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1.
Transfusion ; 2024 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-38853305

RESUMEN

BACKGROUND: Blood transfusion (BT) may be associated with an increased risk of thromboembolism. The associations between transfusion reactions (TRs) during BTs and potential risk factors for the development of thromboembolism in patients underwent blood transfusion have not been analyzed. Therefore, this study aimed to compare risk factors associated with the development of venous thromboembolism (VTE) or pulmonary embolism (PE) between patients underwent blood transfusion with and without TRs. STUDY DESIGNS AND METHODS: The retrospective study was conducted between April 1, 2017, and March 31, 2020, at a medical center in Taiwan. Blood-transfused patients were grouped into two cohorts as follows: those who experienced TRs and those who did not experience TRs. Both cohorts were subjected to follow-up until March 31, 2021. The endpoints for both groups were the occurrence of VTE or PE or the date of March 31, 2021. To investigate between-cohort risk differences, a Kaplan-Meier survival analysis and multiple Cox proportional hazard model was used. RESULTS: A total of 10,759 patients underwent 59,385 transfusion procedures, with 703 patients in the TR group, and 10,056 patients in the non-TR group. The risk of VTE or PE was twice as high in the TR group than in the non-TR group (adjusted hazard ratio 2.53, 95% confidence interval 1.49-4.29, p = .001). Meanwhile, age, female sex, transfusion frequency increment, and being nondiabetic was associated with an increased risk of developing thromboembolism. CONCLUSION: TRs are associated with increased long-term thromboembolism risk in patients underwent blood transfusion. It is imperative for clinicians to acknowledge this and maintain rigorous follow-up.

2.
Postgrad Med J ; 100(1184): 391-398, 2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38308652

RESUMEN

PURPOSE: Boarding, the period in which a patient spends in the emergency department (ED) before admission, may be hazardous to critically ill patients, particularly the elderly. This study investigated the associations of boarding with hospital course, prognosis, and medical expenditure in older patients. METHODS: From January 2019 to December 2021, the medical records of older patients (age ≥ 65) visiting the ED of a tertiary referral hospital who were admitted to the medical intensive care unit (ICU) were retrospectively reviewed. Eligible patients were categorized into two groups according to boarding time with a cutoff set at 6 h. Primary outcomes were in-hospital mortality, ICU/hospital length of stay, and total/average hospitalization cost. Subgroup analyses considered age and disease type. RESULTS: Among 1318 ICU admissions from the ED, 36% were subjected to boarding for over 6 h. Prolonged boarding had a longer ICU (8.9 ± 8.8 vs. 11.2 ± 12.2 days, P < .001) and hospital (17.8 ± 20.1 vs. 22.8 ± 23.0 days, P < .001) stay, higher treatment cost (10.4 ± 13.9 vs. 13.2 ± 16.5 thousands of USD, P = .001), and hospital mortality (19% vs. 25% P = .020). Multivariate regression analysis showed a longer ICU stay in patients aged 65-79 (8.3 ± 8.4 vs. 11.8 ± 14.2 days, P < .001) and cardiology patients (6.9 ± 8.4 vs. 8.8 ± 9.7 days, P = .001). Besides, the treatment cost was also higher for both groups (10.4 ± 14.6 vs. 13.7 ± 17.7 thousands of USD, P = .004 and 8.4 ± 14.0 vs. 11.7 ± 16.6 thousands of USD, P < .001, respectively). CONCLUSION: Extended ED boarding for critically ill medical patients over 65 years old was associated with negative outcomes, including longer ICU/hospital stays, higher treatment costs, and hospital mortality.


Asunto(s)
Enfermedad Crítica , Servicio de Urgencia en Hospital , Mortalidad Hospitalaria , Unidades de Cuidados Intensivos , Tiempo de Internación , Humanos , Anciano , Masculino , Femenino , Enfermedad Crítica/mortalidad , Enfermedad Crítica/economía , Enfermedad Crítica/terapia , Servicio de Urgencia en Hospital/economía , Servicio de Urgencia en Hospital/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Tiempo de Internación/economía , Estudios Retrospectivos , Unidades de Cuidados Intensivos/economía , Unidades de Cuidados Intensivos/estadística & datos numéricos , Anciano de 80 o más Años , Costos de Hospital/estadística & datos numéricos , Admisión del Paciente/estadística & datos numéricos , Admisión del Paciente/economía , Factores de Tiempo
3.
Lab Invest ; 103(7): 100146, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37004912

