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Find video protocols related to scientific articles indexed in Pubmed.
New TNM Staging System for Esophageal Cancer: What Chest Radiologists Need to Know.
Radiographics
PUBLISHED: 10-14-2014
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Esophageal cancer is a leading cause of cancer-related deaths worldwide, and the 5-year relative survival rate remains less than 20% in the United States. The treatment of esophageal cancer should be stage specific for better clinical outcomes. Recent treatment paradigms tend to involve a multimodality approach to management, which includes surgical resection and preoperative or definitive chemoradiation therapy. Accurate pretreatment staging of esophageal cancer is integral for assessing operability and determining a suitable treatment plan. The American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) have published the seventh edition of the staging manual for cancer in the esophagus and esophagogastric junction. Unlike the sixth edition, the revised staging manual is data driven and harmonized with the staging of stomach cancer. Improvements include new definitions for the anatomic classifications Tis, T4, regional lymph node, N, and M and the addition of nonanatomic cancer characteristics (histopathologic cell type, histologic grade, and cancer location). Given the recent increase in the incidence of adenocarcinoma of the distal esophagus, esophagogastric junction, and gastric cardia, the staging of tumors in the esophagogastric junction has been addressed. Radiologists must understand the details of the seventh edition of the AJCC-UICC staging system for esophageal cancer and use appropriate imaging modalities, such as computed tomography (CT), endoscopic ultrasonography, and positron emission tomography/CT, for initial staging. ©RSNA, 2014.
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THE IMPACT OF TIMING OF DIALYSIS INITIATION ON MORTALITY IN PATIENTS WITH PERITONEAL DIALYSIS.
Perit Dial Int
PUBLISHED: 10-07-2014
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? Background: The impact of timing of dialysis initiation on mortality is controversial in patients with peritoneal dialysis (PD). In this study, we analyzed the impact of timing of dialysis initiation on mortality in the incident PD population. ? Methods: Incident patients with PD were selected from the Clinical Research Center (CRC) registry for end-stage renal disease (ESRD), a prospective cohort study on dialysis in Korea. Patients were categorized into 3 groups according to the estimated glomerular filtration rate (eGFR) at the initiation of PD using the Modification of Diet in Renal Disease (MDRD) equation. Group A was defined as eGFR <5mL/min/1.73m(2), group B as eGFR 5 - 10 mL/min/1.73m(2), and group C as eGFR > 10 mL/min/1.73m(2). Cox regression analysis was used to calculate the adjusted hazard ratio (HR) of mortality with group B as the reference. The primary outcome was all-cause mortality. ? Results: A total of 495 incident PD patients were included. The number of patients in group A was 109, group B was 279, and group C was 107. The median follow-up period was 23 months. Multivariate Cox regression analysis showed that group A had a significantly higher risk of all-cause mortality compared with group B (HR 4.13, 95% confidence interval [CI], 1.55 - 11.03, p = 0.005) after adjustment for age, gender, cause of ESRD, serum albumin level, diabetes mellitus, and cardiovascular disease. There was no significant difference in mortality between group C and group B (HR 1.50, 95% CI, 0.59 - 3.80, p = 0.398) after adjustment for clinical variables. ? Conclusion: An eGFR < 5 mL/min/1.73m(2) at the initiation of PD was a significant risk factor for death, while an eGFR >10 mL/min/1.73m(2) at the initiation of PD was not associated with improved survival compared with an eGFR of 5 - 10 mL/min/1.73m(2) at the initiation of PD.
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To Achieve National Self-Sufficiency: Recent Progresses in Deceased Donation in Korea.
Transplantation
PUBLISHED: 09-17-2014
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The disparity between patients awaiting transplantation and available organs has widened, and resultant organ shortage became a world crisis. The transplantation community has made considerable progress in national organ donation system in Korea, and significant growth in the number of deceased donors has been witnessed.
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Clinical Significance of Preexisting Microcalcification in the Iliac Artery in Renal Transplant Recipients.
Transplantation
PUBLISHED: 09-12-2014
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The clinical significance of preexisting microcalcification in the iliac artery is undetermined in renal transplant recipients.
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Clinical outcome in patients with chronic antibody-mediated rejection treated with and without rituximab and intravenous immunoglobulin combination therapy.
Transpl. Immunol.
PUBLISHED: 08-29-2014
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We previously reported that rituximab (RTX) and intravenous immunoglobulin (IVIg) combination therapy (RIT) is effective in treating patients with chronic active antibody-mediated rejection (CAMR), and the proteinuria level can determine the response to RIT. However, the results were not compared to those of patients who did not receive RIT. Fifty-nine patients with CAMR were divided into 2 groups: an RIT treated group (n = 25) and a historic control (HC) group who had not received RIT (n = 29). The RIT group was treated with RTX (375 mg/m(2)) and IVIg (0.4 g/kg) for 4 days. We compared the decline in glomerular filtration rate/month (?eGFR), RIT-related complications, and allograft survival rate in both groups. We also compared the allograft survival rate between patients with high proteinuria (spot urine protein/creatinine [PC] ratio > 3.5 g/g) and low proteinuria (PC ratio < 3.5 g/g). ?eGFR was significantly decreased in the RIT group compared with the HC group after 6 months (P < 0.05). No serious complications were associated with RIT, and only one case of herpes zoster infection developed. The overall allograft survival rate in the RIT group was significantly higher than in the HC group. In both groups, patients with low proteinuria survived better than patients with heavy proteinuria (P < 0.05). The allograft survival rate was greater in the high proteinuria RIT group than that in the HC group. RIT treatment is recommended for delaying the progression of CAMR without serious complications, and is not limited by the presence of heavy proteinuria.
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Effect of dialysis initiation timing on clinical outcomes: a propensity-matched analysis of a prospective cohort study in Korea.
PLoS ONE
PUBLISHED: 08-19-2014
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Controversy persists regarding the appropriate initiation timing of renal replacement therapy for patients with end-stage renal disease. We evaluated the effect of dialysis initiation timing on clinical outcomes. Initiation times were classified according to glomerular filtration rate (GFR).
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Sirolimus conversion efficacy for graft function improvement and histopathology in renal recipients with mild to moderate renal insufficiency.
J. Korean Med. Sci.
PUBLISHED: 07-30-2014
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This study was designed to evaluate whether sirolimus (SRL) conversion effectively improves renal function and histopathology in calcineurin inhibitor (CNI)-treated renal recipients with mild to moderate renal insufficiency. SRL conversion from CNI was performed in patients who underwent kidney transplantation from 6 months to 5 yr prior to screening. Forty-five patients were enrolled. The effect of SRL conversion on graft function was evaluated, and protocol biopsies were performed preconversion and 1 yr after conversion. Overall graft function after SRL conversion gradually improved, and the improvement in renal function was closely associated with the shorter duration of CNI exposure. When we divided the patients by the duration of CNI exposure, the patients with less than 1 yr of CNI exposure demonstrated significant improvement, but patients with a greater than 1 yr CNI exposure did not exhibit significant improvement. In contrast, protocol biopsies demonstrated no significant improvements in the modified "ah" score or other Banff scores after SRL conversion. Furthermore, the duration of CNI treatment prior to SRL conversion was not associated with histological findings 1 yr after SRL conversion. SRL conversion improved graft function in renal recipients with mild to moderate renal insufficiency, but this effect is not accompanied by histological improvement.
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The Role of Maximum Standardized Uptake Value in PET/CT as a Prognostic Factor in Patients with Resected Esophageal Squamous Cell Carcinoma.
