Effect of Institutional Case Volume on In-Hospital Mortality After Deceased Donor Liver Transplantation: A Nationwide Retrospective Cohort Study in Korea.

BACKGROUND: There is still controversy as to whether the case volume affects clinical outcomes after liver transplantation. This nationwide retrospective cohort study aimed to investigate the relationship between institutional case volume and post-transplant outcomes after deceased donor liver transplantation. MATERIAL AND METHODS: The data was extracted from the database of Korean National Healthcare Insurance Service. A total of 2648 adult deceased donor liver transplantations were performed at 54 centers in Korea from January 2007 to December 2016. Centers were divided into high-, medium-, and low-volume centers according to the average annual number of deceased donor liver transplantations as follows: < 10, 10-30, and >30. RESULTS: In-hospital mortality rates in high-, medium-, and low-volume centers were 10.3%, 14.3%, and 17.1%, respectively. Multivariable logistic regression analysis revealed that low-volume centers (adjusted odds ratio 1.953; 95% confidence interval, 1.461-2.611; P < .001) and medium-volume centers (adjusted odds ratio 1.480; 95% confidence interval, 1.098-1.994; P = .010) had a significantly higher in-hospital mortality compared to high-volume centers. Long-term mortality rates were also higher in low-volume centers (P = .007). CONCLUSION: Centers with higher volume showed better in-hospital mortality and long-term survival after deceased donor liver transplantation compared to centers with lower volume.

Impaired development and dysfunction of endothelial progenitor cells in type 2 diabetic mice.

AIM: Dysfunction of circulating endothelial progenitor cells (EPCs) has been shown to affect the development of microvascular diseases in diabetes patients. The aim of this study was to elucidate the development and mechanical dysfunction of EPCs in type 2 diabetes (T2D). METHODS: The colony-forming capacity of EPCs and differentiation potential of bone marrow (BM) c-Kit(+)/Sca-I(+) lineage-negative mononuclear cells (KSL) were examined in T2D mice, db/db mice and KKAy mice, using EPC colony-forming assay (EPC-CFA). RESULTS: T2D mice had fewer BM stem/progenitor cells, and proliferation of KSL was lowest in the BM of db/db mice. In T2D mice, the frequency of large colony-forming units (CFUs) derived from BM-KSL was highly reduced, indicating dysfunction of differentiation into mature EPCs. Only a small number of BM-derived progenitors [CD34(+) KSL cells], which contribute to the supply of EPCs for postnatal neovascularization, was also found. Furthermore, in terms of their plasticity to transdifferentiate into various cell types, BM-KSL exhibited a greater potential to differentiate into granulocyte macrophages (GMs) than into other cell types. CONCLUSION: T2D affected EPC colony formation and differentiation of stem cells to mature EPCs or haematopoietic cells. These data suggest opposing regulatory mechanisms for differentiation into mature EPCs and GMs in T2D mice.

Cytoprotective effect of dieckol on human endothelial progenitor cells (hEPCs) from oxidative stress-induced apoptosis.

Although endothelial progenitor cells (EPCs) have been used to promote revascularization after peripheral or myocardial ischemia, excess amounts of reactive oxygen species (ROS) are often involved in senescence and apoptosis of EPCs, thereby causing defective neovascularization and reduced or failed recovery. Here, we examined the cytoprotective effect of Ecklonia cava-derived antioxidant dieckol (DK) on oxidative stress-induced apoptosis in EPCs to improve EPC bioactivity for vessel repair. Although H2O2 (10 (- 3) M) increased the intracellular ROS level in EPCs, DK (10ug/ml) pretreatment suppressed the H2O2-induced ROS increase and drastically reduced the ratios of apoptotic cells. H2O2-induced ROS increased the phosphorylation of p38 MAPK and JNK; this was inhibited by DK pretreatment. H2O2 treatment increased the phosphorylation of NF-κB, which was blocked by pretreatment with SB 203580, a p38 MAPK inhibitor, or SP 600125, a JNK inhibitor. H2O2 decreased the cellular levels of Bcl-2 and c-IAPs, cellular inhibitors of apoptosis proteins, but increased caspase-3 activation. However, all these effects were inhibited by pretreatment with DK. Injection of DK-mixed EPCs (DK + EPCs) into myocardial ischemic sites in vivo induced cellular proliferation and survival of cells at the ischemic sites and, thereby, enhanced the secretion of angiogenic cytokines at the ischemic sites. These results show that DK + EPC exhibit markedly enhanced anti-apoptotic and antioxidative capabilities, unlike that shown by EPCs alone; thus, they contribute to improved repair of ischemic myocardial injury through cell survival and angiogenic cytokine production.

