Mechanistic study of the Aldo-keto reductase family 1 member A1 in regulating mesenchymal stem cell fate decision toward adipogenesis and osteogenesis.

AIMS: Akr1A1 is a glycolytic enzyme catalyzing the reduction of aldehyde to alcohol. This study aims to delineate the role of Akr1A1 in regulating the adipo-osteogenic lineage differentiation of mesenchymal stem cells (MSCs). MAIN METHODS: MSCs derived from human bone marrow and Wharton Jelly together with gain- and loss-of-function analysis as well as supplementation with the S-Nitrosoglutathione reductase (GSNOR) inhibitor N6022 were used to study the function of Akr1A1 in controlling MSC lineage differentiation into osteoblasts and adipocytes. KEY FINDINGS: Akr1A1 expression, PKM2 activity, and lactate production were found to be decreased in osteoblast-committed MSCs, but PGC-1α increased to induce mitochondrial oxidative phosphorylation. Increased Akr1A1 inhibited the SIRT1-dependent pathway for decreasing the expressions of PGC-1α and TAZ but increasing PPAR γ in adipocyte-committed MSCs, hence promoting glycolysis in adipogenesis. In contrast, Akr1A1 expression, PKM2 activity and lactate production were all increased in adipocyte-differentiated cells with decreased PGC-1α for switching energy utilization to glycolytic metabolism. Reduced Akr1A1 expression in osteoblast-committed cells relieves its inhibition of SIRT1-mediated activation of PGC-1α and TAZ for facilitating osteogenesis and mitochondrial metabolism. SIGNIFICANCE: Several metabolism-involved regulators including Akr1A1, SIRT1, PPARγ, PGC-1α and TAZ were differentially expressed in osteoblast- and adipocyte-committed MSCs. More importantly, Akr1A1 was identified as a new key regulator for controlling the MSC lineage commitment in favor of adipogenesis but detrimental to osteogenesis. Such information should be useful to develop perspective new therapeutic agents to reverse the adipo-osteogenic differentiation of BMSCs, in a way to increase in osteogenesis but decrease in adipogenesis.

The associations of osteoporosis and possible sarcopenia with disability, nutrition, and cognition in community-dwelling older adults.

BACKGROUND: Osteoporosis and sarcopenia, respectively, have detrimental impact on health, and combination of both conditions, termed osteosarcopenia, is becoming an increasingly important disorder in older adults as populations age. This study aimed to explore the relationship between osteoporosis and possible sarcopenia and their joint effect on physical performance, nutritional status, and cognition in community-dwelling older adults. METHODS: This study was conducted at a medical center in Taiwan, which included the adjacent community care station. The participants were recruited through regular activities at the community care station between January 01, 2015 and February 28, 2022. During the study period, dual-energy X-ray absorptiometry and comprehensive geriatric assessment consisting of comorbidity burden, functional status, cognition, mood, and nutritional status were performed during the study period. Possible sarcopenia was identified utilizing the criteria set by the Asian Working Group on Sarcopenia in 2019 using the criteria of low muscle strength alone, and osteoporosis was defined by the World Health Organization criteria. Accordingly, the study subjects were divided into four groups: normal, only osteoporosis, only possible sarcopenia, and possible osteosarcopenia. RESULTS: There were 337 participants (68.6% female) with a median age of 78.0 years (interquartile range: 71.0-85.0 y/o). According to the clinical definition of osteosarcopenia, 78 participants were normal, 69 participants showed possible sarcopenia, 61 participants had osteoporosis, and 129 had osteoporosis with possible sarcopenia. Among the four groups, the prevalence rates of chronic illness, functional capacity, physical performance, cognitive impairment, and malnutrition revealed statistically significant differences. Using logistic regression analysis after adjusting for the other covariates, osteoporosis with possible sarcopenia was associated with an increased odds ratio of cognitive impairment. CONCLUSIONS: The findings suggest that compared to osteoporosis or possible sarcopenia alone, osteoporosis with possible sarcopenia was more likely to be associated with cognitive impairment. Early identification and targeted interventions for cognitive impairment in older adults with osteosarcopenia may be valuable in maintaining cognitive well-being and overall quality of life.

The mean residual life model for the right-censored data in the presence of covariate measurement errors.

