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1.
Eur Geriatr Med ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587613

RESUMO

PURPOSE: Determining the strength and area of the swallowing muscles is important in patients with sarcopenic dysphagia. Although the normative data on the strength of the swallowing muscles have been reported, those of the area of the geniohyoid muscle are poorly investigated. We investigated the cross-sectional area of the geniohyoid muscle in Japanese subjects without dysphagia using ultrasonography to determine the normative and cut-off values. METHODS: 142 subjects without dysphagia were included. The older group (age ≥ 65 years) included 36 (women 27/men 9) subjects, and the younger group (age ≤ 39 years) included 106 (women 54/men 52) subjects. The cross-sectional area of the geniohyoid muscle was measured by ultrasound. The mean of the younger group-2 standard deviation (SD) was calculated and used as a cut-off value for low swallowing muscle mass. RESULTS: The mean (SD) of the area of the geniohyoid muscle of each group was as follows: older women group 167.2 (32.6) mm2, older men group 193.2 (49.5) mm2, younger women group 247.3 (37.4) mm2, younger men group 313.1 (59.2) mm2. The mean 2SD of the geniohyoid muscle area in the younger women group was 172.5 mm2 and in the younger men group 194.7 mm2. CONCLUSION: We found that the cut-off value of the ultrasonographic cross-sectional area of the geniohyoid muscle was 172.5 mm2 for women and 194.7 mm2 for men. These values could be used as cut-off values for the mass of the geniohyoid muscle to identify patients with sarcopenic dysphagia.

2.
Nutrition ; 124: 112438, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38657417

RESUMO

OBJECTIVES: In this study, we aimed to investigate the prevalence of oral frailty and explore its relationship with oral function and sarcopenia among older outpatients. MATERIALS AND METHODS: In this cross-sectional study, we retrospectively included older patients who visited a frailty outpatient clinic. We assessed total oral frailty employing, among other measures, oral diadochokinesis (/ta/ sound) for tongue-lip movement and tongue pressure. Patients who did not meet the cut-off values for three or more of these were classified as having oral frailty. Sarcopenia was assessed according to Asian Working Group for Sarcopenia 2019 criteria and analyzed for the relationship with oral function. RESULTS: The mean ± standard deviation age of the 111 patients was 77.2 ± 5.7 y; 63 were women (57%). Fifteen patients (14%) had either sarcopenia or dynapenia. The overall prevalence of oral frailty was 38%, with no significant difference in its prevalence between the sarcopenia/dynapenia group (44%) and the robust (no sarcopenia/dynapenia) group (35%). The following oral function assessments significantly differed between the sarcopenia/dynapenia group and the robust group: median (interquartile range) total oral frailty score, 2 (2-4) and 2 (1-3) (P = 0.019); tongue-lip motor function, 5.4 ± 1.2 and 5.9 ± 1.2 times/s (P = 0.049); and tongue pressure, 27.3 ± 8.5 kPa and 31.7 ± 8.0 kPa (P = 0.009). CONCLUSIONS: Approximately 40% of patients exhibited a decline in oral function regardless of the presence of sarcopenia. Sarcopenia and dynapenia may particularly affect tongue function. Although assessing patients for sarcopenia is crucial, separate evaluations of oral function should also be considered.

3.
Microscopy (Oxf) ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38662358

RESUMO

High-pressure water freeze fracturing (HPWFF) is a method for preparing water-containing samples such as hydrogels for scanning electron microscopy, in which a sample is placed in a divisible pressure vessel, filled with water, sealed, frozen with liquid nitrogen, then vacuum dried after the vessel is divided. The pressure (about 200 MPa) generated by the phase transition from water to ice is expected to inhibit ice crystal formation that causes large deformation of microstructure in the sample. To maximize the useable sample size, where SEM observation is not affected by ice crystal growth, preparation conditions including the size of pressure vessel were examined in this work. Using pressure vessels 8.0 mm, 5.5 mm and 4.5 mm in diameter, agarose gel, gelatin gel, wheat starch hydrogel, wheat flour noodle and cellulose hydrogel were used to prepare SEM samples. With agarose gel, an area of 3.6 mm in diameter in the 5.5 mm vessel was achieved as the maximum size of the area observable without ice crystal growth. The observable size of other samples was comparable, except for gelatin gel. As a result, observation of the three-dimensional network structure of hydrogels could be performed over a wider range than with the conventional method without shredding or chemical treatment of the samples. Additionally, usability of agarose gel for sample support matrix in HPWFF was demonstrated.

