Hepatitis B Virus DNA-Level Change is Associated With Tumor Recurrence in Patients With Resected Hepatitis B Virus Hepatocellular Carcinoma.

INTRODUCTION: To investigate the significance of perioperative hepatitis B virus (HBV) DNA changes for predicting recurrence in patients with HBV-related hepatocellular carcinoma (HCC) undergoing liver resection (LR). METHODS: From 2013 to 2020, 241 patients with HBV-related HCC who underwent LR in five Hallym university-affiliated hospitals were enrolled. The serum HBV DNA level, together with other clinicopathological variables, was analyzed for association with HCC recurrence. RESULTS: Preoperatively, 99 patients had undetectable HBV DNA and 142 had detectable viral levels. Of those with detectable viral levels, 72 rapidly progressed to undetectable levels within 3 mo after LR (Rapid group), and 70 showed persistently detectable levels (Nonrapid group). The Rapid group had a better recurrence-free survival (RFS) rate than the Nonrapid group (1-y, 3-y RFS = 75.4%, 57.3%, versus 54.7%, 39.9%, respectively, P = 0.012). In the subgroup analysis, the Rapid group had a better RFS rate in early stages (1-y, 3-y RFS = 82.6%, 68.5%, versus 62.8%, 45.8%, respectively, P = 0.005); however, the RFS rates between the two groups were comparable in the advanced stage (1-y, 3-y RFS = 61.1%, 16.7% versus 45.5%, 22.7%, respectively, P = 0.994). Among the 142 patients with preoperatively detectable HBV DNA, persistently detectable HBV DNA within 3 mo postoperatively (hazard ratio [HR] = 1.7, P = 0.022), large tumor size (HR = 2.7, P < 0.001), multiple tumors (HR = 3.2, P < 0.001), and microvascular invasion (HR = 1.7, P = 0.028) were independent risk factors for RFS in multivariate analysis. CONCLUSIONS: Rapidly undetectable HBV DNA after LR is associated with a better prognosis for recurrence in patients with HCC. Therefore, appropriate treatment and/or screening may be necessary for patients who do not return to undetectable HBV DNA after LR.

Long-Term Outcomes of Liver Transplantation in Hepatocellular Carcinoma with Bile Duct Tumor Thrombus: A Comparison with Portal Vein Tumor Thrombus.

Liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) remains controversial. This study analyzed the recurrence and overall survival rates through long-term results after LT in HCC patients with BDTT and compared the results after LT in HCC patients with portal vein tumor thrombus (PVTT). We performed a retrospective study of 45 patients with PVTT, 16 patients with BDTT, and 11 patients with coexisting PVTT and BDTT among HCC patients who underwent LT at a single center from 1999 to 2020. The HCC recurrence rates were 40.4% at 1 year, 30.3.3% at 2 years, and 27.6% at 3 years in the PVTT group; 66.7%, 53.3%, and 46.7% in the BDTT group; and 22.2%, 22.2%, and 0% in the coexisting group (p = 0.183). Overall patient survival rates were 68.4% at 1 year, 54.3% at 2 years, and 41.7% at 3 years in the PVTT group; 81.3%, 62.5%, and 48.2% in the BDTT group; and 63.6%, 27.3%, and 0% in the coexisting group (p = 0.157). In the multivariate analysis, the pre-transplantation model for tumor recurrence after liver transplantation (MoRAL) score and model for end-stage liver disease (MELD) score were found to be independent risk factors for recurrence and survival in all groups. HCC patients with BDTT showed no difference in recurrence and survival compared with HCC patients with PVTT at the long-term follow-up after LT.

Identification of Risk Groups for and Factors Affecting Metabolic Syndrome in South Korean Single-Person Households Using Latent Class Analysis and Machine Learning Techniques: Secondary Analysis Study.

