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Objective: To investigate the correlation between dyspeptic symptoms and gastric motility parameters measured by magnetic resonance imaging (MRI) using volumetry and motility indices in patients with Parkinson’s disease (PD). Materials and methods: In this IRB-approved study, MRI datasets obtained from August 2014 to May 2016 in 38 PD patients were retrospectively analyzed. Patients underwent a 120-minute-long MRI study using a liquid test meal and 8 sets of scans. Gastric content volume (GCV) and total volume (TGV), gastric half emptying time (T1/2), motility index (GMI), accommodation (GA), and emptying (GE) values were acquired. These measurements were compared between patients according to the presence of gastric symptoms: early satiety (n = 25), epigastric pain (n = 13), and dyspepsia (n = 28). Results: Patients with early satiety showed significantly decreased GE of GCV and TGV (p < 0.001 and p = 0.017). Dyspeptic patients had significantly decreased GE of GCV and GMI (p = 0.001 and p = 0.029). GE of GCV at 90 and 120 minutes were significantly lower in patients with early satiety (p = 0.001 and p = 0.002). GE of GCV and GMI at 90 minutes were significantly decreased in patients with dyspepsia (p = 0.004 and p = 0.002). T1/2 of GCV was prolonged in patients with early satiety, epigastric pain, and dyspepsia (p = 0.004, p = 0.041, and p = 0.023). T1/2 of TGV also delayed in patients with early satiety (p = 0.023). GMI at 90 minutes was significantly correlated with dyspepsia on multivariable analysis (p = 0.028). Conclusions: Gastric motility can be quantitatively assessed by MRI, showing decreased GMI, delayed GE, and prolonged T1/2 in PD patients with early satiety or dyspepsia. [ABSTRACT FROM AUTHOR]

Blood stasis in left atrium (LA) or LA appendage (LAA) is thought to be the main cause of thrombus formation and systemic embolism in atrial fibrillation (AF) patients. Paroxysmal and non-paroxysmal AF differ significantly in various aspects. Impact of cardiac hemodynamics on systemic embolism might also differ between the 2 distinct AF entities. This study was performed to evaluate the influence of cardiac hemodynamics on systemic embolism in both paroxysmal and non-paroxysmal AF. Consecutive AF patients undergoing radiofrequency catheter ablation (RFCA) in Korea University Medical Center Anam Hospital between June 1998 and February 2018 were analyzed. Among 2,801 patients who underwent first-time RFCA, a total of 231 patients had either previous ischemic stroke, transient ischemic attack, or arterial embolism. In paroxysmal AF, LA diameter, LA volume (measured with magnetic resonance imaging), left ventricular (LV) ejection fraction, E/e’, LAA flow velocity, and prevalence of spontaneous echocontrast (SEC) and dense SEC were significantly different between patients with and without thromboembolic events. However, only E/e’ was different between patients with and without thromboembolic events in non-paroxysmal AF. The influence of LA diameter, LA volume, LV EF, LAA flow velocity, and dense SEC on thromboembolic events was significantly moderated by the type of AF. In conclusion, paroxysmal and non-paroxysmal AF might have a different mechanism responsible for thrombus formation and consequent embolic events. Relative contribution of hemodynamic parameters and other factors such as atrial myopathy to thromboembolic events in paroxysmal versus non-paroxysmal AF needs further evaluation. [ABSTRACT FROM AUTHOR]

Background & aims: Elastography point quantification is a convenient method for measuring liver stiffness. It can be performed simultaneously with conventional ultrasonography. This study aimed to evaluate its diagnostic performance for assessing hepatic fibrosis in patients with autoimmune liver disease (AILD), including autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC). Methods: The diagnostic performance of elastography point quantification (ElastPQ) was evaluated and compared with that of serum fibrosis markers, including the aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4), using the receiver operating characteristics analysis with histologic evaluation as the reference standard. Results: In 49 AIH patients, sensitivity and specificity of ElastPQ were 93.6% and 44.4%, respectively, for significant fibrosis (≥ F2, cutoff 4.47 kPa), and 63.6% and 86.8% for cirrhosis (F4, cutoff 9.28 kPa). In 41 PBC patients, they were 81.8% and 73.3%, respectively, for significant fibrosis (≥ F2, cutoff 5.56 kPa), and 100% and 81.6%, respectively, for advanced fibrosis (≥ F3, cutoff 6.04 kPa). The areas under the receiver operating characteristic curves of ElastPQ for significant fibrosis (0.77, 95% CI 0.67–0.86) and cirrhosis (0.81, 95% CI 0.65–0.96) were higher than those of APRI and FIB-4 in AILD patients. According to the multivariable analysis, histological activity, steatosis, and body max index (BMI) were not significant factors that influenced the result of ElastPQ. Conclusions: ElastPQ exhibited better diagnostic performance–without the influence of confounding factors–for assessing hepatic fibrosis in AILD patients than serum fibrosis markers. [ABSTRACT FROM AUTHOR]

