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1.
Artigo em Inglês | MEDLINE | ID: mdl-34769606

RESUMO

(1) Background: As the clinical relevance of constipation and sarcopenia is not well studied, we aimed to investigate the association between them in older adults. (2) Methods: A cross-sectional study was conducted on 1278 community-dwelling older adults in South Korea. The Rome IV criteria were used to identify patients with clinically defined constipation, while sarcopenia was defined by the Asian Working Group for Sarcopenia consensus. The cohort was classified into three groups: no constipation, self-reported constipation only, and clinically defined constipation. (3) Results: The presence of constipation was associated with sarcopenia and slow gait speed (p < 0.001). After adjustment for possible covariates, the association with sarcopenia attenuated, while that for slow gait speed persisted. In terms of geriatric parameters, both groups with clinically defined and self-reported constipation had a higher burden of cognitive impairment, IADL disability, and lower QOL scores (p < 0.05) compared with those without constipation. (4) Conclusions: Sarcopenia and slow gait speed associated with constipation in community-dwelling older adults. Individuals with self-reported constipation symptoms alone showed comparable sarcopenic and geriatric burden to those with clinically defined constipation. Clinical suspicion for possible co-existing sarcopenia is warranted in older patients with constipation.


Assuntos
Sarcopenia , Idoso , Estudos de Coortes , Constipação Intestinal/epidemiologia , Estudos Transversais , Avaliação Geriátrica , Força da Mão , Humanos , Vida Independente , Qualidade de Vida , Sarcopenia/epidemiologia
2.
Sensors (Basel) ; 21(20)2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34695940

RESUMO

With the active development of mobile devices, a variety of ultra-small, high-definition, and open platform-based cameras are being mass-produced. In this paper, we established an emulation system to verify the bio-imaging performance of the bulky and expensive high-performance cameras and various smartphone cameras that have been used in bio-imaging devices. In the proposed system, the linearity of the brightness gradient change of four types of cameras was compared and analyzed. Based on these results, three cameras were selected in order of excellent linearity, and gel image analysis results were compared.


Assuntos
Processamento de Imagem Assistida por Computador , Smartphone , Computadores de Mão , Diagnóstico por Imagem
3.
Ann Geriatr Med Res ; 25(3): 160-169, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34610665

RESUMO

The Aging Study of Pyeongchang Rural Area (ASPRA) is a population-based, prospective cohort study of older adults in Pyeongchang, South Korea. Since the initial enrollment of 382 participants, the ASPRA has been maintained and has conducted comprehensive geriatric assessments annually, gradually expanding its population and coverage area. As a cohort study of aging-related conditions and their functional consequences, the ASPRA leveraged Pyeongchang's relatively low annual population movement rate and its healthcare delivery system, which was largely maintained by community health posts. Since its establishment, the ASPRA has reported numerous observational and multicomponent intervention studies on functional decline, geriatric syndrome, and frailty. Here, we discuss the findings and perspectives of ASPRA studies. We hope that the ASPRA enables the further implementation of a longitudinal study design on geriatric parameters and the development of public health strategies targeting aging-related conditions, especially in resource-limited community settings.

4.
Oncology ; 99(10): 665-672, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34515197

RESUMO

BACKGROUND: Due to few efficacious options in later lines of therapy in metastatic colorectal cancer (mCRC), there has been considerable interest in the possibility of retreatment with previously administered agents. This study investigated the efficacy and safety of irinotecan retreatment (IRI2) in patients with refractory mCRC. METHODS: We performed a retrospective analysis of patients with mCRC who were retreated with irinotecan-based regimens. The retreatment regimens with anti-epidermal growth factor receptor therapies were excluded. RESULTS: A total of 64 patients were included. Patients had a median age of 56 years and were offered mainly in the setting of third- or fourth-line therapy with IRI2. The disease control rate was 78.2% including an objective response of 23.5%. Median progression-free survival and overall survival were 5.5 and 19.3 months, respectively. The most frequent grade 3 or higher toxicities were nausea/vomiting (27.9%) and neutropenia (25%). CONCLUSION: IRI2 might be a reasonable option for heavily pretreated patients with mCRC who achieved disease control with prior irinotecan therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/patologia , Humanos , Irinotecano/administração & dosagem , Irinotecano/efeitos adversos , Pessoa de Meia-Idade , Metástase Neoplásica , Retratamento , Estudos Retrospectivos , Resultado do Tratamento
5.
Sensors (Basel) ; 21(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34372383