Thorac Cardiovasc Surg
PUBLISHED: 07-28-2014
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Background?The aim of this study was to evaluate the role of the maximum standardized uptake value (mSUV) of the main mass as a risk factor for recurrence in patients with completely resected esophageal squamous cell carcinoma (ESCC). Patients and Methods?Clinicopathologic factors including primary tumor location, tumor size, depth of tumor invasion, number of positive lymph nodes, angiolymphatic invasion, and mSUV were analyzed as risk factors for recurrence. The prognostic influence of variables on disease-free survival was analyzed using the log-rank test for univariate analysis and the Cox proportional hazards model for multivariate analysis. Results?A total of 102 patients underwent complete resection of ESCC and positron emission tomography/computed tomography was performed. The median follow-up period was 35.0 months (range, 2-94). The average mSUV of the main mass was 5.5?±?4.2. The tumor had recurred in 38 patients (37.3%). Univariate analysis identified that tumor size (> 3.5 cm), depth of tumor invasion (? T2), pathologic stage, and mSUV (> 5.1) were statistically significant prognostic factors for recurrence of ESCC. However, in multivariate analysis, only mSUV (> 5.1, HR?=?4.222, p?=?0.025) was the independent risk factor of recurrence. Conclusions?The mSUV of the main mass was an independent predictor for recurrence with a cutoff value of 5.1.
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The effect of mTOR inhibition on Th17 and Treg differentiation in vitro and in vivo in kidney transplant recipients.
Immunology
PUBLISHED: 07-01-2014
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Sirolimus (SRL) is a promising alternative to calcineurin inhibitors (CNIs), such as tracrolimus (TAC), in kidney transplant recipients (KTRs), but immunologic benefits of conversion from CNIs to SRL is not fully investigated. In the present study, we evaluated the effect of conversion from TAC to SRL on the Th17/Treg axis in three separate studies. First, the effect of SRL on the Th17/Treg axis was evaluated in vitro using peripheral blood mononuclear cells (PBMCs). Second, the effect of conversion from TAC to SRL on the Th17/Treg axis was studied in KTRs. Finally, the effect of SRL on CD8(+) Treg was evaluated. In vitro analysis of PBMCs isolated from KTRs showed that SRL suppressed Th17 cell differentiation but TAC did not. Conversion from TAC to SRL markedly decreased the number of effector memory CD8(+) T cells and significantly increased the proportion of CD4(+) and CD8(+) Tregs as compared to TAC in KTRs. SRL treatment induced the CD8(+) Treg cells, and these cells inhibited the proliferation of allogeneic CD4(+) T cells and Th17 cells. In conclusion, conversion from TAC to SRL favorably regulates Th17 and Treg differentiation in KTRs. These findings provide a rationale for conversion from TAC to SRL in KTRs. This article is protected by copyright. All rights reserved.
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Effects of pretransplant plasmapheresis and rituximab on recurrence of focal segmental glomerulosclerosis in adult renal transplant recipients.
Korean J. Intern. Med.
PUBLISHED: 06-27-2014
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Recurrent focal segmental glomerulosclerosis (FSGS) following renal transplantation is relatively common. However, the risk factors and optimal pretransplant treatment preventing recurrence of FSGS remain controversial.
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Combined treatment of tacrolimus and everolimus increases oxidative stress by pharmacological interactions.
Transplantation
PUBLISHED: 05-15-2014
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Drug-drug interaction between everolimus (EVR) and tacrolimus (TAC) is still undetermined. We evaluated whether EVR enhances TAC-induced organ injury through drug-drug interaction.
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Clinical Significance of Chronic Kidney Disease and Atrial Fibrillation on Morbidity and Mortality in Patients with Acute Myocardial Infarction.
Am. J. Nephrol.
PUBLISHED: 05-13-2014
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Background/Aims: Atrial fibrillation (AF) often coexists with acute myocardial infarction (AMI), and chronic kidney disease (CKD) is a major risk for AMI. However, the combined impact of CKD and AF on the mortality and morbidity in AMI population has not been determined. Methods: Between January 2004 and December 2009, a total of 4,738 AMI patients were enrolled prospectively. Patients were divided into four groups according to the combined status of CKD and AF. The primary endpoint was a combination of 5-year major adverse cardiac and cerebrovascular events (MACCE). Results: The prevalence of AF was significantly higher in CKD patients than in non-CKD patients (6.76 vs. 3.31%, p < 0.001). The highest cumulative event rate of MACCE and death was observed in patients with both CKD and AF (68.5 and 64.0%), respectively. In multivariable analyses, compared with patients with neither AF nor CKD, hazard ratios (HR) for composite of MACCE were 1.66 (95% CI, 1.14-2.41), 1.24 (95% CI, 1.06-1.46), and 2.10 (95% CI, 1.42-3.13) for patients with AF only, those with CKD only, and those with both CKD and AF, respectively (p for interaction = 0.935). Patients with both CKD and AF had a greatest risk for all-cause mortality (HR 2.54; 95% CI, 1.60-4.53), and the significant synergistic interaction was observed between CKD and AF (p for interaction = 0.015). Conclusion: The combined effect of AF and CKD on the risk of MACCE after an AMI is stronger than any separate condition, and it confers a synergistic effect on the all-cause mortality risk. © 2014 S. Karger AG, Basel.
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The impact of high-flux dialysis on mortality rates in incident and prevalent hemodialysis patients.
Korean J. Intern. Med.
PUBLISHED: 05-09-2014
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The effect of high-flux (HF) dialysis on mortality rates could vary with the duration of dialysis. We evaluated the effects of HF dialysis on mortality rates in incident and prevalent hemodialysis (HD) patients.
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Frequency of lymph node metastasis according to the size of tumors in resected pulmonary adenocarcinoma with a size of 30 mm or smaller.
J Thorac Oncol
PUBLISHED: 05-03-2014
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This study analyzed the relation between the tumor size and the lymph node metastasis in adenocarcinoma of the lung with a size of 30 mm or smaller.
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Blocking activator protein 1 activity in donor cells reduces severity of acute graft-versus-host disease through reciprocal regulation of IL-17-producing T cells/regulatory T cells.
Biol. Blood Marrow Transplant.
PUBLISHED: 04-29-2014
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Acute graft-versus-host disease (aGVHD) is a major cause of mortality in allogeneic bone marrow transplantation. Here, the diminishing effect of activator protein 1 (AP-1) blocking with a synthetic retinoid (SR11302) on the severity of aGVHD in a murine model was investigated. MHC-mismatched strain combinations were used in vivo: C57BL/6 (H-2k(b)) donors into lethally irradiated BALB/c (H-2k(d)) recipients. SR11302 inhibited alloreactive T cell response in a dose-dependent manner and negatively regulated signal transducer and activator of transcription 3 (STAT3) activation. AP-1 blocking in T cells inhibited the differentiation of Th1 and Th17. Conversely, Foxp3(+) regulatory T cells (Treg) population dramatically expanded. Transfer of SR11302-treated donor splenocytes into lethally irradiated recipients diminished the lethality and clinical severity of aGVHD. In line with these results, AP-1 blocking in donor splenocytes exhibited reduced Th17/Th1 population and enhanced in vivo Treg population. Beneficial Treg expanding property of SR11302 was associated with the induction of Foxp3 and STAT5 transcription factor, where the inhibiting property of Th17 was achieved by suppressing the phosphorylated form of STAT3 and enhancing SOCS3. In conclusion, the preventive potential of AP-1 inhibitor in aGVHD may be accomplished by altering CD4(+) T cell differentiation through modulating transcription factors.
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Ginseng treatment attenuates autophagic cell death in chronic cyclosporine nephropathy.
Nephrology (Carlton)
PUBLISHED: 04-29-2014
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Chronic cyclosporine (CsA) treatment induces autophagic cell death characterized by excessive autophagosome formation and decreased autophagic clearance. In this study, we evaluated the influence of ginseng treatment on autophagy in chronic CsA nephropathy.
