5763830
Superior patient survival for continuous ambulatory peritoneal dialysis patients treated with a peritoneal dialysis fluid with neutral pH and low glucose degradation product concentration (Balance).
BACKGROUND
In recent years, laboratory and clinical research has suggested the need for peritoneal dialysis fluids (PDFs) that are more biocompatible than the conventional PDFs commonly used today. Bioincompatibility of PDF has been attributed to low pH, lactate, glucose, glucose degradation products (GDPs), and osmolality. PDFs with neutral pH and low GDPs are now available commercially. In vitro and early clinical studies suggest that these solutions are indeed more biocompatible but, as of now, there is no evidence that their use improves patient outcome.


METHODS
Using a dedicated database of over 2000 patients treated with PD in Korea, we were able to conduct a retrospective observational study comparing outcomes for incident continuous ambulatory PD patients treated with a standard, conventional, heat-sterilized PDF to the outcomes for patients treated with a novel, low GDP, neutral-pH PDF prepared in a dual-compartment, double-bag PD system (Balance; Fresenius Medical Care, St. Wendel, Germany). In an intention-to-treat analysis, patient and technique survival, peritonitis-free survival, and peritonitis rates were compared in 611 patients treated with Balance for up to 30 months and 551 patients with a standard PDF (stay . safe; Fresenius Medical Care) treated in the same era and with equivalent follow-up.


RESULTS
The patients were well matched for most relevant characteristics except older age distribution for the patients treated with the standard PDF. Patients treated with Balance had significantly superior survival compared to those treated with the standard PDF (74% vs 62% at 28 months, p = 0.0032). In a multivariate Cox regression model including age, diabetes, and gender, the survival advantage persisted (relative risk of death for Balance 0.75, 95% confidence interval 0.56 - 0.99, p = 0.0465). Modality technique survival was similarin Kaplan-Meieranalysis for both PDFs. No differences were detected in peritonitis-free survival or in peritonitis rates between the two solutions.


CONCLUSION
This study, for the first time, suggests that treatment with a novel biocompatible PDF with low GDP concentration and neutral pH confers a significant survival advantage. The exact mechanisms for such a survival advantage cannot be determined from this study. The usual criticisms of observational studies apply and the results reported here strongly warrant the undertaking of appropriately designed, randomized, controlled clinical trials.
17233032
Changing prescribing practice in CAPD patients in Korea: increased utilization of low GDP solutions improves patient outcome.
BACKGROUND
Novel, biocompatible peritoneal dialysis (PD) solutions have become available in recent years. In 2001, low glucose degradation products (GDP), neutral pH solutions became commercially available in Korea. To date, there are no reports regarding the large scale adoption of these solutions in clinical practice and regarding what, if any, impact these solutions have on patient outcomes.


METHODS
Using a database of almost 4000 patients treated by PD in Korea, we conducted a prospective, longitudinal observational study documenting the patterns of use of one novel low GDP solution (balance, Fresenius Medical Care, St Wendel, Germany) in 1909 PD incident patients between 1 January 2002 and midyear 2005. Outcomes including patient and technique survival and peritonitis rates were analysed using univariate and multivariate analysis.


RESULTS
Prescription of low GDP solutions reached between 70 and 80% by the year 2003 and persisted at this level. Patients prescribed low GDP PD solution tended to be younger and were more likely to be treated in centres with larger enrollment in the database. Survival of diabetic patients treated with the new PD solution was identical to that of the non-diabetic patients treated with standard PD fluids (PDF) and treatment with low GDP PDF independently reduced the relative risk (RR) of death (RR = 0.613; CI 0.50-0.74; P < 0.00001) in a proportional hazards model which included age, diabetes and centre experience. In a univariate analysis, low GDP PD solution was associated with a longer technique survival (P = 0.049) but this effect was not significant in multivariate analysis. No significant differences in peritonitis-free interval or peritonitis rate could be attributed to the prescribed PDF.


CONCLUSION
Prescription of low GDP, pH-neutral PD solutions has rapidly increased in Korea. This change has resulted in a significant improvement in patient and technique survival without any measurable change in peritonitis incidence or rate. Reasons for the improved patient survival cannot be determined from this analysis and require further study.
19782986
Reconstitution and characterization of a new desosaminyl transferase, EryCIII, from the erythromycin biosynthetic pathway.
EryCIII converts alpha-mycarosyl erythronolide B into erythromycin D using TDP-d-desosamine as the glycosyl donor. We report the heterologous expression, purification, in vitro reconstitution, and preliminary characterization of EryCIII. Coexpression of EryCIII with the GroEL/ES chaperone complex was found to enhance greatly the expression of soluble EryCIII protein. The enzyme was found to be highly active with a kcat greater than 100 min-1. EryCIII was quite selective for the natural nucleotide sugar donor and macrolide acceptor substrates, unlike several other antibiotic glycosyl transferases with broad specificity such as desVII, oleG2, and UrdGT2. Within detectable limits, neither 6-deoxyerythronolide B nor 10-deoxymethynolide were found to be glycosylated by EryCIII. Furthermore, TDP-d-mycaminose, which only differs from TDP-d-desosamine at the C4 position, could not be transferred to alphaMEB. These studies lay the groundwork for detailed structural and mechanistic analysis of an important member of the desosaminyl transferase family of enzymes.
29016869
Detection and characterization of focal hepatic lesions: comparative study of MDCT and gadobenate dimeglumine-enhanced MR imaging.
The aim of this study was to compare the diagnostic performance of multidetector row helical CT (MDCT) and gadobenate dimeglumine-enhanced magnetic resonance (MR) imaging (in the detection and characterization of focal liver lesions. Two blind reviewers analyzed the MDCT and MR images of a total of 44 malignant and 85 benign lesions in 46 patients independently. Receiver operating characteristic curves were established to analyze the results for each reviewer and modality.
4624766
FOXO1 impairs whereas statin protects endothelial function in diabetes through reciprocal regulation of Kruppel-like factor 2.
AIMS
Krüppel-like factor 2 (KLF2) is implicated as a key molecule maintaining endothelial function. This study was designed to evaluate the reciprocal regulation of KLF2 by the forkhead transcription factor FOXO1, and the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor atorvastatin, in hyperglycaemic conditions.