Background: Acute rejection is hazardous to graft survival in kidney transplant recipients (KTRs). We aimed to identify novel biomarkers for early diagnosis of acute T cell-mediated rejection (TCMR) in urinary exosomes of KTRs. Methods: Among 458 graft biopsies enrolled in a cross-sectional multicenter study, 22 patients with stable graft function (STA) who had not shown pathologic abnormality and 25 patients who diagnosed biopsy-proven TCMR were analyzed. We performed proteomic analysis using nano-ultra performance liquid chromatography-tandem mass spectrometry (nano-UPLC-MS/MS) to identify candidate biomarkers for early TCMR diagnosis on urinary exosomes. We confirmed the protein levels of each candidate biomarker by western blot analysis. Results: A total of 169 urinary exosome proteins were identified by nano-UPLC-MS/MS. Forty-six proteins showed increased expression in STA patients, while 17 proteins were increased in TCMR patients. Among them, we selected five proteins as candidate biomarkers for early diagnosis of TCMR according to significance, degree of quantity variance, and information from the ExoCarta database. We confirmed the proteomic expression levels of five candidate biomarkers by western blot analysis in each patient. Of all candidate biomarkers, tetraspanin-1 and hemopexin were significantly higher in TCMR patients (STA:TCMR ratio = 1:1.8, P = 0.009, and 1:3.5, P = 0.046, respectively). Conclusions: Tetraspanin-1 and hemopexin were detected in KTR urine and could act as potential diagnostic proteins for TCMR. [ABSTRACT FROM AUTHOR]

The interruption of oral anticoagulation therapy (OAC) after CA of atrial fibrillation (AF) is controversial. The purpose of this study was to evaluate the relationship between successful long-term outcomes of catheter resection and SR maintenance and ischemic stroke risk in Korea. We studied 1,548 consecutive patients who were followed up for more than 2 years after CA of AF. We investigated the incidence of ischemic stroke during long-term follow-up. Compared to the AF recurrence group (n = 619), the sinus rhythm (SR) maintenance group (n = 929) had more paroxysmal AF (74.6% versus 44.4%, p<0.001), smaller LA size (39.9±5.7mm versus 42.3±6.0mm, p<0.001), and younger age (54.2±10.9 years versus 56.4±10.6 years, p<0.001). However, CHA2DS2-VASc scores were not significantly different between the two groups (0.9 vs. 1.1, p = 0.053). The overall incidence of ischemic stroke during the mean follow-up period of 54 months after CA was 0.6%, and was significantly lower in the SR group than the AF recurrence group (0.3% vs. 1.1%, log-rank test p<0.001). However, in sub-analysis in the SR group, the rate of ischemic stroke was significantly increasing in patients with a CHA2DS2-VASc score ≥ 4 compared to those with a CHA2DS2-VASc score < 4 (4.3% vs. 0.2%, log-rank test p<0.001). In conclusion, this long-term follow-up data in patients with AF who underwent successful CA showed that SR maintenance was correlated with a lower rate of ischemic stroke in Korea. However, it was only observed in patients with CHA2DS2-VASc score ≤3. [ABSTRACT FROM AUTHOR]

Purpose: Diabetic nephropathy is the leading cause of end stage renal disease. The number of kidney transplantation (KT) due to diabetic nephropathy is increasing and there is debate on glycemic control after KT. In this study, we used a multi-center database to determine the relationship between post-transplant glycemic control and the outcomes of KT in patients with diabetic nephropathy. Methods: We conducted a retrospective chart review of kidney transplant recipients (KTRs) with diabetic nephropathy from three tertiary hospitals to analyze the association between post-transplant glycemic control and the clinical outcomes of graft failure, including patient death and biopsy-proven acute rejection (BPAR). We assessed time-averaged glucose level and hemoglobin A1c (HbA1c) for 36 months after KT. Results: Among 3,538 KTRs, a total of 476 patients received kidney transplantation because of diabetic nephropathy. Mean time-averaged glucose and HbA1c levels were 147 ± 46 mg/dl and 7.7 ± 1.5%, respectively. Patients with diabetic nephropathy had poor graft and patient survival rate compared with non-diabetic nephropathy. Among KTRs with diabetic nephropathy, the highest quartile of time-averaged glucose was related to poor graft outcomes and the 3rd quartile of time-averaged HbA1c was associated with significantly better graft outcomes than the 1st, 2nd or 4th quartiles. There were no significant differences in the risk of BPAR across the 4 quartiles of glucose and HbA1c. Conclusions: Strict glycemic control before KT might not be related to successful outcomes but poor glycemic control after KT is associated with poor graft outcomes. There was no significant relationship between pre- or post-transplant glycemic control and BPAR. [ABSTRACT FROM AUTHOR]