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Synergistic effects of leflunomide and benazepril in streptozotocin-induced diabetic nephropathy.
Nephron Exp. Nephrol.
PUBLISHED: 03-25-2014
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Leflunomide (LEF) and benazepril have renoprotective effects on diabetic nephropathy (DN) through their anti-inflammatory and anti-fibrotic activities. This study investigated whether combined treatment using LEF and benazepril affords superior protection compared with the respective monotherapies.
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Decrease of immature B cell and interleukin-10 during early-post-transplant period in renal transplant recipients under tacrolimus based immunosuppression.
Transpl. Immunol.
PUBLISHED: 03-25-2014
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B lymphocytes are known to play a role in kidney transplantation (KT) outcomes. Here, we evaluated the proportion of B cell subsets before and after KT. Twenty-one patients, who showed stable allograft function without acute rejection in the month following the KT, were included in this study. Peripheral blood samples were obtained from these patients before transplantation as well as 1month after transplantation. Changes in the proportion of B cell subsets after transplantation were investigated using multi-color flow cytometry. The proportion of lymphocytes in the peripheral blood mononuclear cells (PBMCs) and of CD19(+) B cells in the total leukocyte population did not change after KT. Similarly, the proportions of CD19(+)CD24(+) lymphocytes, mature B cells (CD24(Int)CD38(Inter)/CD19(+)), and memory B cells (CD24(+)CD38(-)/CD19(+)) did not change post-KT. However, the proportion of immature B cells (CD24(+)CD38(+)/CD19(+) B cells) decreased significantly after transplantation (P<0.01). The levels of IL-10, and IL-21, and expression of the B cell marker BLNK also decreased significantly after transplantation. Incubation of PBMCs with tacrolimus (0.1, 1, and 10ng/mL) and mycophenolate mofetil (200?g/mL) an immunosuppressant, resulted in significant reduction in the percentage of immature B cells. In contrast, the proportion of memory and mature B cells was not affected. Taken together, these results show that while the total B lymphocyte count and the proportion of memory/mature B cell subsets do not change after KT, the proportion of immature B cells and the associated cytokines that they secrete decrease significantly.
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Cytokine-mediated bone destruction in rheumatoid arthritis.
J Immunol Res
PUBLISHED: 03-24-2014
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Bone homeostasis, which involves formation and resorption, is an important process for maintaining adequate bone mass in humans. Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation and bone loss, leading to joint destruction and deformity, and is a representative disease of disrupted bone homeostasis. The bone loss and joint destruction are mediated by immunological insults by proinflammatory cytokines and various immune cells. The connection between bone and immunity has been intensely studied and comprises the emerging field of osteoimmunology. Osteoimmunology is an interdisciplinary science investigating the interplay between the skeletal and the immune systems. The main contributors in osteoimmunology are the bone effector cells, such as osteoclasts or osteoblasts, and the immune cells, particularly lymphocytes and monocytes. Physiologically, osteoclasts originate from immune cells, and immune cells regulate osteoblasts and vice versa. Pathological conditions such as RA might affect these interactions, thereby altering bone homeostasis, resulting in the unfavorable outcome of bone destruction. In this review, we describe the osteoclastogenic roles of the proinflammatory cytokines and immune cells that are important in the pathophysiology of RA.
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Use of bortezomib as anti-humoral therapy in kidney transplantation.
J. Korean Med. Sci.
PUBLISHED: 03-11-2014
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This study aimed to investigate the effect of bortezomib in the desensitization and treatment of acute antibody mediated rejection (AAMR) in kidney transplantation. Nine patients who received bortezomib therapy for desensitization (DSZ group, n = 3) or treatment of AAMR (AAMR group, n = 6) were included in this study. In the DSZ group, 2 patients required DSZ owing to positive cross match and 1 owing to ABO mismatch with high baseline anti-ABO antibody titer (1:1,024). Bortezomib was used at 1, 3, 8, and 11 days from the start of the treatment. In the AAMR group, 3 patients showed full recovery of allograft function after bortezomib use and decrease in donor specific anti-HLA antibody (HLA-DSA). However, 3 patients did not respond to bortezomib and experienced allograft failure. In the DSZ group, negative conversion of T-CDC (complement-dependent cytotoxicity) was achieved, and HLA-DSA was decreased to lower than a weak level (median fluorescence intensity [MFI] < 5,000) in 2 patients. In the case of ABO mismatch kidney transplantation, the anti-A/B antibody titer decreased to below the target (? 1:16) after bortezomib therapy. Therefore, bortezomib could be an alternative therapeutic option for desensitization and treatment of AAMR that is unresponsive to conventional therapies.
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Assessment of tubular reabsorption of phosphate as a surrogate marker for phosphate regulation in chronic kidney disease.
Clin. Exp. Nephrol.
PUBLISHED: 03-07-2014
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Fibroblast growth factor 23 (FGF23) and soluble ?-Klotho are emerging potential biomarkers of phosphorus and vitamin D metabolism which change in concentration in early chronic kidney disease (CKD) in order to maintain normal phosphorus levels. Tubular reabsorption of phosphate (TRP) has been commonly used to assess renal tubular phosphate transport. The aim of this study was to evaluate the usefulness of TRP as a surrogate marker of parameters of CKD-mineral bone disease (CKD-MBD) in CKD.
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Clinical application of single incision thoracoscopic surgery: early experience of 264 cases.
J Cardiothorac Surg
PUBLISHED: 03-04-2014
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Single incision thoracoscopic surgery (SITS) is recognized as a difficult procedure and surgeons hesitate to perform this technique. We describe our experience of SITS and determine whether SITS can be a routine approach in minimally invasive surgery.
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The association between body mass index and mortality on peritoneal dialysis: a prospective cohort study.
Perit Dial Int
PUBLISHED: 03-01-2014
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Previous studies have demonstrated that increased body mass index (BMI) is associated with decreased mortality in hemodialysis (HD) patients. However, the association between BMI and survival has not been well established in patients undergoing peritoneal dialysis (PD). The aim of the study was to determine the association between BMI and mortality in the PD population using the Clinical Research Center (CRC) registry for end-stage renal disease (ESRD) cohort in Korea.
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Gene associated with retinoid-interferon-induced mortality 19 attenuates murine autoimmune arthritis by regulation of th17 and treg cells.
PUBLISHED: 02-28-2014
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STAT-3 is a key transcriptional factor in the interleukin-6 (IL-6)-mediated differentiation of Th17 cells. Because Th17 is believed to be a central player in rheumatoid arthritis (RA), we sought to evaluate whether an endogenous inhibitor of the STAT3 gene, GRIM-19 (gene associated with retinoid-interferon-induced mortality 19), could attenuate the progression and severity of murine collagen-induced arthritis (CIA) through suppression of Th17 cells and, reciprocally, could increase expression of Treg cells.
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The AMPK-PPARGC1A pathway is required for antimicrobial host defense through activation of autophagy.