RESUMO

The Short Physical Performance Battery (SPPB) is a widely accepted test for measuring lower extremity function in older adults. However, there are concerns regarding the examination time required to conduct a complete SPPB consisting of three components (walking speed, chair rise, and standing balance tests) in clinical settings. We aimed to assess specific examination times for each component of the electronic Short Physical Performance Battery (eSPPB) and compare the ability of the original three-component examinations (eSPPB) and a faster, two-component examination without a balance test (electronic Quick Physical Performance Battery, eQPPB) to classify sarcopenia. The study was a retrospective, cross-sectional study which included 124 ambulatory outpatients who underwent physical performance examination at a geriatric clinic of a tertiary, academic hospital in Seoul, Korea, between December 2020 and March 2021. For eSPPB, we used a toolkit containing sensors and software (Dyphi, Daejeon, Korea) developed to measure standing balance, walking speed, and chair rise test results. Component-specific time stamps were used to log the raw data. Duration of balance examination, 5 times sit-to-stand test (5XSST), and walking speed examination were calculated. Sarcopenia was determined using the 2019 Asian Working Group for Sarcopenia (AWGS) guideline. The median age was 78 years (interquartile range, IQR: 73,82) and 77 subjects (62.1%) were female. The total mean eSPPB test time was 124.8 ± 29.0 s (balance test time 61.8 ± 12.3 s, 49.5%; gait speed test time 34.3 ± 11.9 s, 27.5%; and 5XSST time 28.7 ± 19.1 s, 23.0%). The total mean eQPPB test time was 63.0 ± 25.4 s. Based on the AWGS criteria, 34 (27.4%) patient's results were consistent with sarcopenia. C-statistics for classifying sarcopenia were 0.83 for eSPPB and 0.85 for eQPPB (p = 0.264), while eQPPB took 49.5% less measurement time compared with eSPPB. Breakdowns of eSPPB test times were identified. Omitting balance tests may reduce test time without significantly affecting the classifying ability of eSPPB for sarcopenia.


Assuntos
Sarcopenia , Idoso , Estudos Transversais , Eletrônica , Feminino , Avaliação Geriátrica , Força da Mão , Humanos , Desempenho Físico Funcional , Estudos Retrospectivos , Sarcopenia/diagnóstico
6.
Artigo em Inglês | MEDLINE | ID: mdl-34299801

RESUMO

Sarcopenia and cognitive decline share the major risk factors of physical inactivity; previous studies have shown inconsistent associations. We aimed to identify the association of sarcopenia and its parameters with cognitive decline. The 3-year longitudinal outcomes of 1327 participants from the Aging Study of the Pyeongchang Rural Area (ASPRA) cohort were analyzed. Cognitive performance was evaluated using the Mini-Mental State Examination (MMSE), and sarcopenia was defined by the following: the original and revised Asian Working Group for Sarcopenia (AWGS), the original and revised European Working Group on Sarcopenia in Older People (EWGSOP), and the Cumulative Muscle Index (CMI), a novel index based on the number of impaired domains of sarcopenia. Approximately half of the participants showed meaningful cognitive decline. Sarcopenia by the original EWGSOP and the CMI were associated with cognitive decline. Only the CMI showed consistent predictability for cognitive impairment even with different criteria of the MMSE score (OR 1.23 [1.04-1.46]; OR 1.34 [1.12-1.59]; OR 1.22 [1.01-1.49], using the 1, 2, and 3 cut-off value, respectively). Of the CMI parameters, gait speed was satisfactorily predictive of 3-year cognitive impairment (OR 0.54 [0.30-0.97]). In conclusion, sarcopenia based on the CMI may be predictive of future cognitive impairment. Gait speed was the single most important indicator of cognitive decline.


