL) as higher-dose physical activity (180 minutes/week).
Participants (n=110) were older adults comprising higher-dose, lower-dose, and control groups who were combined from recent randomized controlled trials. Experimental groups participated in a multimodal exercise program in a supervised laboratory setting for 12 weeks.
The higher-dose group showed a significant improvement in physical functionality (
=0.23,
=0.03) and in overall HR-QOL (
=0.44,
=0.001) including its subcategories over the control group. A group × frailty interaction revealed that frail individuals significantly improved in capacity HR-QOL when they exercised at a higher dose (
(1, 49)=4.57,
=0.038).
This study identifies a positive, predictive relationship between exercise duration and health outcomes (HR-QOL dimensions and frailty) among older adults. Frail individuals in the higher-dose group demonstrated significant recovery of capacity HR-QOL, thus reflecting improvement in their daily activities.
The aim of this study was to examine the association between physical functioning and cardiovascular burden on the cognitive performance of community-dwelling older adults.
Ninety-three adults aged ...60 and older completed a medical evaluation by a geriatrician, performance-based physical tests, and neuropsychological assessments. Cognitive composite scores (memory, speed, and executive) as well as a physical functioning score were created by averaging standardized z-scores of selected tests. A cardiovascular burden index was also computed by totalling the number of cardiovascular risk factors and diseases.
Multiple hierarchical regression analyses reveal that higher level of physical functioning was significantly associated with greater processing speed and better executive functions but was not associated with memory performance. These relations were independent of age, sex, and level of education. Cardiovascular burden was not significantly associated with any cognitive domain.
These results suggest that cognition is related to simple performance-based physical tests and highlight the importance of intervention studies aimed at enhancing cognitive and physical functioning in older adults.
Abstract Purpose To validate a staging system for metastatic uveal melanoma that will facilitate planning, reporting and interpreting the results of clinical trials. Design Reliability and validity ...study. Methods The performance index, the largest diameter of the largest metastasis and alkaline phosphatase level at the time of diagnosis of metastases, and overall survival of 249 patients from 7 ocular oncology centers who died of dissemination were analyzed. Predicted median survival time calculated according to the Helsinki University Hospital Working Formulation was used to assign patients to stages IVa, IVb, and IVc that correspond to predicted survival times of ≥12, <12-6, and <6 months, respectively. The predictions were compared against observed survival. Results The three variables used to assign stage were independent predictors of survival in the validation dataset. Of the 249 patients, 44%, 44%, and 12% classified to Working Formulation stages IVa, IVb, and IVc, respectively. Corresponding median observed survival times were 18.6, 10.7 and 4.6 months and worsened by increasing stage ( P <. 001). Of 201 patients managed without surgical resection of metastases, 41%, 44%, and 15% classified to stages IVa to IVc, and their median observed survival times were 17.2, 10.0 and 4.6 months ( P < .001). Survival of 47 patients who underwent resection did not differ by working formulation stage ( P = .69). Conclusions This multicenter study confirms that the Working Formulation is a reliable and valid, repeatable system for dividing metastatic uveal melanoma into distinct prognostic subgroups, especially for stage-specific reporting of survival in prospective clinical trials.
Uveal melanoma is the most common primary intraocular malignant tumor in adults and is defined by a poor natural outcome, as 50% of patients die from metastases. The aim of this study was to develop ...and characterize a panel of human uveal melanoma xenografts transplanted into immunodeficient mice.
Ninety tumor specimens were grafted into severe combined immunodeficient mice, and 25 transplantable xenografts were then established (28%). Relationship between tumor graft and clinical, biological, and therapeutic features of the patients included were investigated. Characterization of 16 xenografts included histology, molecular analyses by immunohistochemistry, genetic alteration analysis (single-nucleotide polymorphism), and specific tumor antigen expression by quantitative reverse transcription-PCR. Pharmacologic characterization (chemosensitivity) was also done in four models using two drugs, temozolomide and fotemustine, currently used in the clinical management of uveal melanoma.
Take rate of human uveal melanoma was 28% (25 of 90). Tumor take was independent of size, histologic parameters, or chromosome 3 monosomy but was significantly higher in metastatic tumors. Interestingly, in vivo tumor growth was prognostic for a lower metastasis-free survival in patients with primary tumors. A high concordance between the patients' tumors and their corresponding xenografts was found for all parameters tested (histology, genetic profile, and tumor antigen expression). Finally, the four xenografts studied displayed different response profiles to chemotherapeutic agents.
Based on these results, this panel of 16 uveal melanoma xenografts represents a useful preclinical tool for both pharmacologic and biological assessments.