Autophagy
PUBLISHED: 02-25-2014
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AMP-activated protein kinase (AMPK) is a crucial energy sensor and plays a key role in integration of cellular functions to maintain homeostasis. Despite this, it is largely unknown whether targeting the AMPK pathway can be used as a therapeutic strategy for infectious diseases. Herein, we show that AMPK activation robustly induces antibacterial autophagy, which contributes to antimicrobial defense against Mycobacterium tuberculosis (Mtb). AMPK activation led to inhibition of Mtb-induced phosphorylation of the mechanistic target of rapamycin (MTOR) in macrophages. In addition, AMPK activation increased the genes involved in oxidative phosphorylation, mitochondrial ATP production, and biogenesis in Mtb-infected macrophages. Notably, peroxisome proliferator-activated receptor-gamma, coactivator 1? (PPARGC1A) was required for AMPK-mediated antimicrobial activity, as well as enhancement of mitochondrial function and biogenesis, in macrophages. Further, the AMPK-PPARGC1A pathway was involved in the upregulation of multiple autophagy-related genes via CCAAT/enhancer binding protein (C/EBP), ? (CEBPB). PPARGC1A knockdown inhibited the AMPK-mediated induction of autophagy and impaired the fusion of phagosomes with MAP1LC3B (LC3B) autophagosomes in Mtb-infected macrophages. The link between autophagy, mitochondrial function, and antimicrobial activity was further demonstrated by studying LysMCre-mediated knockout of atg7, demonstrating mitochondrial ultrastructural defects and dysfunction, as well as blockade of antimicrobial activity against mycobacteria. Collectively, our results identify the AMPK-PPARGC1A axis as contributing to autophagy activation leading to an antimicrobial response, as a novel host defense mechanism.
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Interdialytic weight gain and cardiovascular outcome in incident hemodialysis patients.
Am. J. Nephrol.
PUBLISHED: 02-07-2014
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Interdialytic weight gain (IDWG) has been regarded as a surrogate of volume overload, but also as a marker of a better nutritional status in end-stage renal disease (ESRD) patients on hemodialysis (HD). This paradoxical meaning of IDWG requires further investigation, particularly in adverse cardiovascular outcomes.
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The effect of combination therapy with rituximab and intravenous immunoglobulin on the progression of chronic antibody mediated rejection in renal transplant recipients.
J Immunol Res
PUBLISHED: 01-29-2014
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The treatment for chronic active antibody-mediated rejection (CAMR) remains controversial. We investigated the efficacy of rituximab (RTX) and intravenous immunoglobulin (IVIg) for CAMR. Eighteen patients with CAMR were treated with RTX (375?mg/m(2)) and IVIg (0.4?g/kg) for 4 days. The efficacy of RTX/IVIg combination therapy (RIT) was assessed by decline in estimated glomerular filtration rate per month (?eGFR) before and after RIT. Patients were divided into responder and nonresponder groups based on decrease and no decrease in ?eGFR, respectively, and their clinical and histological characteristics were compared. Response rate to RIT was 66.7% (12/18), and overall ?eGFR decreased significantly to 0.4 ± 1.7?mL·min(-1) ·1.73?m(-2) per month 6 months after RIT compared to that observed 6 months before RIT (1.8 ± 1.0, P < 0.05). Clinical and histological features between the 12 responders and the 6 nonresponders were not significantly different, but nonresponders had a significantly higher proteinuria levels at the time of RIT (2.5 ± 2.5 versus 7.0 ± 3.5 protein/creatinine (g/g), P < 0.001). The effect of the RIT on ?eGFR had dissipated in all patients by 1 year post-RIT. Thus, RIT delayed CAMR progression, and baseline proteinuria level was a prognostic factor for response to RIT.
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Clinical outcome of kidney transplantation from deceased donors with acute kidney injury by Acute Kidney Injury Network criteria.
J Crit Care
PUBLISHED: 01-29-2014
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In this study, we investigated the outcome of kidney transplantation (KT) from deceased donors with acute kidney injury (AKI), as defined by the Acute Kidney Injury Network criteria.
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Preoperative thrombocytosis is a significant unfavorable prognostic factor for patients with resectable non-small cell lung cancer.
World J Surg Oncol
PUBLISHED: 01-28-2014
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Previous studies have reported that pretreatment thrombocytosis is associated with poor outcomes in several cancer types. This study was designed to evaluate the prognostic significance of preoperative thrombocytosis in patients with non-small cell lung cancer (NSCLC) who undergo surgery.
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A high-affinity protein binder that blocks the IL-6/STAT3 signaling pathway effectively suppresses non-small cell lung cancer.
Mol. Ther.
PUBLISHED: 01-27-2014
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Interleukin-6 (IL-6) is a multifunctional cytokine that regulates immune responses for host defense and tumorigenic process. Upregulation of IL-6 is known to constitutively phosphorylate signal transducer and activator of transcription 3 (STAT3), leading to activation of multiple oncogene pathways and inflammatory cascade. Here, we present the development of a high-affinity protein binder, termed repebody, which effectively suppresses non-small cell lung cancer in vivo by blocking the IL-6/STAT3 signaling. We selected a repebody that prevents human IL-6 (hIL-6) from binding to its receptor by a competitive immunoassay, and modulated its binding affinity for hIL-6 up to a picomolar range by a modular approach that mimics the combinatorial assembly of diverse modules to form antigen-specific receptors in nature. The resulting repebody was highly specific for hIL-6, effectively inhibiting the STAT3 phosphorylation in a dose- and binding affinity-response manner in vitro. The repebody was shown to have a remarkable suppression effect on the growth of tumors and STAT3 phosphorylation in xenograft mice with non-small cell lung cancer by blocking the hIL-6/STAT3 signaling. Structural analysis of the repebody and IL-6 complex revealed that the repebody binds the site 2a of hIL-6, overlapping a number of epitope residues at site 2a with gp130, and consequently causes a steric hindrance to the formation of IL-6/IL-6R? complex. Our results suggest that high-affinity repebody targeting the IL-6/STAT3 pathway can be developed as therapeutics for non-small cell lung cancer.
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Comparative analysis of post-transplant lymphoproliferative disorder after kidney transplantation versus hematopoietic stem cell transplantation.
Transpl. Int.
PUBLISHED: 01-22-2014
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Post-transplant lymphoproliferative disorder (PTLD) is a major complication caused by immune-suppression after transplantation. Survival outcome is known to be poor and the characteristics are not fully understood because of its rare incidence. This single center retrospective study enrolled 41 adult PTLD patients after kidney-transplantation (KT, n = 28) and hematopoietic stem cell transplantation (HSCT, n = 13) from 1992 to 2012. We compared the characteristics and estimated the survival outcomes according to several factors [age-adjusted-IPI (aaIPI), pathologic subtype, viral status, extranodal manifestation] and added some significant parameters to aaIPI scoring system. Post-HSCT-PTLD patients were younger and showed earlier onset, and viral status was more frequently identified. Ten-year OS of the entire group was 44% but the 10-year OS was not significantly different between post-KT-PTLD and post-HSCT-PTLD (39% vs. 56%, P = 0.860). The time onset of PTLD and viral statuses were not meaningful, however, aaIPI, age > 50, extranodal manifestation and monomorphic subtype were predictive for OS. We used those factors for PTLD-specific scoring which showed intermediate-risk (HR = 7.1, P = 0.019) and high-risk (HR = 16.5, P = 0.001) presented worse OS compared to low-risk subgroup. Although the treatment strategies were heterogenous, this study showed comprehensive PTLD data between KT versus HSCT, and our PTLD-specific scoring might be validated by another larger studies.
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Prognostic significance of initial platelet counts and fibrinogen level in advanced non-small cell lung cancer.
J. Korean Med. Sci.
PUBLISHED: 01-21-2014
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Thrombocytosis and coagulation systems activation are commonly associated with disease progression and are suggested poor prognostic factors in patients with malignancies. This study aimed to investigate the prevalence and prognostic significance of thrombocytosis and elevated fibrinogen levels in patients with advanced non-small cell lung cancer (NSCLC). Initial platelet counts and fibrinogen levels were reviewed in 854 patients with histologically proven NSCLC. Thrombocytosis was defined as platelet counts > 450 × 10(9)/L. A serum fibrinogen level > 4.5 g/L was considered high. At the time of diagnosis, initial platelet counts and serum fibrinogen levels were evaluated before treatment. Clinicopathologic data including histological type, tumor, node, metastasis (TNM) stage, performance status, treatment method, and survival time were evaluated. Initial thrombocytosis was found in 6.9% of patients, and elevated fibrinogen levels were found in 55.1% of patients. Patients with thrombocytosis had a significantly poorer prognosis than patients with normal platelet counts (P < 0.001). In multivariate survival analysis, thrombocytosis was an independent prognostic factor (P < 0.001). An elevated serum fibrinogen level was associated with poor prognosis (P < 0.001). In conclusion, initial thrombocytosis and a high fibrinogen level are independent factors for predicting poor prognosis in patients with advanced NSCLC.