RESUMEN

Urokinase plasminogen activator (uPA) is a crucial activator of the fibrinolytic system that modulates tissue remodeling, cancer progression, and inflammation. However, its role in membranous nephropathy (MN) remains unclear. To clarify this issue, an established BALB/c mouse model mimicking human MN induced by cationic bovine serum albumin (cBSA), with a T helper cell type 2-prone genetic background, was used. To induce MN, cBSA was injected into Plau knockout (Plau-/-) and wild-type (WT) mice. The blood and urine samples were collected to measure biochemical parameters, such as serum concentrations of immunoglobulin (Ig)G1 and IgG2a, using enzyme-linked immunoassay. The kidneys were histologically examined for the presence of glomerular polyanions, reactive oxygen species (ROS), and apoptosis, and transmission electron microscopy was used to examine subepithelial deposits. Lymphocyte subsets were determined using flow cytometry. Four weeks post-cBSA administration, Plau-/- mice exhibited a significantly higher urine protein-to-creatine ratio, hypoalbuminemia, and hypercholesterolemia than WT mice. Histologically, compared to WT mice, Plau-/- mice showed more severe glomerular basement thickening, mesangial expansion, IgG granular deposition, intensified podocyte effacement, irregular thickening of glomerular basement membrane and subepithelial deposits, and abolishment of the glycocalyx. Moreover, increased renal ROS levels and apoptosis were observed in Plau-/- mice with MN. B-lymphocyte subsets and the IgG1-to-IgG2a ratio were significantly higher in Plau-/- mice after MN induction. Thus, uPA deficiency induces a T helper cell type 2-dominant immune response, leading to increased subepithelial deposits, ROS levels, and apoptosis in the kidneys, subsequently exacerbating MN progression in mice. This study provides a novel insight into the role of uPA in MN progression.


Asunto(s)
Glomerulonefritis Membranosa , Humanos , Animales , Ratones , Glomerulonefritis Membranosa/metabolismo , Glomerulonefritis Membranosa/patología , Albúmina Sérica Bovina/efectos adversos , Activador de Plasminógeno de Tipo Uroquinasa/genética , Activador de Plasminógeno de Tipo Uroquinasa/efectos adversos , Especies Reactivas de Oxígeno , Inmunoglobulina G/efectos adversos , Inmunidad , Linfocitos T Colaboradores-Inductores/metabolismo , Linfocitos T Colaboradores-Inductores/patología
4.
Pediatr Nephrol ; 38(9): 3065-3070, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37052690

RESUMEN

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are the primary cause of pediatric chronic kidney disease. Maternal body mass index (BMI) before pregnancy, pregestational diabetic mellitus (DM), and gestational diabetic mellitus (GDM) are potential modifiable risk factors for CAKUT in offspring. METHODS: In this case control study, 4619 neonates were enrolled during 2012-2020 from Kaohsiung Veterans General Hospital in Taiwan. Maternal risk factors before and during pregnancy were compared in children with and without CAKUT. The yearly incidence of CAKUT in offspring and maternal overweight were recorded. RESULTS: In total, 73 (1.6%) cases of CAKUT in offspring were identified. Maternal overweight before pregnancy (BMI ≥ 24 kg/m2) was an independent risk factor for CAKUT in offspring. No associations of pregestational DM and GDM with CAKUT in offspring were observed. The incidence rates of CAKUT and maternal obesity have increased in the past 10 years. CONCLUSIONS: Maternal obesity before pregnancy is associated with CAKUT in offspring and should be addressed to ensure better outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information.


Asunto(s)
Diabetes Mellitus , Obesidad Materna , Sistema Urinario , Recién Nacido , Femenino , Humanos , Niño , Embarazo , Sobrepeso , Estudios de Casos y Controles , Riñón/anomalías , Sistema Urinario/anomalías , Factores de Riesgo
5.
Medicina (Kaunas) ; 59(7)2023 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-37512089

RESUMEN

Background and Objectives: The prevalence of type 2 diabetes mellitus in adolescents has increased rapidly in recent decades. However, the role of adipokines on pathophysiology in young-onset type 2 diabetes mellitus (YDM) is not clear. In this article, we explored the relationships between the adipokines (visfatin and retinol binding protein 4 (RBP4)) and metabolic syndrome (MetS) components in both YDM and late-onset type 2 diabetes mellitus (ODM). Materials and Methods: There were 36 patients with YDM (23.6 ± 4.8 years) and 36 patients with ODM (54.3 ± 10.1 years) enrolled. Visfatin, RBP4, and MetS components were measured. The relationships between visfatin, RBP4 and MetS components were assessed in YDM and ODM. Results: The visfatin, but not the RPB4 level, was significantly higher in YDM than in ODM. After adjusting for age and body mass index, visfatin was not related to any MetS components except that there was a negative correlation with fasting plasma glucose (FPG). As for RPB4, triglyceride was found to be positively and FPG negatively related to RBP4 in YDM. However, in ODM, the only positive relationship that existed was between RBP4 and diastolic blood pressure. Conclusions: In conclusion, both visfatin and RBP4 had certain roles in diabetes and MetS although their relationships were different in YDM and ODM. Further studies are needed to explore their physiological and pathological effects in glucose metabolism.


Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Síndrome Metabólico , Adolescente , Humanos , Adipoquinas , Presión Sanguínea , Índice de Masa Corporal , Resistencia a la Insulina/fisiología , Proteínas Plasmáticas de Unión al Retinol
6.
Medicina (Kaunas) ; 59(6)2023 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-37374210

RESUMEN

BACKGROUND: Although cognitive-behavioral therapy is the first-line treatment for insomnia, pharmacotherapy is often prescribed to treat insomnia and related symptoms. In addition, muscle relaxants are commonly prescribed to alleviate muscle soreness when the pain is unbearable. However, pharmacotherapy can lead to numerous side effects. The non-drug strategy intravascular laser irradiation of blood (iPBM) has been advocated to improve pain, wound healing, blood circulation, and blood cell function to relieve insomnia and muscle soreness symptoms. Therefore, we assessed whether iPBM improves blood parameters and compared drug use before and after iPBM therapy. METHODS: Consecutive patients who received iPBM therapy between January 2013 and August 2021 were reviewed. The associations between laboratory data, pharmacotherapies, and iPBM therapy were retrospectively analyzed. We compared patient characteristics, blood parameters, and drug use within the three months before the first treatment and the three months after the last treatment. We also compared the changes before and after treatment in patients who received ≥10 or 1-9 iPBM treatments. RESULT: We assessed 183 eligible patients who received iPBM treatment. Of them, 18 patients reported insomnia disturbance, and 128 patients reported pain in any part of their body. After the treatment, HGB and HCT significantly increased after treatment in both the ≥10 and 1-9 iPBM treatment groups (HGB p < 0.001 and p = 0.046; HCT p < 0.001 and p = 0.029, respectively). Pharmacotherapy analysis revealed no significant differences in drug use before and after treatment, though drug use tended to decrease after iPBM. CONCLUSIONS: iPBM therapy is an efficient, beneficial, and feasible treatment that increases HGB and HCT. While the results of this study do not support the suggestion that iPBM reduces drug use, further larger studies using symptom scales are needed to confirm the changes in insomnia and muscle soreness after iPBM treatment.


Asunto(s)
Terapia por Luz de Baja Intensidad , Mialgia , Trastornos del Inicio y del Mantenimiento del Sueño , Estudios Retrospectivos , Trastornos del Inicio y del Mantenimiento del Sueño/radioterapia , Mialgia/radioterapia , Humanos , Taiwán , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Pruebas Hematológicas , Fármacos Neuromusculares , Hipnóticos y Sedantes , Analgésicos
7.
Cardiovasc Diabetol ; 20(1): 179, 2021 09 08.
Artículo en Inglés | MEDLINE | ID: mdl-34496858

RESUMEN

BACKGROUND: Type 2 diabetes mellitus is common in patients undergoing dialysis. However, the association between anti-diabetic drug use and survival outcomes is rarely discussed. We aimed to investigate whether continued anti-diabetic medication use affects the survival of diabetic dialysis patients and whether different hypoglycemic drug use influences prognosis. METHODS: Using a nationwide database, we enrolled patients with incident end-stage renal disease under maintenance dialysis during 2011-2015 into the pre-existing diabetes dialysis (PDD), incident diabetes after dialysis (IDD), and non-diabetic dialysis (NDD) groups. The PDD group was further subclassified into patients who continued (PDD-M) and discontinued (PDD-NM) anti-diabetic drug use after dialysis. RESULTS: A total of 5249 dialysis patients were examined. The PDD-NM group displayed a significantly higher mortality rate than the IDD, PDD-M, and NDD groups (log-rank test P < 0.001). The PDD-M group had a significantly lower risk of death, regardless of insulin (P < 0.001) or oral hypoglycemic agent (OHA) (P < 0.001) use. Initial insulin administration or OHA had no statistically significant effect on overall mortality in the IDD group. But OHA use had better survival trends than insulin administration for the older (P = 0.02) and male subgroups (P = 0.05). CONCLUSIONS: For dialysis patients with diabetes, continuous administration of anti-diabetic drugs after dialysis and choice of medication may affect outcomes.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Fallo Renal Crónico/terapia , Diálisis Renal , Anciano , Bases de Datos Factuales , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidad , Femenino , Humanos , Hipoglucemiantes/efectos adversos , Incidencia , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/mortalidad , Masculino , Persona de Mediana Edad , Diálisis Renal/efectos adversos , Diálisis Renal/mortalidad , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Taiwán/epidemiología , Factores de Tiempo , Resultado del Tratamiento
8.
Pediatr Nephrol ; 36(11): 3749-3756, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34036446

RESUMEN

BACKGROUNDS: Chronic kidney disease (CKD) is underdiagnosed in children with congenital heart disease (CHD). Our aim was to study the incidence of CKD in CHD children and identify risk factors for CKD. METHODS: CHD patients were enrolled from the Kaohsiung Veterans General Hospital database between 2010 and 2019. Patient age at enrollment was age at first visit to the hospital. The end of follow-up was marked by the last measurement of serum creatinine, urine protein-to-creatinine ratio (UPCR), or urine microalbumin-to-creatinine ratio (UACR) after enrollment, and only patients who underwent the aforementioned tests in 2 different years were included. Patients with an estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m2 were diagnosed as having CKD and were further classified into clinically recognized CKD (CR-CKD, defined as eGFR <60 mL/min/1.73m2, UPCR >0.5, or UACR >30 mg/g) and non-clinically recognized CKD (NCR-CKD). Their demographic data, CHD category, heart surgery types, medications, and contrast-related examinations during follow-up were collected. RESULTS: The study included 359 CHD patients, of whom 167 (46.5%) developed CKD (18 patients with CR-CKD and 341 with NCR-CKD). Patients with CR-CKD were significantly older at enrollment than patients with NCR-CKD. Corrective heart surgery may be a protective factor for CKD. Furthermore, cyanotic heart disease, two or more image-related contrast exposures, and diuretic use may be associated with CKD. CONCLUSION: CHD patients have a high incidence of CKD. The early detection of CKD and prompt corrective heart surgery for CHD may be beneficial for kidney function.