4.
Ann Geriatr Med Res ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38475664

RESUMO

Background: The association of the combination of body mass index (BMI) and weight change at admission with prognoses in patients with heart failure (HF) is unclear. Therefore, we investigated whether body mass index (BMI) and weight changes at admission affect mortality in patients with HF. Methods: This retrospective cohort study lasted 99 months, starting in April 2014, and included 4,862 patients with HF from a Japanese real-world database. Cubic and thin-plate smoothing spline analyses were performed to investigate the association of BMI and weight changes with mortality. The percentage weight change was calculated every 6 months. The study outcome was the presence or absence of death. Results: The patients' mean age was 81.5±9.6 years, and 1,239 (25.5%) patients died. Cubic spline analysis revealed a negative correlation of BMI with mortality hazard ratio (HR) (BMI=18.5 kg/m2 and 25 kg/m2; HR=1.3 [1.2-1.4] and 0.8 [0.7-0.9], respectively). Cubic spline analysis of weight change showed that weight loss tended to increase the mortality HR (weight change rate=-6%, HR=1.1 [1.0-1.2]). Thin-plate smoothing spline analysis showed that the odds ratio (OR) negatively correlated with BMI (1-year mortality: BMI=18.5 kg/m2, 22 kg/m2, and 25 kg/m2; OR at 0% weight change=1.5, 1.0, and 0.7, respectively; 2-year mortality: BMI=18.5 kg/m2, 22 kg/m2, and 25 kg/m2; OR at 0% weight change=1.4, 0.9, and 0.7, respectively). Conclusion: A low BMI in patients with HF was associated with a higher risk of mortality. Weight loss in patients, regardless of BMI, was associated with a higher OR for mortality.

6.
Eur Geriatr Med ; 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38340283

RESUMO

PURPOSE: Frailty and hospitalization-associated disabilities (HAD) are geriatric conditions that should be managed in older patients undergoing pancreatectomy. The Hospital Frailty Risk Score (HFRS) can evaluate frailty based on medical records and could predict postoperative activities of daily living (ADL) decline. This study aimed to investigate whether HFRS affects the postoperative incidence of HAD in older patients who underwent pancreatectomy. METHODS: This retrospective, observational study used data from a nationwide hospital-based database. We included consecutive patients aged ≥ 65 years who were diagnosed with pancreatic cancer (International Statistical Classification of Diseases, 10th revision code C25) and underwent curative pancreatectomy between April 2014 and August 2020. We evaluated preoperative frailty using HFRS. The primary outcome was HAD following pancreatectomy. Logistic regression analysis was performed for analyzing the impact of frailty on HAD following pancreatectomy. RESULTS: We included 671 patients for the analysis (mean age 74.3 ± 5.6, male 54.8%). The prevalence of intermediate and high risk of frailty with HFRS ≥ 5 was 2.7%. The incidence of HAD was significantly higher in the intermediate- and high-risk groups compared to that in the low-risk group (33.3% vs. 8.4%, p < 0.001). Logistic regression analysis demonstrated that intermediate and high risks of frailty increased the likelihood of HAD (odds ratio, 3.55; 95% confidence interval: 1.12-11.2). CONCLUSIONS: The risk of frailty evaluated using the HFRS increased the likelihood of developing HAD in older patients undergoing pancreatectomy. Future research on effective perioperative interventions for preventing postoperative HAD and enhancing postoperative ADL recovery is warranted.