Assuntos
Disfunção Cognitiva , Sarcopenia , Idoso , Envelhecimento , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Estudos Transversais , Avaliação Geriátrica , Força da Mão , Humanos , Músculos , Prevalência , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia
7.
Ann Geriatr Med Res ; 25(2): 65-71, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34187140

RESUMO

South Korea became an aged society in 2017 and is predicted to become a super-aged society by 2025. Therefore, knowing the trends among older adults and identifying the geriatric burden are crucial for both healthcare professionals and policymakers. We previously summarized the general health and socioeconomic profiles of Korean older adults from the 2017 National Survey of Living Conditions and Welfare Needs of Older Koreans. In this update, we briefly summarized the results of the 2020 National Survey of Living Conditions and Welfare Needs of Older Koreans by categorizing them according to their general aging profile, socioeconomic status, lifestyle, and health status. In addition, we reviewed recent updates in the field of frailty and sarcopenia from population-based community cohorts in Korea. We hope this study will serve as a current reference for nationwide statistical data on common clinical and social parameters used in geriatrics and gerontology.

8.
Nat Genet ; 53(6): 881-894, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33972779

RESUMO

Esophageal squamous cell carcinomas (ESCCs) harbor recurrent chromosome 3q amplifications that target the transcription factor SOX2. Beyond its role as an oncogene in ESCC, SOX2 acts in development of the squamous esophagus and maintenance of adult esophageal precursor cells. To compare Sox2 activity in normal and malignant tissue, we developed engineered murine esophageal organoids spanning normal esophagus to Sox2-induced squamous cell carcinoma and mapped Sox2 binding and the epigenetic and transcriptional landscape with evolution from normal to cancer. While oncogenic Sox2 largely maintains actions observed in normal tissue, Sox2 overexpression with p53 and p16 inactivation promotes chromatin remodeling and evolution of the Sox2 cistrome. With Klf5, oncogenic Sox2 acquires new binding sites and enhances activity of oncogenes such as Stat3. Moreover, oncogenic Sox2 activates endogenous retroviruses, inducing expression of double-stranded RNA and dependence on the RNA editing enzyme ADAR1. These data reveal SOX2 functions in ESCC, defining targetable vulnerabilities.


Assuntos
Adenosina Desaminase/metabolismo , Epigenoma , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Proteínas de Ligação a RNA/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Regiões 3' não Traduzidas/genética , Animais , Sequência de Bases , Carcinogênese/genética , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Retrovirus Endógenos/genética , Elementos Facilitadores Genéticos/genética , Regulação Neoplásica da Expressão Gênica , Genoma Humano , Humanos , Interferons/metabolismo , Íntrons/genética , Fatores de Transcrição Kruppel-Like/genética , Camundongos , Organoides/patologia , Ligação Proteica , RNA de Cadeia Dupla/metabolismo , Fatores de Transcrição SOXB1/genética , Proteína Supressora de Tumor p53/metabolismo
9.
Ann Geriatr Med Res ; 25(2): 86-92, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33975418

RESUMO

BACKGROUND: The five times sit-to-stand test (5STS) is one of the most commonly used tests to assess the physical performance of lower extremities. This study assessed the correlation between human interpretation (5STShuman) and a rule-based algorithm (5STSrule) using instrumented 5STS with two sensors. METHODS: We analyzed clinical records of 148 patients who visited the geriatric outpatient clinic of Asan Medical Center between December 2020 and March 2021 and underwent physical performance assessment using the electronic Short Physical Performance Battery (eSPPB) protocol. For STS, time-weight and time-distance curves were constructed using a loadcell and light detection and ranging (LiDAR). We manually assessed the grids of these curves to calculate 5STShuman, while 5STSrule used an empirical rule-based algorithm. RESULTS: In the study population, the mean 5STShuman and 5STSrule times, i.e., 12.2±0.4 and 11.4±0.4 seconds, respectively, did not differ significantly (p=0.232). Linear regression analysis showed that 5STShuman and 5STSrule were positively correlated (ß=0.99, R2=0.99). The measures also did not differ (p=0.381) in classifying sarcopenia according to the Asian Working Group Society criteria, with C-indices of 0.826 for 5STShuman and 0.820 for 5STSrule. CONCLUSION: An empirical rule-based algorithm correlated with human-interpreted 5STS and had comparable classification ability for sarcopenia.

