Future Blood Debt: Projecting Blood Supply and Demand of Korea Based on Subnational Population Projections (2021-2050).

BACKGROUND: South Korea faces a critical challenge with its rapidly declining fertility rates and an increasingly aging population, which significantly impacts the country's blood supply and demand. Despite these nationwide trends, regional disparities in blood supply and demand have not been thoroughly studied. METHODS: This research utilized blood donation data from the Korean Red Cross and blood transfusion data from the Health Insurance Review and Assessment Service. We analyzed these datasets in conjunction with regional population projections to simulate blood supply and demand from 2021 to 2050 across South Korea. Sensitivity analyses were conducted to assess the impact of various factors, including the number of donors, age eligibility criteria for donations, frequency of donations, and blood discard rates. RESULTS: Our projections indicate a decreasing trend in blood supply, from 2.6 million units in 2021 to 1.4 million units by 2050, while demand is expected to peak at 5.1 million units by 2045 before declining. Metropolitan areas, particularly Gyeonggi Province, are projected to experience the most severe shortages. Sensitivity analyses suggest that increasing the donation frequency of existing donors and relaxing age eligibility criteria are more effective strategies in addressing these imbalances than merely increasing the number of new donors. Blood discard rates showed minimal impact on the overall blood shortage. CONCLUSION: The findings emphasize the urgent need for targeted strategies to mitigate national and regional blood supply shortages in South Korea. Encouraging frequent donations from experienced donors and broadening eligibility criteria are critical steps toward stabilizing the blood supply amidst demographic shifts. These strategies must be prioritized to address the impending regional disparities in blood availability.

Sarcopenia as the Mobility Phenotype of Aging: Clinical Implications.

Sarcopenia, which is characterized by an age-related decline in muscle mass and function, poses significant challenges to geriatric care. Its definition has evolved from muscle-specific criteria to include muscle mass, muscle function, and physical performance, recognizing sarcopenia as a physical frailty. Sarcopenia is associated with adverse outcomes, including mortality, falls, fractures, cognitive decline, and admission to long-term care facilities. Neuromechanical factors, protein-energy balance, and muscle protein synthesis-breakdown mechanisms contribute to its pathophysiology. The identification of sarcopenia involves screening tests and a comprehensive assessment of muscle mass, strength, and physical function. Clinical approaches aligned with the principles of comprehensive geriatric assessment prioritize patient-centered care. This assessment aids in identifying issues related to activities of daily living, cognition, mood, nutrition, and social support, alongside other aspects. The general approach to factors underlying muscle loss and functional decline in patients with sarcopenia includes managing chronic diseases and evaluating administered medications, with interventions including exercise and nutrition, as well as evolving pharmacological options. Ongoing research targeting pathways, such as myostatin-activin and exercise mimetics, holds promise for pharmacological interventions. In summary, sarcopenia requires a multifaceted approach, acknowledging its complex etiology and tailoring interventions to individual patient needs.

Comparison of anticholinergic burden with chronic polypharmacy on functional decline and mortality in Korean older people: a retrospective nationwide cohort study.

BACKGROUND: We aimed to evaluate the association of anticholinergic burden and chronic polypharmacy with the incidence of functional decline and all-cause mortality, and to determine the difference between anticholinergic burden and chronic polypharmacy among Korean older people. METHODS: This nationwide cohort study included 42,132 older people aged ≥ 65 years who underwent Korean National Health Insurance Service health examinations from 2007 to 2008. Odds ratios (ORs) and 95% confidence intervals (CIs) for abnormal Timed Up and Go (TUG) test results were assessed using multivariate logistic regression analyses. Hazard ratios (HRs) and 95% CIs for all-cause mortality until the end of 2015 were estimated using multivariable Cox proportional hazards regression analysis. RESULTS: Of the participants, 37.19% had abnormal TUG test results, and 7.66% of those died during the 5.7-year mean follow-up. The abnormal TUG test results OR increased by 27% among individuals with Korean Anticholinergic Burden Scale (KABS) scores ≥ 3 (OR 1.27, 95% CI 1.02-1.58) compared to those with KABS scores of 0. The HRs for all-cause mortality increased for individuals with higher KABS scores (P for trend < 0.001) or chronic polypharmacy (P for trend < 0.001) compared to those for individuals without these conditions. The combination of a higher KABS or chronic polypharmacy and abnormal TUG test results increased the risk of all-cause mortality (All P for trend < 0.001). CONCLUSION: Anticholinergic drug burden shows a better association with functional decline than chronic polypharmacy, and the use of medications and functional decline may be important risk factors for all-cause mortality among older people.