BACKGROUND: The rapid increase of single-person households in South Korea is leading to an increase in the incidence of metabolic syndrome, which causes cardiovascular and cerebrovascular diseases, due to lifestyle changes. It is necessary to analyze the complex effects of metabolic syndrome risk factors in South Korean single-person households, which differ from one household to another, considering the diversity of single-person households. OBJECTIVE: This study aimed to identify the factors affecting metabolic syndrome in single-person households using machine learning techniques and categorically characterize the risk factors through latent class analysis (LCA). METHODS: This cross-sectional study included 10-year secondary data obtained from the National Health and Nutrition Examination Survey (2009-2018). We selected 1371 participants belonging to single-person households. Data were analyzed using SPSS (version 25.0; IBM Corp), Mplus (version 8.0; Muthen & Muthen), and Python (version 3.0; Plone & Python). We applied 4 machine learning algorithms (logistic regression, decision tree, random forest, and extreme gradient boost) to identify important factors and then applied LCA to categorize the risk groups of metabolic syndromes in single-person households. RESULTS: Through LCA, participants were classified into 4 groups (group 1: intense physical activity in early adulthood, group 2: hypertension among middle-aged female respondents, group 3: smoking and drinking among middle-aged male respondents, and group 4: obesity and abdominal obesity among middle-aged respondents). In addition, age, BMI, obesity, subjective body shape recognition, alcohol consumption, smoking, binge drinking frequency, and job type were investigated as common factors that affect metabolic syndrome in single-person households through machine learning techniques. Group 4 was the most susceptible and at-risk group for metabolic syndrome (odds ratio 17.67, 95% CI 14.5-25.3; P<.001), and obesity and abdominal obesity were the most influential risk factors for metabolic syndrome. CONCLUSIONS: This study identified risk groups and factors affecting metabolic syndrome in single-person households through machine learning techniques and LCA. Through these findings, customized interventions for each generational risk factor for metabolic syndrome can be implemented, leading to the prevention of metabolic syndrome, which causes cardiovascular and cerebrovascular diseases. In conclusion, this study contributes to the prevention of metabolic syndrome in single-person households by providing new insights and priority groups for the development of customized interventions using classification.

Arthroscopic transosseous anchorless rotator cuff repair reduces bone defects related to peri-implant cyst formation: a comparison with conventional suture anchors using propensity score matching.

BACKGROUND: The transosseous anchorless repair (ToR) technique was recently introduced to avoid suture anchor-related problems. While favorable outcomes of the ToR technique have been reported, no previous studies on peri-implant cyst formation with the ToR technique exist. Therefore, this study compared the clinical outcomes and prevalence of peri-implant cyst formation between the ToR technique and the conventional transosseous equivalent technique using suture anchors (SA). METHODS: Cases with arthroscopic rotator cuff repair (ARCR) between 2016 and 2018 treated with the double-row suture bridge technique were retrospectively reviewed. Patients were divided into ToR and SA groups. To compare clinical outcomes, 19 ToR and 57 SA cases without intraoperative implant failure were selected using propensity score matching (PSM). While intraoperative implant failure rate was analyzed before PSM, retear rate, peri-implant cyst formation rate, and functional outcomes were compared after PSM. RESULTS: The intraoperative implant failure rate (ToR, 8% vs. SA, 15.3%) and retear rate (ToR, 5.3% vs. SA, 19.3%) did not differ between the two groups (all P>0.05). However, peri-implant cysts were not observed in the ToR group, while they were observed in 16.7% of the SA group (P=0.008). Postoperative functional outcomes were not significantly different between the two groups (all P>0.05). CONCLUSIONS: The ToR technique produced comparable clinical outcomes to conventional techniques. Considering the prospect of potential additional surgeries, the absence of peri-implant cyst formation might be an advantage of ToR. Furthermore, ToR might reduce the medical costs related to suture anchors and, thereby, could be a useful option for ARCR. Level of evidence: III.

Nanoencapsulation of Grapefruit Seed Extract and Cinnamon Oil for Oral Health: Preparation, In Vitro, and Clinical Antimicrobial Activities.