Asunto(s)
Insuficiencia Renal Crónica , Niño , Humanos , Incidencia , Insuficiencia Renal Crónica/epidemiología , Factores de Riesgo
9.
Int J Clin Pract ; 75(3): e13747, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33010055

RESUMEN

AIMS OF THE STUDY: A high prevalence of protein-energy wasting and malnutrition among uremic patients is associated with an increase in morbidity and mortality. We aimed to investigate the modulating effect of daily dietary protein intake (DPI) evaluated by normalised protein catabolic rate (nPCR) on mortality in long-term haemodialysis (HD) patient from a nationwide population-based study. METHODS USED TO CONDUCT THE STUDY: By Taiwan Renal Registry Data System between 2005 and 2012, we divided the long-term HD patients into average nPCR < 1.2 and nPCR ≥ 1.2 groups according to the current guideline. The relation of nPCR with three-year all-cause and cardiovascular (CV) mortality were evaluated. The cox regression method for predicted mortality by nPCR was used. RESULTS OF THE STUDY: Among 88 330 HD patients, 58 122 (65.8%) patients were in average nPCR < 1.2 group and 30 208 (34.2%) in average nPCR ≥ 1.2 group. Both all-cause and cardiovascular (CV) mortality risks were increased in nPCR < 1.2 group after adjusting for demographics and laboratories cofactors in our multivariate cox regression model. Patients with nPCR < 1.2 and albumin ≥ 3.7 had a higher adjusted hazard ratio (aHR) for all-cause and CV mortality (1.16 [95% confidence interval (CI): 1.07-1.25, P < .001]; 1.15 [95% CI: 1.02-1.31, P = .03], respectively), compared with the reference group with nPCR ≥ 1.2 and albumin ≥ 3.7. Interestingly, there was no difference in mortality risk between low DPI subgroup (nPCR < 1.2 and Alb < 3.7) and the reference group (nPCR ≥ 1.2 and Alb < 3.7). Further stratification analysis revealed that low DPI subgroup (nPCR < 1.2, Alb ≥ 3.7 and TC ≥ 150) had an increased risk of both all-cause and CV mortality (aHR 1.14 [95% CI: 1.04-1.25, P = .005]; aHR 1.17 [95% CI: 1.02-1.35, P = .026], respectively). CONCLUSIONS DRAWN FROM THE STUDY: Low DPI (as presented by nPCR) independently correlated with all-cause and CV mortality among HD patients. Mortality risks were higher in low DPI patients even with normoalbuminaemia and non-hypocholesterolaemia. Further investigations on the importance of increasing DPI in HD patients is warranted.


Asunto(s)
Fallo Renal Crónico , Diálisis Renal , Proteínas en la Dieta , Humanos , Fallo Renal Crónico/terapia , Estado Nutricional , Taiwán/epidemiología
10.
Int J Mol Sci ; 22(7)2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33810260

RESUMEN

In recent decades, the obesity epidemic has resulted in morbidity and mortality rates increasing globally. In this study, using obese mouse models, we investigated the relationship among urokinase plasminogen activator (uPA), metabolic disorders, glomerular filtration rate, and adipose tissues. Two groups, each comprised of C57BL/6J and BALB/c male mice, were fed a chow diet (CD) and a high fat diet (HFD), respectively. Within the two HFD groups, half of each group were euthanized at 8 weeks (W8) or 16 weeks (W16). Blood, urine and adipose tissues were collected and harvested for evaluation of the effects of obesity. In both mouse models, triglyceride with insulin resistance and body weight increased with duration when fed a HFD in comparison to those in the groups on a CD. In both C57BL/6J and BALB/c HFD mice, levels of serum uPA initially increased significantly in the W8 group, and then the increment decreased in the W16 group. The glomerular filtration rate declined in both HFD groups. The expression of uPA significantly decreased in brown adipose tissue (BAT), but not in white adipose tissue, when compared with that in the CD group. The results suggest a decline in the expression of uPA in BAT in obese m models as the serum uPA increases. There is possibly an association with BAT fibrosis and dysfunction, which may need further study.