7.
Ann Geriatr Med Res ; 28(1): 86-94, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38229436

RESUMO

BACKGROUND: Although the relationship between medication status, symptomatology, and outcomes has been evaluated, data on the prevalence of polypharmacy and potentially inappropriate medications (PIMs) and the association of polypharmacy and PIMs with swallowing function during follow-up are limited among hospitalized patients aged ≥65 years with dysphagia. METHODS: In this 19-center cohort study, we registered 467 inpatients aged ≥65 years and evaluated those with the Food Intake LEVEL Scale (FILS) scores ≤8 between November 2019 and March 2021. Polypharmacy was defined as prescribing ≥5 medications and PIMs were identified based on the 2023 Updated Beers Criteria. We applied a generalized linear regression model to examine the association of polypharmacy and PIMs with FILS score at discharge. RESULTS: We analyzed 399 participants (median age, 83.0 years; males, 49.8%). The median follow-up was 51.0 days (interquartile range, 22.0-84.0 days). Polypharmacy and PIMs were present in 67.7% of and 56.1% of patients, respectively. After adjusting for covariates, neither polypharmacy (ß = 0.05; 95% confidence interval [CI], -0.04-0.13, p=0.30) nor non-steroidal anti-inflammatory medications (ß = 0.09; 95% CI, -0.02-0.19; p=0.10) were significantly associated with FILS score at discharge. CONCLUSION: The results of this study indicated a high proportion of polypharmacy and PIMs among inpatients aged ≥65 years with dysphagia. Although these prescribed conditions were not significantly associated with swallowing function at discharge, our findings suggest the importance of regularly reviewing medications to ensure the appropriateness of prescriptions when managing older inpatients.

8.
Biochem Biophys Rep ; 37: 101607, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38178924

RESUMO

Renal artery stenosis-induced chronic renal ischemia is an important cause of renal dysfunction, especially in older adults, and its incidence is currently increasing. To elucidate the mechanisms underlying chronic renal hypoperfusion-induced kidney damage, we developed a novel mouse model of renal artery coiling-based chronic hypoperfusion-related kidney injury. This model exhibits decreased renal blood flow and function, atrophy, and parenchymal injury in the coiled kidney, along with compensatory hypertrophy in the non-coiled kidney, without chronic hypertension. The availability of this mouse model, which can develop renal ischemia without genetic modification, will enhance kidney disease research by serving as a new tool to investigate the effects of acquired factors (e.g., obesity and aging) and genetic factors on renal artery stenosis-related renal parenchymal damage.

9.
Exp Anim ; 73(1): 93-100, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-37661429

RESUMO

Exocyst is an octameric protein complex implicated in exocytosis. The exocyst complex is highly conserved among mammalian species, but the physiological function of each subunit in exocyst remains unclear. Previously, we identified exocyst complex component 3-like (Exoc3l) as a gene abundantly expressed in embryonic endothelial cells and implicated in the process of angiogenesis in human umbilical cord endothelial cells. Here, to reveal the physiological roles of Exoc3l during development, we generated Exoc3l knockout (KO) mice by genome editing with CRISPR/Cas9. Exoc3l KO mice were viable and showed no significant phenotype in embryonic angiogenesis or postnatal retinal angiogenesis. Exoc3l KO mice also showed no significant alteration in cholesterol homeostasis or insulin secretion, although several reports suggest an association of Exoc3l with these processes. Despite the implied roles, Exoc3l KO mice exhibited no apparent phenotype in vascular development, cholesterol homeostasis, or insulin secretion.


Assuntos
Mutação com Perda de Função , Proteínas de Transporte Vesicular , Animais , Camundongos , Humanos , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo , Células Endoteliais/metabolismo , Secreção de Insulina , Colesterol , Mamíferos/metabolismo
10.
J Hum Nutr Diet ; 37(1): 227-233, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37805824

RESUMO

BACKGROUND: Consuming texture-modified diets was considered to negatively affect health-related quality of life (HR-QoL). However, the precise relationship between the levels of food texture consumed and HR-QoL remains uncertain. The present study aimed to determine the association between levels of food texture consumed and HR-QoL. METHODS: This cross-sectional study included 122 hospitalised patients aged ≥ 65 years (mean ± SD age 78.9 ± 7.9 years; 48.4% female) who required postacute rehabilitation. Consumed food texture levels were classified using the International Dysphagia Diet Standardization Initiative (IDDSI) framework 2.0. HR-QoL was evaluated using the five-level EuroQoL five-dimension (EQ-5D-5L). The association between food texture levels and HR-QoL was analysed using a multivariate linear regression model. RESULTS: The lower food texture levels consumed were associated with significantly lower EQ-5D-5L scores. Consumption of pureed (IDDSI Level 4) and liqudised (IDDSI Level 3) diets were associated with lower EQ-5D-5L scores among older patients undergoing postacute rehabilitation (regression coefficient -0.304; 95% confidence interval = -0.472 to -0.137 and regression coefficient, -0.444, 95% confidence interval = -0.676 to -0.213, respectivly). CONCLUSIONS: The findings suggest a link between the consumption of pureed and liquidised diets and lower HR-QoL scores in older hospitalised patients undergoing rehabilitation. To establish a clearer cause-and-effect relationship, future research should encompass multicentre and longitudinal studies, building upon the insights from the present study.