Purpose: To retrospectively investigate whether texture features obtained from preoperative CT images of advanced gastric cancer (AGC) patients could be used for the prediction of occult peritoneal carcinomatosis (PC) detected during operation. Materials and methods: 51 AGC patients with occult PC detected during operation from January 2009 to December 2012 were included as occult PC group. For the control group, other 51 AGC patients without evidence of distant metastasis including PC, and whose clinical T and N stage could be matched to those of the patients of the occult PC group, were selected from the period of January 2011 to July 2012. Each group was divided into test (n = 41) and validation cohort (n = 10). Demographic and clinical data of these patients were acquired from the hospital database. Texture features including average, standard deviation, kurtosis, skewness, entropy, correlation, and contrast were obtained from manually drawn region of interest (ROI) over the omentum on the axial CT image showing the omentum at its largest cross sectional area. After using Fisher's exact and Wilcoxon signed-rank test for comparison of the clinical and texture features between the two groups of the test cohort, conditional logistic regression analysis was performed to determine significant independent predictor for occult PC. Using the optimal cut-off value from receiver operating characteristic (ROC) analysis for the significant variables, diagnostic sensitivity and specificity were determined in the test cohort. The cut-off value of the significant variables obtained from the test cohort was then applied to the validation cohort. Bonferroni correction was used to adjust P value for multiple comparisons. Results: Between the two groups, there was no significant difference in the clinical features. Regarding the texture features, the occult PC group showed significantly higher average, entropy, standard deviation, and significantly lower correlation (P value < 0.004 for all). Conditional logistic regression analysis demonstrated that entropy was significant independent predictor for occult PC. When the cut-off value of entropy (> 7.141) was applied to the validation cohort, sensitivity and specificity for the prediction of occult PC were 80% and 90%, respectively. Conclusion: For AGC patients whose PC cannot be detected with routine imaging such as CT, texture analysis may be a useful adjunct for the prediction of occult PC. [ABSTRACT FROM AUTHOR]

Background: Limited data are available regarding optimal selection criteria for pancreas transplant alone (PTA) to minimize aggravation of diabetic nephropathy. Methods: A total of 87 type 1 diabetic patients were evaluated before and after PTA at a single center from January, 1999 to December, 2015, together with 87 matched non-transplanted type 1 diabetic subjects who were candidates for PTA to compare deterioration of native kidney function. A total of 163 patients (79 in the transplanted group and 84 in the nontransplanted group) were finally enrolled after excluding nine patients with estimated glomerular filtration rate less than 60 mL/min/1.73 m2 and two patients with moderate proteinuria (≥ 1.5 g/day). Results: A total of seven recipients (8.9%) had end-stage renal disease post-transplant whereas only one patient (1.2%) developed end-stage renal disease in the nontransplanted group during their follow-up period (median 12.0, range 6–96 months) (p = 0.03). Furthermore, a composite of severe renal dysfunction and end-stage renal disease (31.6% vs 2.4%) was significantly higher in the transplanted group (p < 0.001). Multivariate Cox regression analysis revealed that a higher level of tacrolimus at six months post-transplant (HR = 1.648, CI = 1.140–2.385, p = 0.008) was the only significant factor associated with end-stage renal disease. Conclusions: There is a considerable risk for deterioration of renal function in PTA recipients post-transplant compared with non-transplant diabetic patients. With rather strict selection criteria such as preoperative proteinuria and estimated glomerular filtration rate, PTA should be considered in diabetic patients to minimize post-transplant aggravation of diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Spontaneous echo-contrast (SEC) and thrombus observed in trans-esophageal echocardiography (TEE) is known as a strong surrogate marker for future risk of ischemic stroke in patients with atrial fibrillation (AF) or atrial flutter (AFL). The efficacy of non-vitamin K antagonist oral anticoagulants (NOAC) compared to warfarin to prevent SEC or thrombus in patients with AF or AFL is currently unknown. AF or AFL patients who underwent direct current cardioversion (DCCV) and pre-DCCV TEE evaluation from January 2014 to October 2016 in a single center were analyzed. The prevalence of SEC and thrombus were compared between patients who received NOAC and those who took warfarin. NOAC included direct thrombin inhibitor and factor Xa inhibitors. Among 1,050 patients who were considered for DCCV, 424 patients anticoagulated with warfarin or NOAC underwent TEE prior to DCCV. Eighty patients who were anticoagulated for less than 21 days were excluded. Finally, 344 patients were included for the analysis (180 warfarin users vs. 164 NOAC users). No significant difference in the prevalence of SEC (44.4% vs. 43.9%; p = 0.919), dense SEC (13.9% vs. 15.2%; p = 0.722), or thrombus (2.2% vs. 4.3%; p = 0.281) was observed between the warfarin group and the NOAC group. In multivariate analysis, there was no association between NOAC and risk of SEC (odds ratio [OR]: 1.4, 95% CI: 0.796–2.297, p = 0.265) or thrombus (OR: 3.4, 95% CI: 0.726–16.039, p = 0.120). In conclusion, effectiveness of NOAC is comparable to warfarin in preventing SEC and thrombus in patients with AF or AFL undergoing DCCV. However, numerical increase in the prevalence of thrombus in NOAC group warrants further evaluation. [ABSTRACT FROM AUTHOR]