Asunto(s)
Tejido Adiposo Pardo/metabolismo , Obesidad/metabolismo , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo , Animales , Dieta Alta en Grasa/efectos adversos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Obesidad/etiología , Activador de Plasminógeno de Tipo Uroquinasa/sangre , Activador de Plasminógeno de Tipo Uroquinasa/genética
11.
Molecules ; 24(23)2019 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-31756973

RESUMEN

: Background: The relationship between urokinase-type plasminogen activator (uPA) and the development of type 2 diabetes mellitus (T2DM) was investigated in the study by using mice and cell models, as well as patients with T2DM. METHODS: In mice models, wild-type and uPA knockout (uPA-/-) BALB/c mice were used for induction of T2DM. In cell models, insulin secretion rate and ß cell proliferation were assessed in normal and high glucose after treating uPA siRNA, uPA, or anti-uPA antibody. In our clinical study, patients with T2DM received an oral glucose-tolerance test, and the relationship between uPA and insulin secretion was assessed. RESULTS: Insulin particles and insulin secretion were mildly restored one month after induction in wild-type mice, but not in uPA-/- mice. In cell models, insulin secretion rate and cell proliferation declined in high glucose after uPA silencing either by siRNA or by anti-uPA antibody. After treatment with uPA, ß cell proliferation increased in normal glucose. In clinical study, patients with T2DM and higher uPA levels had better ability of insulin secretion than those with lower uPA levels. CONCLUSION: uPA may play a substantial role in insulin secretion, ß cell regeneration, and progressive development of T2DM. Supplementation of uPA might be a novel approach for prevention and treatment of T2DM in the future.


Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Células Secretoras de Insulina/metabolismo , Regeneración , Activador de Plasminógeno de Tipo Uroquinasa/deficiencia , Animales , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patología , Células Secretoras de Insulina/patología , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo
12.
Eur J Clin Invest ; 48(6): e12937, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29675916

RESUMEN

BACKGROUND: Among multiple causes, diabetic nephropathy (DN) is the major underlying renal disease that leads to end-stage renal disease (ESRD), and early diagnosis can effectively prevent or delay the progression to ESRD. Therefore, the current study aimed to develop noninvasive, accurate detection markers. MATERIALS & METHODS: For this study, 62 diabetes mellitus (DM) patients, 59 DN patients and 21 healthy controls (HCs) were recruited. All participants' serum samples were subjected to concavanalin (Con) A affinity chromatography, which utilizes glycoproteins to discover potential markers. RESULTS: From nano LC-MS and Western blot analysis, apolipoprotein A-IV (ApoA4) was selected which featured a gradual, almost twofold increase in the order of HC, DM and DN. In the Con A-based ELISA, the DM group was 1.91-fold higher than the HC group, while the DN group was 2.56-fold higher than the HCs and 1.33-fold higher than the DM group. In addition, significant positive correlations were observed between ApoA4 and blood urea nitrogen levels and between ApoA4 and creatine levels, while significant negative correlations were seen between serum protein levels and between serum albumin levels in comparisons of DM and DN samples. CONCLUSIONS: Serum Con A-bound ApoA4 levels were higher in the DM group than in HCs, and further increased in the DN group. Levels of ApoA4 were positively correlated with blood urea nitrogen and creatine, but negatively correlated with serum protein and albumin. This evidence supports serum Con A-bound ApoA4 as a circulating marker for predicting the progression of renal impairment in DM patients.


Asunto(s)
Apolipoproteínas A/sangre , Diabetes Mellitus Tipo 2/sangre , Nefropatías Diabéticas/sangre , Anciano , Proteínas Sanguíneas/metabolismo , Nitrógeno de la Urea Sanguínea , Western Blotting , Estudios de Casos y Controles , Cromatografía Liquida , Concanavalina A/metabolismo , Creatinina/sangre , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/etiología , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Espectrometría de Masas , Persona de Mediana Edad , Pronóstico , Albúmina Sérica/metabolismo
13.
J Pineal Res ; 65(1): e12482, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29480949

RESUMEN

Membranous nephropathy (MN), a type of glomerular nephritis, is one of the most common causes of nephrotic syndrome in adults. Although it is known that melatonin plays a protective role in MN, the role of melatonin receptors in the pathophysiology of MN is unclear. Using an experimental MN model and clinical MN specimens, we studied melatonin receptor expression and found that melatonin receptor 1A (MTNR1A) expression was significantly downregulated in renal tubular epithelial cells. Molecular studies showed that the transcription factor pituitary homeobox-1 (PITX1) promoted MTNR1A expression via direct binding to its promoter. Treatment of a human tubular cell line with albumin to induce injury resulted in the stable reduction in MTNR1A and PITX1 expression. PITX1 levels were significantly downregulated in tubular epithelial cells from mice MN kidneys and MN renal specimens. Knockdown of MTNR1A, PITX1, or cyclic adenosine monophosphate-responsive element-binding protein (CREB) decreased E-cadherin (CDH1) expression, but upregulated Per2 and α-smooth muscle actin (αSMA) expression. Blockade of the MTNR1A receptor with luzindole in MN mice further impaired renal function; this was accompanied by CDH1 downregulation and Per2 and αSMA upregulation. Together, our results suggest that in injured tissue, decreased PITX1 expression at the MTNR1A promoter regions leads to decreased levels of MTNR1A in renal tubular epithelial cells, which increases the future risk of MN.


