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Protein growth differentiation factor 11 (GDF11) plays crucial roles in cellular processes, including differentiation and development; however, its clinical relevance in breast cancer patients is poorly understood. We enrolled 68 breast cancer patients who underwent surgery at our hospital and assessed the expression of GDF11 in tumorous, ductal carcinoma in situ (DCIS), and non-tumorous tissues using immunohistochemical staining, with interpretation based on histochemical scoring (H-score). Our results indicated higher GDF11 expressions in DCIS and normal tissues compared to tumorous tissues. In addition, the GDF11 H-score was lower in the patients with a tumor size ≥ 2 cm, pathologic T3 + T4 stages, AJCC III-IV stages, Ki67 ≥ 14% status, HER2-negative, and specific molecular tumor subtypes. Notably, the patients with triple-negative breast cancer exhibited a loss of GDF11 expression. Spearman correlation analysis revealed associations between GDF11 expression and various clinicopathological characteristics, including tumor size, stage, Ki67, and molecular subtypes. Furthermore, GDF11 expression was positively correlated with mean corpuscular hemoglobin concentration and negatively correlated with neutrophil count, as well as standard deviation and coefficient of variation of red cell distribution width. These findings suggest that a decreased GDF11 expression may play a role in breast cancer pathogenesis.
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BACKGROUND: Chronic kidney disease (CKD) affects around 10% of the global population and has been estimated to affect around 50% of individuals with type 2 diabetes and 50% of those with heart failure. The guideline-recommended approach is to manage with disease-modifying therapies, but real-world data suggest that prescribing rates do not reflect this in practice. OBJECTIVE: To develop a cross-specialty consensus on optimal management of the patient with CKD using a modified Delphi method. DESIGN: An international steering group of experts specialising in internal medicine, endocrinology/diabetology, nephrology and primary care medicine developed 42 statements on aspects of CKD management including identification and screening, risk factors, holistic management, guidelines, cross-specialty alignment and education. Consensus was determined by agreement using an online survey. PARTICIPANTS: The survey was distributed to cardiologists, nephrologists, endocrinologists and primary care physicians across 11 countries. MAIN OUTCOMES AND MEASURES: The threshold for consensus agreement was established a priori by the steering group at 75%. Stopping criteria were defined as a target of 25 responses from each country (N=275), and a 4-week survey period. RESULTS: 274 responses were received in December 2022, 25 responses from Argentina, Australia, Brazil, Guatemala, Mexico, Singapore, South Korea, Taiwan, Thailand, Turkey and 24 responses from Egypt. 53 responses were received from cardiologists, 52 from nephrologists, 55 from endocrinologists and 114 from primary care physicians. 37 statements attained very high agreement (≥90%) and 5 attained high agreement (≥75% and <90%). Strong alignment between roles was seen across the statements, and different levels of experience (2-5 years or 5+ years), some variation was observed between countries. CONCLUSIONS: There is a high degree of consensus regarding aspects of CKD management among healthcare professionals from 11 countries. Based on these strong levels of agreement, the steering group derived 12 key recommendations focused on diagnosis and management of CKD.
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Diabetes Mellitus Tipo 2 , Nefrología , Insuficiencia Renal Crónica , Humanos , Consenso , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/terapia , Nefrólogos , Nefrología/métodosRESUMEN
AIM: To assess the role of hyperfiltration for diabetic kidney disease (DKD) progression. MATERIALS AND METHODS: A retrospective observational cohort study enrolled type 2 diabetes (T2D) patients with an initial estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73m2 or higher. Patients were categorized into two groups: hyperfiltration (eGFR exceeding the age- and gender-specific 95th percentile values from a prior national cohort study) and normofiltration. Rapid DKD progression was defined as an eGFR decline of more than 5 mL/min/1.73m2/year. We used a linear mixed effect model and Cox regression with time-varying covariate model to compare eGFR changes and identify factors associated with rapid DKD progression. RESULTS: Of the enrolled 7563 T2D patients, 7.2% had hyperfiltration. The hyperfiltration group exhibited a higher rate of eGFR decline compared with the normofiltration group (-2.0 ± 0.9 vs. -1.1 ± 0.9 mL/min/1.73m2/year; P < .001). During an average follow-up period of 4.65 ± 3.86 years, 24.7% of patients with hyperfiltration experienced rapid DKD progression, compared with 15.7% of patients with normofiltration (P < .001). Cox regression analyses identified that initial hyperfiltration was a significant determinant of rapid DKD progression, with a hazard ratio of 1.66 (95% confidence interval: 1.41-1.95; P < .001). When combined with albuminuria, the risk of progression was further compounded (hazard ratio 1.76-3.11, all P < .001). CONCLUSIONS: In addition to using the current Kidney Disease: Improving Global Outcomes CGA classification system, considering glomerular hyperfiltration status can improve the accuracy of predicting DKD progression.