In this article, we consider the mean residual life regression model in the presence of covariate measurement errors. In the whole cohort, the surrogate variable of the error-prone covariate is available for each subject, while the instrumental variable (IV), which is related to the underlying true covariates, is measured only for some subjects, the calibration sample. Without specifying distributions of measurement errors but assuming that the IV is missing at random, we develop two estimation methods, the IV calibration and cohort estimators, for the regression parameters by solving estimation equations (EEs) based on the calibration sample and cohort sample, respectively. To improve estimation efficiency, a synthetic estimator is derived by applying the generalized method of moment for all EEs. The large sample properties of the proposed estimators are established and their finite sample performance are evaluated via simulation studies. Simulation results show that the cohort and synthetic estimators outperform the IV calibration estimator and the relative efficiency of the cohort and synthetic estimators mainly depends on the missing rate of IV. In the case of low missing rate, the synthetic estimator is more efficient than the cohort estimator, while the result can be reversed when the missing rate is high. We illustrate the proposed method by application to data from the patients with stage 5 chronic kidney disease in Taiwan.

Effect of frailty, physical performance, and chronic kidney disease on mortality in older patients with diabetes : a retrospective longitudinal cohort study.

BACKGROUND: Declined renal function is associated with physical function impairment and frailty in a graded fashion. This study aimed to examine the relationship between renal function, frailty and physical performance with mortality in older patients with diabetes, while also determining their combined effects on patient outcome. METHODS: A retrospective longitudinal study was conducted in elderly patients with diabetes. Kidney disease staging was based on clinical practice guidelines of the International Society of Nephrology, and chronic kiney disease (CKD) was defined as urinary albumin to creatinine ratio (UACR) > 30 mg/g, persistent reduction in estimated glomerular filtration rate (eGFR) below 60 mL/min per 1.73 m2 or both. The modified Rockwood frailty index (RFI) was composed of cumulative health deficits, and physical function was determined by handgrip strength (HGS). Additionally, a timed up and go (TUG) test was assessed at baseline. Kaplan-Meier survival and Cox proportional hazard analyses were used to analyze the association between CKD, frailty, physical function and mortality. RESULTS: For the 921 enrolled patients, their mean age was 82.0 ± 6.7 years. After a median 2.92 (interquartile range [IQR] 1.06-4.43) year follow-up, the survival rate was 67.6% and 85.5% in patients with and without CKD, respectively. The mortality hazard ratio (crude HR) with CKD was 5.92 for those with an RFI higher than 0.313 (95% CI 3.44-10.18), 2.50 for a TUG time longer than 21 s (95% CI 1.22-5.13), and 2.67 for an HGS lower than 10.57 kg in females or 20.4 kg in males (95% CI 1.12-6.37). After multivariate adjustment, the mortality hazard ratio for an RFI ≥ 0.313 was 5.34 (95% CI 2.23-12.80) in CKD patients, but not in patients without CKD. In subgroup analysis, patients experiencing CKD and frailty, or physical function impairment, had the lowest survival proportion followed by only frailty/declined physical function, only CKD, without CKD, and non-frailty/non-physical impairment. CONCLUSION: CKD, frailty and physical function impairment were all associated with an increased mortality risk in older patients with diabetes, while the combined effects of these 3 factors were seen on patient outcome.

Patterns of biopsy-proven renal diseases in geriatric patients: A single medical center experience.

The elderly population is expanding rapidly, and that has become a major healthcare burden in terms of chronic kidney disease. The distribution patterns of kidney diseases in these elderly patients remain largely unclear. Here, we compared biopsy-based renal disease patterns between elderly and nonelderly patients. We performed a single-center, retrospective study (1992-2008) on biopsy-proven renal diseases to compare results between geriatric patients (age ≥ 65 years; n = 254) and nongeriatric patients (18 ≤ age < 65 years; n = 2592). Renal pathology was interpreted by pathologists based on light microscopy, immunofluorescence, and electron microscopy. The ages of the geriatric and nongeriatric groups were 71.8 ±â€…4.5 (65.1-87.3) and 39.7 ±â€…17.6 (18-64.9) years, respectively, and 74% and 41% of them, respectively, were men. In the geriatric group, the most frequent diagnosis was membranous nephropathy (46.1%), followed by minimal change disease/focal segmental glomerulosclerosis (16.9%), diabetic nephropathy (8.3%), hypertensive nephrosclerosis (7.5%), and IgA nephropathy (5.9%). The geriatric group had more membranous nephropathy and less lupus nephritis and IgA nephropathy than the nongeriatric group. Furthermore, the 5-year survival rate of the geriatric group was significantly low. Our results demonstrated the different distributions of renal biopsy patterns in geriatric patients diagnosed with acute or chronic progressive kidney injury and proteinuria through renal biopsy.