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Correction of anemia with continuous erythropoietin receptor activator in Korean patients on long-term hemodialysis.
J. Korean Med. Sci.
PUBLISHED: 01-17-2014
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Continuous erythropoietin receptor activator (CERA) is an erythropoietin with a long-half life. This study investigated the efficacy of CERA for correcting anemia in Korean patients on dialysis. Patients (? 18 yr) who were not receiving any ESAs for more than 8 weeks were randomly assigned to either intravenous CERA once every 2 weeks (n=39) or epoetin beta thrice-weekly (n=41) during a 24-week correction phase. Hemoglobin (Hb) response was defined as increase of Hb by at least 1 g/dL and Hb ? 11 g/dL without red blood cell (RBC) transfusion. Median dialysis duration was 1.7 (0.3-20.8) and 1.6 (0.4-13.8) yr in CERA and epoetin beta group, respectively. Hemoglobin response rate of CERA was 79.5% (95% confidence interval [CI], 63.5-90.7). As the lower limit of 95% CI was higher than pre-specified 60% response rate, it can be concluded that CERA corrected anemia (P<0.05). Hb response rate of epoetin beta was 87.8% (95% CI, 73.8-95.9) (P=0.37). Median time to response was 12 weeks in CERA and 10.3 weeks in epoetin beta (P=0.03). It is suggested that once every 2 weeks administration of CERA is effective for correcting anemia in Korean patients on long-term hemodialysis with longer time-to-response than thrice weekly epoetin beta. (ClinicalTrials.gov registry No. NCT00546481).
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Mechanical thromboprophylaxis is sufficient to prevent the lower extremity deep vein thrombosis after kidney transplantation.
Ann Surg Treat Res
PUBLISHED: 01-14-2014
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Deep vein thrombosis (DVT) is a severe and common complication that occurs after the major operation. Despite the commonality of DVT there is limited data on the incidence of DVT after kidney transplantation (KT). Furthermore, most studies have been retrospective in design and were conducted in western countries. The aim of this study was to evaluate the incidence of lower extremity DVT with mechanical thromboprophylaxis within 1 month of KT in Korea.
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Dipeptidyl peptidase IV inhibitor MK-0626 attenuates pancreatic islet injury in tacrolimus-induced diabetic rats.
PLoS ONE
PUBLISHED: 01-01-2014
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Tacrolimus (TAC)-induced pancreatic islet injury is one of the important causes of new-onset diabetes in transplant recipients. This study was performed to evaluate whether a dipeptidyl peptidase IV (DPP IV) inhibitor is effective in improving TAC-induced diabetes mellitus by reducing pancreatic islet injury.
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Early nephrology referral reduces the economic costs among patients who start renal replacement therapy: a prospective cohort study in Korea.
PLoS ONE
PUBLISHED: 01-01-2014
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The nature of cost-saving effects of early referral to a nephrologist in patients with chronic kidney disease (CKD) is not fully evaluated. We evaluated the health care costs before and after dialysis according to the referral time.
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Comparison of the impact of high-flux dialysis on mortality in hemodialysis patients with and without residual renal function.
PLoS ONE
PUBLISHED: 01-01-2014
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The effect of flux membranes on mortality in hemodialysis (HD) patients is controversial. Residual renal function (RRF) has shown to not only be as a predictor of mortality but also a contributor to ?2-microglobulin clearance in HD patients. Our study aimed to determine the interaction of residual renal function with dialyzer membrane flux on mortality in HD patients.
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Unresolved subclinical hypothyroidism is independently associated with progression of chronic kidney disease.
Int J Med Sci
PUBLISHED: 01-01-2014
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Patients with chronic kidney disease (CKD) often have subclinical hypothyroidism. However, few reports have investigated changes in the status of subclinical hypothyroidism in CKD patients and its clinical significance in CKD progression.
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The effect of postoperative change in bronchial angle on postoperative pulmonary function after upper lobectomy in lung cancer patients.
Interact Cardiovasc Thorac Surg
PUBLISHED: 11-14-2013
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Upper lobectomy inevitably leads to an upward displacement of the remaining lower lobe. Such displacement may result in bronchial angulation, thereby narrowing the airway. We hypothesized that the degree of displacement of the bronchus is associated with the degree of exacerbation of postoperative pulmonary dysfunction. This study investigated whether bronchial angulation affects postoperative pulmonary function.
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Use of blood tests to predict upper gastrointestinal lesions in patients with chronic kidney disease.
J. Investig. Med.
PUBLISHED: 09-27-2013
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Anemia and iron deficiency are common complications in patients with chronic kidney disease (CKD). However, information about the diagnostic indicators of bleeding-related upper gastrointestinal (GI) tract lesions is sparse and few studies have investigated anemic upper GI tract lesions.
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Treatment response and adverse reactions in older tuberculosis patients with immunocompromising comorbidities.
Yonsei Med. J.
PUBLISHED: 08-07-2013
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The aim of this study was to elucidate the effects of immunocompromising comorbidities on treatment response and adverse reactions in older tuberculosis (TB) patients.
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Prognostic factors for post-recurrence survival in patients with completely resected Stage I non-small-cell lung cancer.
Eur J Cardiothorac Surg
PUBLISHED: 06-27-2013
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The clinical course from recurrence to cancer-related death after curative resection has not been clearly elucidated in non-small-cell lung cancer (NSCLC). This study examined the clinical outcomes after postoperative recurrence in patients with completely resected Stage I NSCLC.
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Effect of Conversion from ESA with Shorter Half-Life to CERA Once Monthly for Maintaining Hb Concentration in Pre-Dialysis CKD Patients.
Kidney Blood Press. Res.
PUBLISHED: 06-26-2013
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Background: The purpose of this study is to identify whether hemoglobin (Hb) concentrations can be maintained, and to investigate changes in biomarkers, when switching from erythropoietin stimulating agents (ESA) with shorter half-life to once-monthly subcutaneous methoxy polyethylene glycol-epoetin ? (CERA) in pre-dialysis chronic kidney disease (CKD) patients. Methods: Pre-dialysis CKD patients (n=191) aged ?18 years who maintained their Hb level 10-12 g/dL through use of epoetin-?, epoetin-?, or darbepoetin-? were enrolled. Hb levels and CERA dose was assessed prospectively for 24 weeks. Serum biomarkers related to coagulation, endothelial function, and iron metabolism were measured at weeks 0 and 24. Results: Baseline Hb concentration was 10.8±0.6 g/dL Twelve and 24 weeks after conversion, mean Hb levels were 11.9±0.9 and 11.2±0.9 g/dL, respectively. The mean monthly CERA dose required to maintain Hb levels was gradually reduced. Of total 387 dose adjustments, dose increases and decreases occurred in 35 (9.0%) and 352 (91.0%) episodes, respectively. Hb overshoot occurred in 14 (9.7%) patients. P-selectin was significantly decreased, whereas VCAM was significantly increased 24 weeks after conversion (P < 0.05). Serum soluble transferrin receptor E-selectin and prohepcidin levels were similar before and after switching to CERA (P=N-S). Conclusion: Conversion from ESA with shorter half-life to subcutaneous once-monthly CERA in pre-dialysis CKD patients can efficaciously maintain Hb. The CERA dose requirement decreased significantly. The conversion ratio may need to be reduced when switching from ESA with shorter half-life to CERA. CERA may change biomarkers associated with platelet reactivity and endothelial microenvironment. © 2013 S. Karger AG, Basel.