10.
Ann Geriatr Med Res ; 25(2): 79-85, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33975422

RESUMO

BACKGROUND: Owing to the growing older population, appropriate tools are needed for frailty screening in community-dwelling older people. We investigated the association between geriatric conditions and health-related outcomes using the five-item Fatigue, Resistance, Ambulation, Illnesses, & Loss of Weight (FRAIL) scale in a Korean rural community setting. METHODS: We performed comprehensive geriatric assessments, including the FRAIL scale, in 1,292 community-dwelling people (mean age, 74.6 years) in the Aging Study of Pyeongchang Rural Area. These populations were prospectively followed up for 3 years to analyze the outcomes of death, institutionalization, disability, and quality of life. We investigated the association between frailty status and outcomes using the FRAIL scale. RESULTS: According to the FRAIL scale, 524 (36.5%) participants were prefrail and 297 (23.0%) were frail. According to the adjusted model, the degree of frailty status was significantly associated with concurrent geriatric syndromes and 3-year incidences of mortality, institutionalization, and disability; Kaplan-Meier analysis showed significant differences in 3-year survival based on frailty status (92.6% for robust, 85.7% for prefrail, and 74.2% for frail; log-rank p<0.001). CONCLUSION: The five-item FRAIL scale can be used to screen for accompanying geriatric syndromes and is associated with the 3-year health-related outcomes in community-dwelling Korean older adults. From the public health perspective, this simple screening tool for frailty assessment might be applicable to older populations in Korea.

11.
Diabetes Res Clin Pract ; 174: 108751, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33722701

RESUMO

AIMS: To investigate the incidence of and risk factors for new-onset type 2 diabetes mellitus (DM) developed during chemotherapy that included steroids in cancer patients without DM. METHODS: This multicenter, prospective, and observational cohort study enrolled 299 cancer patients without DM (aged > 18 years), planning 4-8 cycles of adjuvant chemotherapy. The endpoints were the incidence, remission rate, and independent determinants of new-onset DM during chemotherapy. RESULTS: Between April 2015 and March 2018, 270 subjects with colorectal cancer or breast cancer (mean age, 51.0 years) completed the follow up (mean 39 months). Of whom, 17 subjects (6.3%) developed DM within a median time of 90 days (range, 17-359 days). Male sex (hazard ratio [HR], 15.839; 95% confidence interval [CI], 2.004-125.20) and impaired fasting glucose (IFG) at baseline (HR, 8.307; CI, 1.826-37.786) were independent risk factors. Six months after chemotherapy completion, 11/17 subjects (64.7%) experienced DM remission, associated with a significantly higher C-peptide level at baseline (C-peptide levels, 1.3 ng/mL in subjects with remission and 0.9 ng/mL in subjects without remission, age- and sex-adjusted P = 0.007). CONCLUSIONS: DM incidence was 6.3% in patients who received chemotherapy with dexamethasone. Close monitoring for hyperglycemia is recommended, especially for men with IFG. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03062072).


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Hiperglicemia/epidemiologia , Estado Pré-Diabético/epidemiologia , Glicemia/análise , Neoplasias da Mama/patologia , Neoplasias Colorretais/patologia , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/patologia , Progressão da Doença , Feminino , Humanos , Hiperglicemia/induzido quimicamente , Hiperglicemia/patologia , Incidência , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/induzido quimicamente , Estado Pré-Diabético/patologia , Prognóstico , Estudos Prospectivos , República da Coreia/epidemiologia , Fatores de Risco , Taxa de Sobrevida
12.
J Gerontol A Biol Sci Med Sci ; 76(12): 2249-2255, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33780526