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Estudios de Cohortes , Tasa de Filtración Glomerular , Estudios Retrospectivos , Factores de Riesgo , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/complicaciones , Albuminuria/complicaciones , Glomérulos RenalesRESUMEN
Objective: Breast cancer is the second most common malignancy globally and a leading cause of cancer death in women. Analysis of factors related to disease-free survival (DFS) has improved understanding of the disease and characteristics related to recurrence. The aim of this study was to investigate the predictors of DFS in patients with breast cancer to enable the identification of patients at high risk who may benefit from prevention interventions. Methods: We retrospectively analyzed 559 women with breast cancer who underwent treatment between 2004 and 2022. The study endpoint was DFS. Recurrence was defined as local recurrence, regional recurrence, distant metastases, contralateral breast cancer, other second primary cancer, and death. Baseline tumor-related characteristics, treatment-related characteristics, sociodemographic and biochemical data were analyzed using Cox proportional hazards analysis. Results: The median DFS was 45 months (range, 2 to 225 months). Breast cancer recurred in 86 patients (15.4%), of whom 10 had local recurrence, 10 had regional recurrence, 17 had contralateral breast cancer, 29 had distant metastases, 10 had second primary cancer, and 10 patients died. Multivariate forward stepwise Cox regression analysis showed that AJCC stage III, Ki67 ≥14%, albumin, platelet, and red cell distribution width-standard deviation (RDW-SD) were predictors of worse DFS. In addition, the effects of albumin, platelet, and RDW-SD on disease recurrence were confirmed by structural equation model (SEM) analysis. Conclusion: In addition to the traditional predictors of worse DFS such as AJCC stage III and Ki67 ≥14%, lower pretreatment circulating albumin, higher pretreatment circulating platelet count and RDW-SD could significantly predict worse DFS in this study, and SEM delineated possible causal pathways and inter-relationships of albumin, platelet, and RDW-SD contributing to the disease recurrence among Chinese women with breast cancer.
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BACKGROUND: The residual risks of atherosclerotic cardiovascular disease in statin-treated patients with diabetes remain unclear. This study was conducted to identify factors associated with these residual risks in patients with no prior vascular event. METHODS: Data on 683 statin-using patients with type 2 diabetes mellitus (T2DM) from the Taiwan Diabetes Registry were used in this study. Patients aged < 25 or > 65 years at the time of diabetes diagnosis and those with diabetes durations ≥ 20 years were excluded. The United Kingdom Prospective Diabetes Study risk engine (version 2.01; https://www.dtu.ox.ac.uk/riskengine/ ) was used to calculate 10-year residual nonfatal and fatal coronary heart disease (CHD) and stroke risks. Associations of these risks with physical and biochemical variables, including medication use and comorbidity, were examined. RESULTS: The 10-year risks of nonfatal CHD in oral anti-diabetic drug (OAD), insulin and OAD plus insulin groups were 11.8%, 16.0%, and 16.8%, respectively. The 10-year risks of nonfatal stroke in OAD, insulin and OAD plus insulin groups were 3.0%, 3.4%, and 4.3%, respectively. In the multivariate model, chronic kidney disease (CKD), neuropathy, insulin use, calcium-channel blocker (CCB) use, higher body mass indices (BMI), low-density lipoprotein (LDL), fasting glucose, log-triglyceride (TG), and log-alanine transaminase (ALT) levels were associated with an increased CHD risk. The residual risk of stroke was associated with CKD, neuropathy, CCB use, and lower LDL cholesterol levels, higher BMI and diastolic blood pressure. CONCLUSION: This study indicated that insulin was probably a residual risk factor of CHD but not stroke, and that there was a possible presence of obesity paradox in patients with T2DM on statin therapy. In addition to lowering TG and normalizing fasting glucose levels, lower LDL cholesterol level is better for reduction of risk of CHD on statin therapy. On the other hand, lower LDL cholesterol level could potentially be related to higher risk of stroke among populations receiving statin therapy. These findings suggest potential therapeutic targets for residual cardiovascular risk reduction in patients with T2DM on statin therapy.