Assuntos
Alimentos , Qualidade de Vida , Idoso , Feminino , Humanos , Masculino , Estudos Transversais , Dieta , Projetos Piloto , Inquéritos e Questionários , Idoso de 80 Anos ou mais
11.
J Cachexia Sarcopenia Muscle ; 15(1): 370-379, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38115133

RESUMO

BACKGROUND: Recently, the Asian Working Group for Cachexia (AWGC) published a consensus statement on diagnostic criteria for cachexia in Asians. We aimed to validate the criteria in adult patients in Japan with advanced cancer. METHODS: We conducted a single-institution retrospective cohort study between April 2021 and October 2022. The AWGC criteria include chronic comorbidities and either a weight loss of >2% over 3-6 months or a body mass index (BMI) of <21 kg/m2 . In addition, any of the following items were required: anorexia as a subjective symptom, decreased grip strength as an objective measurement and an elevated C-reactive protein (CRP) level as a biomarker. We used the cut-off value of grip strength of 28/18 kg for male/female individuals and CRP level of 5 mg/L. RESULTS: Of the 449 consecutive patients, 85 of those who could not be evaluated because of end-of-life or refractory symptoms (n = 41) or missing data (n = 44) were excluded from the primary analysis. The prevalence of the AWGC-defined cachexia was 76% (n = 277), and the median survival time (MST) for all patients was 215 (95% confidence interval [CI] 145-270) days. The prevalence of the following criteria was significantly higher in patients with cachexia than in those without cachexia: a BMI of <21 kg/m2 (65% vs. 15%, P < 0.001), a weight loss of >2% in 6 months (87% vs. 14%, P < 0.001), anorexia (75% vs. 47%, P < 0.001), a grip strength of <28 kg in male individuals (63% vs. 28%, P < 0.001) and CRP level of >5 mg/L (85% vs. 56%, P < 0.001). Overall survival was significantly shorter in patients with cachexia than in those without cachexia (MST 157 days, 95% CI 108-226 days vs. MST 423 days, 95% CI 245 days to not available, P = 0.0023). The Cox proportional hazards analysis showed that best supportive care (hazard ratio [HR] 2.91, P ≤ 0.001), lung cancer (HR 1.67, P = 0.0046), an Eastern Cooperative Oncology Group Performance Status score of ≥3 (HR 1.58, P = 0.016), AWGC-defined cachexia (HR 1.56, P = 0.015), an age of ≥70 years (HR 1.53, P = 0.0070), oedema (HR 1.31, P = 0.022) and head/neck cancer (HR 0.44, P = 0.023) were found to be the significant predictors for mortality. CONCLUSIONS: We demonstrated that AWGC-defined cachexia has a significant prognostic value in advanced cancer.


Assuntos
Caquexia , Neoplasias Pulmonares , Adulto , Humanos , Masculino , Feminino , Idoso , Caquexia/diagnóstico , Caquexia/epidemiologia , Caquexia/etiologia , Estudos Retrospectivos , Anorexia/complicações , Redução de Peso , Neoplasias Pulmonares/complicações
12.
Clin Oral Investig ; 27(12): 7635-7642, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37953327

RESUMO

OBJECTIVE: To assess the associations between oral health status and short-term functional outcomes in hospitalized patients aged over 65 years with acute ischemic stroke. MATERIALS AND METHODS: This retrospective observational analysis included older adult patients (age, ≥ 65 years) admitted for acute ischemic stroke. The oral health status at admission was evaluated using the Oral Health Assessment Tool (OHAT). Patients were categorized into the normal oral health (OHAT score, 0-2) or poor oral health (OHAT score, ≥ 3) group. Stroke severity, Functional Oral Intake Scale (FOIS), and medical history were compared. Multivariate analysis was used to determine the association between the OHAT score and modified Rankin Scale (mRS) score at discharge, FOIS score at discharge, and length of hospital stay. RESULTS: The study comprised 129 patients (mean age: 78.8 ± 7.7 years). The poor oral health group (n = 22) had a higher stroke severity and lower FOIS scores than the normal oral health group (n = 107). The poor oral health group exhibited significantly higher rates of moderate to severe disability at discharge (odds ratio = 9.18, 95% confidence interval [CI]: 1.74-48.30, P = 0.009), lower FOIS scores at discharge (ß = -0.96, 95% CI: -1.71 to -0.20, P = 0.014), and longer hospital stays (ß = 10.70, 95% CI: 0.80-20.61, P = 0.034) than the other group. CONCLUSION: In older patients with acute ischemic stroke, poor oral health status at admission was associated with worse short-term functional outcomes, including increased disability, dysphagia, and longer hospital stay. CLINICAL RELEVANCE: Assessing and addressing the oral health status of this population can potentially improve short-term functional outcomes and enhance comprehensive stroke care.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Saúde Bucal , AVC Isquêmico/complicações , Hospitalização
13.
Artigo em Inglês | MEDLINE | ID: mdl-37998296

