Prognostic implication of elevated cardiac troponin I in patients visiting emergency department without diagnosis of coronary artery disease.

OBJECTIVES: Elevated cardiac troponin is not uncommon in patients visiting emergency department (ED) even without coronary artery disease, but its prognostic implication is not well understood in such patients. METHODS: In this retrospective single-center registry, we investigated clinical outcome of patients visiting ED without documented coronary artery disease. Patients were categorized according to the maximal value of Siemens ADVIA Centaur TnI-Ultra assay (TnI) within 24 h after visit. Primary endpoint was 180-day all-cause death that included cardiac and non-cardiac death. RESULTS: A total of 35,205 patients with median age 61 years and male gender 54.7% were included. Below the lowest level of detection (LOD) (≤0.006 ng/mL), between LOD and assay-specific <99th percentile (0.007-0.039 ng/mL), below median of ≥99th percentile (0.040-0.149 ng/mL), and above median of ≥99th percentile (≥0.150 ng/mL) TnI were found in 18,502 (52.6%), 11,338 (32.2%), 3,029 (8.6%), and 2,336 (6.6%) patients. In the 180-day follow-up period, 4,341 (12.3%) all-cause death including 694 (2.0%) cardiovascular death and 3,647 (10.4%) non-cardiovascular death developed. The risks of all-cause, cardiovascular, and non-cardiovascular death increased across higher TnI strata (hazard ratio [HR]=1.3 to 2.4; 2.0 to 9.3; 1.3 to 1.7; p<0.001, all). Analyses of multivariate models showed consistent results. CONCLUSIONS: In patients visiting ED, elevated TnI was associated with higher risk of 180-day cardiovascular and non-cardiovascular death. Patients with elevated TnI may need additional evaluation or careful follow-up even without primary diagnosis of coronary artery disease.

Effects of the methanol fraction of modified Seonghyangjeongki-san water extract on transient ischaemic brain injury in mice.

CONTEXT: Recently in Korean medicine, the antioxidant and anti-inflammatory activities of Seonghyangjeongki-san (SHJKS) were reported. However, studies on the specific mechanisms of action of SHJKS for the treatment of ischaemic stroke are still lacking. OBJECTIVE: This study investigates the mechanism of action of the water extract methanol fraction of modified SHJKS (SHJKSmex) on cerebral ischaemic injury. MATERIALS AND METHODS: C57BL/6 male mice were orally administered SHJKSmex (30, 100, or 300 mg/kg) for 3 consecutive days (2 days, 1 day, and 1 h, respectively) before middle cerebral artery occlusion (MCAO). Twenty-four hours after MCAO, the infarct volumes were measured, brain edoema indices were calculated, and neurological deficit scores were determined. Inflammation-related substances in the ipsilateral hemisphere were determined by western blotting, dichlorofluorescin diacetate, thiobarbituric acid-reactive substances assay, and enzyme-linked immunosorbent assay. RESULTS: SHJKSmex pre-treatment at 300 mg/kg decreased infarct volume by 87% and mean brain water content by 90% of the MCAO control group. Moreover, SHJKSmex effectively suppressed the expression of inducible nitric oxide synthase, reactive oxygen species, interleukin 1, and caspases-8 and -9 and increased the B-cell lymphoma 2/Bcl-2-associated X protein ratio (Bcl-2/Bax) in ischaemic mouse brain. The hippocampal pyramidal cell densities were significantly increased in the 300 mg/kg SHJKSmex-administered group compared to the MCAO control group. DISCUSSION AND CONCLUSIONS: SHJKSmex protected the brain from ischaemic stroke in mice through its antioxidant, anti-inflammatory, and antiapoptotic activities. Our findings suggest that SHJKSmex is a promising therapeutic candidate for the development of a new formulation for ischaemia-induced brain damage.

Pregnenolone as a potential candidate for hormone therapy for female reproductive disorders targeting ERß.