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Diabetes Mellitus Tipo 2 , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Insuficiencia Renal Crónica , Accidente Cerebrovascular , Humanos , LDL-Colesterol , Estudios Prospectivos , Taiwán , Insulina , Bloqueadores de los Canales de Calcio , GlucosaRESUMEN
Background: Transcription factor 21 (TCF21, epicardin, capsuling, pod-1) is expressed in the epicardium and is involved in the regulation of cell fate and differentiation via epithelial-mesenchymal transformation during development of the heart. In addition, TCF21 can suppress the differentiation of epicardial cells into vascular smooth muscle cells and promote cardiac fibroblast development. This study aimed to explore whether TCF21 gene (12190287G/C) variants affect coronary artery disease risk. Methods: We enrolled 381 patients who had stable angina, 138 with ST elevation myocardial infarction (STEMI), and 276 healthy subjects. Genotyping of rs12190287 of the TCF21 gene was performed. Results: Higher frequencies of the CC genotype were found in the patients with stable angina/STEMI than in the healthy controls. After adjusting for diabetes mellitus, hypertension, age, sex, smoking, body mass index and hyperlipidemia, the patients with the CC genotype of the TCF21 gene were associated with 2.49- and 9.19-fold increased risks of stable angina and STEMI, respectively, compared to the patients with the GG genotype. Furthermore, TCF21 CC genotypes showed positive correlations with both stable angina and STEMI, whereas TCF21 GG genotypes exhibited a negative correlation with STEMI. Moreover, the stable angina and STEMI patients with the CC genotype had significantly elevated high-sensitivity C-reactive protein levels than those with the GG genotype. In addition, significant associations were found between type 2 diabetes mellitus, hypertension, and hyperlipidemia with TCF21 gene polymorphisms (p for trend < 0.05). Conclusion: TCF21 gene polymorphisms may increase susceptibility to stable angina and STEMI.
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Angina Estable , Diabetes Mellitus Tipo 2 , Hiperlipidemias , Hipertensión , Infarto del Miocardio con Elevación del ST , Humanos , Angina Estable/genética , Infarto del Miocardio con Elevación del ST/genética , China , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genéticaRESUMEN
In 2022, the American Diabetes Association and the European Association for the Study of Diabetes emphasized that type 2 diabetes care is a person-centered holistic care concept. This article summarizes the concepts of holistic care for individuals with type 2 diabetes and proposes a complete model of the six-layer whole-person care circle for individuals with type 2 diabetes. This model treats individuals with type 2 diabetes as the core of care and adopts their specific needs, preferences, and values to design individualized care plans. The overall goal of care is to maintain quality of life and to avoid or delay complications. Management methods must be holistic. Based on people and comprehensive considerations, six circles of care are listed. The first layer is caregivers, taking into account the influence of the family and the community on the individual. The second layer is multi-professional and multi-disciplinary team care, which provides support to individuals with diabetes. The third layer emphasizes the need for the following thirteen principles in diabetes care: monitoring and screening for complications, behavior modification for healthy habits, monitoring and continuous assessment, reducing the risk of hypoglycemia, effective implementation and care organization, considering underlying physiological conditions, avoiding therapeutic inertia, considering social determinants of health, psychological factors, structured diabetes education, language proficiency, shared decision-making, and considering regional healthcare institutions and related resources. The fourth layer is the decision cycle of care, which applies the principles of care and conducts continuous and dynamic case management based on the decision cycle. The fifth layer is the healthcare network through which health providers provide hospital, long-term care, and primary clinics/ primary network care referrals based on the needs of individual with diabetes. The sixth layer leverages the chronic care model to construct a supportive healthcare system comprising organizational support, clinical information systems, delivery system design, decision support, self-management support, and community resources. This proposed model may provide a reference for constructing healthcare systems to care for patients with type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/terapia , Calidad de Vida , Atención a la Salud , Cuidadores , Atención Dirigida al PacienteRESUMEN
BACKGROUND: Inflammation has been associated with vascular access (VA) dysfunction. The adipocytokine leptin can directly induce pro-inflammatory T helper 1 immune responses and the pathogenesis of chronic inflammation. We explored the association between plasma leptin and VA dysfunction in patients on maintenance hemodialysis (HEMO). METHODS: A total of 344 consecutive patients who received anastomosis for VA at a single HEMO center between June 1, 2010 and December 31, 2021 were screened. Of these patients, 267 met the inclusion criteria and were included. ELISA was used to measure circulating levels of leptin. RESULTS: The VA dysfunction group had a higher leptin level than the patent VA group. A higher concentration of leptin was independently and significantly associated with an elevated risk of VA dysfunction. Multiple logistic regression analysis showed that leptin, female sex, and hypertension were independently associated with VA dysfunction, even after adjusting for known biomarkers. We then evaluated the ability of leptin, female sex, and hypertension to predict the risk of VA dysfunction, and the area under the curve (AUC) for leptin was 0.626 (p = 0.0001). When leptin, female sex, and hypertension were added to this multivariate model, the AUC increased to 0.679 (p = 0.001) for leptin and hypertension, and 0.690 for leptin, hypertension, and female sex (p = 0.004). In addition, plasma leptin levels were associated with sex, body mass index, and hemoglobin. CONCLUSIONS: In addition to the association between leptin and VA dysfunction, hypertension and female sex independently predicted VA dysfunction in patients with HEMO.