Establishment of isolation and expansion protocols for human cardiac C-kit-positive progenitor cells for stem cell therapy.

Although cardiac stem cells (CSCs) have emerged in regeneration research, the number of isolated CSCs is low, making a sufficient supply of functional elements an important consideration in cardiovascular research. In this study, we established an efficient method for CSC isolation. We directly compared cultures of single cells to human cardiac-derived c-kit-positive progenitor cells (hCPCs(c-kit+)). The two protocols employed enzymatically digested hCPCs(c-kit+) (ED-hCPCs) with tissue-expanded hCPC(c-kit+) (TE-hCPCs). Using fluorescence-activated cell sorting, we showed the concentration of c-kit in TE-hCPCs to be higher than in ED-hCPCs, although the total number of c-kit positive cells resulting from ED-hCPCs was similar to that resulting from TE-hCPCs. The cardiomyocyte-associated proteins, GATA4 and Nkx2-5, which were expressed during hCPCs expansion, did not differ between the isolation methods. Importantly, the expression of the CSC stem cell marker, c-kit, was more efficiently preserved using the ED-hCPCs versus the TE-hCPCs method. In a cell proliferation assay, the ED-hCPCs method produced a significantly greater number of cells. Finally, hCPCs derived using both protocols differentiated into endothelial, smooth muscle, and cardiomyocyte lineages. In conclusion, the single-cell culture protocol using an enzymatic digestion method may be more useful to isolate human cardiac-derived c-kit-positive elements compared with the tissue expansion method.

Assessment of nurses' nutritional knowledge regarding therapeutic diet regimens.

Metabolic diseases and cardiovascular disease (CVD), the incidence of which is currently increasing in Korea, can be managed well with dietary education and modification. However, it has yet to be established whether nurses have sufficient knowledge to impart appropriate nutritional counseling to patients with these diseases. Our study involved 506 nurses working at Asan Medical Center, Samsung Medical Center, and Seoul National University Hospital between March and May, 2006. The questionnaire was comprised of 42 diet-related questions pertaining to diabetes, obesity, and CVD. Nurses' correct-response rate for overall nutritional knowledge was worse than reported in Western countries (58.4%), and particularly so with regard to obesity and CVD. Although many nurses were aware of the therapeutic aspects of nutrients in relation to CVD, most of them had limited knowledge about low-cholesterol diets and sources of water-soluble fiber, fatty acids and the specific food items that prevent CVD. Our results suggest that there is an urgent need to update the contents of nutrition education for nurses to reflect the current changes in the Korean diet and the increasing incidence of metabolic diseases and CVD.

Cell cycle and immune-related processes are significantly altered in chronic GVHD.

Currently, the pathogenesis of chronic GVHD is unclear. To elucidate the molecular characteristics underlying chronic GVHD, we analyzed the gene expression profiles of 21 mononuclear cell samples from allogeneic hematopoietic stem cell transplantation (HSCT) recipients. Self organizing map (SOM) clustering showed that the entire expression profiles of chronic GVHD samples were clearly different from those of the non-GVHD samples, and significance analysis of microarray (SAM) demonstrated that 120 genes, including PTDSS1, VAV1 and CD3D, were up-regulated, and 5 genes, including calnexin, were down-regulated in GVHD patients. Gene ontology annotation revealed that these genes are related to the phosphorous metabolism and lipid biosynthesis. Quantitative real time polymerase chain reaction (qRT-PCR) experiments validated the up-regulation of PTDSS1, VAV1 and CD3D in separate samples. Pathway-wise global test revealed that differential gene expression in cell cycle and T cell immune-associated pathways were significant between GVHD patients and non-GVHD patients. Seventeen classifier genes selected using a PAM (prediction analysis of microarray) algorithm showed favorable performance (prediction accuracy=0.85) for identifying patients with chronic GVHD. In conclusion, we identified differentially expressed genes and pathways in chronic GVHD patients using microarray analysis, and we also selected diagnostic genes predicting chronic GVHD status.

Two different types of obsession: autogenous obsessions and reactive obsessions.