Many steroid hormones such as estrogen (E2) bind to their receptors for the regulation of biological processes. Pregnenolone (P5) is the precursor form of almost all steroid hormones and is often used to treat skin disorders and neurological complications. However, the mechanism and physiological function of P5 in reproductive organs are not well established. In this study, we investigated the effects of P5 on activation and expression of E2 receptor (ER) in the uteri and ovaries. To study the mechanism of P5 directly, Ishikawa cells were transfected with E2 response element (ERE)-luciferase plasmid and isoforms of ER. ERE-luciferase activity induced by P5 was similar to that induced by E2, and P5 showed high activity for ERß without any relevance to P5-metabolizing hormones such as progesterone (P4) and E2. In an animal study, immature female rats treated with P5 showed upregulation of ERα and downregulation of ERß in the uteri, which is the main organ expressing ERα. In ERß-expressing organ ovaries, estrogen receptor 1, estrogen receptor 2, and P4 receptor were all downregulated by P5 and E2. Also, a decrease of ovarian cell proliferation and viability was observed in response to P5 relative to the control, suggesting that P5 may be a candidate for antiproliferative hormone of ovarian cancer. These findings suggest that P5 stimulates ERE promoter by ERß-mediated signaling in the uteri and ovaries. Activation of ERß by P5 may help in understanding the mechanism of ER-related female reproductive diseases such as endometriosis and ovarian cancer.

Usefulness of serum leucine-rich alpha-2 glycoprotein as a disease activity biomarker in patients with rheumatoid arthritis.

Our study aimed to investigate whether serum leucine-rich alpha-2-glycoprotein (LRG) levels are elevated in patients with rheumatoid arthritis (RA). In addition, we assessed their correlation with disease activity parameters and pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α). Our study included 69 patients with RA and 48 age- and sex-matched healthy controls. Serum concentrations of TNF-α and LRG were determined by enzyme-linked immunosorbent assay. Serum LRG concentrations were significantly elevated in patients with RA compared with those in healthy controls (30.8 ± 14.4 vs. 22.2 ± 6.1 ng/mL; P<0.001). In patients with RA, serum LRG levels were found to be correlated with disease activity score 28 (DAS28), erythrocyte sedimentation rate, and C-reactive protein levels (γ=0.671; γ=0.612; and γ=0.601, P<0.001, respectively), but not with serum TNF-α levels. Serum LRG levels in patients with an active disease status (DAS28≥2.6) were significantly higher than those in remission (DAS28<2.6) (36.45 ± 14.36 vs. 24.63 ± 8.81 ng/mL; P<0.001). Our findings suggest that serum LRG could contribute to the inflammatory process independent of TNF-α and it may be a novel biomarker for assessing inflammatory activity in patients with RA.

New molecular bridge between RelA/p65 and NF-κB target genes via histone acetyltransferase TIP60 cofactor.

The nuclear factor-κB (NF-κB) family is involved in the expressions of numerous genes, in development, apoptosis, inflammatory responses, and oncogenesis. In this study we identified four NF-κB target genes that are modulated by TIP60. We also found that TIP60 interacts with the NF-κB RelA/p65 subunit and increases its transcriptional activity through protein-protein interaction. Although TIP60 binds with RelA/p65 using its histone acetyltransferase domain, TIP60 does not directly acetylate RelA/p65. However, TIP60 maintained acetylated Lys-310 RelA/p65 levels in the TNF-α-dependent NF-κB signaling pathway. In chromatin immunoprecipitation assay, TIP60 was primarily recruited to the IL-6, IL-8, C-IAP1, and XIAP promoters in TNF-α stimulation followed by acetylation of histones H3 and H4. Chromatin remodeling by TIP60 involved the sequential recruitment of acetyl-Lys-310 RelA/p65 to its target gene promoters. Furthermore, we showed that up-regulated TIP60 expression was correlated with acetyl-Lys-310 RelA/p65 expressions in hepatocarcinoma tissues. Taken together these results suggest that TIP60 is involved in the NF-κB pathway through protein interaction with RelA/p65 and that it modulates the transcriptional activity of RelA/p65 in NF-κB-dependent gene expression.

Transcription factor Sox4 is required for PUMA-mediated apoptosis induced by histone deacetylase inhibitor, TSA.

PUMA is a crucial regulator of apoptotic cell death mediated by p53-dependent and p53-independent mechanisms. In many cancer cells, PUMA expression is induced in response to DNA-damaging reagent in a p53-dependent manner. However, few studies have investigated transcription factors that lead to the induction of PUMA expression via p53-independent apoptotic signaling. In this study, we found that the transcription factor Sox4 increased PUMA expression in response to trichostatin A (TSA), a histone deacetylase inhibitor in the p53-null human lung cancer cell line H1299. Ectopic expression of Sox4 led to the induction of PUMA expression at the mRNA and protein levels, and TSA-mediated up-regulation of PUMA transcription was repressed by the knockdown of Sox4. Using luciferase assays and chromatin immunoprecipitation, we also determined that Sox4 recruits p300 on the PUMA promoter region and increases PUMA gene expression in response to TSA treatment. Taken together, these results suggest that Sox4 is required for p53-independent apoptotic cell death mediated by PUMA induction via TSA treatment.