Objective: Bkv-miR-B1-5p, one of the microRNAs encoded by BK virus, was recently reported to be elevated in the blood among the patients with BK virus nephropathy (BKVN). Urinary exosome was suggested to be a possible source of biomarker for kidney diseases, but it was unknown whether it could contain viral microRNA as well as human microRNAs. The aim of this study was to evaluate whether urinary exosomal BK viral microRNA were expressed during replication and could be used to diagnose BKVN in kidney transplant recipients. Materials and methods: In a cross-sectional multicenter study, we collected and analyzed 458 graft biopsies from 385 kidney transplant recipients. Urine samples were collected at the time of graft biopsy, and microRNAs in urinary exosome were measured once. For 13 patients with BKVN and 67 age, sex-matched kidney transplant recipients, we measured BK viral microRNA B1-5p, 3p and human microRNA-16 in urinary exosomal fraction and compared the diagnostic value with BK viral load in plasma and urine. Results: Pathology proven BKVN was diagnosed in 13 patients (2.8%). High levels of bkv-miR-B1-5p and bkv-miR-B1-3p were shown in all patients with BKVN. Meanwhile, plasma BK viral load assay (cut-off value of ≥ 4.0 log10 copies/mL) showed false negative in 3 cases and urinary BK viral load assay (cut-off value of ≥ 7.0 log10 copies/mL) showed false negative in 1 case among these 13 patients. The receiver operator characteristics curve analysis for bkv-miR-B1-5p and bkv-miR-B1-5p/miR-16 showed excellent discriminative power for the diagnosis of BKVN, with area under the curve values of 0.989 and 0.985, respectively. Conclusions: This study suggests that urinary exosomal bkv-miR-B1-5p and bkv-miR-B1-5p/miR-16 could be surrogate markers for the diagnosis of BKVN. [ABSTRACT FROM AUTHOR]

Purpose: The Grading system for Adrenal Pheochromocytoma and Paraganglioma (GAPP) was proposed for predicting the metastatic potential of pheochromocytoma and paraganglioma to overcome the limitations of the Pheochromocytoma of the Adrenal Scaled Score (PASS). However, to date, no study validating the GAPP has been conducted, and previous studies did not include mutations in the succinate dehydrogenase type B (SDHB) gene in the score calculation. In this retrospective cohort study, we validated the prediction ability of GAPP and assessed whether it would be improved by inclusion of the loss of SDHB immunohistochemical staining. Methods: We divided the tumors into non-metastatic and metastatic groups based on the presence of synchronous or metachronous metastases. The GAPP score and PASS at the initial operation were measured. Moreover, we combined some GAPP parameters with the immunohistochemical staining of SDHB to obtain a modified GAPP (M-GAPP) score. Results: Metastasis occurred in 15/72 (20.8%) patients, with a mean follow-up of 43.5 months. Loss of SDHB staining was more frequent (P = 0.044) in the metastatic group. The GAPP score (P = 0.006), PASS (P = 0.003), and M-GAPP score (P<0.001) were all higher in the metastatic group. Twelve of 40 (30.0%) moderately or poorly differentiated tumors, as defined by the GAPP score, and 12/34 (35.3%) tumors with a PASS ≥4 were metastatic. Conversely, 10/19 (52.6%) tumors with an M-GAPP score ≥3 were metastatic. The area under the curve of the M-GAPP score (0.822) was significantly higher than that of the GAPP (0.728) (P = 0.012), but similar to that of the PASS (0.753) (P = 0.411). The GAPP (P = 0.032) and M-GAPP scores (P = 0.040), but not PASS (P = 0.200), negatively correlated with metastasis-free survival. Conclusion: The GAPP was validated, and M-GAPP, a combination of some GAPP parameters and loss of SDHB staining, might be useful for the prediction of the metastatic potential of pheochromocytoma and paraganglioma. [ABSTRACT FROM AUTHOR]