Combined Functional Assessment for Predicting Clinical Outcomes in Stroke Patients After Post-acute Care: A Retrospective Multi-Center Cohort in Central Taiwan.

Background and Objective: In 2014, Taiwan's National Health Insurance administration launched a post-acute care (PAC) program for patients to improve their functions after acute stroke. The present study was aimed to determine PAC assessment parameters, either alone or in combination, for predicting clinical outcomes. Methods: We retrospectively enrolled stroke adult patients through one PAC network in central Taiwan between January 2014 and December 2020. We collected data on post-stroke patients' functional ability at baseline and after PAC stay. The comprehensive assessment included the following: Modified Rankin Scale (MRS), Functional Oral Intake Scale (FOIS), Mini-Nutritional Assessment (MNA), Berg Balance Scale (BBS), Fugl-Meyer Assessment (FMA), Mini-Mental State Examination (MMSE), aphasia test, and quality of life. The above items were assessed first at baseline and again at discharge from PAC. Logistic regression was used to determine factors that were associated with PAC length of stay (LOS), 14-day hospital readmission, and 1-year mortality. Results: A total of 267 adults (mean age 67.2 ± 14.7 years) with completed data were analyzed. MRS, activities of daily living (ADLs), instrumental activities of daily living (IADLs), BBS, and MMSE all had improved between disease onset and PAC discharge. Higher baseline and greater improvement of physical and cognitive functions between initial and final PAC assessments were significantly associated with less readmission, and lower mortality. Furthermore, the improved ADLs, FOIS, MNA, FMA-motor, and MMSE scores were related to LOS during PAC. Using logistic regression, we found that functional improvements ≥5 items [adjusted odds ratio (aOR) = 0.16; 95% confidence interval (CI) = 0.05-0.45] and improved MMSE (aOR = 0.19; 95% CI = 0.05-0.68) were significantly associated with reduced post-PAC mortality or readmission. Whereas, functional improvements ≥7 items, improved FOIS, and MNA significantly prolonged LOS during PAC. Conclusion: Physical performance parameters of patients with acute stroke improved after PAC. PAC assessment with multiple parameters better predicted clinical outcomes. These parameters could provide information on rehabilitation therapy for acute stroke patients receiving PAC.

Decoy Receptor 3 Suppresses T-Cell Priming and Promotes Apoptosis of Effector T-Cells in Acute Cell-Mediated Rejection: The Role of Reverse Signaling.

Background: Decoy receptor 3 (DcR3) belongs to the tumor necrosis factor (TNF) receptor superfamily and neutralizes TNF ligands, including FasL and TRAIL, to prevent T activation during T-cell priming. However, the cellular mechanisms underlying acute cell-mediated rejection (ACMR) remain unknown. Methods: We generated DcR3 transgenic (Tg) mice and mice with high DcR3 expression (HDE) to study both in vivo and in vitro. FasR RNA knockdown in immortalized CD4+CD8+ T-cells was used to survey the role of DcR3 on FasR/Fas-associated protein with death domain (FADD)/caspase 8 pathway and its cross-link to TNF receptor-associated factor 1 (TNFR1)-associated death domain protein (TRADD) in suppressing TNFR1. TNF/TRADD knockout mice were used to show the importance of TNF adaptor protein. Results: DcR3.Fc suppressed C57BL/6 female T-cell activation and transformation into CD4+CD69+, CD4+CD44+, and CD4+CD25+Foxp3+ when compared with isotype IgG1 and its co-treatment with FasL/TRAIL after exposing to bone marrow-derived dendritic cells (BMDCs) that carried alloantigen with male H-Y and minor antigenic determinant. Interleukin-17 and interferon-γ productions by BMDC-activated T-cells were lowered after co-treating with DcR3.Fc. DcR3.Fc induced effector T-cells (Teffs) and was susceptible to FasR-mediated apoptosis through the FADD/TRADD/caspase 8 pathway. After exposing to DcR3.Fc, TRADD was silenced, likely turning down the inflammatory response. The systemic effects of DcR3 Tg mice and HDE phenotype induced by the promoter of cytomegalovirus not only attenuated ACMR severity but also ameliorated the high serum creatinine and blood urea nitrogen levels even with high T-cell exposure frequencies. Besides this, DcR3 has minor biological effects on both MHC-matched and MHC-mismatched models. Conclusions: High DcR3 doses protect renal tubular epithelial cells from acute T-cell attack during the T-cell priming stage via interfering with TNF ligand-mediated reverse signaling and possibly promoting Teff apoptosis through FasR upregulation. Our findings supported that the decoy receptor is involved in T-cell modulation in kidney transplant rejection.