RESUMO

Japanese diet adherence has been inversely correlated with muscle weakness. In this study, we aimed to validate that association. Longitudinal data from 1699 individuals aged ≥50 years (mean age 62.5 ± 6.9 years, 50.4% female) at two time points (2007 and 2011) were used. Participants without muscle weakness from several regions in Japan were included. The 12-component revised Japanese Diet Index (rJDI12) classified by tertiles assessed adherence to the Japanese dietary pattern. Muscle weakness was defined as a handgrip strength of ˂18 kg for females and ˂28 kg for males based on the Asian Working Group for Sarcopenia criteria 2019. A multivariate logistic approach was used to determine the relationship between rJDI12 tertile and the occurrence of muscle weakness by calculating the odds ratio (OR) and its 95% confidence interval (95% CI) throughout the observation period. Muscle weakness was negatively correlated with the highest rJDI12 tertile (OR [95% CI] 0.891 [0.814, 0.973] for T3). This association was consistent in sensitivity analyses with multiple imputations of missing values. Closely following the Japanese dietary pattern appears to reduce the occurrence of muscle weakness among the aging population in this study, suggesting it may prevent frailty and sarcopenia in the aging population.


Assuntos
Dieta , Sarcopenia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Coortes , População do Leste Asiático , Força da Mão , Debilidade Muscular/epidemiologia , Sarcopenia/epidemiologia
14.
Nutrients ; 15(20)2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37892446

RESUMO

Sarcopenic dysphagia (SD) is an emerging concern in geriatric medicine. This study aimed to identify the prevalence, progression, and distinct attributes of SD in patients in the Department of Geriatric Medicine. Older adult patients admitted between 2021 and 2022 were enrolled. The department conducts a comprehensive geriatric assessment (CGA) combined with a multidisciplinary team-based intervention, setting the standard for medical care. We diligently assessed the occurrence and development of dysphagia at both the admission and discharge phases. Of the 180 patients analyzed (38.9% male, mean age 86.0 ± 6.6 years), 22.8% were diagnosed with SD at admission, thrice the rate of other dysphagia variants. Only one patient had new-onset dysphagia during hospitalization, attributed to SD. Patients with SD showed a better recovery rate (18.9%) than those with other dysphagia types. Patients with diminished swallowing capacity had compromised nutritional profiles, diminished energy and protein consumption, and extended fasting durations. Although sarcopenia is a prevalent inducer of dysphagia in older adults, an integrated approach in geriatric medicine involving rehabilitation, nutrition, and dentistry is pivotal. Strategies rooted in CGA promise potential for addressing dysphagia.


Assuntos
Transtornos de Deglutição , Sarcopenia , Humanos , Masculino , Idoso , Idoso de 80 Anos ou mais , Feminino , Transtornos de Deglutição/epidemiologia , Prevalência , Estado Nutricional , Sarcopenia/epidemiologia , Sarcopenia/reabilitação , Deglutição
15.
Biochem Pharmacol ; 218: 115899, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37907138

RESUMO

Ras homolog gene family member A (RhoA) belongs to the Rho GTPase superfamily, which was first studied in cancers as one of the essential regulators controlling cellular function. RhoA has long attracted attention as a key molecule involved in cell signaling and gene transcription, through which it affects cellular processes. A series of studies have demonstrated that RhoA plays crucial roles under both physiological states and pathological conditions in cardiovascular diseases. RhoA has been identified as an important regulator in cardiac remodeling by regulating actin stress fiber dynamics and cytoskeleton formation. However, its underlying mechanisms remain poorly understood, preventing definitive conclusions being drawn about its protective role in the cardiovascular system. In this review, we outline the characteristics of RhoA and its related signaling molecules, and present an overview of RhoA classical function and the corresponding cellular responses of RhoA under physiological and pathological conditions. Overall, we provide an update on the novel signaling under RhoA in the cardiovascular system and its potential clinical and therapeutic targets in cardiovascular medicine.