Pancreas transplantation is considered a therapeutic option for patients with complicated diabetes mellitus. In this study, we compared survival rate between patients on the waiting list for pancreas transplant alone(PTA), simultaneous pancreas–kidney(SPK) transplant, and pancreas after kidney(PAK) transplant and transplant recipients. A total of 503 patients (PTA:n = 116; SPK:n = 303; PAK:n = 84) and 280 PT recipients (PTA:n = 89; SPK:n = 155; PAK:n = 36) were retrospectively analyzed at our center between February 2000 and December 2015; 11.9%(60/503) of the patients on the waiting list and 4.3%(12/280) of the PT recipients died. The overall survival rate was higher in the waiting list group for the first year (99.3% vs. 97.8%), after which it was significantly higher in PT group (p = 0.039). The overall relative risk of all-cause mortality for transplant recipients was 2.145(p = 0.285) for PTA, 0.688(p = 0.735) for PAK, however,0.361 (p = 0.012) for SPK compared with that for the waiting list patients. SPK transplant recipients had considerable higher survival benefits, despite the relatively long waiting period, especially after 1 year. In addition, PTA and PAK can also be considered as a treatment option as patient survival was not poor. [ABSTRACT FROM AUTHOR]

Background: Beta-blockers are first-line therapy in patients with congenital long-QT syndrome (LQTS). Objective: This study sought to determine the differences in effectiveness of beta-blockers on risk reduction according to LQTS genotype. Methods: We searched MEDLINE, EMBASE, and CENTRAL databases to investigate the use of beta-blockers (atenolol, nadolol, propranolol, and metoprolol) in patients with LQTS. Hazard ratio (HR) and relative risk (RR) were extracted or calculated from studies reporting cardiac events (syncope, aborted cardiac arrest (ACA), or sudden cardiac death (SCD)). Results: Among 2,113 articles searched, 10 studies (7 registry-based cohort studies (Cohort) and 3 interrupted time series studies (ITS)) involving 9,727 patients were included. In a meta-analysis using a random-effect model, the use of beta-blocker was associated with significant risk reduction of all cardiac events (HR 0.49, p<0.001 in Cohort; RR 0.39, p<0.001 in ITS) and serious cardiac events (ACA or SCD) (HR 0.47, p<0.001 in Cohort). In both LQT1 and LQT2, the risk was reduced with beta-blocker therapy in Cohort (HR 0.59 in LQT1; HR 0.39 in LQT2) as well as ITS (RR 0.29 in LQT1; RR 0.48 in LQT2). Among the beta-blockers, nadolol showed a significant risk reduction in both LQT1 and LQT2 (HR 0.47 and 0.27, respectively), whereas atenolol and propranolol decreased the risk only in LQT1 (HR 0.36 and 0.46, respectively). Metoprolol showed no significant reduction in either genotype. In LQT3, beta-blocker therapy was not as effective as LQT1 or LQT2; however, it was inconclusive due to data insufficiency. Conclusion: This meta-analysis showed that beta-blockers were effective in reducing risk of cardiac events in patients with LQTS. Among them, nadolol was effective in LQT1 and LQT2, whereas other drugs showed different effectiveness depending on LQT genotype. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the association of computed tomography (CT) texture features of locally advanced rectal cancer with neoadjuvant chemoradiotherapy (CRT) response and disease-free survival (DFS). Methods and findings: The institutional review board approved this retrospective study. 95 patients who received neoadjuvant CRT, followed by surgery, for locally advanced rectal cancer were included. Texture features (entropy, uniformity, kurtosis, skewness, and standard deviation) were assessed in pretreatment CT images and obtained without filtration and with Laplacian of Gaussian spatial filter of various filter values (1.0, 1.5, 2.0, and 2.5). Dworak pathologic grading was used for treatment response assessment. Independent t-test was used to compare each texture feature between the treatment responder and non-responder groups. DFS was assessed with Kaplan-Meier method, and differences were compared with log-rank test. Cox proportional hazards models were constructed to predict prognosis based on stage, age, and each texture feature. Treatment responders (n = 32) showed significantly lower entropy, higher uniformity, and lower standard deviation in no filtration, fine (1.0), and medium (1.5) filter values. Entropy, uniformity, and standard deviation without filtration showed significant difference in DFS in Kaplan-Meier analysis (P = 0.015, 0.025, and 0.038). Homogeneous texture features (≤ 6.7 for entropy, > 0.0118 for uniformity, and ≤ 28.06 for standard deviation) were associated with higher DFS. Entropy, uniformity, and standard deviation were independent texture features in predicting DFS (P = 0.017, 0.03, and 0.036) Conclusions: Homogeneous texture features are associated with better neoadjuvant CRT response and higher DFS in patients with locally advanced rectal cancer. [ABSTRACT FROM AUTHOR]