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Hipertensión , Leptina , Humanos , Femenino , Diálisis Renal/efectos adversos , Biomarcadores , Hipertensión/complicaciones , Inflamación/complicaciones , Índice de Masa CorporalRESUMEN
This study estimates the association between sarcopenia and blood biochemical parameters, nutritional intake, anthropometric measurements, physical performance, and physical activity in patients with type 2 diabetes mellitus (T2DM). Participants were recruited from a primary care clinic in Kaohsiung City. According to the diagnosis criteria of the Asian Working Group for Sarcopenia (AWGS) in 2019, 110 patients with T2DM (aged 50-80 years) were divided into three groups: non-sarcopenia (n = 38), possible sarcopenia (n = 31), and sarcopenia (n = 41). Blood samples were collected, and nutritional intake was evaluated by a registered dietitian. A food frequency questionnaire and a Godin leisure-time exercise questionnaire were used to assess their daily vitamin D intake and physical activity. There were significant differences in age, serum vitamin D levels, nutritional intake, anthropometric measurements, and physical performance between the three groups. In elderly patients with T2DM, reduced serum 25-hydroxyvitamin D [25(OH)D] levels and daily energy intake were significantly associated with possible sarcopenia. Age, lower BMI, reduced serum 25(OH)D, and reduced dietary protein and vitamin D intake were significantly associated with sarcopenia. These findings may serve as the basis for intervention trials to reduce the prevalence of sarcopenia.
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Diabetes Mellitus Tipo 2 , Sarcopenia , Anciano , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Taiwán/epidemiología , Sarcopenia/epidemiología , Sarcopenia/etiología , Composición Corporal , Ingestión de Alimentos , Ejercicio Físico , Vitamina DRESUMEN
BACKGROUND: Diabetes is associated with disability development. Healthy behaviors and psychosocial support can help patients manage their disease. PURPOSE: To examine the role of various behavioral and psychological factors in buffering the effect of diabetes on disability development over time in Taiwanese adults. METHODS: Data on 5,131 adults aged ≥50 years were obtained from the Taiwan Longitudinal Study on Aging. A cohort sequential multilevel design was employed to analyze the association between behavioral and psychosocial factors and the risk of disability over a 11-year period. RESULTS: In patients with diabetes, having social support and exercising more than six times a week were associated with 4% and 49% reductions in the risk of disability, respectively (ßdiabetes*socialsupport = -0.285, p = .006; ßdiabetes*exercise3 = -2.612, p = .007). Exercising more than six times a week had an additional significant protective effect against disability development per year (ßdiabetes*exercises3*age = -0.241, p = .038). Depression did not significantly interact with diabetes. However, a trajectory analysis revealed that individuals who had both diabetes and depression had the highest disability score from middle age among all participants. CONCLUSIONS: Engaging in frequent exercise is the most influential factor for reducing the risk of disability in patients with diabetes. Social support provides an additional benefit for disability prevention in individuals with diabetes.
Diabetes can lead to several diseases that affect the heart, vessels, brain, kidneys, and nerves. These diseases can cause disabilities in people with diabetes. Disabilities among people with diabetes lead to higher death rates, depression, and poor life quality. All these have become a great burden to our public health care system. Several past studies let us know healthy behaviors and good social support have positive effects on reducing complications of diabetes. Healthy behaviors, such as healthy diets, regular exercises, and proper stress management. Good social support and participation are known to reduce dementia in people with diabetes. However, it remains unclear about interactions and exact associations among all these factors. This study was designed to find out how health behaviors and social support help people with diabetes reduce the risks of disabilities. By analyzing data from Taiwan Longitudinal Study on Aging, we found that exercising more than six times a week reduced disability risk the most for people with diabetes. Social support, although not as effective as exercising, provided additional positive effects to reducing disability risks of people with diabetes.