RESUMO

BACKGROUND: Growing evidence supports the clinical importance of evaluating frailty in older adults, with its strong outcome relevance. We aimed to assess whether the Short Physical Performance Battery (SPPB) correlates with frailty status according to phenotype and deficit accumulation models and can be used as a link between these models. METHODS: We analyzed records of 1064 individuals from the Aging Study of Pyeongchang Rural Area, a population-based, prospective cohort from South Korea. Frailty was determined using the Cardiovascular Health Study (CHS) phenotype (phenotype model), 26- and 34-item frailty indices (deficit accumulation model). Associations of SPPB score and frailty with a composite outcome of mortality or long-term institutionalization were assessed. Crosswalks for SPPB, the CHS frailty phenotype, and the frailty index were created. RESULTS: The mean age of the study population was 76.0 years, and 583 (54.8%) were women. According to the CHS phenotype, 26- and 34-item frailty indices, 242 (22.7%), 161 (15.1%), and 280 (26.3%) participants, respectively, had frailty. Sensitivities/specificities for classifying CHS phenotype, 26- and 34-item frailty indices were 0.93/0.55, 0.71/0.84, and 0.80/0.83 by SPPB cut points of ≤9, ≤6, and ≤7, respectively. C-index of SPPB score (0.78) showed a predictive ability for the composite outcome that was comparable to that of CHS frailty phenotype (0.79), 26- (0.78), and 34-item frailty indices (0.79). CONCLUSIONS: We could create a crosswalk linking frailty phenotype and frailty index from correlations between SPPB and frailty models. This result may facilitate clinical adoption of the frailty concept in a broader spectrum of older adults.

13.
PLoS One ; 16(2): e0245987, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33539372

RESUMO

PURPOSE: To explore how symptom perception affects functioning in patients with advanced cancer. MATERIALS AND METHODS: We conducted a cross-sectional observational study of 459 advanced cancer patients at the national cancer center. Functioning was assessed using the World Health Organization Disability Assessment Schedule (WHODAS) II, and symptoms were evaluated using the Memorial Symptom Assessment Scale-Short Form. Confirmatory factor analysis was conducted to develop a structural model based on different symptom perceptions, such as somatic sensation and experienced symptoms. RESULTS: The structural model of disability revealed a significant direct pathway involving somatic sensation (ß = 16.11, p < 0.001). Experienced symptoms significantly affected somatic sensations (ß = 0.717, p < 0.001) but were not directly associated with disability. Unidimensional models exhibited a poor fit. In contrast, a complex model with first-order (somatic sensation) and second-order (experienced symptoms) factors provided an excellent fit, with comparative fit indexes (CFIs) and Tucker Lewis indexes (TLI) of more than 0.950 threshold. CONCLUSIONS: Our findings suggest that relationships to functioning may vary between somatic sensations versus experienced symptoms. The structure of symptoms is best conceptualized by direct somatic sensation and indirect experienced symptoms. A better understanding of symptom perception and the relationship between symptoms and function would facilitate the development of effective rehabilitation programs.


Assuntos
Neoplasias/patologia , Neoplasias/psicologia , Psicometria , Adulto , Idoso , Estudos Transversais , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Percepção , Qualidade de Vida , Adulto Jovem
14.
Diabetes Metab J ; 45(2): 175-182, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32431107

RESUMO

Background: Although studies have shown that obesity is associated with aeroallergen sensitization (atopy), controversy still exists. We aimed to investigate the association between metabolic status, obesity, and atopy stratified by sex and menopausal status. Methods: A total of 1,700 adults from the 2010 Korean National Health and Nutrition Examination Survey were classified into metabolically healthy nonobese (MHNO), metabolically unhealthy nonobese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO) by body mass index and insulin resistance. Atopy was defined as a positive response to at least one aeroallergen. Multiple regression analysis was used to evaluate the risk of immunoglobulin E (IgE) elevation or atopy in relation to the degree of metabolic abnormality and obesity. Results: In premenopausal women, total IgE was positively correlated with obesity and insulin resistance. MUNO participants had a higher risk of having elevated total IgE compared to MHNO participants (odds ratio [OR], 2.271; 95% confidence interval [CI], 1.201 to 4.294), while MHO participants did not show a significant difference (OR, 1.435; 95% CI, 0.656 to 3.137) in premenopausal women. MUNO, but not MHO was also associated with atopy (OR, 2.157; 95% CI, 1.284 to 3.625). In men and postmenopausal women, there was no significant difference between metabolic status, obesity, and atopy among groups. Conclusion: Increased insulin resistance is associated with total IgE and atopy in premenopausal women but not in postmenopausal women or men.