A pore-scale reactive transport modeling study for quorum sensing-driven biofilm dispersal in heterogeneous porous media.

Microorganisms regulate the expression of energetically expensive phenotypes via a collective decision-making mechanism known as quorum sensing (QS). This study investigates the intricate dynamics of biofilm growth and QS-controlled biofilm dispersal in heterogeneous porous media, employing a pore-scale reactive transport modeling approach. Model simulations carried out under various fluid flow conditions and biofilm growth scenarios reveal that QS processes are influenced not only by the biomass density of biofilm colonies but also by a complex interplay between pore architecture, flow velocity, and the rates of biofilm growth and dispersal. This study demonstrates that pore architecture controls the initiation of QS processes and advection gives rise to oscillatory growth of biofilms. Such oscillation is suppressed if biofilm dynamics are in favor of sustaining a sufficiently high signal concentration, such as fast growth or slow dispersal rates. By establishing a mathematical framework, this study contributes to the fundamental understanding of QS-controlled biofilm dynamics in complex environments.

Circulating lumican as a potential biomarker for osteosarcopenia in older adults.

In vitro and animal experiments demonstrated that lumican exerts anabolic effects on bone and muscle by stimulating osteoblastogenesis, suppressing osteoclastogenesis and increasing myogenesis. However, the relationship between circulating lumican and musculoskeletal phenotypes in humans remains unclear. We aimed to analyze the relationship between serum lumican levels and osteosarcopenia in older adults. Blood samples were collected from 134 participants (age: 65 years and older) who underwent comprehensive assessment of bone and muscle phenotypes. Osteoporosis and sarcopenia were diagnosed based on World Health Organization and Asian consensus guidelines, respectively. Osteosarcopenia was defined as the simultaneous presence of osteoporosis and sarcopenia. After adjusting for sex, age, and body mass index, older adults with osteosarcopenia had 20.2 % lower serum lumican levels than those without (P = 0.010). The odds ratio (OR) for osteosarcopenia per standard deviation decrease in serum lumican level was 4.17 (P = 0.003). Consistently, higher serum lumican levels were correlated with higher bone mass at all measured sites (P = 0.004 to 0.045) and higher grip strength (P = 0.023). Furthermore, participants in the lowest tertile (T1) had 7.56-fold higher OR for osteosarcopenia (P = 0.024) than those in the highest lumican tertile (T3). In conclusion, these findings clinically validate previous experimental data showing the musculoskeletal protective effects of lumican and suggest that blood lumican levels could be used as a potential biomarker to assess the risk of not only osteosarcopenia but also osteoporosis or sarcopenia in older adults.

Phenotype validation of the Korean working group on sarcopenia guideline.

BACKGROUND: This study aimed to validate the proposed Korean Working Group on Sarcopenia (KWGS) guideline, which introduces the concept of functional sarcopenia, in older Korean adults. METHODS: Data from the Aging Study of Pyeongchang Rural Area, a longitudinal cohort of community-dwelling older adults, were utilized to compare frailty status and institutionalization-free survival among participants according to sarcopenia status. Based on the KWGS guideline, severe sarcopenia was defined as low muscle mass and strength with slow gait speed; sarcopenia (not severe) was defined as low muscle mass with low muscle strength or slow gait speed; and functional sarcopenia was defined as low muscle strength and slow gait speed without low muscle mass. RESULTS: Among the 1302 participants, 329 (25.3 %) had severe sarcopenia, 147 (11.3 %) had sarcopenia (not severe), and 277 (21.3 %) had functional sarcopenia. Frailty was significantly greater in participants with any phenotype of sarcopenia than in those without sarcopenia. Additionally, participants with functional sarcopenia were frailer than those with sarcopenia (not severe). Furthermore, the rates of institutionalization and mortality were higher in participants with any phenotype of sarcopenia than in those without sarcopenia. There was no statistical difference between the rates of sarcopenia (not severe) and those with functional sarcopenia. These findings remained consistent after adjusting for age and sex. CONCLUSIONS: Each phenotype according to the KWGS guideline was associated with significantly greater frailty and increased risk of institutionalization and mortality. Functional sarcopenia was associated with greater frailty and had comparable prognosis with sarcopenia (not severe).