Longitudinal Assessment of Retinal Nerve Fiber Layer and Ganglion Cell Complex Thicknesses in Patients With Large Optic Disc Cups and Normal Intraocular Pressure and Visual Fields.

PRCIS: The thicknesses of the circumpapillary retinal nerve fiber layer (cpRNFL) and ganglion cell complex (GCC) did not change during 5 years in physiological large disc cupping. PURPOSE: We evaluated longitudinal changes in the thicknesses of the cpRNFL and GCC in large disc cupping with a normal intraocular pressure (IOP) (<21 mm Hg) and visual field. METHODS: This retrospective, consecutive case series study included 269 eyes of 269 patients with large disc cupping and normal IOP. We analyzed patient demographics, IOP, central corneal thickness, vertical cup-to-disc ratios using color fundus photography, the thicknesses of the cpRNFL and GCC using RTVue-100, and mean deviation using visual field examinations. RESULTS: The differences in IOP, vertical cup-to-disc ratios, and mean deviation between the baseline and each follow-up visit were not statistically significant. The baseline average and mean average at 60 months follow-up of the cpRNFL thickness were 106.5±8.5 and 105.1±9.3 µm, respectively; differences between the baseline and each follow-up visit were not statistically significant. The baseline average and mean average at 60 months follow-up of the GCC thickness were 82.8±9. and 81.5±9.2 µm, respectively; differences between baseline and each follow-up visit were not statistically significant. CONCLUSIONS: The thicknesses of the cpRNFL and GCC did not change in well-maintained optic nerve head findings with normal IOP and visual field during a 5-year follow-up period. Optical coherence tomography evaluations of the thicknesses of the cpRNFL and GCC help accurately diagnose physiological optic disc cupping.

Gelsolin negatively regulates the activity of tumor suppressor p53 through their physical interaction in hepatocarcinoma HepG2 cells.

As a transcription factor, p53 modulates several cellular responses including cell-cycle control, apoptosis, and differentiation. In this study, we have shown that an actin regulatory protein, gelsolin (GSN), can physically interact with p53. The nuclear localization of p53 is inhibited by GSN overexpression in hepatocarcinoma HepG2 cells. Additionally, we demonstrate that GSN negatively regulates p53-dependent transcriptional activity of a reporter construct, driven by the p21-promoter. Furthermore, p53-mediated apoptosis was repressed in GSN-transfected HepG2 cells. Taken together, these results suggest that GSN binds to p53 and this interaction leads to the inhibition of p53-induced apoptosis by anchoring of p53 in the cytoplasm in HepG2 cells.

Beekeeping Genetic Resources and Retrieval of Honey Bee Apis mellifera L. Stock in the Russian Federation: A Review.

The loss of honey bees has drawn a large amount of attention in various countries. Therefore, the development of efficient methods for recovering honey bee populations has been a priority for beekeepers. Here we present an extended literature review and report on personal communications relating to the characterization of the local and bred stock of honey bees in the Russian Federation. New types have been bred from local colonies (A. mellifera L., A. m. carpatica Avet., A. m. caucasia Gorb.). The main selection traits consist of a strong ability for overwintering, disease resistance and different aptitudes for nectar collection in low and high blooming seasons. These honey bees were certified by several methods: behavioral, morphometric and genetic analysis. We illustrate the practical experience of scientists, beekeepers and breeders in breeding A. mellifera Far East honey bees with Varroa and tracheal mite resistance, which were the initial reasons for breeding the A. mellifera Far Eastern breed by Russian breeders, Russian honey bee in America, the hybrid honey bee in Canada by American breeders, and in China by Chinese beekeepers. The recent achievements of Russian beekeepers may lead to the recovery of beekeeping areas suffering from crossbreeding and losses of honey bee colonies.

Effects of cigarette smoke on Haemophilus influenzae-induced otitis media in a rat model.