Assuntos
Sistema Cardiovascular , Quinases Associadas a rho , Actinas/metabolismo , Sistema Cardiovascular/metabolismo , Proteínas rho de Ligação ao GTP , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/genética , Proteína rhoA de Ligação ao GTP/metabolismo , Transdução de Sinais/fisiologia , Humanos
16.
Clin Nutr ESPEN ; 57: 494-500, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37739697

RESUMO

BACKGROUND & AIMS: Data regarding the delivery of nutrition and nutritional infusions to patients with terminal cancer remain limited; therefore, this real-world analysis investigated differences in nutrition delivery and infusion statuses for patients with terminal-stage cancers. METHODS: Patients who had died following hospitalization for more than seven days due to neoplasms between April 2014 and December 2018 were identified using the medical claims database of Japan. Data regarding oral diets, enteral feeding, infusion volumes, and infusion energies were extracted. The maximum observation period was 28 days prior to patient death. RESULTS: A total of 12,908 patients were included in our analysis. The proportion of patients without dietary or enteral nutrition increased closer to their dates of death. Observations were recorded at 28 (18.9%), 21 (20.9%), 14 (24.6%), 7 (33.0%), and 0 (80.2%) days prior to death. The infusion volumes given to the patients, as well as their energy contents, decreased near death (P-value for the trend <0.001). CONCLUSIONS: Our study revealed the current status of nutritional therapy for patients with terminal cancer in Japan. The number of patients receiving only parenteral nutrition increased near death, while the amount of nutritional intake was low.


Assuntos
Ingestão de Alimentos , Estado Nutricional , Humanos , Bases de Dados Factuais , Nutrição Enteral , Hospitalização
17.
Sci Rep ; 13(1): 15649, 2023 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-37730951

RESUMO

Familial hypercholesterolemia (FH) is an inherited autosomal dominant disorder that is associated with a high plasma level of low-density lipoprotein (LDL) cholesterol, leading to an increased risk of cardiovascular diseases. To develop basic and translational research on FH, we here generated an FH model in a non-human primate (cynomolgus monkeys) by deleting the LDL receptor (LDLR) gene using the genome editing technique. Six LDLR knockout (KO) monkeys were produced, all of which were confirmed to have mutations in the LDLR gene by sequence analysis. The levels of plasma cholesterol and triglyceride were quite high in the monkeys, and were similar to those in FH patients with homozygous mutations in the LDLR gene. In addition, periocular xanthoma was observed only 1 year after birth. Lipoprotein profile analysis showed that the plasma very low-density lipoprotein and LDL were elevated, while the plasma high density lipoprotein was decreased in LDLR KO monkeys. The LDLR KO monkeys were also strongly resistant to medications for hypercholesterolemia. Taken together, we successfully generated a non-human primate model of hypercholesterolemia in which the phenotype is similar to that of homozygous FH patients.


Assuntos
Traumatismos Craniocerebrais , Hipercolesterolemia , Hiperlipoproteinemia Tipo II , Animais , Humanos , Primatas , Hiperlipoproteinemia Tipo II/genética , Lipoproteínas LDL , Macaca fascicularis
18.
Pancreas ; 52(4): e249-e255, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37747930

RESUMO

OBJECTIVES: Frailty risk may be associated with poor prognoses in acute pancreatitis patients. However, this has not been shown with adjustments for prognosis-related factors. This study aimed to determine whether frailty risk is associated with poor prognoses in acute pancreatitis patients, even after adjusting for prognosis-related factors. METHODS: The study included 7001 middle-aged and older patients (mean age, 66.2 ± 14.5 years, 65.3% male) 40 years or older who were registered in a Japanese nationwide database. Frailty risk was defined as a Hospital Frailty Risk Score ≥5 points. Outcomes were 30-day and in-hospital mortality, length of stay, and 30-day readmission rate. RESULTS: Frailty risk was independently positively associated with 30-day mortality (odds ratio [OR], 1.847; 95% confidence interval [CI], 1.118-3.051) and in-hospital mortality (OR, 2.504; 95% CI, 1.677-3.739) after adjustment for acute pancreatitis severity and patient characteristics. In addition, frailty risk was positively associated with a longer length of stay (coefficient, 11.393; 95% CI, 9.631-13.154). However, no association was found between frailty risk and the 30-day readmission rate (OR, 1.092; 95% CI, 0.793-1.504). CONCLUSIONS: Our findings highlight the importance of rapid and automated frailty risk assessment using the Hospital Frailty Risk Score for the early identification of high-risk acute pancreatitis patients.