Higher Plasma Stromal Cell-Derived Factor 1 Is Associated with Lower Risk for Sarcopenia in Older Asian Adults.

BACKGRUOUND: Despite the protective effects of stromal cell-derived factor 1 (SDF-1) in stimulating muscle regeneration shown in experimental research, there is a lack of clinical studies linking circulating SDF-1 concentrations with muscle phenotypes. In order to elucidate the role of SDF-1 as a potential biomarker reflecting human muscle health, we investigated the association of plasma SDF-1 levels with sarcopenia in older adults. METHODS: This cross-sectional study included 97 community-dwelling participants who underwent a comprehensive geriatric assessment at a tertiary hospital in South Korea. Sarcopenia was defined by specific cutoff values applicable to the Asian population, whereas plasma SDF-1 levels were determined using an enzyme immunoassay. RESULTS: After accounting for sex, age, and body mass index, participants with sarcopenia and low muscle mass exhibited plasma SDF-1 levels that were 21.8% and 18.3% lower than those without these conditions, respectively (P=0.008 and P=0.009, respectively). Consistently, higher plasma SDF-1 levels exhibited a significant correlation with higher skeletal muscle mass index (SMI) and gait speed (both P=0.043), and the risk of sarcopenia and low muscle mass decreased by 58% and 55% per standard deviation increase in plasma SDF-1 levels, respectively (P=0.045 and P=0.030, respectively). Furthermore, participants in the highest SDF-1 tertile exhibited significantly higher SMI compared to those in the lowest tertile (P=0.012). CONCLUSION: These findings clinically corroborate earlier experimental discoveries highlighting the muscle anabolic effects of SDF- 1 and support the potential role of circulating SDF-1 as a biomarker reflecting human muscle health in older adults.

The Unique Relationship between Neuro-Critical Care and Critical Illness-Related Corticosteroid Insufficiency : Implications for Neurosurgeons in Neuro-Critical Care.

The brain houses vital hormonal regulatory structures such as the hypothalamus and pituitary gland, which may confer unique susceptibilities to critical illness-related corticosteroid insufficiency (CIRCI) in patients with neurological disorders. In addition, the frequent use of steroids for therapeutic purposes in various neurological conditions may lead to the development of steroid insufficiency. This abstract aims to highlight the significance of understanding these relationships in the context of patient care and management for physicians. Neurological disorders may predispose patients to CIRCI due to the role of the brain in hormonal regulation. Early recognition of CIRCI in the context of neurological diseases is essential to ensure prompt and appropriate intervention. Moreover, the frequent use of steroids for treating neurological conditions can contribute to the development of steroid insufficiency, further complicating the clinical picture. Physicians must be aware of these unique interactions and be prepared to evaluate and manage patients with CIRCI and steroid insufficiency in the context of neurological disorders. This includes timely diagnosis, appropriate steroid administration, and careful monitoring for potential adverse effects. A comprehensive understanding of the interplay between neurological disease, CIRCI, and steroid insufficiency is critical for optimizing patient care and outcomes in this complex patient population.

Newly developed care food enhances grip strength in older adults with dysphagia: a preliminary study.

BACKGROUND/OBJECTIVES: Maintaining total muscle mass in the older adults with swallowing difficulty (dysphagia) is important for preserving swallowing function. Increasing protein intake can help sustain lean body mass in the older adults. The aim of this study was to evaluate the effect of various high-protein texture-modified foods (HPTMFs) on muscle mass and perform dietary assessment in ≥ 65-yrs-old patients with dysphagia. SUBJECTS/METHODS: Participants (n = 10) received the newly developed HPTMFs (average 595.23 ± 66.75 kcal/day of energy, 54.22 ± 6.32 g/day of protein) for 10 days. Relative hand-grip strength (RHS), mid-upper arm circumference (MUAC), body composition, mini nutritional assessment (MNA), mini dietary assessment (MDA), and Euro Quality-of-Life questionnaire 5-dimensional classification (EQ-5D) were assessed. RESULTS: After 10 days, an increase in MUAC (26.36 ± 2.35 cm to 28.50 ± 3.17 cm, P = 0.013) and RHS (0.38 ± 0.24 kg/kg body weight to 0.42 ± 0.22 kg/kg body weight, P = 0.046) was observed. Although MNA, MDA, EQ-5D, subjective health status, muscle mass, and calf circumference showed a tendency to increase after intervention, no significant differences were found. CONCLUSIONS: These results suggest that the HPTMFs can be used for improving the nutritional and health status in patients with dysphagia.