We propose that obsessions are categorized into two subtypes, i.e. autogenous obsessions and reactive obsessions, which are different in terms of identifiability of their evoking stimuli, subjective experiences, contents, and subsequent cognitive processes. Autogenous obsessions tend to come abruptly into consciousness without identifiable evoking stimuli, which are perceived as ego-dystonic and aversive enough to be repelled, and include sexual, aggressive, and immoral thoughts or impulses. On the other hand, reactive obsessions are evoked by identifiable external stimuli, which are perceived as relatively realistic and rational enough to do something toward the stimuli, and include thoughts about contamination, mistake, accident, asymmetry, loss, etc. Through three empirical studies, we confirmed the differences between the two types of obsessional intrusion in their frequency, subjective experiences, subsequent appraisal and control strategy. In particular, autogenous obsessions led to high appraisal on 'control over thought' and 'importance of thought' and frequent use of 'avoidant control strategies', while reactive obsessions linked with high appraisal on 'responsibility' and frequent use of 'confrontational control strategies'. These findings are expected to provide a basis for classifying and explaining the heterogeneous phenomena of obsessive-compulsive disorder.

Spine needle biopsy simulator using visual and force feedback.

OBJECTIVE: Biopsy with an inserted needle is an important procedure for lesion detection in the spine, but is difficult to perform due to the presence of many critical organs near the spine. This article presents a spine needle biopsy simulator, based on visual and force feedback, which can be used to plan the optimal path of a needle and to practice the procedure without risk. MATERIALS AND METHODS: The simulator is composed of a 3D human model, a visual-feedback component, a force-feedback component, and an evaluation module. The human model is based on 3D CT data. The visual-feedback component provides an oblique section, multiplanar reformatting images, and a volume-rendered image. Of these, the oblique section display is very useful for planning a 3D path for the needle. During simulation, the force-feedback component generates and provides realistic forces acting on the biopsy needle in real time by synchronizing them to visual feedback. After each simulation, the evaluation module provides a performance analysis for the trainee. RESULTS: For an XCT abdomen volume data set of 256 x 256 x 256, the update rate of image rendering due to needle movement is over 25 Hz, with a force-feedback rate of 1 kHz. This performance proved to be good enough for the trainee to learn the relationship between visual and force feedback. CONCLUSIONS: The simulator is useful for the planning of and training in complicated 3D spine needle biopsy procedures. It may be used as an educational tool for beginners, a practice tool to increase expertise, or a test bed for new procedures.

Development of rat prostatitis model by oral administration of isoflavone and its characteristics.

Inflammation of the prostate can be induced experimentally in rats by the subcutaneous administration of estrogen. However, it is usually achieved at the price of some alteration in the sex steroid hormone balance and morphological changes in the prostate. In this study, a soy-extracted isoflavone mixture with weak estrogenic activity was administered orally in an attempt to induce prostatitis in a more physiologic way and to characterize the inflammation induced. A total of 36 male Sprague-Dawley rats, 8 weeks old, were divided into 2 groups. The control group was fed with only an AIN-76A diet containing no detectable phytoestrogen and the experimental group was fed with AIN-76A and a soy- extracted isoflavone mixture (genistein 60.0% and daidzein 19.6%), 300 mg/kg body weight for 9 weeks. The sequential body weight and prostate weight at necropsy were measured. A histologic examination and histomorphometry assessed the changes in the prostate. The serum concentrations of testosterone and dihydrotestosterone were measured to estimate the effects on the androgen level. Intraprostatic concentrations of genistein and daidzein were measured by gas chromatography/ mass spectroscopy (GC/MS). While no sign of prostate inflammation was apparent in the control group, severe inflammatory changes in the stroma, increased epithelial detachment and inflammatory exudates within the glandular lumen of the dorsolateral prostate were observed in more than 80%(15/18) of the experimental group. However, there was no significant difference in the ventral prostate between the two groups. The daidzein and genistein concentrations in both the lateral and ventral prostates were significantly higher in the experimental group than in the control group where no isoflavone was detectable. In addition, the concentrations were much higher in the dorsolateral than in the ventral prostate. Although the body weight gain was not consistent in the experimental group, there were no significant differences in the prostate weight and serum androgen level between groups. In summary, when a soy-extracted genistein and daidzein-rich isoflavone mixture was administered orally into rats, prostatic inflammation with characteristic lobe specificity developed. The present method of inducing prostatitis seems to be a more physiologic than an estrogen-induced experimental model, and sequential pharmacokinetic studies might help in establishing this model as a more valuable tool in assisting future research in this field.