This study aimed to formulate mucoadhesive antimicrobial nanoparticles using natural antimicrobials and biopolymers for oral health and verify their antimicrobial activity in clinical studies. A combination of grapefruit seed extract and cinnamon oil (GCN) and chitosan/carrageenan (CS/CR) were selected as synergistic antimicrobial combinations and mucoadhesive wall materials for nanoparticles, respectively. GCN nanoparticles (NPs; size = 357 nm and polydispersity index = 0.188) prepared by ionic gelation between CS and CR exhibited synergistic antimicrobial activity between grapefruit seed extract and cinnamon oil and significantly higher antimicrobial activity against Streptococcus mutans and sobrinus than free GCN in a time-kill assay. The clinical antibacterial activity of GCN was significantly increased and sustained by nanoencapsulation in the mouth-rinse test and GCN NP-treated drinking yogurt. These results suggest that GCN-loaded CS/CR nanoencapsulation is a promising technique that can inhibit oral bacteria with or without the presence of other food ingredients.

Antimicrobial and indicator properties of edible film containing clove bud oil-loaded chitosan capsules and red cabbage for fish preservation.

For safe preservation and consumption of fish, freshness monitoring and antimicrobial control is crucial. Edible films comprising natural antimicrobial and spoilage indicator agents represent a convenient method for such preservation. Edible chitosan-based films were prepared using red cabbage (RC) and clove bud oil (CBO)-loaded chitosan/carrageenan capsules as spoilage indicator and antimicrobial agents, respectively. CBO-loaded capsules were prepared by the ionic gelation of chitosan and carrageenan. Films containing CBO capsules exhibited significantly higher antimicrobial activity than films containing non-encapsulated free CBO, as confirmed by minimum inhibitory concentration and time-kill assays. The highest antimicrobial activity was observed in the largest capsules (1.7 µm). After incubation for 48 h, the pH of fish peptone agar containing Pseudomonas fluorescens increased from approximately 6.0 to 9.0, and a color change from purple to deep blue was clearly observed during the growth of fish-spoiling bacteria. Thus, our results suggested that edible films containing CBO-loaded capsules and RC showed the potential to inhibit microbial growth in fish and to visibly indicate fish freshness.

Skimmed milk fermented by lactic acid bacteria inhibits adipogenesis in 3T3-L1 pre-adipocytes by downregulating PPARγ via TNF-α induction in vitro.

The murine 3T3-L1 pre-adipocyte cell line is widely used as an in vitro model for adipogenesis because of its similarities to primary fat cells. The aim of this study was to investigate the intracellular mechanisms by which skimmed milk fermented by two lactic acid bacteria (LAB), Enterococcus faecalis and Lactobacillus plantarum, inhibited the differentiation of 3T3-L1 pre-adipocytes. Skimmed milk fermented by both LAB, but not non-fermented skimmed milk, significantly reduced the accumulation of lipid droplets and cellular triglycerides in a concentration-dependent manner. The mRNA and protein levels of peroxisome proliferator-activated receptor γ (PPARγ) were markedly inhibited in the presence of skimmed milk fermented by both LAB. Furthermore, the skimmed milk fermented by both LAB decreased the mRNA and protein expressions of PPARγ-targeting genes, lipoprotein lipase and adipocyte fatty acid-binding protein. Under the same circumstances, resistin mRNA expression was downregulated, but not leptin mRNA expression. In contrast, skimmed milk fermented by both LAB significantly upregulated tumor necrosis factor-α (TNF-α). These results suggest that LAB-fermented skimmed milk inhibits adipogenesis by inhibiting a master transcription factor PPARγ via the upregulation of the proinflammatory cytokine TNF-α in 3T3-L1 cells.

Quercetin delivery characteristics of chitosan nanoparticles prepared with different molecular weight polyanion cross-linkers.