Unmet Needs and Barriers in Providing Hospital Care for Older Adults: A Qualitative Study Using the Age-Friendly Health System Framework.

Purpose: This study aims to identify unmet needs and barriers for improving inpatient care for older adults at an academic hospital in Korea by using a qualitative focus group design and the Age-Friendly Health Systems (AFHS) framework. Patients and Methods: A total of 14 healthcare providers and employees participated in focus group interviews. Participants included medical doctors, registered nurses, a receptionist, a patient transporter, a pharmacist, a physical therapist, and a social worker. The data were analyzed qualitatively, as per the Consolidated Criteria for Reporting Qualitative Research guidelines. The analysis method encompassed a thematic framework analysis via the AFHS 4Ms framework, consisting of the four domains "What Matters", "Medication", "Mentation", and "Mobility". Results: Multiple barriers and unmet needs were identified using the AFHS 4Ms framework in the provision of inpatient care for older adults at the hospital. The main barriers identified in the "What matters" domain are a lack of shared decision-making and individualized care plans, as well as economic and safety-conscious preferences among some older patients. In the "Medications" domain, the main barriers to providing adequate and safe pharmacotherapy include patient and caregiver-related factors, increased complexity of medication use, and lack of institutional support systems. In the "Mentation" domain, the main issues identified are communication barriers related to patients, caregiver factors, and insufficient delirium management due to a lack of adequate processes/environments such as delirium identification. In the "Mobility" domain, the main challenges include reduced mobility and geriatric complications, unnecessary mobility restrictions, and the increased risk of falls due to lack of resources and environmental factors. Conclusion: The study highlighted the need for improvements in inpatient care for older adults at an academic hospital in Korea. Identified unmet needs and barriers can be used to guide a more patient-centered approaches for an age-friendly inpatient environment.

The Clinical Frailty Scale as a Risk Assessment Tool for Dysphagia in Older Inpatients: A Cross-Sectional Study.

BACKGROUND: Dysphagia is a common problem with potentially serious consequences including malnutrition, dehydration, pneumonia, and death. However, there are challenges in screening for dysphagia in older adults. We assessed the feasibility of using the Clinical Frailty Scale (CFS) as a risk assessment tool for dysphagia. METHODS: This cross-sectional study was conducted at a tertiary teaching hospital from November 2021 to May 2022 and included 131 older patients (age ≥65 years) admitted to acute wards. We used the Eating Assessment Tool-10 (EAT-10), which is a simple measure for identifying individuals at risk of dysphagia, to assess the relationship between EAT-10 score and frailty status as measured using the CFS. RESULTS: The mean age of the participants was 74.3±6.7 years, and 44.3% were male. Twenty-nine (22.1%) participants had an EAT-10 score ≥3. The CFS was significantly associated with an EAT-10 score ≥3 after adjusting for age and sex (odds ratio=1.48; 95% confidence interval [CI], 1.09-2.02). The CFS was able to classify the presence of an EAT-10 score ≥3 (area under the receiver operating characteristic [ROC] curve=0.650; 95% CI, 0. 544-0.756). The cutoff point for predicting an EAT-10 score ≥3 was a CFS of 5 according to the highest Youden index, with a sensitivity of 82.8% and a specificity of 46.1%. The positive and negative predictive values were 30.4% and 90.4%, respectively. CONCLUSION: The CFS can be used as a tool to screen for the risk of swallowing difficulty in older inpatients to determine clinical management encompassing drug administration routes, nutritional support, prevention of dehydration, and further evaluation of dysphagia.

Trends in Frailty Prevalence Among Older Adults in Korea: A Nationwide Study From 2008 to 2020.