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Influence of N-acetylcysteine on Klotho expression and its signaling pathway in experimental model of chronic cyclosporine nephropathy in mice.
Transplantation
PUBLISHED: 06-15-2013
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Cyclosporine A (CsA)-associated oxidative stress has been proposed as an important mechanism of renal injury. This study was designed to examine whether N-acetylcysteine (NAC), a well-known antioxidant, affects Klotho, antiaging gene, expression and its signaling pathway in an experimental model of chronic CsA nephropathy.
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Severe Rhabdomyolysis Associated With Concurrent Use of Simvastatin and Sirolimus After Cisplatin-Based Chemotherapy in a Kidney Transplant Recipient.
Exp Clin Transplant
PUBLISHED: 05-29-2013
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Objectives: Cardiovascular disease is the most common cause of sickness and death for long-term kidney transplant recipients, and dyslipidemia is an important risk factor for developing cardiovascular disease. Lipid-lowering strategies, with the use of statins, have been shown to reduce the cardiovascular risks related to dyslipidemia, but concomitant use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and immunosuppressive agents may increase the risk of rhabdomyolysis owing to a drug-drug interaction. We report a case of simvastatin-induced rhabdomyolysis and acute kidney injury triggered by addition of sirolimus and cisplatin-based chemotherapy to a kidney transplant recipient who had previously tolerated chronic statin therapy.
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Inactivation of multidrug resistant (MDR)- and extensively drug resistant (XDR)-Mycobacterium tuberculosis by photodynamic therapy.
Photodiagnosis Photodyn Ther
PUBLISHED: 05-27-2013
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We investigated the effects of photodynamic therapy (PDT) on anti-tuberculosis (TB) activity by measuring inactivation rates, expressed as D-value, of MDR- and XDR-Mycobacterium tuberculosis (M. tb) clinical strains in vitro. Approximately 10(6) colony forming unit per milliliter (CFU/ml) of the bacilli were irradiated with various doses of laser light after exposure to photosensitizers. Survival of M. tb was measured by enumerating CFU in 7H10 medium to measure D-values. No inactivation of M. tb was observed when exposed to photosensitizers (radachlorin or DH-I-180-3) only or laser light only (P>0.1). Treatment with a combination of photosentizer and laser inactivated M. tb although there was a significant difference between the types of photosensitizers applied (P<0.05). Linear inactivation curves for the clinical M. tb strains were obtained up to laser doses of 30J/cm(2) but prolonged irradiation did not linearly inactivate M. tb, yielding sigmoid PDT inactivation curves. D-values of M. tb determined from the slope of linear regression lines in PDT were not significantly different and ranged from 10.50 to 12.13J/cm(2) with 670nm laser irradiation at 100mW/cm(2) of the fluency rate, except for a drug-susceptible strain among the clinical strains tested. This suggests that PDT inactivated M. tb clinical strains regardless of drug resistance levels of the bacilli. Intermittent and repeated PDT allowed acceleration of the inactivation of the bacilli as a way to avoid the sigmoid inactivation curves. In conclusion, PDT could be alternative as a new option for treatment for MDR- and XDR-tuberculosis.
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TLR3-triggered reactive oxygen species contribute to inflammatory responses by activating signal transducer and activator of transcription-1.
J. Immunol.
PUBLISHED: 05-13-2013
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Intracellular reactive oxygen species (ROS) are essential secondary messengers in many signaling cascades governing innate immunity and cellular functions. TLR3 signaling is crucially involved in antiviral innate and inflammatory responses; however, the roles of ROS in TLR3 signaling remain largely unknown. In this study, we show that TLR3-induced ROS generation is required for the activation of NF-?B, IFN-regulatory factor 3, and STAT1-mediated innate immune responses in macrophages. TLR3 induction led to a rapid increase in ROS generation and a physical association between components of the NADPH oxidase (NOX) enzyme complex (NOX2 and p47(phox)) and TLR3 via a Ca(2+)-c-Src tyrosine kinase-dependent pathway. TLR3-induced ROS generation, NOX2, and p47(phox) were required for the phosphorylation and nuclear translocation of STAT1 and STAT2. TLR3-induced activation of STAT1 contributed to the generation of inflammatory mediators, which was significantly attenuated in NOX2- and p47(phox)-deficient macrophages, suggesting a role for ROS-STAT1 in TLR3-mediated innate immune responses. Collectively, these results provide a novel insight into the crucial role that TLR3-ROS signaling plays in innate immune responses by activating STAT1.
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Clinical characteristics and outcomes in renal transplant recipients with renal cell carcinoma in the native kidney.
Korean J. Intern. Med.
PUBLISHED: 05-01-2013
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We investigated the incidence and clinical characteristics of renal cell carcinoma (RCC) in the native kidney of renal transplant recipients.
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Prognostic factors of pulmonary metastasis from colorectal carcinoma.
Interact Cardiovasc Thorac Surg
PUBLISHED: 04-23-2013
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This study was conducted to investigate the prognostic factors of pulmonary metastases, focusing on the time of detection of pulmonary metastases related to adjuvant chemotherapy in patients with colorectal cancer (CRC).
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Clinical characteristics and treatment of patients with IgA nephropathy and hepatitis B surface antigen.
Ren Fail
PUBLISHED: 03-18-2013
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The aim of this study is to investigate the clinical characteristics and our experience of treating patients with IgA nephropathy (IgAN) and IgA nephropathy with hepatitis B surface antigen (HBs-IgAN).
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The prognostic value of abdominal aortic calcification in peritoneal dialysis patients.
Int J Med Sci
PUBLISHED: 03-15-2013
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This study evaluated the prognostic value of the aortic calcification index (ACI), an estimate of abdominal aortic calcification by plain abdominal computed tomography (CT), in terms of left ventricular (LV) diastolic dysfunction, mortality, and nonfatal cardiovascular (CV) events in peritoneal dialysis (PD) patients.
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The imbalance of T helper 17/regulatory T cells and memory B cells during the early post-transplantation period in peripheral blood of living donor liver transplantation recipients under calcineurin inhibitor-based immunosuppression.
Immunology
PUBLISHED: 03-12-2013
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There is limited clinical research regarding the changes in peripheral lymphocyte subsets during the early post-operative period of liver transplantation. Serial changes of T cells and B cells in living donor liver transplantation (LDLT) recipients during the early post-transplantion period were prospectively investigated. From June 2010 to February 2011, 27 consecutive LDLT recipients were enrolled. Percentages of T helper type 1 (Th1; interferon-?-producing), Th2 (interleukin-4-producing), Th17 (interleukin-17-producing), regulatory T (Treg; CD4(+) CD25(+) FoxP3(+) ), memory B (CD19(+) CD24(hi) CD38(-) ) and mature B (CD19(+) CD24(int) CD38(int) ) cells were measured using fluorescence-activated cell sorting. Patients were followed up for a median of 9.9 months (range 6.8-15.5 months) after transplantation. Serial monitoring of immunological profiles showed no significant suppression of Th1, Th2, Th17, mature B or memory B cells, whereas frequencies of Treg cells significantly decreased. Interleukin-17 production by central and effector memory cells was not suppressed during the early post-operative period. The continuous production of interleukin-17 by the memory T cells may contribute to the persistence of Th17 cells. This prospective study demonstrated that current immunosuppression maintained the effector T or memory B cells during the early post-transplantation period but significantly suppressed Treg cells. Serial immune monitoring may suggest clues for optimal or individualized immunosuppression during the early post-operative period in clinical practice.