Simultaneous determination of anions and cations by ion-exclusion chromatography-cation-exchange chromatography with tartaric acid/18-crown-6 as eluent.

Ion-exclusion chromatography-cation-exchange chromatography was developed for the simultaneous separation of common inorganic anions and cations (Cl-, NO3- and SO4(2-); Na+, NH4+, K+, Mg2+ and Ca2+) on a weakly acidic cation-exchange column by elution with weak acid. Generally, the resolution among these monovalent cations was only moderate, thereby hindering the determination of these analytes in natural-water samples. Therefore, 18-crown-6 was added to the eluent to improve the resolution. A good separation of these anions and cations on a weakly acidic cation-exchange column was achieved in 30 min by elution with 5 mM tartaric acid/6 mM 18-crown-6/methanol-water (7.5:92.5). The ion-exclusion chromatography-cation-exchange chromatography method developed here was successfully applied to the separation of major anions and cations in an environmental water sample.

Reduced need for alveolar bone grafting by presurgical orthopedics and primary gingivoperiosteoplasty.

OBJECTIVE: The purpose of this study was to evaluate if narrowing and approximation of the alveolar cleft through presurgical alveolar molding followed by gingivoperiosteoplasty (GPP) at the time of lip repair reduces the need for a bone-grafting procedure. DESIGN: This was a retrospective blind study of patients with unilateral or bilateral alveolar clefts who underwent presurgical infant alveolar molding and GPP by a single surgeon. Alveolar bone formation was assessed prior to the eruption of the maxillary lateral incisor or canine by clinical examination, panoramic and periapical radiographs, and/or a dental CT scan. The criterion for bone grafting was inadequate bone stock to permit the eruption and maintenance of the permanent dentition. SETTING: This study was performed at the Institute of Reconstructive Plastic Surgery by the members of the Cleft Palate Team. PATIENTS: All patients with unilateral (n = 16) or bilateral (n = 2) alveolar clefts who underwent presurgical infant alveolar molding and GPP by a single surgeon from 1985 to 1988 were studied. The control population consisted of all alveolar cleft patients (n = 14) who did not undergo alveolar modeling or GPP during the same time period. INTERVENTIONS: Presurgical alveolar modeling was performed with an intraoral acrylic molding plate. This plate was modified on a weekly basis to align the alveolar segments and close the alveolar gap. The surgical intervention consisted of a modified Millard GPP. MAIN OUTCOME MEASURES: The primary study outcome measure was the elimination of the need for a secondary bone graft in patients who underwent presurgical alveolar molding and GPP. RESULTS: Of the 20 sites in the 18 patients who underwent GPP, 12 sites did not require an alveolar bone graft. Of the 8 sites requiring a bone graft, 4 presented minimal bony defects. All 14 patients in the control group required bone grafts. CONCLUSIONS: In this series of 20 alveolar cleft sites treated with presurgical orthopedics and GPP, 60% did not need a secondary alveolar bone graft in the mixed dentition.

In vitro andin vivo antifungal activities of 6-[(N-4-bromophenyl) amino]-7-chloro-5,8-quinolinediones.

Antifungal activities of 6-[(N-4-bromophenyl)amino]-7-chloro-5,8-quinolinedione (RCK7) were tested. The MIC values of RCK7 were determined for antifungal suceptibility,in vitro againstAspergillus niger, Cryptococcus neoformans andTrichophyton mentagrophyte by standard agar streak method.In vitro, RCK7 showed more potent antifungal activity than fluconazole and ketoconazole. Also, RCK7 was tested forin vivo antifungal activity in the treatment of systemic infection withCandida albicans in normal mice. The therapeutic potential of RCK7 had been assessed by evaluating their survival rate against systemic infections compared with that of ketoconazole. ED(50) of intraperitoneally administered RCK7 was 2.05+/-0.30 mg/kg but that of ketoconazole was 8.00+/-0.73 mg/kg, respectively. When RCK7 was administered intravenously at the ED(50) (2.05 mg/kg), the colony counts ofCandida albicans in the liver after 7 days and 14 days were reduced as likely as ketoconazole at the ED(50) (8.00 mg/kg), and the better survival rates than ketoconazole's were achieved after 14 days. The results suggest that RCK7 may be a potent antifungal agent.