As a new humanized monoclonal antibody against the interleukin-6 receptor, tocilizumab is currently used for the treatment of rheumatoid arthritis (RA) patients. Tocilizumab was reported to provoke drug-related liver toxicity, although there have been no reports on significant liver toxicity from tocilizumab in Korean patients with RA to date. Here, we describe the first case of tocilizumab-related liver toxicity in a patient with complicated RA, accompanied with macrophage activation syndrome, who had received tacrolimus and prednisolone and in whom both conventional disease modifying anti-rheumatic drugs, including methotrexate, leflunomide and sulfasalazine or tumor necrotizing factor-alpha blockades, were contraindicated due to drug eruption and a history of lung cancer.
Antirheumatic Agents ; Arthritis, Rheumatoid* ; Drug Eruptions ; Humans ; Interleukin-6 ; Liver ; Lung Neoplasms ; Macrophage Activation Syndrome* ; Macrophage Activation* ; Macrophages* ; Methotrexate ; Prednisolone ; Sulfasalazine ; Tacrolimus ; Tranexamic Acid*

The aim of this study was to prepare inclusion nanocomplexes of hyaluronic acid-β-cyclodextrin and simvastatin (HA-β-CD/SIM) and evaluate in vitro anti-inflammation effects on lipopolysaccharide (LPS)-activated synoviocytes and chondrogenic differentiation effects on rat adipose-derived stem cells (rADSCs). The β-CD moieties in HA-β-CD could incorporate SIM to form HA-β-CD/SIM nanocomplexes with diameters of 297–350 nm. HA-β-CD/SIM resulted in long-term release of SIM from the nanocomplexes for up to 63 days in a sustained manner. In vitro studies revealed that HA-β-CD/SIM nanocomplexes were able to effectively and dose-dependently suppress the mRNA expression levels of proinflammatory markers such as matrix metallopeptidase-3 (MMP-3), MMP-13, cyclooxygenase-2 (COX-2), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), interleukin-6 (IL-6), and tumor necrosis factor (TNF-α) in LPS-stimulated synoviocytes. HA-β-CD/SIM-treated rADSCs significantly and dose-dependently enhanced mRNA expressions of aggrecan, collagen type II (COL2A1), and collagen type X (COL10A1), implying that HA-β-CD/SIM greatly induced the chondrogenic differentiation of rADSCs. Conclusively, HA-β-CD/SIM nanocomplexes will be a promising therapeutic material to alleviate inflammation as well as promote chondrogenesis.
Aggrecans ; Animals ; Chondrogenesis ; Collagen Type II ; Collagen Type X ; Cyclooxygenase 2 ; In Vitro Techniques* ; Inflammation ; Interleukin-6 ; Rats ; RNA, Messenger ; Simvastatin* ; Stem Cells ; Thrombospondins ; Tumor Necrosis Factor-alpha

Tuberous sclerosis is a rare disease, which occurs sporadically or hereditarily and is recognized by its neurological and dermatological manifestations and may be accompanied with renal anomalies. The classical triad is composed of seizure, mental retardation and adenoma sebaceum on face. We experienced two cases of tuberous sclerosis in sporadic forms by mutation without any familial history which suggests the diseases were occurred by mutation rather than by autosomal dominant inheritance. In the first case, a 24-year-female patient with hypertension and abnormal renal function tests which were noted on the routine prenatal check at 32 weeks of gestation delivered normally at 37 weeks. The daughter of patient had seizure when she was 6 years old and was diagnosed as polycystic kidney disease by abdominal computed tomography. This case developed sporadic form of disease without familial history but, the daughter of patient might inherited by autosomal dominant form. The patient's clinical feature was characterized by history of epilepsy, painless abdominal mass due to polycystic kidney disease, abnormal renal function, skin abnormalites including angiofibroma and shagreen patch. Abdominal computed tomography demonstrated numerous variable sized cysts throughout both kidney. In second case, the patient was a 32-year-female patient complaining of 5kg weight gain, abdominal distension due to palpable masses. Her clinical feature was characterized by bilateral huge renal angiomyolipoma with normal renal function and skin abnormality such as erythematous papule on the face. Abd CT and MRI revealed huge angiomyolipoma of about 15cm X 18.5cm X 30cm and 14.5cm X 18cm X 30cm respectively. We presented the two cases with brief review of the literatures.
Angiofibroma ; Angiomyolipoma ; Child ; Epilepsy ; Humans ; Hypertension ; Intellectual Disability ; Kidney ; Magnetic Resonance Imaging ; Nuclear Family ; Polycystic Kidney Diseases ; Pregnancy ; Rare Diseases ; Seizures ; Skin ; Skin Abnormalities ; Tuberous Sclerosis* ; Weight Gain ; Wills