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Diabetes Mellitus , Personas con Discapacidad , Adulto , Persona de Mediana Edad , Humanos , Estudios Longitudinales , Envejecimiento , Conductas Relacionadas con la SaludRESUMEN
BACKGROUND: Mannose-binding lectin (MBL) has been associated with cardiovascular disease and its complications, the progression of diabetic nephropathy, and complement-mediated renal interstitial injury. However, the relationship between plasma MBL concentration with both heart failure and renal function is unclear. In this study, we examined associations of plasma MBL with both renal function and heart failure in patients with stable coronary artery disease (CAD). METHODS: We enrolled 348 consecutive stable CAD patients and used ELISA to evaluate plasma concentrations of MBL. Renal function was classified into KDIGO G1, G2 and G3a-G4 groups according to the eGFR of ≥ 90, 60-89 and 15-59, ml/min/1.73 m2, respectively. Patients with a left ventricular ejection fraction (LVEF) ≤ 40 % were classified to have heart failure. RESULTS: A significant positive association was found between MBL with diabetes mellitus, current smoker, blood urea nitrogen, creatinine, and brain natriuretic peptide, and a significant negative association was found between MBL with eGFR and LVEF. KDIGO stage G3a-G4 and heart failure increased along with tertiles of MBL (p for trend < 0.05). Multivariate analysis showed that compared to the patients with a low MBL concentration, the odds ratios of having KDIGO stage G3a-G4 were 1.89 (1.01-3.55) times and 2.37 (1.25-4.59) times higher for those with medium and high MBL concentrations. Furthermore, compared to the patients with a low MBL concentration, the OR of having heart failure were 1.97 (1.01-3.93) times higher for those with high MBL concentrations. Moreover, multivariate analysis showed an independent association between plasma MBL concentration with both KDIGO stage G3a-G4 and heart failure (LVEF < 40 %). In addition, the effect of MBL on both LVEF and eGFR was confirmed by structural equation model analysis. CONCLUSION: There are associations between circulating MBL concentration with both heart failure and renal function in stable CAD patients, suggesting that increased plasma MBL may contribute to the pathogenesis of both chronic kidney disease and heart failure.
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Enfermedades Cardiovasculares , Enfermedad de la Arteria Coronaria , Insuficiencia Cardíaca , Humanos , Enfermedad de la Arteria Coronaria/complicaciones , Volumen Sistólico , Función Ventricular Izquierda , Insuficiencia Cardíaca/complicacionesRESUMEN
Background: Ficolin-3 (FCN3) is a well-known circulating pattern recognition molecule which plays a role in host immune responses to cancer via activation of the lectin complement pathway. Nevertheless, the clinical significance of FCN3 in patients with hepatocellular carcinoma (HCC) is unclear. Methods: Eighty-seven HCC patients who received hepatectomy at our hospital were included. Immunohistochemical staining was used to assess the FCN3 expression in both tumorous and non-tumorous tissues from the patients, who were classified into high and low expression groups. Differences in clinicopathological characteristics between the two groups were then analyzed. Results: Survival was significantly associated with FCN3 immunohistochemical score (p for trend = 0.048). Kaplan-Meier analysis revealed a higher overall survival rate in the patients with a high FCN3 expression than in those with a low FCN3 expression (p=0.031). A high FCN3 expression in tumor tissue was independently associated with better overall survival (p=0.042). However, multivariate analysis showed that FCN3 expression was not an independent risk factor for overall survival. Conclusion: Our findings suggest that FCN3 is significantly related to the prognosis of HCC. FCN3 may be a prognostic marker in patients with HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/metabolismo , Estimación de Kaplan-Meier , Lectinas/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/metabolismo , Pronóstico , FicolinasRESUMEN
Introduction: The prevalence of cardiovascular disease (CVD) and CVD-related deaths in patients with schizophrenia is high. An elevated risk of CVD has been associated with low heart rate variability (HRV). There is increasing evidence that fatty acid-binding protein (FABP)3 and FABP4 play roles in the development and progression of CVD. This study aimed to explore the association of circulating FABP3/FABP4 levels with HRV in patients with chronic schizophrenia. Methods: We included 265 consecutive patients with chronic schizophrenia who attended a disease management program. We used an enzyme-linked immunosorbent assay for the measurement of plasma concentrations of FABP3 and FABP4. Standard HRV was recorded at baseline following a standard protocol. Mean high- and low-frequency (HF/LF) HRV values were analyzed by tertile of FABP3 and FABP4 using one-way analysis of variance, and linear regression analysis was performed to assess trends. Results: A positive association between FABP3 and creatinine was found in multiple regression analysis. In addition, negative associations between levels of hematocrit, hemoglobin, HF HRV, and estimated glomerular filtration rate (eGFR) with FABP3 were also found. Moreover, positive associations between FABP4 with body mass index, diabetes mellitus, hypertension, systolic blood pressure, low-density lipoprotein-cholesterol, triglycerides, creatinine, and FABP3 were found. Furthermore, negative associations between levels of high-density lipoprotein-cholesterol, eGFR, and HF HRV with FABP4 were found. We also found a significant inverse association between FABP3 and HF HRV (p for trend = 0.008), and significant inverse associations between FABP4 with HF and LF HRV (p for trend = 0.007 and 0.017, respectively). Discussion: Together, this suggests that elevated levels of FABP3 and FABP4 may be linked to health problems related to CVD in patients with chronic schizophrenia.