The aim of the study was to investigate the effects of cross-linkers on quercetin (QUE) absorption characteristics of QUE-loaded chitosan nanoparticles (CS-NPs). CS-NPs (461.2-482.7 nm) were prepared by ionic gelation at pH 3.5 using tripolyphosphate (367.9 Da), dextran sulfate (>15 kDa), arabic gum (AG, >250 kDa), or hyaluronic acid (HA, >1000 kDa). Mucoadhesion and cell permeation of QUE were significantly increased by positive charged CS-NPs due to interactions with negatively charged mucosal layer. Moreover, CS-AG and CS-HA NPs prepared with relatively higher MW cross-linkers exhibited significantly higher adhesion and permeation than the others. These results were verified by a cellular antioxidant activity assay; CS-AG (137.5 unit) and CS-HA NPs (126.5 unit) showed significantly higher activities after internalization into Caco-2 cells. Therefore, encapsulation within CS-NPs prepared using high MW cross-linkers such as AG and HA is found to be potentially valuable techniques for improving the QUE absorption.

Lactobacillus plantarum Reduces Low-Grade Inflammation and Glucose Levels in a Mouse Model of Chronic Stress and Diabetes.

This study aimed to examine the effects of Lactobacillus plantarum, a lactic acid bacteria strain isolated from kimchi, on the development of low-grade inflammation and type 2 diabetes mellitus (T2DM) exacerbated by chronic stress. C57BL/6 mice were fed either a high-fat diet (HFD) and randomized into an HFD group or a group that was fed an HFD and subjected to chronic cold exposure-related stress (HFDS), or mice were fed a normal diet (ND) and randomized into an ND group or a group that was fed an ND and subjected to chronic cold exposure-related stress (NDS). Lactobacillus plantarum LRCC5310 (108, 1010 CFU) and LRCC5314 (108, 1010 CFU) as well as L. gasseri BNR17 (108 CFU), as a positive control, were administered orally twice every day to all the mice for 12 weeks. The expression of Glut4 and adiponectin, main glucose transporter-related genes, was upregulated in the LRCC5310- and LRCC5314-treated groups. Levels of serum proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6]) and of mRNAs of proinflammatory genes (Tnf-α, Il-6, Ccl2, leptin) were elevated in HFDS mice. The expression of proinflammatory genes was downregulated in LRCC5310- and LRCC5314-treated groups; this was not the case for Tnf-α expression in HFDS mice. Levels of serum corticosterone and mRNA levels of stress-related genes (Npy, Y2r) were decreased in lactic acid bacteria (LAB)-fed groups, with only LRCC5314 downregulating Npy expression in HFDS mice. These results suggest that the LAB strains can normalize the expression of metabolic genes, inhibit inflammatory responses, and suppress stress in HFDS mice.

Synergistic antimicrobial properties of nanoencapsulated clove oil and thymol against oral bacteria.

This study aimed to improve the antimicrobial activity of natural extracts against oral bacteria by synergistic combination and nanoencapsulation. Among five natural antimicrobials: clove oil, thymol, naringin, naringenin, and licorice, clove oil and thymol were selected by comparing the antimicrobial activities against Streptococcus mutans and Streptococcus sobrinus before and after nanoencapsulation. The combination of clove oil and thymol (CLTY) was nanoencapsulated using chitosan and poly-γ-glutamic acid. While free CLTY showed additive and synergistic antimicrobial activity against S. mutans and S. sobrinus, respectively, CLTY nanoparticles (NPs) exhibited synergistic activity against both strains in a time-kill kinetic assay. CLTY NPs significantly decreased the growth of salivary S. mutans during testing, compared with free CLTY in the mouth rinse test. These results indicate that nanoencapsulation can significantly increase the synergistic antimicrobial activity of CLTY and maintain its antimicrobial activity in oral cavities for a longer time.

The MAO Inhibitor Tranylcypromine Alters LPS- and Aß-Mediated Neuroinflammatory Responses in Wild-type Mice and a Mouse Model of AD.