Asunto(s)
Células Epiteliales/metabolismo , Glomerulonefritis Membranosa/metabolismo , Túbulos Renales/metabolismo , Factores de Transcripción Paired Box/metabolismo , Receptor de Melatonina MT1/metabolismo , Animales , Inmunoprecipitación de Cromatina , Femenino , Regulación de la Expresión Génica/genética , Regulación de la Expresión Génica/fisiología , Glomerulonefritis Membranosa/genética , Inmunohistoquímica , Ratones , Ratones Endogámicos BALB C , Regiones Promotoras Genéticas/genética , Interferencia de ARN
14.
Clin Exp Nephrol ; 21(4): 694-704, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27599981

RESUMEN

BACKGROUND: Type 2 diabetes mellitus (DM) and associated complications are common in patients with chronic kidney disease (CKD) and can increase morbidity and mortality. A longitudinal 5-year observational study was conducted to investigate whether the use of anti-diabetic medications or not affected survival rates of diabetic dialysis patients. METHODS: Using a data sample of a million patients from Taiwan's National Health Insurance Database, a retrospective cohort study surveyed patients with type 2 DM who began dialysis between 2002 and 2007. The study population was classified into groups using or not using anti-diabetic drugs. The group using anti-diabetic drugs was then categorized into 3 subgroups, including use of only oral hypoglycemic agents (OHAs), only insulin, and OHAs-combined insulin groups. Subjects of these four groups were followed 5 years or to date of death. Three major areas were analyzed: (1) demographic data and medical history; (2) survival prognosis and causes of death; and (3) effects on survival prognosis of different classes of OHAs. RESULTS: A total of 912 patients fitting inclusion criteria were enrolled and followed-up for 5 years or to date of death. A total 465 patients died, and those not using anti-diabetic drugs (67.34 %) had a higher mortality rate than those using anti-diabetic drugs (46.42 %). After the multivariate analysis, group of OHAs-combined insulin had the lowest risk of death (HR 0.36, 95 % CI 0.27-0.47), followed by OHAs alone (HR 0.49, 95 % CI 0.38-0.63) and then insulin alone (HR 0.67, 95 % CI 0.51-0.88). To clarify four classes of OHAs (sulfonylurea, α-glucosidase inhibitors, meglitinide, and thiazolidinedione) are used in Taiwan for uremia patient with type 2 DM, and in our study, there were no significant differences in survival prognosis for the four drugs. Finally, the most common cause of death was infectious disease and there were no significant differences among the four groups. CONCLUSION: This 5-year observational study results suggested that diabetic dialysis patients with anti-diabetic drugs had a lower risk of death compared with those without anti-diabetic drugs. Despite insulin therapy, appropriate OHAs should play an important role in treating these patients.


Asunto(s)
Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Nefropatías Diabéticas/terapia , Hipoglucemiantes/uso terapéutico , Diálisis Renal , Anciano , Biomarcadores/sangre , Glucemia/metabolismo , Distribución de Chi-Cuadrado , Bases de Datos Factuales , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidad , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/mortalidad , Quimioterapia Combinada , Femenino , Humanos , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/clasificación , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Factores Protectores , Diálisis Renal/efectos adversos , Diálisis Renal/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Taiwán , Factores de Tiempo , Resultado del Tratamiento
15.
J Biomed Sci ; 23: 24, 2016 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-26846181

RESUMEN

BACKGROUND: suPAR biomarker generally considered a pathogenic factor in FSGS. However, studies have been published that dispute this conclusion. The current study was designed to investigate the roles of uPA and suPAR in FSGS in clinical and mouse models. METHODS: Clinical subjects including those with biopsy-proven FSGS and MCD were enrolled. To verify the role of uPA in FSGS, Adriamycin was used to induce FSGS in uPA knockout (uPA(-/-)) and BALB/c (WT) mice. Proteinuria and suPAR, the cleaved/intact forms of the circulating suPAR, and possible proteases involving cleavage of the suPAR were also studied. RESULTS: FSGS clinical cases presented significantly higher serum levels of suPAR and Cr and lower serum levels of uPA. In the mice model, the uPA(-/-) group exhibited faster disease progression and worsening proteinuria than the WT group. In addition, the uPA(-/-) group had higher plasma suPAR levels, glomerular cell apoptosis, and dysregulation of the Th1/Th2 balance. In an analysis of suPAR variants in FSGS, both the intact and cleaved forms of the suPAR were higher in clinical subjects and the mouse model. However, the process of suPAR cleavage was not mediated by enzymatic activities of the uPA, elastase, or cathepsin G. CONCLUSIONS: A deficiency of uPA accelerated the progression of Adriamycin-induced mouse FSGS model. Decrease of serum uPA levels may be an indicator of the progression of FSGS in clinical subjects and animal models.