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Enfermedades Cardiovasculares , Esquizofrenia , Humanos , Frecuencia Cardíaca , Esquizofrenia/complicaciones , Creatinina , Proteínas de Unión a Ácidos Grasos , Colesterol , Proteína 3 de Unión a Ácidos GrasosRESUMEN
BACKGROUND: Liver-type fatty acid-binding protein (L-FABP) is widely expressed in hepatocytes and plays a role in lipid metabolism. It has been demonstrated to be overexpressed in different types of cancer; however, few studies have investigated the association between L-FABP and breast cancer. The aim of this study was to assess the association between plasma concentrations of L-FABP in breast cancer patients and the expression of L-FABP in breast cancer tissue. METHOD: A total of 196 patients with breast cancer and 57 age-matched control subjects were studied. Plasma L-FABP concentrations were measured using ELISA in both groups. The expression of L-FABP in breast cancer tissue was examined using immunohistochemistry. RESULT: The patients had higher plasma L-FABP levels than the controls (7.6 ng/mL (interquartile range 5.2-12.1) vs. 6.3 ng/mL (interquartile range 5.3-8.5), p = 0.008). Multiple logistic regression analysis showed an independent association between L-FABP and breast cancer, even after adjusting for known biomarkers. Moreover, the rates of pathologic stage T2+T3+T4, clinical stage III, positive HER-2 receptor status, and negative estrogen receptor status were significantly higher in the patients with an L-FABP level greater than the median. Furthermore, the L-FABP level gradually increased with the increasing stage. In addition, L-FABP was detected in the cytoplasm, nuclear, or both cytoplasm and nuclear of all breast cancer tissue examined, not in the normal tissue. CONCLUSIONS: Plasma L-FABP levels were significantly higher in the patients with breast cancer than in the controls. In addition, L-FABP was expressed in breast cancer tissue, which suggests that L-FABP may be involved in the pathogenesis of breast cancer.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/metabolismo , Proteínas de Unión a Ácidos Grasos , Biomarcadores , Hígado/metabolismoRESUMEN
BACKGROUND: Intrinsic capacity (IC) is a novel concept focusing on normal and healthy aging. The effect of IC on the risk of chronic kidney disease (CKD) according to KDIGO category in older type 2 diabetes mellitus (T2DM) patients has rarely been studied. We investigated whether a decline in IC is associated with the risk of CKD according to KDIGO 2012 categories. METHODS: This is a cross-sectional study. The exposure variables (IC score and body mass index) and outcome variable (KDIGO categories of the risk of CKD) were collected at the same timepoint. A total of 2482 older subjects with T2DM managed through a disease care program were enrolled. The five domains of IC, namely locomotion, cognition, vitality, sensory, and psychological capacity were assessed. Based on these domains, the IC composite score was calculated. CKD risk was classified according to the KDIGO 2012 CKD definition. Univariate and multivariate analyses were used to assess the association between IC score and KDIGO categories of risk of CKD. RESULTS: The KDIGO CKD risk category increased in parallel with IC score (p for trend < 0.0001). In multivariate analysis, compared to those with an IC score 0, the odds ratio of having a KDIGO moderately increased to very high risk category of CKD was 1.76 (1.31-2.37) times higher for those with an IC score of 2-5. Furthermore, an increased IC score was associated with a higher prevalence of moderate and severe obesity. Moreover, there was a synergistic interaction between IC score and obesity on the KDIGO moderately increased to very high risk category of CKD (synergy index = 1.683; 95% CI 0.630-3.628), and the proportion of the KDIGO moderately increased to very high risk category of CKD caused by this interaction was 25.6% (attributable proportion of interaction = 0.256). CONCLUSIONS: Our findings indicate that IC score may be closely related to the KDIGO moderately increased to very high risk category of CKD. In addition, there may be a synergistic interaction between IC score and obesity, and this synergistic interaction may increase the KDIGO CKD risk stage.