► Glucose ingestion improves older adults’ ability to coordinate concurrent tasks. ► It also increases activation in right ventral–lateral prefrontal regions. ► Variations in glucose regulation ...modulate glucose effects on behavioral and activation data. ► NIRS is an efficient way to study glucose effects in older adults.
Glucose enhancing effects in older adults have mostly been observed for episodic memory, but have recently been found for attentional control performance. Yet, brain activation patterns underlying these effects are still unknown.
The present study examined the acute effects of glucose ingestion on prefrontal brain activation during the execution of a divided attention task in fasting non-diabetic older adults.
Twenty older adults (60 years and older) took part in the study that included two experimental sessions. After an overnight fast, participants received either a glucose drink (50g) or a placebo (saccharin) drink, following which they completed a dual-task. During task execution, prefrontal activation was recorded with functional near-infrared spectroscopy (fNIRS). A repeated-measures design was used such that each participant served as his or her own control. The two experimental sessions were counterbalanced among participants and were performed two weeks apart.
When participants were in the glucose condition, they showed similar dual-task costs for both tasks, whereas in the placebo condition they prioritized one task over the other, with a significantly larger dual-task cost for the non-prioritized task (p<0.01). Differential brain activation was also observed in right ventral–lateral prefrontal regions for oxygenated hemoglobin and deoxygenated hemoglobin, with more activation apparent in the glucose condition (p<0.05). Furthermore, behavioral and activation data were influenced by individual differences in glucose regulation.
Glucose ingestion appears to momentarily enhance fasting seniors’ capacity to coordinate more equally two concurrent tasks and this is reflected in brain activation patterns.
The objective of this prospective study was to assess overall survival and event-free survival in patients with intraocular unilateral retinoblastoma (Reese-Ellsworth group V) treated by primary ...enucleation with or without adjuvant therapy depending on histopathologic risk factors.
Patients (n = 123) were divided into three groups on the basis of risk factors for extraocular relapse and metastasis assessed on centralized histologic examination of enucleated eyes. Group 1 (n = 70) had minimal or no choroidal involvement and/or prelaminar or no optic nerve involvement and received no adjuvant therapy. Group 2 (n = 52) had massive choroidal involvement and/or intra- or retrolaminar optic nerve involvement and/or anterior segment involvement and received four courses of adjuvant chemotherapy. Group 3 (n = 1) had invasion of the surgical margin of the optic nerve and/or microscopic extrascleral involvement and received six courses of adjuvant chemotherapy with intrathecal thiotepa, consolidation chemotherapy, and autologous stem-cell rescue. Genetic testing was also performed.
Median follow-up for the 123 patients was 71 months. No disease progression, relapse, or distant metastasis occurred during follow-up. No second malignancies occurred. This requires confirmation with longer follow-up. Secondary bilateralization occurred in two patients with identified RB1 germline mutation. Adjuvant chemotherapy was well tolerated, with limited toxicity. Molecular testing found constitutional RB1 gene mutations in only nine of 100 evaluated patients.
The survival rate of 100% was excellent, including 57% of patients who received no adjuvant therapy, suggesting that chemotherapy could be de-escalated in some patients, especially those with massive choroidal involvement.
Background
Solid evidence of the safety and effectiveness of retinoblastoma (RB) conservative treatment using thermotherapy and systemic chemotherapy with long‐term follow‐up is scarce, especially in ...low‐resource countries.
Aims
This study examined the outcomes of this treatment and associated predictors in Vietnam to strengthen the current RB treatment protocol focusing on preserving eye and vision in low‐resource settings.
Methods and results
A prospective cohort study was conducted at Ho Chi Minh City Eye Hospital in Vietnam from 2005 to 2019. All eligible patients with bilateral RB (one eye already removed and another eye classified as group A or B) and without previous treatment were recruited. All patients received thermotherapy and six cycles of systemic three‐agent chemotherapy repeated every 4 weeks. A standardized questionnaire was used to collect information on study participants' age, symptoms, tumor characteristics, treatment, and outcomes. Among 50 eyes of all 50 patients with a median age of 9 (4–20) months, 34 eyes were in group B (68%). The median follow‐up time was 60 (60–84) months. All 139 preserved tumors regressed mostly to type 4 (70.4%) and type 3 (23.7%) scars. Kaplan–Meier analysis found the overall globe‐salvage rate at 5 years of 91.9% (95% CI: 80.1%–97.7%). Most eyes (41/50, 82%, 95% CI: 69.2%–90.2%) had a final visual acuity ≥0.1. The visual acuity is higher when tumors regressed to a type 4 scar (p = .007, AOR = 8.098, 95% CI: 1.79–36.53) which also shows less enucleation than a type 3 scar (p = .002, AOR = 0.06, 95% CI: 0.01–0.37%). Gender effect on visual acuity after treatment was significant and may be due to discrimination. No major complications were recorded.