Assuntos
Resistência à Insulina , Adulto , Estudos Transversais , Feminino , Humanos , Imunoglobulina E , Masculino , Inquéritos Nutricionais , Fatores de Risco
15.
Gut ; 70(10): 1954-1964, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33208407

RESUMO

OBJECTIVE: Lipotoxic hepatocyte injury is a primary event in non-alcoholic steatohepatitis (NASH), but the mechanisms of lipotoxicity are not fully defined. Sphingolipids and free cholesterol (FC) mediate hepatocyte injury, but their link in NASH has not been explored. We examined the role of free cholesterol and sphingomyelin synthases (SMSs) that generate sphingomyelin (SM) and diacylglycerol (DAG) in hepatocyte pyroptosis, a specific form of programmed cell death associated with inflammasome activation, and NASH. DESIGN: Wild-type C57BL/6J mice were fed a high fat and high cholesterol diet (HFHCD) to induce NASH. Hepatic SMS1 and SMS2 expressions were examined in various mouse models including HFHCD-fed mice and patients with NASH. Pyroptosis was estimated by the generation of the gasdermin-D N-terminal fragment. NASH susceptibility and pyroptosis were examined following knockdown of SMS1, protein kinase Cδ (PKCδ), or the NLR family CARD domain-containing protein 4 (NLRC4). RESULTS: HFHCD increased the hepatic levels of SM and DAG while decreasing the level of phosphatidylcholine. Hepatic expression of Sms1 but not Sms2 was higher in mouse models and patients with NASH. FC in hepatocytes induced Sms1 expression, and Sms1 knockdown prevented HFHCD-induced NASH. DAG produced by SMS1 activated PKCδ and NLRC4 inflammasome to induce hepatocyte pyroptosis. Depletion of Nlrc4 prevented hepatocyte pyroptosis and the development of NASH. Conditioned media from pyroptotic hepatocytes activated the NOD-like receptor family pyrin domain containing 3 inflammasome (NLRP3) in Kupffer cells, but Nlrp3 knockout mice were not protected against HFHCD-induced hepatocyte pyroptosis. CONCLUSION: SMS1 mediates hepatocyte pyroptosis through a novel DAG-PKCδ-NLRC4 axis and holds promise as a therapeutic target for NASH.

16.
Clin Interv Aging ; 15: 2175-2182, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204082

RESUMO

Purpose: The importance of evaluating frailty status of older adults in clinical practice has been gaining attention with cumulative evidence showing its relevance in clinical outcomes and decision-making. We aimed to develop and validate whether the functional age predicted by an electronic continuous short physical performance battery (eSPPB) could predict frailty status. Patients and Methods: We reviewed medical records of outpatients (N=834) of Asan Medical Center, aged 51-95 years. We used the eSPPB data of 717 patients as a development cohort, and that of 117 patients, who also underwent comprehensive geriatric assessments, as a validation cohort. Frailty index was calculated by counting deficits of 45 geriatric items including comorbidities, daily functions, mobility, mood, and cognition. For functional age, we used balance score (0-4), gait speed (m/s), and stand-up time (s) measured 5 times in the chair rise test. Results: From the development cohort, we established a functional age using the formula (83.61 - 1.98*[balance score] - 5.21*[gait speed] + 0.23*[stand-up time]), by multivariate linear regression analysis with chronological age as a dependent variable (R2 = 0.233). In the validation cohort, the functional age positively correlated with frailty index (p < 0.001). C-statistics classifying frailty (defined as frailty index ≥0.25) was higher (p < 0.001) with functional age (0.912) than that with chronological age (0.637). A cut-off functional age of ≥77.2 years maximized Youden's J when screening for frailty, with sensitivity of 94.4% and specificity of 80.8%. Conclusion: A newly developed functional age predictor using eSPPB parameters can predict the frailty status as defined by the deficit accumulation method and may serve as a physical biomarker of human aging.


Assuntos
Idoso Fragilizado/estatística & dados numéricos , Fragilidade/diagnóstico , Estado Funcional , Avaliação Geriátrica/métodos , Desempenho Físico Funcional , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Fragilidade/epidemiologia , Fragilidade/fisiopatologia , Humanos , Masculino , República da Coreia/epidemiologia
17.
Clin Colorectal Cancer ; 19(3): e140-e150, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32402681