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Introduction: Of all psychiatric disorders, schizophrenia is associated with the highest risk of all-cause mortality. This study aimed to investigate independent risk factors for all-cause mortality in patients with chronic schizophrenia. In addition, the possible causal inter-relationships among these independent risk factors and all-cause mortality were also explored. Methods: We conducted an analysis of 1,126 patients with chronic schizophrenia from our psychiatric department from April 2003 to August 2022, and retrospectively reviewed their medical records. The study endpoint was all-cause mortality. Baseline clinical characteristics including sociodemographic data, biochemical data, lifestyle factors, comorbidities and antipsychotic treatment were examined with Cox proportional hazards analysis. Results: The all-cause mortality rate was 3.9% (44 patients). Multivariate Cox regression analysis revealed that several factors were independently associated with all-cause mortality, including diabetes mellitus (DM), hypertension, heart failure, gastroesophageal reflux disease (GERD), peptic ulcer disease, ileus, underweight, fasting glucose, triglycerides, albumin, and hemoglobin. Structural equation modeling (SEM) analysis revealed that several factors had statistically significant direct effects on all-cause mortality. Heart failure, hypertension, underweight, age at onset, and ileus showed positive direct effects, while albumin and hemoglobin demonstrated negative direct effects. In addition, several factors had indirect effects on all-cause mortality. GERD indirectly affected all-cause mortality through ileus, and peptic ulcer disease had indirect effects through albumin and ileus. Ileus, underweight, DM, and hypertension also exhibited indirect effects through various pathways involving albumin, hemoglobin, and heart failure. Overall, the final model, which included these factors, explained 13% of the variability in all-cause mortality. Discussion: These results collectively suggest that the presence of DM, hypertension, heart failure, GERD, peptic ulcer disease, ileus, and underweight, along with lower levels of albumin or hemoglobin, were independently associated with all-cause mortality. The SEM analysis further revealed potential causal pathways and inter-relationships among these risk factors contributing to all-cause mortality in patients with chronic schizophrenia.
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OBJECTIVES: This study aims to independently and externally validate the Risk Prediction Model for Diabetic Kidney Disease (RPM-DKD) in patients with type 2 diabetes mellitus (T2DM). DESIGN: This is a retrospective cohort study. SETTING: Outpatient clinics at Lee's United Clinics, Taiwan, China. PARTICIPANTS: A total of 2504 patients (average age 55.44 years, SD, 7.49 years) and 4455 patients (average age 57.88 years, SD, 8.80 years) were included for analysis in the DKD prediction and progression prediction cohorts, respectively. EXPOSURE: The predicted risk for DKD and DKD progression for each patient were all calculated using the RPM-DKD. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was overall incidence of DKD. Secondary outcomes included DKD progression. The discrimination, calibration and precision of the RPM-DKD score were assessed. RESULTS: The DKD prediction cohort and progression prediction cohort consisted of patients with 2504 and 4455 T2DM, respectively. The RPM-DKD examined in this study showed moderately discriminative ability with area under the curve ranged from 0.636 to 0.681 for the occurrence of DKD and 0.620 to 0.654 for the progression of DKD. The Hosmer-Lemeshow χ2 test indicted the RPM-DKD was not well calibrated for predicting the occurrence of DKD and overestimated the progression of DKD. The precision for predicting the occurrence and progression of DKD were 43.2% and 42.2%, respectively. CONCLUSIONS: On external validation, the RPM-DKD cannot accurately predict the risk of DKD occurrence and progression in patients with T2DM.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Humanos , Persona de Mediana Edad , Nefropatías Diabéticas/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Estudios Retrospectivos , Taiwán/epidemiología , Factores de RiesgoRESUMEN
OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) has been associated with an increased risks of corrected QT (QTc) prolongation and left ventricular hypertrophy (LVH), both of which are associated with the development of cardiovascular disease. Rotating night shift work and a higher risk of incident NAFLD have been reported in male steelworkers. This study aimed to investigate the association of the severity of NAFLD with a prolonged QTc interval and LVH in a large cohort of Chinese male steelworkers. METHODS: We examined baseline data of 2998 male steel workers aged 26 to 71 years at two plants. All workers at both plants received regular health assessments, including 12-lead ECG and echocardiography. Abdominal ultrasonography was performed to evaluate the severity of NAFLD. QTc prolongation was defined as follows: normal ≤ 430 ms, borderline 431-450 ms, and abnormal ≥ 451 ms. LVH was defined as a left ventricular mass index (LVMI) >131 g/m2. Associations of NAFLD with an abnormal QTc interval and LVH were examined using univariate and multivariate analyses. RESULTS: The QTc interval and the LVMI were significantly correlated with the NAFLD fibrosis score, and the severity of NAFLD was correlated with an abnormal QTc interval and LVH (p for trend < 0.05). Multivariate analysis showed that in comparison to the workers without NAFLD, the odds ratios of having an abnormal QTc interval and LVH were 2.54 (95% CI: 1.22-5.39, p = 0.013) times and 2.23 (95% CI: 1.02-5.01, p = 0.044) times higher in the workers with moderate/severe NAFLD. CONCLUSIONS: NAFLD may be closely associated with the risks of an abnormal QTc interval and LVH, suggesting that regular electrocardiogram and echocardiogram monitoring could be used to evaluate the risk of arrhythmia and LVH in male steelworkers with NAFLD.