Fibrinogen, 1 of 13 coagulation factors responsible for normal blood clotting, is synthesized by hepatocytes. Detailed roles of the orphan nuclear receptors regulating fibrinogen gene expression have not yet been fully elucidated. Here, we identified estrogen-related receptor gamma (ERRγ) as a novel transcriptional regulator of human fibrinogen gene expression. Overexpression of ERRγ specially increased fibrinogen expression in human hepatoma cell line. Cannabinoid receptor types 1(CB1R) agonist arachidonyl-2'-chloroethylamide (ACEA) up-regulated transcription of fibrinogen via induction of ERRγ, whereas knockdown of ERRγ attenuated fibrinogen expression. Deletion analyses of the fibrinogen γ (FGG) gene promoter and ChIP assays revealed binding sites of ERRγ on human fibrinogen γ gene promoter. Moreover, overexpression of ERRγ was sufficient to increase fibrinogen gene expression, whereas treatment with GSK5182, a selective inverse agonist of ERRγ led to its attenuation in cell culture. Finally, fibrinogen and ERRγ gene expression were elevated in liver tissue of obese patients suggesting a conservation of this mechanism. Overall, this study elucidates a molecular mechanism linking CB1R signaling, ERRγ expression and fibrinogen gene transcription. GSK5182 may have therapeutic potential to treat hyperfibrinogenemia. [ABSTRACT FROM AUTHOR]

It remains inconclusive whether hyperuricemia is a true risk factor for kidney graft failure. In the current study, we investigated the association of hyperuricemia and graft outcome. We performed a multi-center cohort study that included 2620 kidney transplant recipients. The patients were classified as either normouricemic or hyperuricemic at 3 months after transplantation. Hyperuricemia was defined as a serum uric acid level ≥ 7.0 mg/dL in males or ≥ 6.0 mg/dL in females or based on the use of urate-lowering medications. The two groups were compared before and after propensity score matching. A total of 657 (25.1%) patients were classified as hyperuricemic. The proportion of hyperuricemic patients increased over time, reaching 44.2% of the total cohort at 5 years after transplantation. Estimated glomerular filtration rate and donor type were independently associated with hyperuricemia. Hyperuricemia was associated with graft loss according to multiple Cox regression analysis before propensity score matching (hazard ratio [HR] = 1.56, 95% confidence interval [CI] = 1.14–2.13, P = 0.005) as well as after matching (HR = 1.65, 95% CI = 1.13–2.42, p = 0.010). Cox regression models using time-varying hyperuricemia or marginal structural models adjusted with time-varying eGFR also demonstrated significant hazards of hyperuricemia for graft loss. Cardiovascular events and recipient survival were not associated with hyperuricemia. Overall, hyperuricemia, especially early onset after transplantation, showed an increased risk for graft failure. Further studies are warranted to determine whether lowering serum uric acid levels would be beneficial to graft survival. [ABSTRACT FROM AUTHOR]

Purpose: To find differential CT features of colorectal schwannomas from gastrointestinal stromal tumors (GISTs). Materials and Methods: CT features of 13 pathologically proven colorectal schwannomas and 21 GISTs were retrospectively reviewed. The following CT items were analyzed: size, longitudinal and transverse location, shape, margin, homogeneity, necrosis, surface ulceration, calcification, degree of attenuation, the presence of enlarged lymph node (LN), and metastasis. Among the features, significant variables were evaluated using univariate statistical tests. The optimal cut-off point of tumor size was obtained by ROC analysis. Binary logistic regression analysis was used to find the most independent CT variables. Results: Small size, non-rectum location, smooth margin, homogeneous high attenuation without necrosis, and the presence of enlarged LNs were found to be significant variables to differentiate schwannomas from GISTs (P<0.05). The optimized cut-off point for tumor size in distinguishing GISTs from schwannomas was 3.9 cm (AUC = 0.808, sensitivity = 66.7%, specificity = 92.3%, P<0.0001). Binary regression analysis revealed that only non-rectum location remained independent predictor for schwannomas differentiated from GISTs (odds ratio = 31.667, P = 0.001). Conclusion: Colorectal schwannomas usually located in non-rectum and appear as small subepithelial nodules showing homogeneous high attenuation and smooth margin. Schwannomas exclusively accompany with enlarged LNs. [ABSTRACT FROM AUTHOR]