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Plasma cell-rich acute rejection with monoclonal gammopathy in a renal transplant recipient.
Exp Clin Transplant
PUBLISHED: 03-06-2013
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Plasma cell infiltration into a renal allograft comprises a spectrum of lesions from acute rejection to posttransplant lymphoproliferative disease. We report an unusual case of plasma cell infiltration into a renal allograft with monoclonal gammopathy. A 42-year-old woman was admitted because of graft dysfunction after noncompliance with immunosuppressive therapy for 5 months. A graft biopsy showed acute T-cell-mediated rejection and massive plasma cell infiltration. Despite initial treatment with steroids and antithymocyte globulin, there was persistence of graft dysfunction, monoclonal gammopathy, and plasma cell infiltration. Subsequent treatment with bortezomib improved graft function and caused the monoclonal gammopathy to resolve. Immunohistochemical evaluation of markers of B cells (CD20 and CD138) and the ratio of kappa-to-lambda light chain (15:1) showed that infiltrating cells were plasma cells producing kappa light chain. This suggested that plasma cell-rich acute rejection with monoclonal gammopathy in this patient might have been in an early stage of kappa light chain-producing posttransplant lymphoproliferative disease confined to the renal allograft, and that bortezomib may be effective in treating a patient with this condition.
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Clinical impact of the baseline donor-specific anti-human leukocyte antigen antibody measured by Luminex single antigen assay in living donor kidney transplant recipients after desensitization therapy.
Transpl. Int.
PUBLISHED: 03-03-2013
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The aim of this study is to investigate the clinical impact of donor-specific anti-HLA-antibody (HLA-DSA) baseline levels, measured using the Luminex single antigen assay (LSA), in living donor kidney transplantation (LDKT). Total 129 cases of LDKT were divided into four groups according to baseline mean fluorescence intensity (MFI) HLA-DSA values: Strong (n = 6), >10 000; Moderate (n = 8), 5 000-10 000; Weak (n = 11), 1 000-5 000, Negative (n = 104), <1 000. Pretransplant desensitization (DSZ) was performed to decrease the MFI to weak or negative values before KT. Clinical outcomes in the four groups were compared. After DSZ, HLA-DSA decreased to weak or negative levels in all patients; Acute rejections developed more frequently in strong group [5/6 (83.3%)] compared with other three groups (P < 0.05), and especially acute antibody-mediated rejection (AAMR) developed almost exclusively in strong group [4/6 (66.7%)]. Strong HLA-DSA levels at baseline were more predictive of AAMR than either type of XM (complement-dependent lymphocytotoxicity or flow cytometry) in ROC analysis. Allograft function in this group showed significant deterioration during follow-up compared with the other groups. In conclusion, strong HLA-DSA levels at baseline are associated with worse allograft outcome even after successful desensitization; therefore, strict monitoring and strong maintenance immunosuppression may be required in such patients.
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Interleukin-6 upregulates Th17 response via mTOR/STAT3 pathway in acute-on-chronic hepatitis B liver failure.
J. Gastroenterol.
PUBLISHED: 02-19-2013
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Interleukin (IL)-17-producing CD4(+) T cells (Th17) have been shown to play crucial roles in the pathogenesis of hepatitis B virus (HBV)-associated acute-on-chronic liver failure (ACLF). However, the mechanism underlying the enhanced Th17 responses in these patients remains elusive. In this study, the relevance of the IL-6/signal transducer and activator of transcription 3 (STAT3)/mammalian target of rapamycin (mTOR)/Th17 loop in HBV-associated ACLF was investigated.
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Human adipose tissue derived mesenchymal stem cells aggravate chronic cyclosporin nephrotoxicity by the induction of oxidative stress.
PLoS ONE
PUBLISHED: 02-17-2013
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The aim of this study was to investigate whether hATMSCs protect against cyclosporine (CsA)-induced renal injury. CsA (7.5 mg/kg) and hATMSCs (3×10(6)/5 mL) were administered alone and together to rats for 4 weeks. The effect of hATMSCs on CsA-induced renal injury was evaluated by assessing renal function, interstitial fibrosis, infiltration of inflammatory cells, and apoptotic cell death. Four weeks of CsA-treatment produced typical chronic CsA-nephropathy. Combined treatment with CsA and hATMSCs did not prevent these effects and showed a trend toward further renal deterioration. To evaluate why hATMSCs aggravated CsA-induced renal injury, we measured oxidative stress, a major mechanism of CsA-induced renal injury. Both urine and serum 8-hydroxydeoxyguanosine(8-OHdG) levels were higher in the CsA+hATMSCs group than in the CsA group (P<0.05). An in vitro study showed similar results. Although the rate of apoptosis did not differ significantly between HK-2 cells cultured in hATMSCs-conditioned medium and those cultured in DMEM, addition of CsA resulted in greater apoptosis in HK-2 cells cultured in hATMSCs-conditioned medium. Addition of CsA increased oxidative stress in the hATMSCs-conditioned medium. The results of our study suggest that treatment with hATMSCs may aggravate CsA-induced renal injury because hATMSCs cause oxidative stress in the presence of CsA.
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Clinical implication of microscopic anthracotic pigment in mediastinal staging of non-small cell lung cancer by endobronchial ultrasound-guided transbronchial needle aspiration.
J. Korean Med. Sci.
PUBLISHED: 02-06-2013
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Microscopic anthracotic pigment (MAP) is frequently observed in endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) specimen in non-small cell lung cancer, but its clinical interpretation is not well-known. The aim of this study was to evaluate the clinical implication of MAP in mediastinal staging of non-small cell lung cancer. From May 2010 to July 2011, consecutive potentially operable non-small cell lung cancer patients who underwent EBUS-TBNA for mediastinal staging were recruited. Of the total 133 patients, 102 (76.7%) were male patients. Median age was 68 yr. Total 279 mediastinal lymph nodes were sampled by EBUS-TBNA; station 4R (100, 35.8%) and station 7 (86, 30.8%) were the most common sites. Malignant lymph nodes were 100 (35.8%). MAP was observed in 61 (21.7%) lymph nodes, and among them only 3 were malignant lymph nodes (P < 0.001). The lymph nodes with MAP were smaller (9.0 vs 10.8 mm, P = 0.001) and showed low standard uptake values on FDG-PET (4.4 vs 4.7, P = 0.256). In multivariate analysis, MAP was negatively associated with malignant lymph node (adjusted OR, 0.12; 95% CI, 0.03-0.42; P < 0.001). In potentially operable non-small cell lung cancer patients, MAP in endobronchial ultrasound-guided transbronchial needle aspiration specimens is strongly associated with benign mediastinal and hilar lymph nodes.
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Type III membranoproliferative glomerulonephritis in a patient with primary Sjögrens syndrome.
Clin. Nephrol.
PUBLISHED: 01-30-2013
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Renal involvement in the form of glomerulonephritis in Sjögrens syndrome (SS) is less common and usually a latent sequel in the course of the disease. We report a patient with Type III membarnoproliferative glomerulonephritis (MPGN) with hypothyroidism, which precedes the onset of the clinical manifestation of SS. She received immunosuppressions consisting of i.v. cyclophosphamide and high-dose corticosteroid and subsequently oral corticosteroid resulting in complete remission of nephrotic syndrome. To our knowledge, this is the first report of successfully treated Type III MPGN associated with SS.
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Early referral to a nephrologist improved patient survival: prospective cohort study for end-stage renal disease in Korea.