Characteristics and Outcome Determinants of Hospitalized Older Patients with Cognitive Dysfunction.

Cognitive dysfunction commonly occurs among older patients during admission and is associated with adverse prognosis. This study evaluated clinical characteristics and outcome determinants in hospitalized older patients with cognitive disorders. The main outcomes were length of stay, readmission within 30 days, Barthel index (BI) score at discharge, BI score change (discharge BI score minus BI score), and proportion of positive BI score change to indicate change of activities of daily living (ADL) change during hospitalization. A total of 642 inpatients with a mean age of 79.47 years (76-103 years) were categorized into three groups according to the medical history of dementia, and Mini-Mental State Examination (MMSE) scores at admission. Among them, 74 had dementia diagnosis (DD), 310 had cognitive impairment (CI), and 258 had normal MMSE scores. Patients with DD and CI generally had a higher risk of many geriatric syndromes, such as multimorbidities, polypharmacy, delirium, incontinence, visual and auditory impairment, fall history, physical frailty. They had less BI score, BI score change, and proportion of positive BI score change ADL at discharge. (DD 70.0%, CI 79.0%), suggesting less ADL change during hospitalization compared with those with normal MMSE scores (92.9%; p < 0.001). Using multiple regression analysis, we found that among patients with DD and CI, age (p = 0.008) and walking speed (p = 0.023) were predictors of discharge BI score. In addition, age (p = 0.047) and education level were associated with dichotomized BI score change (positive vs. non-positive) during hospitalization. Furthermore, the number and severity of comorbidities predicted LOS (p < 0.001) and readmission (p = 0.001) in patients with cognitive disorders. It is suggested that appropriate strategies are required to improve clinical outcomes in these patients.

Prediction of 30-Day Readmission in Hospitalized Older Adults Using Comprehensive Geriatric Assessment and LACE Index and HOSPITAL Score.

(1) Background: Elders have higher rates of rehospitalization, especially those with functional decline. We aimed to investigate potential predictors of 30-day readmission risk by comprehensive geriatric assessment (CGA) in hospitalized patients aged 65 years or older and to examine the predictive ability of the LACE index and HOSPITAL score in older patients with a combination of malnutrition and physical dysfunction. (2) Methods: We included patients admitted to a geriatric ward in a tertiary hospital from July 2012 to August 2018. CGA components including cognitive, functional, nutritional, and social parameters were assessed at admission and recorded, as well as clinical information. The association factors with 30-day hospital readmission were analyzed by multivariate logistic regression analysis. The predictive ability of the LACE and HOSPITAL score was assessed using receiver operator characteristic curve analysis. (3) Results: During the study period, 1509 patients admitted to a ward were recorded. Of these patients, 233 (15.4%) were readmitted within 30 days. Those who were readmitted presented with higher comorbidity numbers and poorer performance of CGA, including gait ability, activities of daily living (ADL), and nutritional status. Multivariate regression analysis showed that male gender and moderately impaired gait ability were independently correlated with 30-day hospital readmissions, while other components such as functional impairment (as ADL) and nutritional status were not associated with 30-day rehospitalization. The receiver operating characteristics for the LACE index and HOSPITAL score showed that both predicting scores performed poorly at predicting 30-day hospital readmission (C-statistic = 0.59) and did not perform better in any of the subgroups. (4) Conclusions: Our study showed that only some components of CGA, mobile disability, and gender were independently associated with increased risk of readmission. However, the LACE index and HOSPITAL score had a poor discriminating ability for predicting 30-day hospitalization in all and subgroup patients. Further identifiers are required to better estimate the 30-day readmission rates in this patient population.

Trajectory of Estimated Glomerular Filtration Rate and Malnourishment Predict Mortality and Kidney Failure in Older Adults With Chronic Kidney Disease.