Background: The main purpose of performing radiofrequency catheter ablation (RFCA) in atrial fibrillation (AF) patients is to improve the quality of life (QoL) and alleviate AF-related symptoms. We aimed to determine the qualitative and quantitative effects of RFCA on the QoL in AF patients. Methods: We performed a systemic review and meta-analysis using a random effects model. We searched for the studies that reported the physical component summary score (PCS) and mental component summary score (MCS) of the short form-36, a validated system to assess and quantify the QoL, before and after RFCA in AF patients. PCS and MCS are T-scores with a mean of 50 and standard deviation of 10. Results: Of the 470 studies identified through systematic search, we included 13 studies for pre-RFCA vs. the post-RFCA analysis and 5 studies for treatment success vs. AF recurrence analyses. In the pre-RFCA vs. post-RFCA analysis, RFCA was associated with a significant increase in both the PCS (weighted mean difference [WMD] = 6.33 [4.81–7.84]; p < 0.001) and MCS (WMD = 7.80 [6.15–9.44]; p < 0.001). The ΔPCS (post-RFCA PCS–pre-RFCA PCS) and ΔMCS values were used for the treatment success vs. AF recurrence analysis. Patients with successful ablation had a higher ΔPCS (WMD = 7.46 [4.44–10.49]; p < 0.001) and ΔMCS (WMD = 7.59 [4.94–10.24]; p < 0.001). Conclusions: RFCA is associated with a significant increase in the PCS and MCS in AF patients. Patients without AF recurrence after RFCA had a better improvement in the PCS and MCS than patients who had AF recurrence. [ABSTRACT FROM AUTHOR]

Background: Image texture analysis is a noninvasive technique for quantifying intratumoral heterogeneity, with derived texture features reported to be closely related to the treatment outcome of tumors. Gastric cancer is one of the most common tumors and the third leading cause of cancer-related deaths worldwide. Although trastuzumab is associated with a survival gain among patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer, optimal patient selection is challenging. The purpose of this study was to determine whether CT texture features of HER2-positive gastric cancer were related to the survival rate after trastuzumab treatment. Methods and Findings: Patients diagnosed with HER2-positive advanced gastric cancer from February 2007 to August 2014 were retrospectively selected. Using in-house built software, histogram features (kurtosis and skewness) and gray-level co-occurrence matrices (GLCM) features (angular second moment [ASM], contrast, entropy, variance, and correlation) were derived from the CT images of HER2-positive advanced gastric cancer in 26 patients. All the patients were followed up for more than 6 months, with no confirmed deaths. The patients were dichotomized into a good and poor survival group based on cutoff points of overall survival of 12 months. A receiver-operating characteristics (ROC) analysis was performed to test the ability of each texture parameter to identify the good survival group. Kaplan–Meier curves for patients above and below each threshold were constructed. Using a threshold of >265.8480 for contrast, >488.3150 for variance, and ≤0.1319×10−3. for correlation, all of the area under the ROC curves showed fair accuracy (>0.7). Kaplan–Meier analysis showed statistically significant survival difference between two groups according to optimal cutoff values of contrast, variance, correlation and ASM. However, as this study had a small number of patients, a further study with a larger population will be needed to validate the results. Conclusions: Heterogeneous texture features on CT images were associated with better survival in patients with HER2-positive advanced gastric cancer who received trastuzumab-based treatment. Therefore, texture analysis shows potential to be a clinically useful imaging biomarker providing additional prognostic information for patient selection. [ABSTRACT FROM AUTHOR]

Background: Pre-transplant cardiovascular (CV) risk factors affect the development of CV events even after successful kidney transplantation (KT). However, the impact of pre-transplant CV risk factors on allograft failure (GF) has not been reported. Methods and Findings: We analyzed the graft outcomes of 2,902 KT recipients who were enrolled in a multi-center cohort from 1997 to 2012. We calculated the pre-transplant CV risk scores based on the Framingham risk model using age, gender, total cholesterol level, smoking status, and history of hypertension. Vascular disease (a composite of ischemic heart disease, peripheral vascular disease, and cerebrovascular disease) was noted in 6.5% of the patients. During the median follow-up of 6.4 years, 286 (9.9%) patients had developed GF. In the multivariable-adjusted Cox proportional hazard model, pre-transplant vascular disease was associated with an increased risk of GF (HR 2.51; 95% CI 1.66–3.80). The HR for GF (comparing the highest with the lowest tertile regarding the pre-transplant CV risk scores) was 1.65 (95% CI 1.22–2.23). In the competing risk model, both pre-transplant vascular disease and CV risk score were independent risk factors for GF. Moreover, the addition of the CV risk score, the pre-transplant vascular disease, or both had a better predictability for GF compared to the traditional GF risk factors. Conclusions: In conclusion, both vascular disease and pre-transplant CV risk score were independently associated with GF in this multi-center study. Pre-transplant CV risk assessments could be useful in predicting GF in KT recipients. [ABSTRACT FROM AUTHOR]