Asunto(s)
Glomeruloesclerosis Focal y Segmentaria/metabolismo , Receptores del Activador de Plasminógeno Tipo Uroquinasa/metabolismo , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo , Animales , Modelos Animales de Enfermedad , Femenino , Glomeruloesclerosis Focal y Segmentaria/genética , Glomeruloesclerosis Focal y Segmentaria/patología , Humanos , Glomérulos Renales/metabolismo , Glomérulos Renales/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Receptores del Activador de Plasminógeno Tipo Uroquinasa/genética , Células TH1/metabolismo , Células TH1/patología , Células Th2/metabolismo , Células Th2/patología , Activador de Plasminógeno de Tipo Uroquinasa/genética
16.
BMC Geriatr ; 16: 10, 2016 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-26758511

RESUMEN

BACKGROUND: Metabolic syndrome's (MetS) role in predicting cardiovascular diseases and diabetes has been confirmed in many large cohort studies. Nontraditionally, hematogram components are significantly related to MetS in many different age groups. However, little is known about its role among the elderly. METHODS: We enrolled 18,907 subjects over the age of 65 years who underwent regular health examinations. They were divided into three groups according to age: young old (YO: ≥ 65 and < 74 years old), old old (OO: ≥ 75 and < 84 years old), and oldest old (ODO: ≥ 85 years old). The MetS components were determined, and correlations between MetS and hematogram components were evaluated using Pearson and multivariate linear regression analyses. The hematogram components were the independent variables evaluated separately against the dependent variable (MetS components). RESULTS: While SBP and HDL-C increased, most other MetS and hematogram parameters decreased in men with age. Fewer significant differences were noted among the women. In the YO and OO groups for both genders, the subjects with MetS had higher WBC and Hb. None of the hematogram components were different for subjects with or without MetS in the ODO group. Multiple regression results show that most of the relationships between hematogram and MetS components disappeared in the ODO groups. The WBC levels were mainly correlated with WC and TG. At the same time, Hb was associated with BP, FPG, and LDL-C. Compared to WBC and Hb, PLT was least related to MetS, except in the cases of LDL-C and TG. Among the MetS components, BMI, LDL-C, and TG were consistently related to all the hematogram components in YO and OO men. However, only TG had the same consistency among YO and OO women. CONCLUSIONS: This study's three major findings are as follows: WBC and Hb are associated with MetS, even among the YO and OO groups, regardless of gender; among the three hematogram components, Hb had the strongest and PLT had the weakest correlation with MetS; and TG is not the only component with relatively higher r values, and it is related to all hematogram components.


Asunto(s)
Envejecimiento/fisiología , Recuento de Células Sanguíneas/métodos , Hemoglobinas/análisis , Síndrome Metabólico/sangre , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Síndrome Metabólico/epidemiología , Factores de Riesgo , Factores Sexuales , Estadística como Asunto , Taiwán/epidemiología
17.
J Res Med Sci ; 21: 99, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-28163745

RESUMEN

BACKGROUND: It is intriguing and imperative that the comparison of the iron preparations in hemodialysis (HD) patients. This study aimed to observe the short-term efficacy of parenteral iron sucrose and ferric chloride in HD patients. MATERIALS AND METHODS: This was a consecutive 10-week single-blind study in Taiwan. An intravenous iron supplement of 100 mg/week was administered as an infusion in 100 ml of normal saline, until a total dose of 1000 mg was achieved. The primary outcome was evaluated by the changes in serum hematocrit (Hct) levels. The changes in serum Hct and iron indices were evaluated every 2 weeks for 10 weeks. The results were collected from 21 April to 4 July 2013. RESULTS: A total of 56 HD patients completed the study. Subjects were randomized into an iron sucrose group (26 patients) and a ferric chloride group (30 patients). Between the two treatment groups, there were no statistically significant differences in the change in serum Hct, ferritin, iron, or total iron binding capacity (P > 0.05). In the iron sucrose group, the increase in Hct levels was statistically significant at weeks 4, 8, and 10. In the ferric chloride group, the increase in Hct levels was statistically significant at week 8. No obvious major side effects were observed in both groups. CONCLUSION: In the study subjects, parenteral iron sucrose was as effective and safe as ferric chloride for treating anemia in HD patients.

18.
BMC Nephrol ; 16: 83, 2015 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-26077152

RESUMEN

BACKGROUND: Chronic kidney disease (CKD) is highly prevalent in Taiwan. More than two-thirds of end-stage renal disease is associated with diabetes mellitus (DM) or hypertension (HTN). Therefore, the formulation of a special preventative policy of CKD in these patients is essential. This study surveyed 14 traditional risk factors and identified their effects on CKD in patients with HTN/DM and compared these with their effects in the general population. METHODS: This study included 5328 cases and 5135 controls in the CKD/HTN/DM outpatient and health centres of 10 hospitals from 2008 to 2010. Fourteen common effect factors were surveyed (four demographic, five disease and five lifestyle), and their effects on CKD were tested. Significance tests were adjusted by the Bonferroni method. Results of the stratified analyses in the variables were presented with significant heterogeneity between patients with different comorbidities. RESULTS: Male, ageing, low income, hyperuricemia and lack of exercise habits were risk factors for CKD, and their effects in people with different comorbidities were identical. Anaemia was a risk factor, and there was an additive effect between anaemia and HTN on CKD. Patients with anaemia had a higher risk when associated with HTN [odds ratio (OR) = 6.75, 95% confidence limit (95% CI) 4.76-9.68] but had a smaller effect in people without HTN (OR 2.83, 95% CI 2.16-3.67). The association between hyperlipidaemia-related factors and CKD was also moderated by HTN. It was a significant risk factor in people without HTN (OR = 1.67, 95% CI 1.38-2.01) but not in patients with HTN (OR =1.03, 95% CI 0.89-1.19). Hepatitis B, hepatitis C, betel nut chewing, smoking, alcohol intake and groundwater use were not associated with CKD in multivariate analysis. CONCLUSIONS: We considered that patients with HTN and anaemia were a high CKD risk population. Physicians with anaemic patients in outpatient clinics need to recognise that patients who also have HTN might be latent CKD cases.