METHODS AND RESULTS
Exposure of human umbilical vein endothelial cells to 30 mM glucose activated FOXO1 and suppressed KLF2. These effects were reversed by FOXO1 small interfering RNA. Adenoviral transfection of constitutively active FOXO1 suppressed KLF2 expression. Interestingly, atorvastatin inhibited FOXO1 by increasing phosphorylation and also by inhibiting nuclear localization and replenished KLF2 in high-glucose conditions. This effect of atorvastatin was attenuated by mevalonate. Chromatin immunoprecipitation analysis demonstrated that glucose increased whereas atorvastatin decreased FOXO1 binding to the promoter region of the KLF2 gene. In the vessels of Otsuka Long-Evans Tokushima Fatty rats, animal models of type 2 diabetes, FOXO1 was activated and KLF2 was suppressed, and this was reversed by atorvastatin treatment. The arteries from Otsuka Long-Evans Tokushima Fatty rats showed impairment of endothelium-dependent vasodilatation, and both atorvastatin and KLF2 gene therapies restored it.


CONCLUSIONS
Suppression of KLF2 by FOXO1 may be a plausible mechanism of diabetic endothelial dysfunction. High-glucose-induced, FOXO1-mediated KLF2 suppression was reversed by atorvastatin, suggesting that intensive statin treatment could be a therapeutic option in diabetic vascular dysfunction.
30377164
Primary postpartum hemorrhage: outcome of pelvic arterial embolization in 251 patients at a single institution.
PURPOSE
To evaluate the safety and efficacy of pelvic arterial embolization (PAE) for the treatment of primary postpartum hemorrhage (PPH) and to determine the factors associated with clinical outcomes.


MATERIALS AND METHODS
This retrospective single-center study was institutional review board approved, and informed consent was waived. Outcomes were analyzed in 251 patients who underwent PAE for primary PPH between January 2000 and February 2011. Mode of delivery, causes of bleeding, detailed laboratory and treatment records, and clinical outcomes were recorded. Clinical success was defined as cessation of bleeding after initial session of PAE without the need for additional PAE or surgery. Univariate and multivariate analyses were performed to determine the factors related to clinical outcomes.


RESULTS
The clinical success rate was 86.5% (217 of 251). Among the 34 failed cases, 12 underwent repeat PAE, 16 underwent additional surgery, and three recovered with conservative management. Overall bleeding control was achieved in 98.0% (246 of 251) of the patients. Overall mortality was 2% (five of 251) after the first (n = 3) or second (n = 1) session of PAE or additional surgery (n = 1). Among the 113 patients with long-term follow-up, 110 (97.3%) maintained a regular menstrual cycle and 11 had successful pregnancies. Univariate analysis showed that cesarean section delivery, disseminated intravascular coagulation (DIC), and massive transfusion of more than 10 red blood cell units were related to failed PAE. Multivariate analysis showed that DIC (odds ratio, 0.36; P = .04) and massive transfusion (odds ratio, 0.10; P < .001) were significantly related to clinical failure.


CONCLUSION
PAE is safe and effective for managing primary PPH. Patients with DIC and massive transfusion were likely to have poor results after PAE.
26011151
Atypical Imaging Features of Epstein-Barr Virus–Positive Primary Central Nervous System Lymphomas in Patients without AIDS
BACKGROUND AND PURPOSE: Recent clinical experience with EBV-positive PCNSL in patients without acquired immune deficiency syndrome showed that they tended to have atypical features seen on conventional MR imaging. The purpose of our study was to evaluate the MR imaging features of EBV-positive PCNSL in patients without AIDS and to compare these imaging findings with those of EBV-negative PCNSL. MATERIALS AND METHODS: MR images were obtained in 55 consecutive patients with pathologically proved EBV-positive (n = 10) or EBV-negative (n = 45) PCNSL. We statistically analyzed the differences between the patient groups regarding the occurrence of tumor necrosis or hemorrhage and ADC, rCBVmax, rCBVr, and the Cho/NAA ratio in the tumor area. RESULTS: Tumor necrosis and hemorrhage were observed in 9 (90%) and 7 (70%), respectively, of the patients with EBV-positive PCNSL; necrosis was observed in 8 (18%), and hemorrhage, in 3 (7%) patients with EBV-negative PCNSL (P < .0001 each). The necrotic core was hyperintense relative to contralateral white matter, as seen on DWI in 4 patients with EBV-positive PCNSL, though the ADC between the 2 patient groups did not differ significantly. rCBVmax, rCBVr, and the Cho/NAA ratios did not differ significantly between the 2 groups. The sensitivity and specificity of necrosis and hemorrhage for differentiating the 2 groups were 89.2% and 81.7% and 78.5% and 94.1%, respectively. CONCLUSIONS: Our initial clinical experience with a small number of patients suggests that EBV-positive PCNSL in patients without AIDS tends to present with atypical MR imaging features.