BACKGROUND: Many epidemiologic studies have reported on the controversial concept of the obesity paradox. The presence of acute kidney injury (AKI) can accelerate energy-consuming processes, particularly in patients requiring continuous renal replacement therapy (CRRT). Thus, we aimed to investigate whether obesity can provide a survival benefit in this highly catabolic condition. METHODS: We conducted an observational study in 212 patients who had undergone CRRT owing to various causes of AKI between 2010 and 2014. The study end point was defined as death that occurred within 30 days after the initiation of CRRT. RESULTS: Patients were categorized into three groups according to tertiles of body mass index (BMI). During ≥30 days after the initiation of CRRT, 39 patients (57.4%) in the highest tertile died, as compared with 58 patients (78.4%) in the lowest tertile (P = 0.02). In a multivariable analysis adjusted for cofounding factors, the highest tertile of BMI was significantly associated with a decreased risk of death (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.37–0.87; P = 0.01). This significant association remained unaltered for 60-day (HR, 0.64; 95% CI, 0.43–0.94; P = 0.03) and 90-day mortality (HR, 0.66; 95% CI, 0.44–0.97; P = 0.03). CONCLUSION: This study showed that a higher BMI confer a survival benefit over a lower BMI in AKI patients undergoing CRRT.
Acute Kidney Injury* ; Body Mass Index* ; Epidemiologic Studies ; Humans ; Mortality* ; Obesity ; Observational Study ; Renal Replacement Therapy*

Barium sulfate is an inert material used as a radiographic contrast medium during upper gastrointestinal contrast studies for evaluation of patients with dysphagia. Oral barium aspiration is an uncommon but well-reported complication of this procedure. While barium aspiration of small amounts may not cause any symptoms, massive barium aspiration can be life-threatening, particularly in elderly patients with multiple comorbidities. In this case report, we describe an elderly patient with multiple comorbidities who presented with thyrotoxicosis and dysphagia, and then died after massive barium aspiration. Despite administration of intensive medical care with ventilator support and therapeutic bronchoalveolar lavage to remove the aspirated barium, the patient died of multiple organ failure 9 days after barium aspiration. Clinicians should pay attention to elderly patients with predisposing factors for aspiration in whom upper gastrointestinal barium contrast studies are indicated, and should consider other diagnostic tools for evaluation of dysphagia in this population.
Aged* ; Barium Sulfate* ; Barium* ; Bronchoalveolar Lavage ; Causality ; Comorbidity ; Deglutition Disorders* ; Humans ; Multiple Organ Failure ; Thyrotoxicosis ; Ventilators, Mechanical

PURPOSE: The aim of study was to compare the differentiation capacity of mesenchymal stem cells (MSCs) obtained from human bone marrow (BM) according to the age of the donors. MATERIALS AND METHODS: MSCs were isolated from the BM of young (n=16, 12.5+/-5.8 years) and elder (n=4, 48.5+/-7.2 years) patients with the consent of them. We analyzed the cell morphology and the cell surface markers of the MSCs. In addition, we assessed the cell senescence with serial cultures from both age groups. Cell pluripotentiality was analyzed by osteogenic, chondrogenic, and adipogenic induction media. We performed RT-PCR, a measurement of expression of alkaline phosphatase, and staining with von Kossa, safranin O, and oil red O stain. RESULTS: All of the MSC samples tested, irrespective of the age of the donors, MSCs were all successfully isolated from twenty bone marrows. However, the number of cells of from the young donors was five times greater than that of the elderly donors. Senescence was observed over 10 passages in both age groups. The immunophenotypes of both age groups showed similar patterns. MSCs obtained from young and older donors showed the potential to differentiate into osteogenic, chondrogenic, and adipogenic lineages with no difference for both age groups. CONCLUSION: Our study supports that age does not influence the pluripotential capacity of human BM derived MSCs.
Aged ; Aging* ; Alkaline Phosphatase ; Bone Marrow* ; Cell Aging ; Humans* ; Mesenchymal Stromal Cells* ; Tissue Donors