Exposure to cigarette smoke (CS) is a factor that could delay or worsen the recovery of otitis media (OM) by causing inflammatory swelling of the Eustachian tube (ET). However, despite the suggested relationship, little is known about the association between OM and CS. Therefore, we aimed to evaluate the effects of CS on the development, progression, and recovery of OM, as well as the histological and molecular changes caused by CS exposure, by using a rat model of OM infected with non-typeable Haemophilus influenzae (NTHi). Eighty Sprague-Dawley rats with normal middle ears (MEs) were divided into four groups (n = 20 rats/group): control, CS, OM, and CS + OM. The CS and CS + OM groups were exposed to CS for 2 weeks. The inflammatory reaction to NTHi was more intense and lasted longer in the CS + OM group than in the other groups. Goblet cell proliferation and mucus secretion in the ET were more significant in the CS and CS + OM groups than in the other groups. These findings suggested that because CS directly affects the ET and ME mucosa, bacterial OM can become more severe and may resolve more slowly in the presence of CS exposure rather than in its absence.

Risk factors related to unnecessary emergency medical services transport for pediatric patients.

OBJECTIVES: This study evaluated unnecessary emergency medical services (EMS) transport for pediatric patients depending on whether they received emergency department (ED) treatment after EMS transport. METHODS: Pediatric patients were divided into two groups according to whether they received treatment at the ED (ED treatment) or did not receive treatment at the ED (non-ED treatment). RESULTS: The non-ED treatment group comprised 65 of the total 794 patients. The elapsed time from scene to arrival at the ED was longer in the non-ED treatment group than in the ED treatment group. Weekdays as the days of EMS transport, ground falls rather than traffic accidents as the reason for non-disease-related symptoms, and no immobilization for prehospital treatment were risk factors for non-ED treatment in EMS-transported patients. Causes of not receiving ED treatment for the non-ED treatment group were the patient's or caregiver's decision (12%) and the doctor's suggestion (88%). CONCLUSIONS: Weekdays rather than weekends, ground falls rather than traffic accidents, and no immobilization before hospital are risk factors for not receiving ED treatment. The most common cause of not receiving ED treatment is the doctor's suggestion.

Effect of Watch-Type Haptic Metronome on the Quality of Cardiopulmonary Resuscitation: A Simulation Study.

OBJECTIVES: The aim of this study was to test the applicability of haptic feedback using a smartwatch to the delivery of cardiac compression (CC) by professional healthcare providers. METHODS: A prospective, randomized, controlled, case-crossover, standardized simulation study of 20 medical professionals was conducted. The participants were randomly assigned into haptic-first and non-haptic-first groups. The primary outcome was an adequate rate of 100-120/min of CC. The secondary outcome was a comparison of CC rate and adequate duration between the good and bad performance groups. RESULTS: The mean interval between CCs and the number of haptic and non-haptic feedback-assisted CCs with an adequate duration were insignificant. In the subgroup analysis, both the good and bad performance groups showed a significant difference in the mean CC interval between the haptic and non-haptic feedback-assisted CC groups-good: haptic feedback-assisted (0.57-0.06) vs. non-haptic feedback-assisted (0.54-0.03), p < 0.001; bad: haptic feedback-assisted (0.57-0.07) vs. non-haptic feedback-assisted (0.58-0.18), p = 0.005-and the adequate chest compression number showed significant differences- good: haptic feedback-assisted (1,597/75.1%) vs. non-haptic feedback-assisted (1,951/92.2%), p < 0.001; bad: haptic feedbackassisted (1,341/63.5%) vs. non-haptic feedback-assisted (523/25.4%), p < 0.001. CONCLUSIONS: A smartwatch cardiopulmonary resuscitation feedback system could not improve rescuers' CC rate. According to our subgroup analysis, participants might be aided by the device to increase the percentage of adequate compressions after one minute.

Epigenetically altered miR-1247 functions as a tumor suppressor in pancreatic cancer.

Altered expression of microRNAs has been strongly implicated in human cancers, and growing evidence is emerging that a number of miRNAs are downregulated in cancer associated with CpG island hypermethylation. Although pancreatic cancer is one of the most malignant human cancers, the roles of miRNAs underlying the tumorigenesis of pancreatic cancer are still poorly understood. In the present study, we explored the molecular functional role of microRNA-1247 as tumor suppressor associated with epigenetic alteration in pancreatic cancer. CpG islands methylation of miR-1247 is frequently observed in various pancreatic cancer cell lines and in primary pancreatic tumors, but not in normal pancreatic tissue. Ectopic expression of miR-1247 in five pancreatic cancer cell lines results in suppressing of cell growth, proliferation, migration, and invasion in vitro and tumorigenicity of pancreatic cancer cells in vivo. Interestingly, we found one putative target gene of miR-1247, regulator of chromosome condensation 2 (RCC2), harbored miR-1247 target sequences in the 3' UTR of its mRNA. In functional studies in vitro to understand the interaction between miR-1247 and RCC2, decreasing of RCC2 gene expression by miR-1247 was observed by immunoblotting and immunohistochemistry at both mRNA and protein levels. Moreover, luciferase reporter assay confirmed that RCC2 was a direct target of miR-1247. Taken together, our data suggest that CpG island hypermethylation of miR-1247 is responsible for its downregulation in pancreatic cancer, and ectopic expression of miR-1247 functions as a potential tumor suppressor targeting RCC2 in pancreatic cancer cells.