Objective: The trajectory patterns of estimated glomerular filtration rates (eGFR) in chronic kidney disease (CKD) older adults with malnourishment and their association with subsequent patient outcomes have not been elucidated. We aimed to assess the eGFR trajectory patterns for predicting patient survival and kidney failure in the elderly without or with malnourishment. Materials and Methods: Based on a prospective longitudinal cohort, CKD patients aged 65 years or older were enrolled from 2001 to 2013. Among the 3,948 patients whose eGFR trajectory patterns were analyzed, 1,872 patients were stratified by the absence or presence of malnourishment, and 765 patients were identified and categorized as having malnourishment. Four eGFR trajectory patterns [gradual decline (T0), early non-decline and then persistent decline (T1), persistent increase (T2), and low baseline and then progressive increase (T3)] were classified by utilizing a linear mixed-effect model with a quadratic term in time. The malnourishment was defined as body mass index < 22 kg/m2, serum albumin < 3.0 mg/dL, or Geriatric Nutritional Risk Index (GNRI) < 98. This study assessed the effectiveness of eGFR trajectory patterns in a median follow-up of 2.27 years for predicting all-cause mortality and kidney failure. Results: The mean age was 76.9 ± 6.7 years, and a total of 82 (10.7%) patients with malnourishment and 57 (5.1%) patients without malnourishment died at the end of the study. Compared with the reference trajectory T0, the overall mortality of T1 was markedly reduced [adjusted hazard ratio (aHR) = 0.52, 95% confidence interval (CI) 0.32-0.83]. In patients with trajectory, T3 was associated with a high risk for kidney failure (aHR = 5.68, 95% CI 3.12-10.4) compared with the reference, especially higher risk in the presence of malnourishment. Patients with high GNRI values were significantly associated with a lower risk of death and kidney failure, but patients with malnourishment and concomitant alcohol consumption had a higher risk of kidney failure. Conclusions: Low baseline eGFR and progressively increasing eGFR trajectory were high risks for kidney failure in CKD patients. These findings may be attributed to multimorbidity, malnourishment, and decompensation of renal function.

Impacts of Heart Failure and Physical Performance on Long-Term Mortality in Old Patients With Chronic Kidney Disease.

Background: In patients with chronic kidney disease (CKD), physical functional limitations and heart failure (HF) are common, and each is associated with adverse outcomes. However, their joint effects on mortality are not clear. Design and Methods: Using administration data from the geriatric department in a tertiary hospital, retrospective longitudinal analyses of patients aged ≥65 years with CKD were consecutively enrolled from February 2010 to November 2015. Baseline CKD stages, HF with reduced and preserved ejection fraction (HFrEF and HFpEF), Rockwood frailty index, handgrip strength (HGS), 6-m walking speed, and timed up-and-go test were used to predict the prevalence of frailty, physical disability, and all-cause mortality. Results: Among 331 old patients with CKD, their mean age was 81.3 ± 6.6 years. CKD stages showed the following distributions: stage 3, 74.9%; stage 4, 15.7%; stage 5, 9.4%. The prevalence of HF was 23.3%, and Rockwood frailty was 74.3%. Rockwood frailty and HF were both significantly associated with CKD stages. After a mean follow-up period of 3.1 ± 2.1 years, 44 patients died, and a crude analysis showed that stage 4, stage 5 CKD, low HGS, and Rockwood frailty index were associated with mortality. Regarding the survival of these patients, the adjusted mortality hazard ratio for CKD stage 5 was 3.84 against stage 3A [95% confidence interval (CI) 1.51-9.75], 1.04 (95% CI 1.01-1.07) for higher Rockwood frailty score, 4.78 (95% CI 1.26-18.11) for HFrEF, and 3.47 (95% CI 1.15-10.42) for low HGS. Survival analysis using Kaplan-Meier survival plots showed that patients with both HF and poor HGS had the poorest survival. Conclusions: Our study shows that both low physical performance and HF were common in old CKD patients and were associated with CKD stages. HF, frailty, and HGS all independently predicted the mortality of these CKD patients. The mortality is especially high amongst individuals with both HF and decreased HGS.

Physical frailty and long-term mortality in older people with chronic heart failure with preserved and reduced ejection fraction: a retrospective longitudinal study.