RESUMO

INTRODUCTION: Whether patients with resectable colorectal liver metastases (CRLM) gain a survival benefit from perioperative chemotherapy remains controversial. The benefit of including bevacizumab in chemotherapy also remains unclear. MATERIAL AND METHODS: Seventy-six patients with CRLM were randomly assigned to either 6 cycles of FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin)/FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) with bevacizumab before and after surgery or 12 cycles after surgery. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and compared by the log-rank test. RESULTS: The median PFS of all patients was 37.4 months at 5.4 years follow-up, and the median overall survival (OS) was not reached. The PFS between the perioperative group and the postoperative group did not reveal a statistical difference (P = .280). The OS was significantly better in the perioperative group (hazard ratio [HR], 0.60; 95% confidence interval [CI],) 0.35-1.02; P = .049). In subgroup patients with carcinoembryonic antigens (CEA) ≥ 5 ng/mL or those with over 2 liver metastases, perioperative group had longer OS than postoperative group (CEA: HR, 0.49; 95% CI, 0.25-0.93; P = .030; number of liver metastases: HR, 0.55; 95% CI, 0.30-0.99; P = .049). The largest liver metastases size, disease-free interval, and sidedness did not affect PFS or OS. There was no difference between the 2 groups in postoperative complications with bevacizumab or adverse events during chemotherapy. CONCLUSIONS: In patients with resectable CRLMs, perioperative chemotherapy had no effect on PFS, but improved OS. Patients with high CEA levels or over 2 liver metastases may benefit from perioperative chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Camptotecina/análogos & derivados , Neoplasias Colorretais/terapia , Neoplasias Hepáticas/terapia , Terapia Neoadjuvante/estatística & dados numéricos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Antígeno Carcinoembrionário/sangue , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/estatística & dados numéricos , Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Hepatectomia/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Período Perioperatório/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Intervalo Livre de Progressão , Estudos Prospectivos , Tomografia Computadorizada por Raios X
18.
Int J Colorectal Dis ; 35(7): 1273-1282, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32347342

RESUMO

PURPOSE: The high incidence of metachronous colorectal tumours in patients with hereditary non-polyposis colorectal cancer (HNPCC) encourages extended resection (ER); however, the optimal surgical approach remains unclear. We evaluated the incidences of metachronous colorectal neoplasms following curative colorectal cancer segmental resection (SR) vs ER in patients with HNPCC and investigated patients' oncologic outcomes according to surgical modality and mismatch repair status. METHODS: We retrospectively investigated medical records of patients with HNPCC (per the Amsterdam II criteria) treated for primary colon cancer at our institution between 2001 and 2017. All patients underwent intensive endoscopic surveillance. RESULTS: We included 87 patients (36 who underwent SR and 51 who underwent ER). The cumulative incidence of metachronous adenoma was higher in the SR group. One patient in the SR group (2.8%) and 3 in the ER group (5.9%) developed metachronous colon cancer; the difference was not significant (P = 0.693). Four patients in the SR group (11.1%) and 1 in the ER group (2.0%) developed distant recurrences; again, the difference was not significant (P = 0.155). Moreover, no significant differences were observed in the 5-year overall survival rates of patients in the SR and ER groups (88.2% vs 95.5%, P = 0.446); the same was true for 5-year disease-free survival rates (79.5% vs 91.0%, P = 0.147). CONCLUSION: The incidence of metachronous cancer was not significantly different between the ER and SR groups; however, that of cumulative metachronous adenoma was higher in the SR group. Hence, intensive surveillance colonoscopy may be sufficient for patients with HNPCC after non-extensive colon resection.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Colorretais , Segunda Neoplasia Primária , Neoplasias Colorretais Hereditárias sem Polipose/cirurgia , Humanos , Recidiva Local de Neoplasia , Segunda Neoplasia Primária/epidemiologia , Estudos Retrospectivos
19.
Cancer Res Treat ; 52(4): 1135-1144, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32340084