Asunto(s)
Síndrome de QT Prolongado , Enfermedad del Hígado Graso no Alcohólico , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/epidemiología , Hipertrofia Ventricular Izquierda/etiología , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Electrocardiografía , Arritmias Cardíacas/epidemiología , Arritmias Cardíacas/etiología , China/epidemiologíaRESUMEN
Background: Obesity and cognitive function decline are independent risk factors for chronic kidney disease (CKD). However, few studies have examined the combined effects of obesity status and cognitive function on change in CKD risk. We aimed to evaluate the association between obesity status, cognitive function and CKD risk change in patients with type 2 diabetes mellitus (T2DM). Methods: Data on 3399 T2DM patients were extracted from a diabetes disease management program between 2006 and 2018. Univariate and multivariate analyses were used to assess the association between obesity, cognitive decline, and CKD risk change. Three indexes, including the relative excess risk of interaction (RERI), attributable proportion of interaction (API), and synergy index (SI), were used to analyze interactions. CKD risk was classified according to the KDIGO 2012 CKD definition. Results: In multivariate analysis, the hazard ratio (HR, 95%Cis) for CKD risk progression was 1.34 (1.12-1.61) times higher in the moderate and severely obese patients compared with the normal weight patients, and 1.34 (1.06-1.67) times higher in the patients with a Mini-Mental State Examination (MMSE) score ≤18 compared to those with an MMSE score ≥24. There was a synergistic interaction between moderate and severe obesity and MMSE score ≤18 on CKD risk progression (SI=4.461; 95% CI: 1.998-9.962), and the proportion of CKD risk progression caused by this interaction was 52.7% (API=0.527; 95% CI: 0.295-0.759). However, normal weight and MMSE score ≥24 were not beneficial on CKD risk improvement in the patients with a moderate risk and very high-risk stage of CKD. Conclusion: There may be a synergistic interaction between obesity and cognitive function decline, and the synergistic interaction may increase the risk of CKD progression.
Asunto(s)
Disfunción Cognitiva , Diabetes Mellitus Tipo 2 , Insuficiencia Renal Crónica , Cognición , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , Estudios de Cohortes , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Progresión de la Enfermedad , Tasa de Filtración Glomerular , Humanos , Obesidad/complicaciones , Obesidad/epidemiología , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND: Growth differentiation factor 1 (GDF1) is a member of the transforming growth factor-ß (TGF-ß) superfamily and a protective mediator against the development of post-infarction cardiac remodeling by negatively regulating MEK-ERK1/2 and Smad signaling pathways in the heart. The TGF-ß/SMAD pathway has been shown to play a key role in the development of hepatic fibrosis. In addition, fatty liver disease has been associated with reduced MEK/ERK1/2 signaling. However, no previous study has investigated the association between GDF1 and liver fibrosis. Therefore, the aim of this study was to investigate the association between plasma GDF1 and liver fibrosis in patients with stable angina. METHODS: We included 327 consecutive patients with stable angina. ELISA was used to measure circulating levels of GDF1, and the fibrosis-4 index was used to assess liver fibrosis. RESULTS: The advanced liver fibrosis group had lower median plasma GDF1 levels than those with minimal liver fibrosis. There was a significant negative association between GDF1 plasma level and fibrosis-4 index (r = -0.135, p = 0.019). A lower concentration of GDF1 was significantly and independently associated with an increased risk of liver fibrosis when concentration was analyzed as a continuous variable and by tertile. In addition, fibrosis-4 index, aspartate aminotransferase (AST)-to-platelet ratio index, and AST/alanine aminotransferase ratio were significantly associated with GDF1 concentration. CONCLUSIONS: Our results indicated an association between low plasma GDF1 and liver fibrosis in the enrolled patients. Further investigations into the role of plasma GDF1 in the pathogenesis of liver fibrosis are warranted.