BACKGROUND: Frailty, a syndrome characterized by a decline in function reserve, is common in older patients with heart failure (HF) and is associated with prognosis. This study aimed to evaluate the impact of frailty on outcomes in older patients with preserved and reduced cardiac function. METHODS: In total, 811 adults aged ≥65 years were consecutively enrolled from 2009 to 2018. HF was diagnosed according to the ICD9 code and a 2D echocardiogram was categorized by reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). The index date was registered at the time of HF. All patients received a comprehensive geriatric assessment, and clinical outcomes were examined with adjustment of the other prognostic variables. RESULTS: Mean age was 80.5 ± 7.1 years. The prevalence of HF, HFpEF, HFrEF, Fried, and Rockwood frailty indicators was 28.5, 10.4, 9.7, 52.5, and 74.9%, respectively. At baseline, scores in the Timed Up and Go test was closely associated with the severity of HF, either with HFpEF or HFrEF. After a mean follow-up of 3.2 ± 2.0 years, we found that HF patients with low handgrip strength (HGS) had the poorest survival, followed by non-HF patients with decreased HGS, and HF with fair HGS in comparison with non-HF with fair HGS (p = 0.008) if participants were arbitrarily divided into two HGS groups. In all patients, a high Rockwood frailty index was independently associated with increased mortality (adjusted hazard ratio [aHR] = 1.05; 95% confidence interval [CI]: 1.0004 to 1.10). In addition, the adjusted mortality HR was 3.42 with decreased HGS (95% CI: 1.03 to 11.40), 7.65 with use of mineralocorticoid receptor antagonist (95% CI: 2.22 to 26.32), and 1.26 with associated multi-comorbidities assessed by Charlson comorbidity index (95% CI: 1.05 to 1.51). CONCLUSIONS: Our study results indicate that frailty and decreased physical functions were associated with HF. Besides, frailty and HGS predicted prognosis in the patients, and there was a combined effect of HF and low HGS on survival.

Effects of kidney function, serum albumin and hemoglobin on dementia severity in the oldest old people with newly diagnosed Alzheimer's disease in a residential aged care facility: a cross-sectional study.

BACKGROUND: Chronic kidney disease (CKD), low serum albumin, and anemia are known risk factors for cognitive decline in older people. We investigated the association between kidney function and cognitive impairment severity in oldest-old people with a diagnosis of Alzheimer's disease (AD). METHODS: A cross-sectional study of patients aged 80 years and older was conducted at a veterans' home in Taiwan between 2012 and 2016. Their estimated glomerular filtration rate (eGFR) was determined using the Modification of Diet in Renal Diseases (MDRD) equation. Cognitive function was evaluated with the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR). RESULTS: A total of 84 patients (age mean ± SD, 86.6 ± 3.9 years) had MMSE scores of 10.1 ± 6.7, and CDR scores of 1.6 ± 0.7. The average eGFR was 61.7 ± 21.5 mL/min/1.73m2. The mean hemoglobin concentration was 12.7 ± 1.7 g/dl, and the mean albumin concentration was 4.5 ± 4.8 g/dl. Multivariate regression analyses showed that scores of CDR were significantly correlated with eGFR after adjustment for potential confounders. The scores of MMSE were significantly correlated with serum albumin and hemoglobin after adjustment for potential confounders. CONCLUSIONS: We found dementia severity was significantly associated with kidney function, serum albumin, and hemoglobin in the oldest-old with AD. We recommend that oldest-old people with a diagnosis of AD be evaluated to determine kidney function, as well as nutritional and hematological status. Further study is needed to establish whether prevention of CKD deterioration, and correction of malnutrition and anemia may help to slow cognitive decline in oldest-old people with dementia.

Health-Related Quality of Life Measured by EQ-5D in Relation to Hospital Stay and Readmission in Elderly Patients Hospitalized for Acute Illness.

We evaluated the predictability of self-reported Health-related quality of life (HRQoL) assessed by the 3-level 5-dimensional Euro-Quality of Life tool (EQ-5D-3L) and the EQ-Visual Analog Scale (EQ-VAS) on clinical outcomes of elderly patients who were admitted to an acute geriatric ward. A total of 102 participants (56.9% men) with a median age of 81.0 years (interquartile range or IQR: 76.0-85.3 years) were studied. The age-adjusted Charlson comorbidity index was 5.0 (IQR: 4.0-6.0) with a median length of stay (LOS) of 9.0 days (IQR: 7.0-15.0 days). No death occurred during hospitalization, and within 30 days after discharge, 15 patients were readmitted. During hospitalization, the EQ-5D-3L index was 0.440 at admission and that improved to 0.648 at discharge (p < 0.001). EQ-VAS scores also improved similarly from 60 to 70 (p < 0.001). Physical, cognitive function, frailty parameters (hand grip strength and walking speed), and nutritional status at admission all improved significantly during hospitalization and were related to EQ-5D-3L index or EQ-VAS scores at discharge. After controlling for relevant factors, EQ-5D-3L index at admission was found to be associated with LOS. In addition, EQ-VAS was marginally related to readmission. HRQoL assessment during hospitalization could be useful to guide clinical practice and to improve outcome.