Asunto(s)
Anemia/epidemiología , Diabetes Mellitus/epidemiología , Hipertensión/epidemiología , Hiperuricemia/epidemiología , Renta/estadística & datos numéricos , Insuficiencia Renal Crónica/epidemiología , Conducta Sedentaria , Adulto , Factores de Edad , Anciano , Consumo de Bebidas Alcohólicas/epidemiología , Areca , Estudios de Casos y Controles , Femenino , Agua Subterránea , Hepatitis B/epidemiología , Hepatitis C/epidemiología , Humanos , Hiperlipidemias/epidemiología , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Factores de Riesgo , Factores Sexuales , Fumar/epidemiología , Taiwán/epidemiología
19.
J Biomed Sci ; 21: 32, 2014 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-24750591

RESUMEN

BACKGROUND: Membranous nephropathy (MN) is a common cause of nephrotic syndrome that may progress to end-stage renal disease (ESRD). The formation of MN involves the in situ formation of subepithelial immune deposits and leads to albuminuria; however, the underlying mechanism of how MN leads to ESRD remains unclear. The aim of this study was to investigate the expression and biological functions of phosphotriesterase-related protein (PTER) in MN. RESULTS: In the progression of MN, the expression of PTER increased significantly and was mainly expressed in the renal tubular cells. Both mRNA and protein expression levels of PTER were increased in a concentration- and time-dependent manner in the in vitro albuminuria tubular cell model. Silencing the expression of PTER by RNA interference diminished albuminuria-induced inflammatory and pro-fibrotic cytokines production. CONCLUSIONS: Our findings reveal that PTER may sense albuminuria in the progression of MN, induce tubular cell activation and lead to ESRD.


Asunto(s)
Albuminuria/genética , Proteínas Portadoras/biosíntesis , Glomerulonefritis Membranosa/genética , Albuminuria/diagnóstico , Albuminuria/inmunología , Animales , Proteínas Portadoras/inmunología , Línea Celular , Regulación de la Expresión Génica , Glomerulonefritis Membranosa/diagnóstico , Glomerulonefritis Membranosa/inmunología , Humanos , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/genética , Fallo Renal Crónico/inmunología , Túbulos Renales/inmunología , Túbulos Renales/patología , Ratones , Síndrome Nefrótico/genética , Síndrome Nefrótico/inmunología , Síndrome Nefrótico/patología , Hidrolasas de Triéster Fosfórico/metabolismo
20.
Heliyon ; 10(6): e27957, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38532997

RESUMEN

Importance: Previous investigations have found that time to positive blood culture (TTP) is a prognostic factor for clinical outcomes. In fact, what the emergency physician sees from the medical information system is TAT (turnaround time) defined as time required to post a bacterial culture report. We propose a definition of blood culture TAT that more closely aligns with clinical considerations by measuring the time from starting specimen culture to the release of an official blood culture report.We were curious to know whether the duration of TAT is as intricately linked to the prognosis of bacteremia as TTP. Objectives: To examine the association between TAT and outcomes of adult patients who present to the ED with community acquired bacteremia. Design: Setting, and Participants: This retrospective study utilized electronic medical records from Kaohsiung Veterans General Hospital (KVGH), a 1000-bed tertiary medical center in Taiwan. Patients were adults aged 18 years and older who presented to ED (Emergency department) for initial diagnosis of community acquired bacteremia from January 1, 2016 to March 31, 2021. Data analysis was performed from December 2022 to January 2023.Main outcomes and measures.The primary outcomes included mortality in the ED, all-cause in-hospital mortality, length of hospital stay, and all-cause 30-day mortality in relation to the individual first report of positive blood culture TAT. Results: A total of 4011 eligible patients with bacteremia were evaluated, of which 207 patients had a blood culture TAT of ≤48 h. The overall 30-day all-cause mortality rate was 13%. Contrary to expectation, no statistically significant differences were observed in clinical prognosis between the TAT groups (≤48 versus >48 h). Subgroup analyses indicated that the length of TAT did not have a significant effect on clinical prognosis in patients who underwent lactate level assessment. Furthermore, no difference in clinical outcome was noted between TAT groups (≤48 versus >48 h) in terms of Gram-negative bacilli or Gram-positive cocci bacteremia. However, in patients with delayed antibiotic treatment (>3 h), a shorter TAT was significantly associated with a fatal outcome. Conclusion: In adults with community-acquired bacteremia, this study did not observe a significant association between blood culture TAT and clinical prognosis, except in cases of delayed antibiotic treatment.

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