Combinatorial effects of an epigenetic inhibitor and ionizing radiation contribute to targeted elimination of pancreatic cancer stem cell.

Pancreatic cancer is associated with a high mortality rate, owing to de novo and acquired drug resistance, thereby leading to highly invasive and metastatic pancreatic cancer cells. Therefore, targeting pancreatic cancer stem cells (CSCs) may be a novel therapeutic strategy for the treatment of pancreatic cancer. Here, we combined a DNA methylation inhibitor (5-aza-2'-deoxycytidine; 5-aza-dC) and ionizing radiation (IR) to improve anti-cancer effects by inhibiting growth and proliferation and promoting apoptosis of pancreatic cancer cells in vitro and in vivo. Importantly, the combinatorial effect of 5-aza-dC with IR on sphere-forming pancreatic cancer cells was preferentially targeted toward CSCs through the downregulation of regulatory factors of self-renewal and CSC surface markers. We next performed the RNA sequencing to understand the underlying cellular mechanisms of the combined treatment with IR and 5-aza-dC in pancreatic cancer cells. Global transcriptome profiling indicated that the expression of the Oct4-centered transcriptional network of genes was significantly downregulated in cells with combination treatment. Our data suggested that combination treatment with DNA methylation inhibitor and IR may be a novel therapeutic strategy for pancreatic cancer. Overall, these findings support the use of epigenetic therapy in combination with radiotherapy to improve therapeutic efficacy by targeting and eradicating pancreatic CSCs.

Pregnenolone sulfate regulates prolactin production in the rat pituitary.

Pregnenolone sulfate (PS) is a neuroactive steroid hormone produced in the brain. In this study, the effects of PS on synthesis and secretion of rat pituitary prolactin (PRL) were examined. To accomplish this, GH3 rat pituitary adenoma cells were treated with PS, which showed significantly increased mRNA and protein levels of PRL compared with the control. The mechanism of action responsible for the effects of PS on PRL synthesis and secretion was investigated by pretreating cells with inhibitors of traditional PRL- or the PS-related signaling pathway. PS-stimulated PRL transcription was significantly reduced by inhibitors of PKA, PKC and MAPK, but unchanged by GABAAR and NMDAR inhibitors. Western blotting analysis revealed that the total ERK1/2 level was upregulated in a time-dependent manner following PS treatment. An approximate 10% increase in GH3 cell proliferation was also observed in response to PS relative to the control. In the animal study, levels of PRL in the pituitary and in serum were elevated by PS. PS-stimulated PRL synthesis was also found to be associated with decreased expression of PRL target genes such as GNRH1, FSHB and LHB. These findings show that PS upregulates PRL synthesis and secretion in vivo and in vitro via MAPK signaling, suggesting that it has the potential for use as a therapeutic hormone to treat PRL-related disorders such as hypoprolactinemia and low milk supply.

Psoriatic arthritis: latest treatments and their place in therapy.

Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory disease that may affect peripheral and axial joints, entheses, skin and nails, and other organs. Treatment with nonsteroidal anti-inflammatory drugs, steroid and disease-modifying antirheumatic drugs had been the backbone of traditional management of PsA for many years. However, improvement in our understanding of immunopathogenesis of PsA has led to new immunomodulatory therapies. Introduction of novel agents has raised the bar for treatment and helped drive research into additional therapeutic options.

The adverse effect of 4-tert-octylphenol on fat metabolism in pregnant rats via regulation of lipogenic proteins.