BACKGROUND: We aimed to evaluate the nationwide trend of the prevalence of frailty in older adults in Korea from 2008 to 2020 to inform future geriatric healthcare policies. METHODS: The study used data of individuals aged 65 years and older from the Korea National Health and Nutrition Examination Survey, a nationwide repeated cross-sectional survey. Frailty was defined using frailty index, classified as non-frail (frailty index ≤ 0.15), pre-frail (0.15 < frailty index ≤ 0.25), or frail (frailty index > 0.25). RESULTS: The study included 17,784 individuals, with the mean age of 72.4 and mean frailty index of 0.2. The prevalence of frailty in older adults in South Korea decreased significantly from 2008 (41.1%) to 2020 (23.1%). The decrease in the frailty index was observed in all age groups (all P < 0.05). As components of frailty index, we found that certain comorbidities, such as dyslipidemia, diabetes mellitus, and cardiovascular disease, have increased over time, while factors such as chewing difficulty, activity limitation, and smoking, have decreased. CONCLUSION: The prevalence of frailty in older adults in South Korea has decreased significantly during the study period. Historical improvements in healthcare access and preventive measures may have contributed to this trend.

Effect of polydopamine and fluoride ion coating on dental enamel remineralization: an in vitro study.

BACKGROUND: Fluoride treatment is one of the most effective dental caries prevention methods. To continuously prevent dental caries, stably immobilizing the fluoride on the tooth enamel is highly desirable. This study aimed to evaluate the remineralization of tooth enamels by one-pot coating using polydopamine and fluoride ions. METHODS: To prepare the enamel specimens for polydopamine- and fluoride ion-coating, they were treated with polydopamine- and fluoride-containing gels. The enamel specimens were collected from human molars in a blind manner (n = 100) and were randomized into five treatment groups (n = 20, each): 1) untreated, 2) polydopamine-coated, 3) fluoride-containing gel-treated, 4) F varnish-treated, and 5) polydopamine- and fluoride ion-coated enamels. Vickers hardness number (VHN), morphology, and fluoride contents of the specimens were measured before and after the pH-cycling regimen. RESULTS: Polydopamine- and fluoride ion-coated enamels showed the highest fluoride content and lowest VHN reduction among the samples. The fluoride content of the polydopamine/fluoride ion (PD/F)-coated enamel was increased to 182 ± 6.6%, which was far higher than that of the uncoated enamel (112.3 ± 32.8%, P < 0.05). The changes in the VHN values (ΔVHN) of PD/F-coated enamel substrates showed a slight reduction in the VHN (-3.6%, P < 0.05), which was far lower than that in the control group (-18.9%, P < 0.05). In addition, scanning electron microscopy clearly supported the effect of polydopamine- and fluoride ion-coatings on the remineralization of enamel specimens. CONCLUSION: Our findings suggest that one-pot treatments with polydopamine and fluoride ions could significantly enhance remineralization by inhibiting enamel demineralization through the prolonged retention of fluoride ions.

Lack of association between serum myonectin levels and sarcopenia in older Asian adults.

Myonectin is a muscle-secreted factor that helps maintain homeostasis in the body by regulating several functions, including lipid metabolism. Previous studies suggested that myonectin may play a role in muscle health in an autocrine manner, but its impact on human skeletal muscle is still unclear. We aimed to investigate the relationship of serum myonectin levels with sarcopenia and related muscle parameters. We conducted a cross-sectional study of 142 older adults whose muscle mass, grip strength, gait speed, chair stands, and short physical performance battery (SPPB) were evaluated in the geriatric clinic of a tertiary medical center. Sarcopenia was defined based on Asian-specific cutoff values, and circulating myonectin levels were measured using an enzyme immunoassay. Before and after adjusting for age, sex, and body mass index, the serum myonectin level was not significantly different when the patients were stratified by status of sarcopenia, muscle mass, muscle strength, and physical performance. Furthermore, whether given as a continuous variable or divided into quartile groups, the serum myonectin level had no association with the skeletal muscle mass, grip strength, gait speed, chair stand test, or SPPB score. Our findings did not confirm the potential role of myonectin in muscle metabolism observed in experimental research. Thus, serum myonectin levels cannot predict the risk of sarcopenia in older Asian adults.

Comparative Study of the Accuracy of At-Point Clinical Frailty Scale and Morse Fall Scale in Identifying High-Risk Fall Patients among Hospitalized Adults.