Assuntos
Fragilidade , Pancreatite , Pessoa de Meia-Idade , Humanos , Masculino , Idoso , Idoso de 80 Anos ou mais , Feminino , Fragilidade/diagnóstico , Pancreatite/diagnóstico , Estudos Retrospectivos , Japão/epidemiologia , Doença Aguda , Fatores de Risco , Hospitais , Mortalidade Hospitalar , Prognóstico , Tempo de Internação
19.
Nutrition ; 116: 112147, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37544191

RESUMO

OBJECTIVES: This study aimed to investigate body mass index (BMI) and rate of weight change associated with adverse outcomes in Asian patients with chronic kidney disease. METHODS: A retrospective cohort study was performed between April 2014 and June 2022 using the administrative claims database compiled by the Japan Medical Data Center. Patients were defined as individuals with comorbidities with chronic kidney disease stages 3 to 5 on admission and were aged ≥40 y with BMI at admission and BMI information from a previous admission 3 to 12 mo earlier. Restricted cubic spline analysis and thin-plate smoothed spline analysis were performed. RESULTS: A total of 10 802 individuals were analyzed. The mean age was 74.6 ± 11.3 y, number of men was 7175 (66.4%), and 2115 (19.6%) deaths were recorded. Smoothed splines for BMI found that low BMI was associated with high hazard ratio (HR) (BMI = 18.5 kg/m2; HR = 1.3 [1.2-1.4]). Smoothed splines of weight change found higher HR with increasing rate of weight change for both weight gain and loss (weight change rate = -10%; HR = 1.4 [1.3-1.5]; weight change rate = 10%; HR = 1.2 [1.1-1.3]). In thin-plate smoothed spline analysis, the U-curve had a higher odds ratio as BMI decreased in patients with or without dialysis and as the degree of weight change increased. CONCLUSIONS: We found trends in BMI and rate of weight change associated with mortality in Asian patients with chronic kidney disease.


Assuntos
População do Leste Asiático , Insuficiência Renal Crônica , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Massa Corporal , Estudos Retrospectivos , Fatores de Risco , Feminino
20.
Nutrition ; 115: 112152, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37544211

RESUMO

OBJECTIVE: Conventional diagnostic criteria for cachexia are based on Western studies. The aim of this study was to investigate trends in body mass index (BMI) and the rate of weight change associated with adverse outcomes in Asian patients with advanced cancer. METHODS: This retrospective cohort study was conducted using the administrative claims database compiled by the Japan Medical Data Center Inc. The study was conducted between April 2014 and September 2022 on patients with advanced cancer. A Cox regression model was used to perform a restricted cubic spline analysis with four knots for BMI and weight change. Additionally, thin-plate smoothed splines were used to generate contour plots of the odds ratios of BMI and weight change for mortality. RESULTS: The study analyzed 48 600 patients. The mean age was 71.9 ± 10 y. There were 33 051 men (68%) and 17 853 deaths (37%). The smoothed splines for BMI showed that low BMI was associated with high hazard ratio (HR, [95% confidence interval]; BMI = 18.5 kg/m2, HR, 1.2; [1.1-1.2]; BMI = 25 kg/m2, HR, 0.9; [0.9-0.9]). The smoothed spline of weight change showed a higher HR with an increasing rate of weight change (weight change rate -10%, HR, 1.1; [1.1-1.2]; weight change rate +10%, HR, 1; [1-1]). In the thin-plate smoothed spline analysis, patients with BMI <17 to 18.5 kg/m2 were at a higher risk for death regardless of weight change. CONCLUSIONS: Low BMI, a large degree of weight change, or a combination of both, predicted death in Asian patients with advanced cancer.

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