RESUMO

PURPOSE: We evaluated the efficacy and safety of avelumab, an anti-PD-L1 antibody, in patients with metastatic or unresectable colorectal cancer (mCRC) with mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) or POLE mutations. Materials and Methods: In this prospective, open-label, multicenter phase II study, 33 patients with mCRC harboring dMMR/MSI-H or POLE mutations after failure of ≥1st-line chemotherapy received avelumab 10 mg/kg every 2 weeks. dMMR/MSI-H was confirmed with immunohistochemical staining (IHC) by loss of expression of MMR proteins or polymerase chain reaction (PCR) for microsatellite sequences. POLE mutation was confirmed by next-generation sequencing (NGS). The primary endpoint was the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors ver. 1.1. RESULTS: The median age was 60 years, and 78.8% were male. Thirty patients were dMMR/MSI-H and three had POLE mutations. The ORR was 24.2%, and all of the responders were dMMR/MSI-H. For 21 patients with MSI-H by PCR or NGS, the ORR was 28.6%. At a median follow-up duration of 16.3 months, median progression-free survival and overall survival were 3.9 and 13.2 months in all patients, and 8.1 months and not reached, respectively, in patients with MSI-H by PCR or NGS. Dose interruption and discontinuation due to treatment-related adverse events occurred in four and two patients, respectively, with no treatment-related deaths. CONCLUSION: Avelumab displayed antitumor activity with manageable toxicity in patients with previously treated mCRC harboring dMMR/MSI-H. Diagnosis of dMMR/MSI-H with PCR or NGS could be complementary to IHC to select patients who would benefit from immunotherapy.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , DNA Polimerase II/genética , Proteínas de Ligação a Poli-ADP-Ribose/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Reparo de Erro de Pareamento de DNA , Feminino , Seguimentos , Humanos , Infusões Intravenosas , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Mutação , Intervalo Livre de Progressão , Estudos Prospectivos
20.
Oncologist ; 25(3): e502-e511, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32162799

RESUMO

BACKGROUND: Polypharmacy is an important issue in the care of older patients with cancer, as it increases the risk of unfavorable outcomes. We estimated the prevalence of polypharmacy, potentially inappropriate medication (PIM) use, and drug-drug interactions (DDIs) in older patients with cancer in Korea and their associations with clinical outcomes. SUBJECTS, MATERIALS, AND METHODS: This was a secondary analysis of a prospective observational study of geriatric patients with cancer undergoing first-line palliative chemotherapy. Eligible patients were older adults (≥70 years) with histologically diagnosed solid cancer who were candidates for first-line palliative chemotherapy. All patients enrolled in this study received a geriatric assessment (GA) at baseline. We reviewed the daily medications taken by patients at the time of GA before starting chemotherapy. PIMs were assessed according to the 2015 Beers criteria, and DDIs were assessed by a clinical pharmacist using Lexi-comp Drug Interactions. We evaluated the association between polypharmacy and clinical outcomes including treatment-related toxicity, and hospitalization using logistic regression and Cox regression analyses. RESULTS: In total, 301 patients (median age 75 years; range, 70-93) were enrolled; the most common cancer types were colorectal cancer (28.9%) and lung cancer (24.6%). Mean number of daily medications was 4.7 (±3.1; range, 0-14). The prevalence of polypharmacy (≥5 medications) was 45.2% and that of excessive polypharmacy (≥10 medications) was 8.6%. PIM use was detected in 137 (45.5%) patients. Clinically significant DDIs were detected in 92 (30.6%) patients. Polypharmacy was significantly associated with hospitalization or emergency room (ER) visits (odds ratio: 1.73 [1.18-2.55], p < .01). Neither polypharmacy nor PIM use showed association with treatment-related toxicity. CONCLUSION: Polypharmacy, PIM use, and potential major DDIs were prevalent in Korean geriatric patients with cancer. Polypharmacy was associated with a higher risk of hospitalization or ER visits during the chemotherapy period. IMPLICATIONS FOR PRACTICE: This study, which included 301 older Korean patients with cancer, highlights the increased prevalence of polypharmacy in this population planning to receive palliative chemotherapy. The prevalence of polypharmacy and excessive polypharmacy was 45.2% and 8.6%, respectively. The prescription of potentially inappropriate medications (PIMs) was detected in 45.5% and clinically significant drug-drug interaction in 30.6% of patients. Given the association of polypharmacy with increased hospitalization or emergency room visits, this study points to the need for increased awareness and intervention to minimize polypharmacy in the geriatric cancer population undergoing chemotherapy. Moreover, specific criteria for establishing PIMs should be adopted for the treatment of older adults with cancer.


Assuntos
Neoplasias , Polimedicação , Idoso , Interações Medicamentosas , Humanos , Prescrição Inadequada , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Lista de Medicamentos Potencialmente Inapropriados , República da Coreia/epidemiologia , Fatores de Risco
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