Author Correction: Severe Decline of Estimated Glomerular Filtration Rate Associates with Progressive Cognitive Deterioration in the Elderly: A Community-Based Cohort Study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Symptomatic menopausal transition and risk of subsequent stroke.

OBJECTIVE: To examine the long-term risk of stroke in women who have experienced symptomatic menopausal transition. METHODS: In this nationwide, population-based cohort study conducted from January 1, 2000 to December 31, 2013, we identified 22,058 women with no prior history of stroke, who experienced symptomatic menopausal transition at ≥45 years of age. Moreover, 22,058 women without symptomatic menopause were matched by propensity scores and enrolled as a comparison group. The propensity score was calculated by using all characteristic variables of each subject, including demographics (age and monthly income), comorbidities (hypertension, hyperlipidemia, diabetes mellitus, obesity, chronic kidney disease, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, dysrhythmia, peripheral artery occlusive disease), Charlson's comorbidity index score, clinic visit frequency, and long-term medications (antihypertensives, antidiabetic agents, statins, antiplatelets, aspirin, warfarin, and hormone replacement therapy). The primary endpoint was the development of stroke after the onset of symptomatic menopausal transition. The Fine and Gray's proportional subhazards model was performed to assess the association between symptomatic menopausal transition and subsequent stroke. All subjects were followed up until December 31, 2013. RESULTS: During a mean follow-up of 8.5 years (standard deviation 4.7 years, maximum 14 years), 2,274 (10.31%) women with symptomatic menopausal transition, and 1,184 (5.37%) matched comparison participants developed stroke. The incidence rates were 11.17 per 1,000 person-years in the symptomatic menopausal transition group compared with 8.57 per 1,000 person-years in the comparison group. The risk of developing stroke was significantly higher in women with symptomatic menopausal transition (crude subhazard ratio, 1.31; 95% confidence interval (CI) [1.22-1.41]; P < 0.001). After adjusting for demographics, comorbidities, clinic visit frequency, and long-term medications, the risk of stroke remained statistically significant (adjusted subhazard ratio, 1.30; 95% CI [1.21-1.40]; P < 0.001). Moreover, subgroup analyses revealed no evidence for inconsistent effects for symptomatic menopausal transition on subsequent risk of stroke across all subgroups except age, comorbidities, hypertension, and use of antihypertensives. Women with early menopausal transition (before age 50), without comorbid condition, without hypertension, or without use of antihypertensives are at a higher risk of stroke. The longer duration of symptomatic menopausal transition was associated with higher risk of stroke (P for trend < 0.001). CONCLUSION: In this large-scale retrospective cohort study, symptomatic menopausal transition was statistically significantly associated with a 30% increased risk of stroke. Further prospective studies are required to confirm our findings.

Predictors of Mortality in the Oldest Old Patients with Newly Diagnosed Alzheimer Disease in a Residential Aged Care Facility.

BACKGROUND: In Taiwan, the causes of death and related factors in the oldest old people with Alzheimer disease (AD) are not well characterized. We investigated the factors associated with mortality in the oldest old patients with newly diagnosed AD admitted to a long-stay residential facility. METHODS: We performed a prospective study of newly diagnosed AD patients at a veterans' home between 2012 and 2016. At admission, all eligible participants received a comprehensive geriatric assessment, including demographic variables, lifestyle habits, cognitive evaluations, medical conditions (comorbidities, Age-Adjusted Charlson Comorbidity Index score, and polypharmacy), nutritional status evaluated by the Mini Nutritional Assessment-Short Form and body mass index (BMI), and global functional status. A Cox proportional hazards model was used to evaluate the predictive values of clinical parameters for all-cause mortality. RESULTS: The cohort comprised 84 newly diagnosed AD patients (mean age 86.6 ± 3.9 years) with a mean follow-up period of 2.1 ± 1.2 years. The overall median survival was 3.5 years from the time of AD diagnosis (95% confidence interval, 3.1-3.9 years). BMI was significantly lower in the deceased group than in the alive group (20.7 ± 2.9 vs. 22.6 ± 3.4, p = 0.023). Logistic regression demonstrated that the clinical parameters significantly associated with mortality were high global comorbidity, low nutritional status (malnutrition and underweight), and impaired physical function at the time of AD diagnosis. CONCLUSION: Comorbidity burden, nutritional status, and physical functional status at the time of dementia diagnosis are important contributors to poor outcome in the oldest old. Efforts to control concurrent chronic disorders, nutritional interventions, and physical independency as a long-term care strategy for dementia may provide survival benefit.