Alkylphenols such as 4-tert-octylphenol (OP), nonylphenol, and bisphenol A are classified as endocrine-disrupting chemicals (EDCs). Digestion and metabolism of food are controlled by many endocrine factors, including insulin, glucagon, and estrogen. These factors are differentially regulated during pregnancy. The alteration of nutritional intake and fat metabolism may affect the maintenance of pregnancy and supplementation of nutrients to the fetus, and therefore can cause severe metabolic diseases such as ketosis, marasmus and diabetes mellitus in pregnant individuals. In this study, we examined the effects of OP on fat metabolism in pregnant rats. Ethinyl estradiol (EE) was also administered as an estrogenic positive control. In our results, rats treated with OP showed significantly reduced body weights compared to the control group. In addition, histological analysis showed that the amount of fat deposited in adipocytes was reduced by OP treatment. To study the mechanism of action of OP in fat metabolism, we examined the expression levels of fat metabolism-associated genes in rat adipose tissue and liver by real-time PCR. OP and EE negatively regulated the expression of lipogenic enzymes, including FAS (fatty acid synthase), ACC-1 (acetyl-CoA carboxylase-1), and SCD-1 (stearoyl-CoA desaturase-1). The levels of lipogenic enzyme-associated transcription factors such as C/EBP-α (CAAT enhancer binding protein alpha) and SREBP-1c (sterol regulatory element binding protein-1c) were also reduced in both liver and adipose tissue. In summary, these findings suggest that OP has adverse effects on fat metabolism in pregnant rats and inhibits fat deposition via regulating lipogenic genes in the liver and adipose tissue. The altered fat metabolism by OP may affect the nutrition balance during pregnancy and can cause metabolism-related diseases.

Immunologic and non-immunologic complications of a third kidney transplantation.

BACKGROUND/AIMS: Patients who undergo repeat kidney transplantations (KTs) are considered at high risk for experiencing immunologic and non-immunologic complications. In this study, we investigated the clinical outcomes, including medical and surgical complications, of patients who underwent a third KT at our center. METHODS: Between March 1969 and December 2012, a total of 2,110 KTs were performed at the Seoul St. Mary's Hospital. Of them, we examined 11 patients who underwent a third KT, and investigated the allograft outcomes and complication rates. RESULTS: The mean follow-up duration after KT was 72.4 ± 78.3 months. The mean age at KT was 38.2 ± 8.0 years, and seven patients (63.6%) were males. Nine patients (81.8%) underwent living-donor KT. A cross-match test yielded positive results in four of the nine patients, and all underwent pretransplant desensitization therapy. After KT, three patients (27.2%) showed delayed graft function. Acute rejection developed in four patients (36.4%), and surgical complications that required surgical correction occurred in three patients. Allograft failure developed due to acute rejection (n = 3) or chronic rejection (n = 1) in four patients. Allograft survival rates at 1, 5, and 10 years were 81.8%, 42.9%, and 42.9%, respectively; however, the allograft survival rate at 5 years was > 80% in patients who underwent KT only after results of the panel reactive antibody test became available. CONCLUSIONS: Thus, a third KT procedure may be acceptable, although aggressive pretransplant immune monitoring and patient selection may be required to reduce the risks of acute rejection and surgical complications.

Risk factors in the progression of BK virus-associated nephropathy in renal transplant recipients.

BACKGROUND/AIMS: BK virus-associated nephropathy (BKVAN) is an important cause of allograft dysfunction in kidney transplant recipients. It has an unfavorable clinical course, and no definite treatment guidelines have yet been established. Here, we report our center's experience with biopsy-proven BKVAN and investigate factors associated with its progression. METHODS: From January 2004 to April 2013, 25 patients with BKVAN were diagnosed by biopsy at Seoul St. Mary's Hospital. Of the 25 patients, 10 were deceased-donor transplant recipients and 15 were living-donor transplant recipients. Three of the patients underwent retransplantation. The primary immunosuppressant used was tacrolimus in 17 patients and cyclosporine in eight patients. RESULTS: BKVAN was observed at a mean duration of 22.8 ± 29.1 months after transplantation. The mean serum creatinine level at biopsy was 2.2 ± 0.7 mg/dL. BKVAN occurred with acute rejection in eight patients (28%). Immunosuppression modification was performed in 21 patients (84%). Additionally, leflunomide and intravenous immunoglobulin were administered to 13 patients (52%) and two (8%), respectively. Allograft loss occurred in five patients (27.8%) during the follow- up period at 0.7, 17.1, 21.8, 39.8, and 41.5 months after the BKVAN diagnosis. Advanced stages of BKVAN, increased creatinine levels, and accompanying acute rejection at the time of BKVAN diagnosis increased the risk of allograft failure. CONCLUSIONS: The clinical outcomes in patients with biopsy-proven BKVAN were unfavorable in the present study, especially in patients with advanced-stage BKVAN, poor renal function, and acute allograft rejection.