BACKGROUND: Falls are a major concern among hospitalized adults, and it is essential to identify high-risk patients to prevent falls. This retrospective cohort study conducted at the Asan Medical Center, Korea, compared the screening abilities of the at-point Clinical Frailty Scale (CFS) and Morse Fall Scale (MFS) to identify patients at high risk for falls among hospitalized adults. METHODS: We assessed the records of at-point CFS, MFS, and fall incidence during hospitalization of 2,028 patients aged 18 or older included in this study. We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) for each tool. RESULTS: Twenty-five patients (1.23%) experienced falls during hospitalization. The mean at-point CFS score was significantly higher in those with falls than in those without falls. The mean MFS score did not differ significantly between the two groups. The optimal cutoff points for the at-point CFS and MFS scores were 5 and 45, respectively. At these cutoffs, the at-point CFS demonstrated a sensitivity of 76.0%, specificity of 54.0%, PPV of 2.0%, and NPV of 99.4%, whereas the MFS demonstrated a sensitivity of 60.0%, specificity of 68.1%, PPV of 2.2%, and NPV of 99.4%. The AUC values for the at-point CFS and MFS were 0.68 and 0.63, respectively, with no significant difference (p=0.31). CONCLUSION: The at-point CFS is a valid screening tool for assessing fall risk in hospitalized adults, as it effectively identifies fall risk with a performance similar to that of the MFS.

The Unique Relationship between Neuro-Critical Care and Critical Illness-Related Corticosteroid Insufficiency : Implications for Neurosurgeons in Neuro-Critical Care.

The brain houses vital hormonal regulatory structures such as the hypothalamus and pituitary gland, which may confer unique susceptibilities to critical illness-related corticosteroid insufficiency (CIRCI) in patients with neurological disorders. In addition, the frequent use of steroids for therapeutic purposes in various neurological conditions may lead to the development of steroid insufficiency. This abstract aims to highlight the significance of understanding these relationships in the context of patient care and management for physicians. Neurological disorders may predispose patients to CIRCI due to the role of the brain in hormonal regulation. Early recognition of CIRCI in the context of neurological diseases is essential to ensure prompt and appropriate intervention. Moreover, the frequent use of steroids for treating neurological conditions can contribute to the development of steroid insufficiency, further complicating the clinical picture. Physicians must be aware of these unique interactions and be prepared to evaluate and manage patients with CIRCI and steroid insufficiency in the context of neurological disorders. This includes timely diagnosis, appropriate steroid administration, and careful monitoring for potential adverse effects. A comprehensive understanding of the interplay between neurological disease, CIRCI, and steroid insufficiency is critical for optimizing patient care and outcomes in this complex patient population.

Associations of social interactions during the COVID-19 pandemic with cognitive function among the South Korean older adults.

BACKGROUND: We aimed to demonstrate the associations between social interactions within social distancing norms during the coronavirus disease 2019 (COVID-19) pandemic and cognitive function among South Korean older adults. METHODS: Data from the 2017 and 2020 Survey of Living Conditions and Welfare Needs of Korean Older Persons were used. There were 18,813 participants (7,539 males; 11,274 females). T-test and multiple logistic regression analyses verified whether the mean difference in older adults' cognitive function before and during the COVID-19 pandemic was statistically significant. We also examined the associations between social interactions and cognitive function. The key results were presented as odds ratios (ORs) and 95% confidence intervals (CI). RESULTS: All participants were more likely to experience cognitive impairment during the COVID-19 pandemic than before (males: OR 1.56, 95% CI 1.3-1.78; females: OR 1.26, 95% CI: 1.14-1.40). Cognitive impairment increased linearly with the decreased frequency of face-to-face contact with non-cohabiting children. Possible cognitive impairment was greater for females who had not visited senior welfare centers for the past year (OR 1.43, 95% CI 1.21-1.69). CONCLUSION: Korean older adults' cognitive function declined during the COVID-19 pandemic and was associated with reduced social interactions because of social distancing measures. Alternative interventions should be promoted for safely restoring social networks, considering the adverse effects of long-term social distancing on older adults' mental health and cognitive function.

Accurate Prediction of Cancer Prognosis by Exploiting Patient-Specific Cancer Driver Genes.

Accurate prediction of the prognoses of cancer patients and identification of prognostic biomarkers are both important for the improved treatment of cancer patients, in addition to enhanced anticancer drugs. Many previous bioinformatic studies have been carried out to achieve this goal; however, there remains room for improvement in terms of accuracy. In this study, we demonstrated that patient-specific cancer driver genes could be used to predict cancer prognoses more accurately. To identify patient-specific cancer driver genes, we first generated patient-specific gene networks before using modified PageRank to generate feature vectors that represented the impacts genes had on the patient-specific gene network. Subsequently, the feature vectors of the good and poor prognosis groups were used to train the deep feedforward network. For the 11 cancer types in the TCGA data, the proposed method showed a significantly better prediction performance than the existing state-of-the-art methods for three cancer types (BRCA, CESC and PAAD), better performance for five cancer types (COAD, ESCA, HNSC, KIRC and STAD), and a similar or slightly worse performance for the remaining three cancer types (BLCA, LIHC and LUAD). Furthermore, the case study for the identified breast cancer and cervical squamous cell carcinoma prognostic genes and their subnetworks included several pathways associated with the progression of breast cancer and cervical squamous cell carcinoma. These results suggested that heterogeneous cancer driver information may be associated with cancer prognosis.