Role of prognostic biomarker decoy receptor 3 and immunomodulation in kidney diseases.

Decoy receptor 3 (DcR3), also known as tumor necrosis factor receptor superfamily member 6b (TNFRSF6B), was recently identified as a novel biomarker for predicting progression of kidney diseases with potential immune modulation. The purpose of this review is to discuss the current evidence related to DcR3 in kidney diseases and to compare the differences between human and animal studies both in vivo and in vitro. High serum DcR3 predicts the occurrence of peritonitis in patients receiving chronic peritoneal dialysis and is positively correlated with inflammatory markers such as interleukin-6, high-sensitivity C-reactive protein, and adhesion molecules in patients on maintenance hemodialysis (HD). Higher serum DcR3 levels not only independently predict cardiovascular and all-cause mortality in HD patients but also identify older adults on HD at risk of protein-energy wasting in combination with a low geriatric nutritional risk index. Recently, renal tubular epithelial cells (RTECs) expressing DcR3 have also been used to predict progression of chronic kidney disease. Expression of DcR3 was correlated with a 2-fold increase in serum creatinine or failure of kidney allograft. DcR3 could protect renal myofibroblasts against Fas-induced apoptosis and subsequently lead to renal fibrosis. Locally expressed DcR3 in the RTECs may suppress the FasL-Fas-mediated apoptosis of T cells, resulting in an accumulation of allo-reactive T cells. In addition to traditional biological functions, recombinant DcR3.Fc and cytomegalovirus promoter-driven human DcR3 plasmid are able to modulate the activation and differentiation of dendritic cells and macrophages via "non-decoy" action. Both progressive IgA nephropathy and autoimmune crescentic glomerulonephritis in mice can be suppressed after hydrodynamics-based gene delivery of DcR3 plasmid. DcR3-mediated effects in vitro could be surveyed via over-expressing DcR3 or addition of recombinant DcR3.Fc, and CD68-driven DcR3 transgenic mice are suitable for investigating systemic effect in vivo. Inhibition of DcR3 expression in human may be a promising approach for pathomechanism.

Effects of the bass brushing method on dental plaque and pneumonia in older adults hospitalized with pneumonia after discharge: A randomized controlled trial.

AIM: The purpose of this pilot study was to evaluate the effects of the Bass brushing method on dental plaque and pneumonia in older adults hospitalized with pneumonia after discharge. BACKGROUND: Poor oral hygiene may lead to pneumonia. Complications of pneumonia in older adults can be life-threatening during hospitalization and after discharge. METHODS: Older adults hospitalized with pneumonia (n = 30) were randomly assigned to intervention (with the Bass brushing method; n = 15) or control (with usual care; n = 15) groups. Dental plaque index and pneumonia as detected on chest x-rays were evaluated prior to the intervention (baseline) and every month for six months after discharge. RESULTS: Participants in the intervention group experienced a sustained reduction in dental plaque from the fourth to the sixth months (p = .024; p = .025; p = .000, respectively) that was not found in the control group. There were no group differences in detected pneumonia throughout the follow-up period. Pneumonia as detected on the chest x-rays at baseline (p = .001) and dental plaque index (p = .021) were significant predictors of the risk of pneumonia across groups. CONCLUSIONS: The Bass brushing method is a simple and effective oral hygiene practice that reduces dental plaque in older adults hospitalized with pneumonia after discharge.

A Study of Frailty, Mortality, and Health Depreciation Factors in Older Adults.

This study used 23 factors (eight interval variables and 15 dummy variables) as proxies for health depreciation. We used 1248 older adults from the Center for Geriatrics and Gerontology of Taichung Veterans General Hospital (Taiwan) to examine the association among frailty, health depreciation, and mortality in older adults. This study found that a significant positive correlation existed between frailty and mortality in older adults. Further, we applied a recursive bivariate probit model to examine the association between health depreciation factors, frailty, and mortality. Our results showed that health depreciation factors, such as Charlson's comorbidity index, diabetes and hyperlipidemia, significantly increased older adults' frailty; in contrast, albumin and mini nutritional assessment significantly decreased older adults' frailty. Through the frailty regression, we confirmed not only that health depreciation factors significantly influenced mortality, but also that creatinine, myocardial infarction, and malignant tumors could directly and significantly increase older adults' mortality.