Conclusion
Conservative treatment of early‐stage RB is safe and effective. Long‐term, thorough follow‐ups of patients post‐treatment are needed. The regression patterns of scars could be a useful indicator of treatment failure.
Central artery stiffness is a confirmed predictor of cardiovascular health status that has been consistently associated with cognitive dysfunction and dementia. The European Society of Hypertension ...has established a threshold of arterial stiffness above which a cardiovascular event is likely to occur. However, the threshold at which arterial stiffness alters brain integrity has never been established.
The aim of this study is to determine the arterial stiffness cut-off value at which there is an impact on the white matter microstructure. This study has been conducted with 53 cognitively elderly without dementia. The integrity of the white matter was assessed using diffusion tensor metrics. Central artery stiffness was evaluated by measuring the carotid-femoral pulse wave velocity (cfPWV). The statistical analyses included 4 regions previously denoted vulnerable to increased central arterial stiffness (the corpus callosum, the internal capsule, the corona radiata and the superior longitudinal fasciculus).
The results of this study call into question the threshold value of 10 m/s cfPWV established by the European Society of Hypertension to classify patients in neuro-cardiovascular risk groups. Our results suggest that the cfPWV threshold value would be approximately 8.5 m/s when the microstructure of the white matter is taken as a basis for comparison.
Adjustment of the cfPWV value may be necessary for a more accurate distinction between lower and higher risk group of patients for white matter microstructural injury related to arterial stiffness. Targeting the highest risk group for prevention methods may, in turn, help preserve brain health and cognitive functions.
•DTI (FA, RD) analysis of white matter microstructure reveals that the cfPWV cut-off value (10 m/s) may be too high•This study rather suggests a value of cfPWV cut-off of 8.5 m/s to separate lower and higher neurovascular risk groups•Better executive function performance is correlated with higher FA and lower RD in participants with a cfPWV above 8.5 m/s.
Patients with liver metastases of uveal melanoma (LMUM) die from their metastatic evolution within 2 years. We established a nomogram to choose a treatment adapted to life expectancy. From 2002 to ...2013, we reviewed 224 patients with LMUM selected by liver MRI. A nomogram was developed based on a Cox model. The predictive performance of the model was assessed according to the C-statistic, Kaplan-Meier curve, and calibration plots. The median follow-up was 49.2 months (range, 0.6-70.9). The survival rates at 6, 12, and 24 months were 0.88 (0.95 CI 0.84-0.93), 0.68 (0.95 CI 0.62-0.75), and 0.26 (0.95 CI 0.21-0.33), respectively. The four factors selected for the nomogram with a worse prognosis were: A disease-free interval between the UM and LMUM groups of less than 6 months (HR = 3.39; 0.95 CI 1.90-6.05), more than 10 LMUM (HR = 3.95; 0.95 CI 1.97-4.43), a maximum LMUM of more than 1200 mm2 (HR = 2.47; 0.95 CI 1.53-3.98), and a lactate dehydrogenase (LDH) value greater than 1.5 (HR = 3.72; 0.95 CI 2.30-6.00). The model achieved relatively good discrimination and calibration (C-statistic 0.71). This nomogram could be useful for decision-making and risk stratification for therapeutic options.
It is well established that sex differences exist in the manifestation of vascular diseases. Arterial stiffness (AS) has been associated with changes in cerebrovascular reactivity (CVR) and cognitive ...decline in aging. Specifically, older adults with increased AS show a decline on executive function (EF) tasks. Interestingly, the relationship between AS and CVR is more complex, where some studies show decreased CVR with increased AS, and others demonstrate preserved CVR despite higher AS. Here, we investigated the possible role of sex on these hemodynamic relationships. Acquisitions were completed in 48 older adults. Pseudo-continuous arterial spin labeling (pCASL) data were collected during a hypercapnia challenge. Aortic pulse wave velocity (PWV) data was acquired using cine phase contrast velocity series. Cognitive function was assessed with a comprehensive neuropsychological battery, and a composite score for EF was calculated using four cognitive tests from the neuropsychological battery. A moderation model test revealed that sex moderated the relationship between PWV and CVR and PWV and EF, but not between CVR and EF. Together, our results indicate that the relationships between central stiffness, cerebral hemodynamics and cognition are in part mediated by sex.
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