BACKGROUND: Cardiovascular disease and chronic kidney disease share several common risk factors. The Framingham risk score is hypothesized to predict chronic kidney disease development. We determined if the Framingham risk scoring system can correctly predict incident chronic kidney disease in the general population. METHODS: This study included 9,080 subjects who participated in the Korean Genome and Epidemiology Study between 2001 and 2014 and had normal renal function. The subjects were classified into low- (< 10%), intermediate- (10–20%), and high- (> 20%) risk groups based on baseline Framingham risk scores. The primary endpoint was de novo chronic kidney disease development (estimated glomerular filtration rate [eGFR], < 60 mL/min/1.73 m²). RESULTS: During a mean follow-up duration of 8.9 ± 4.3 years, 312 (5.3%), 217 (10.8%), and 205 (16.9%) subjects developed chronic kidney disease in the low, intermediate, and high risk groups, respectively (P < 0.001). Multivariable analysis after adjustment for confounding factors showed the hazard ratios for the high- and intermediate risk groups were 2.674 (95% confidence interval [CI], 2.197–3.255) and 1.734 (95% CI, 1.447–2.078), respectively. This association was consistently observed irrespective of proteinuria, age, sex, obesity, or hypertension. The predictive power of this scoring system was lower than that of renal parameters, such as eGFR and proteinuria, but increased when both were included in the prediction model. CONCLUSION: The Framingham risk score predicted incident chronic kidney disease and enhanced risk stratification in conjunction with traditional renal parameters in the general population with normal renal function.
Cardiovascular Diseases ; Cohort Studies ; Epidemiology ; Follow-Up Studies ; Genome ; Glomerular Filtration Rate ; Hypertension ; Obesity ; Prospective Studies ; Proteinuria ; Renal Insufficiency, Chronic ; Risk Factors

The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations without a race coefficient have gained recognition across the United States. We aimed to test whether these new equations performed well in Korean patients with chronic kidney disease (CKD). Methods: This study included 2,149 patients with CKD G1–G5 without kidney replacement therapy from the Korean Cohort Study for Outcome in Patients with CKD (KNOW-CKD). The estimated glomerular filtration rate (eGFR) was calculated using the new CKD-EPI equations with serum creatinine and cystatin C. The primary outcome was 5-year risk of kidney failure with replacement therapy (KFRT). Results: When we adopted the new creatinine equation [eGFRcr (NEW)], 81 patients (23.1%) with CKD G3a based on the current creatinine equation (eGFRcr) were reclassified as CKD G2. Accordingly, the number of patients with eGFR of <60 mL/min/1.73 m2 decreased from 1,393 (64.8%) to 1,312 (61.1%). The time-dependent area under the receiver operating characteristic curve for 5-year KFRT risk was comparable between the eGFRcr (NEW) (0.941; 95% confidence interval [CI], 0.922–0.960) and eGFRcr (0.941; 95% CI, 0.922–0.961). The eGFRcr (NEW) showed slightly better discrimination and reclassification than the eGFRcr. However, the new creatinine and cystatin C equation [eGFRcr-cys (NEW)] performed similarly to the current creatinine and cystatin C equation. Furthermore, eGFRcr-cys (NEW) did not show better performance for KFRT risk than eGFRcr (NEW). Conclusion: Both the current and the new CKD-EPI equations showed excellent predictive performance for 5-year KFRT risk in Korean patients with CKD. These new equations need to be further tested for other clinical outcomes in Koreans.

BACKGROUND: Aldosterone-induced glomerular hyperfiltration can lead to masked preoperative renal dysfunction in primary aldosteronism(PA) patients. We evaluated whether PA patients had a higher prevalence of acute kidney injury (AKI) after unilateral adrenalectomy. In addition, we identified risk factors for AKI in these subjects. METHODS: This retrospective study included 107 PA patients, and 186 pheochromocytoma patients as a control group, all of whom underwent adrenalectomy between January 2006 and November 2017 at Yonsei University Severance Hospital. The primary outcome was AKI within 48 hours after adrenalectomy. Univariate and multivariate logistic regression analyses were performed to identify predictors of AKI after adrenalectomy. RESULTS: Overall incidence of AKI was 49/293 (16.7%). In PA patients, the incidence of AKI was 29/107 (27.1%). In contrast, incidence of AKI was 20/186 (10.7%) in pheochromocytoma patients. Univariate and multivariate logistic regression analysis both showed a higher risk of postoperative AKI in PA patients compared to pheochromocytoma patients. In addition, old age, diabetes, longer duration of hypertension, lower preoperative estimated glomerular filtration rate, high aldosterone-cortisol ratio (ACR) and lateralization index (LI) were identified as independent risk factors for postoperative AKI in PA patients after unilateral adrenalectomy. CONCLUSION Incidence and risk of postoperative AKI were significantly higher in PA patients after surgical treatment. High ACR on the tumor side and high LI were associated with higher risk of AKI in PA patients compared to pheochromocytoma patients.