PLoS ONE
PUBLISHED: 01-25-2013
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The timing of referral to a nephrologist may influence the outcome of chronic kidney disease patients, but its impact has not been evaluated thoroughly. The results of a recent study showing an association between early referral and patient survival are still being debated. A total of 1028 patients newly diagnosed as end-stage renal disease (ESRD) from July 2008 to October 2011 were enrolled. Early referral (ER) was defined as patients meeting with a nephrologist more than a year before dialysis and dialysis education were provided, and all others were considered late referral (LR). The relationship of referral pattern with mortality in ESRD patients was explored using a Cox proportional hazards regression models. Time from referral to dialysis was significantly longer in 599 ER patients than in 429 LR patients (62.3 ± 58.9 versus 2.9 ± 3.4 months, P<0.001). Emergency HD using a temporary vascular catheter was required in 485 (47.2%) out of all patients and in 262 (43.7%) of ER compared with 223 (52.0%) of LR (P = 0.009). After 2 years of follow-up, the survival rate in ER was better than that in LR (hazard ratio [HR] 2.38, 95% confidence interval [CI] 1.27-4.45, P = 0.007). In patients with diabetes nephropathy, patient survival was also significantly higher in ER than in LR (HR 4.74, 95% CI 1.73-13.00, P = 0.002). With increasing age, HR also increased. Timely referral to a nephrologist in the predialytic stage is associated with reduced mortality.
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Predictive factors for node metastasis in patients with clinical stage I non-small cell lung cancer.
Ann. Thorac. Surg.
PUBLISHED: 01-17-2013
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Accurate clinical staging of non-small cell lung cancer (NSCLC) is essential for developing a treatment plan and evaluating suitability for minimally invasive surgery. The aim of this study was to evaluate predictive factors for metastasis of N1 and N2 nodes in clinical stage I NSCLC.
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Rifampin-associated tubulointersititial nephritis and Fanconi syndrome presenting as hypokalemic paralysis.
BMC Nephrol
PUBLISHED: 01-14-2013
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Rifampin is one of the most important drugs in first-line therapies for tuberculosis. The renal toxicity of rifampin has been reported sporadically and acute tubulointerstitial nephritis (ATIN) is a frequent histological finding. We describe for the first time a case of ATIN and Fanconi syndrome presenting as hypokalemic paralysis, associated with the use of rifampin.
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Ginseng treatment attenuates chronic cyclosporine nephropathy via reducing oxidative stress in an experimental mouse model.
Am. J. Nephrol.
PUBLISHED: 01-08-2013
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This study was performed to investigate whether ginseng extract has a protective effect in an experimental mouse model of chronic cyclosporine (CsA) nephropathy.
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Survival Advantage of Peritoneal Dialysis Relative to Hemodialysis in the Early Period of Incident Dialysis Patients: A Nationwide Prospective Propensity-Matched Study in Korea.
PLoS ONE
PUBLISHED: 01-01-2013
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The impact of dialysis modality on survival is still somewhat controversial. Given possible differences in patients characteristics and the cause and rate of death in different countries, the issue needs to be evaluated in Korean cohorts.
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Oral administration of ginseng ameliorates cyclosporine-induced pancreatic injury in an experimental mouse model.
PLoS ONE
PUBLISHED: 01-01-2013
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This study was performed to investigate whether ginseng has a protective effect in an experimental mouse model of cyclosporine-induced pancreatic injury.
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Curcumin attenuates acute graft-versus-host disease severity via in vivo regulations on Th1, Th17 and regulatory T cells.
PLoS ONE
PUBLISHED: 01-01-2013
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In this study we examined the in vivo and in vitro effects and mechanisms of action of curcumin on the development of acute graft-versus-host disease (GVHD) using a murine model.
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Small heterodimer partner-targeting therapy inhibits systemic inflammatory responses through mitochondrial uncoupling protein 2.
PLoS ONE
PUBLISHED: 01-01-2013
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The orphan nuclear receptor, small heterodimer partner (SHP), appears to play a negative regulatory role in innate immune signaling. Emerging evidence warrants further study on the therapeutic targeting of SHP to suppress excessive and deleterious inflammation. Here we show that fenofibrate, which targets SHP, is required for inhibiting systemic inflammation via mitochondrial uncoupling protein 2 (UCP2). In vivo administration of fenofibrate ameliorated systemic inflammatory responses and increased survival upon experimental sepsis through SHP. An abundance of SHP was observed in mice fed fenofibrate and in cultured macrophages through LKB1-dependent activation of the AMP-activated protein kinase pathway. Fenofibrate significantly blocked endotoxin-triggered inflammatory signaling responses via SHP, but not via peroxisome proliferator-activated receptor (PPAR)-?. In addition to the known mechanism by which SHP modulates innate signaling, we identify a new role of fenofibrate-induced SHP on UCP2 induction, which is required for the suppression of inflammatory responses through modulation of mitochondrial ROS production. These data strongly suggest that the SHP-inducing drug fenofibrate paves the way for novel therapies for systemic inflammation by targeting SHP.
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Comparison of estimating equations for the prediction of glomerular filtration rate in kidney donors before and after kidney donation.
PLoS ONE
PUBLISHED: 01-01-2013
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The aim of this study is to investigate the usefulness of the GFR-estimating equations to predict renal function in kidney donors before and after transplantation. We compared the performance of 24-hour-urine-based creatinine clearance (24 hr urine-CrCl), the Cockcroft-Gault formula (eGFRCG), the Modification of Diet in Renal Disease equation (eGFRMDRD), and the Chronic Kidney Disease Epidemiology Collaboration equation (eGFRCKD-EPI) with technetium-diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) clearance (mGFR) in 207 potential kidney donors and 108 uninephric donors. Before donation, eGFRCKD-EPI showed minimal bias and did not show a significant difference from mGFR (P?=?0.65, respectively) while 24 hr urine-CrCl and eGFRMDRD significantly underestimated mGFR (P<0.001 for each). Precision and accuracy was highest in eGFRCKD-EPI and this better performance was more dominant when renal function is higher than 90 mL·min(-1)·1.73 m(-2). After kidney donation, eGFRMDRD was superior to other equations in precision and accuracy in contrast to before donation. Within individual analysis, eGFRMDRD showed better performance at post-donation compared to pre-donation, but eGFRCKD-EPI and eGFRCG showed inferior performance at post-donation. In conclusion, eGFRCKD-EPI showed better performance compared to other equations before donation. In a uninephric donor, however, eGFRMDRD is more appropriate for the estimation of renal function than eGFRCKD-EPI.
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Comparison of adverse drug reaction profiles of two tacrolimus formulations in rats.
Immunopharmacol Immunotoxicol
PUBLISHED: 10-04-2011
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Tacrobell(®) (TB) is a generic tacrolimus which showed the comparable efficacy to original product, Prograf(®) (PG) in renal transplantation, but toxicity between two drugs is unclear. The aim of this study was to compare the toxicity between these two formulations. TB and PG (0.5, 1 and 2?mg/kg/day) was administered to rats for 4 weeks. The rat survival rate, kidney, liver and pancreas injury was investigated. The survival rate was similar between TB- and PG-treated rats. TB and PG induced renal dysfunction in a dose-dependent manner. Compared to PG treatment in equal dose, TB treatment reduced urinary creatinine clearance in a less degree and renal interstitial fibrosis was comparable between two regimens. The r-glutamyl transpeptidase was aggravated by tacrolimus treatment, and this was not different between TB and PG treatment. In the intraperitoneal glucose tolerance test, a significant diabetogenic effect was observed in all tacrolimus treated-rats. The glucose tolerance of TB-treated rats was similar to those of PG-treated rats in each dose. The decrement in pancreatic ?-cell mass by tacrolimus showed the dose-dependent response and it was comparable between TB and PG treatment. In conclusion, TB is similar to PG in terms of nephrotoxicity, hepatoxicity and diabetogenic effect.
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