Assessment of Frailty Index at 66 Years of Age and Association With Age-Related Diseases, Disability, and Death Over 10 Years in Korea.

Importance: A frailty index has been proposed as a measure of aging among older individuals. However, few studies have examined whether a frailty index measured at the same chronologic age at younger ages could forecast the development of new age-related conditions. Objective: To examine the association of the frailty index at 66 years of age with incident age-related diseases, disability, and death over 10 years. Design, Setting, and Participants: This retrospective nationwide cohort study used the Korean National Health Insurance database to identify 968 885 Korean individuals who attended the National Screening Program for Transitional Ages at 66 years of age between January 1, 2007, and December 31, 2017. Data were analyzed from October 1, 2020, to January 2022. Exposures: Frailty was defined using a 39-item frailty index ranging from 0 to 1.00 as robust (<0.15), prefrail (0.15-0.24), mildly frail (0.25-0.34), and moderately to severely frail (≥0.35). Main Outcomes and Measures: The primary outcome was all-cause death. Secondary outcomes were 8 age-related chronic diseases (congestive heart failure, coronary artery disease, stroke, type 2 diabetes, cancer, dementia, fall, and fracture) and disability qualifying for long-term care services. Cox proportional hazards regression and cause-specific and subdistribution hazards regression were used to examine hazard ratios (HRs) and 95% CIs for the outcomes until the earliest of date of death, the occurrence of relevant age-related conditions, 10 years from the screening examination, or December 31, 2019. Results: Among the 968 885 participants included in the analysis (517 052 women [53.4%]), the majority were classified as robust (65.2%) or prefrail (28.2%); only a small fraction were classified as mildly frail (5.7%) or moderately to severely frail (1.0%). The mean frailty index was 0.13 (SD, 0.07), and 64 415 (6.6%) were frail. Compared with the robust group, those in the moderately to severely frail group were more likely to be women (47.8% vs 61.7%), receiving medical aid insurance for low income (2.1% vs 18.9%), and less active (median, 657 [IQR, 219-1133] vs 319 [IQR, 0-693] metabolic equivalent task [min/wk]). After adjusting for sociodemographic and lifestyle characteristics, moderate to severe frailty was associated with increased rates of death (HR, 4.43 [95% CI, 4.24-4.64]) and new diagnosis of all chronic diseases, including congestive heart failure (adjusted cause-specific HR, 2.90 [95% CI, 2.67-3.15]), coronary artery disease (adjusted cause-specific HR, 1.98 [95% CI, 1.85-2.12]), stroke (adjusted cause-specific HR, 2.22 [95% CI, 2.10-2.34]), diabetes (adjusted cause-specific HR, 2.34 [95% CI, 2.21-2.47]), cancer (adjusted cause-specific HR, 1.10 [95% CI, 1.03-1.18]), dementia (adjusted cause-specific HR, 3.59 [95% CI, 3.42-3.77]), fall (adjusted cause-specific HR, 2.76 [95% CI, 2.29-3.32]), fracture (adjusted cause-specific HR, 1.54 [95% CI, 1.48-1.62]), and disability (adjusted cause-specific HR, 10.85 [95% CI, 10.00-11.70]). Frailty was associated with increased 10-year incidence of all the outcomes, except for cancer (moderate to severe frailty adjusted subdistribution HR, 0.99 [95% CI, 0.92-1.06]). Frailty at 66 years of age was associated with greater acquisition of age-related conditions (mean [SD] conditions per year for the robust group, 0.14 [0.32]; for the moderately to severely frail group, 0.45 [0.87]) in the next 10 years. Conclusions and Relevance: The findings of this cohort study suggest that a frailty index measured at 66 years of age was associated with accelerated acquisition of age-related conditions, disability, and death over the next 10 years. Measuring frailty at this age may offer opportunities to prevent age-related health decline.