Although hyponatremia is related to poorer outcomes in several clinical settings, its significance remains unresolved in kidney transplantation. Data on 1,786 patients who received kidney transplantations between January 2000 and December 2011 were analyzed. The patients were divided into two groups according to the corrected sodium values for serum glucose 3 months after their transplantations (<135 mmol/L vs. ≥135 mmol/L). Subsequently, the hazard ratios (HRs) for biopsy-proven acute rejection, graft failure, and all-cause mortality were calculated after adjustments for several immunological and non-immunological covariates. 4.0% of patients had hyponatremia. Patients with hyponatremia had higher risks for graft failure and all-cause mortality than did the counterpart normonatremia group; the adjusted HRs for graft failure and mortality were 3.21 (1.47–6.99) and 3.03 (1.21–7.54), respectively. These relationships remained consistent irrespective of heart function. However, hyponatremia was not associated with the risk of acute rejection. The present study addressed the association between hyponatremia and graft and patient outcomes in kidney transplant recipients. Based on the study results, our recommendation is to monitor serum sodium levels after kidney transplantations. [ABSTRACT FROM AUTHOR]

Background: Population aging is a major health concern in Asian countries and it has affected the age distribution of patients with end-stage renal disease (ESRD). As a consequence, the need for kidney transplantation in the geriatric population has increased, but the shortage of donors is an obstacle for geriatric renal transplantation. The aim of this study was to evaluate risk factors for graft failure and death in geriatric renal transplantation. Methods: Kidney transplantations performed in a tertiary hospital in South Korea from May 1995 to December 2014 were retrospectively reviewed. Recipients younger than 60 years of age or who underwent other organ transplantations were excluded. The Kaplan-Meier method was used to assess patient and graft survival. A Cox regression analysis was used to evaluate risk factors for graft failure and patient death. Results: A total of 229 kidney transplantation patients were included. Graft survival at 1, 5, and 10 years were 93.2%, 82.9%, and 61.2% respectively. Patient survival at 1, 5, and 10 years were 94.6%, 86.9%, and 68.8%, respectively. According to the Cox multivariate analysis, ABO incompatibility (hazard ratio [HR] 3.91, p < 0.002), DGF (HR 3.544, p < 0.004), CMV infection (HR 2.244, p < 0.011), and HBV infection (HR 6.349, p < 0.015) were independent risk factors for graft survival. Recipient age (HR 1.128, p < 0.024), ABO incompatibility (HR 3.014, p < 0.025), CMV infection (HR 2.532, p < 0.010), and the number of HLA mismatches (HR 1.425, p < 0.007) were independent risk factors for patient death. Conclusion: Kidney transplantation in the geriatric population showed good clinical outcomes. ABO incompatibility, DGF, CMV infection, and HBV infection were risk factors for graft failure and the recipient age, ABO incompatibility, CMV infection, and the number of HLA mismatches were risk factors for patient death in geriatric renal transplantation. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is an irreversible neurodegenerative disorder that is characterized by the abnormal aggregation of amyloid-β into neurotoxic oligomers and plaques. Although many disease-modifying molecules are currently in Alzheimer clinical trials, a small molecule that inhibits amyloid-β aggregation and ameliorates the disorder has not been approved to date. Herein, we report the effects of a potent small molecule, 6-methoxy-2-(4-dimethylaminostyryl) benzofuran (KMS88009), that directly disrupts amyloid-β oligomerization, preserving cognitive behavior when used prophylactically and reversing declines in cognitive behavior when used therapeutically. KMS88009 exhibited excellent pharmacokinetic profiles with extensive brain uptake and a high level of safety. When orally administered before and after the onset of Alzheimer's disease symptoms, KMS88009 significantly reduced assembly of amyloid-β oligomers and improved cognitive behaviors in the APP/PS1 double transgenic mouse model. The unique dual mode of action indicates that KMS88009 may be a powerful therapeutic candidate for the treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]