Monoamine oxidase (MAO) has been implicated in neuroinflammation, and therapies targeting MAO are of interest for neurodegenerative diseases. The small-molecule drug tranylcypromine, an inhibitor of MAO, is currently used as an antidepressant and in the treatment of cancer. However, whether tranylcypromine can regulate LPS- and/or Aß-induced neuroinflammation in the brain has not been well-studied. In the present study, we found that tranylcypromine selectively altered LPS-induced proinflammatory cytokine levels in BV2 microglial cells but not primary astrocytes. In addition, tranylcypromine modulated LPS-mediated TLR4/ERK/STAT3 signaling to alter neuroinflammatory responses in BV2 microglial cells. Importantly, tranylcypromine significantly reduced microglial activation as well as proinflammatory cytokine levels in LPS-injected wild-type mice. Moreover, injection of tranylcypromine in 5xFAD mice (a mouse model of AD) significantly decreased microglial activation but had smaller effects on astrocyte activation. Taken together, our results suggest that tranylcypromine can suppress LPS- and Aß-induced neuroinflammatory responses in vitro and in vivo.

Regorafenib Regulates AD Pathology, Neuroinflammation, and Dendritic Spinogenesis in Cells and a Mouse Model of AD.

The oral multi-target kinase inhibitor regorafenib, which targets the oncogenic receptor tyrosine kinase (RTK), is an effective therapeutic for patients with advanced gastrointestinal stromal tumors or metastatic colorectal cancer. However, whether regorafenib treatment has beneficial effects on neuroinflammation and Alzheimer's disease (AD) pathology has not been carefully addressed. Here, we report the regulatory function of regorafenib in neuroinflammatory responses and AD-related pathology in vitro and in vivo. Regorafenib affected AKT signaling to attenuate lipopolysaccharide (LPS)-mediated expression of proinflammatory cytokines in BV2 microglial cells and primary cultured microglia and astrocytes. In addition, regorafenib suppressed LPS-induced neuroinflammatory responses in LPS-injected wild-type mice. In 5x FAD mice (a mouse model of AD), regorafenib ameliorated AD pathology, as evidenced by increased dendritic spine density and decreased Aß plaque levels, by modulating APP processing and APP processing-associated proteins. Furthermore, regorafenib-injected 5x FAD mice displayed significantly reduced tau phosphorylation at T212 and S214 (AT100) due to the downregulation of glycogen synthase kinase-3 beta (GSK3ß) activity. Taken together, our results indicate that regorafenib has beneficial effects on neuroinflammation, AD pathology, and dendritic spine formation in vitro and in vivo.

Resveratrol-loaded chitosan-γ-poly(glutamic acid) nanoparticles: Optimization, solubility, UV stability, and cellular antioxidant activity.

The objective of this study was to investigate the effects of the particle size of resveratrol (RSV)-loaded nanoparticles (NPs) on their solubility and stability and to optimize their preparation conditions for their solubility and stability. RSV-loaded NPs were prepared using chitosan and γ-poly(glutamic acid) (γ-PGA). Although the solubility and stability of RSV have been significantly increased using chitosan/γ-PGA nanoencapsulation, as the NP size decreased, the solubility increased, but the stability decreased. In order to understand the interrelationship of particle size, solubility, and stability, the target values of RSV solubility and ultraviolet (UV) stability for the aforementioned optimization were determined at two levels: solubility >153 µg/mL, UV stability >12 % (S153U12) and solubility >150 µg/mL, UV stability >18 % (S150U18). The S150U18-NPs (258 nm) showed a significantly higher UV stability and tyrosinase inhibition activity against UVA than S153U12-NPs (87 nm) (p < 0.01). Although insignificant, the S153U12-NPs exhibited higher solubility than the S150U18-NPs. In addition, the cellular antioxidant activity was significantly higher in the S153U12-NPs than the S150U18-NPs (p < 0.05). These results demonstrated that the solubility and stability of RSV-loaded NPs may be influenced by their particle size, which could be controlled by the chitosan and γ-PGA concentrations.

Nanoencapsulation of synergistic antioxidant fruit and vegetable concentrates and their stability during in vitro digestion.

BACKGROUND: Natural antioxidants have received increased attention owing to their safe use without side effects; however, their application has been limited because of lower antioxidant activity and stability during digestion when compared with those of synthetic antioxidants. Although research is ongoing to overcome these problems, it is still challenging to find effective solutions. In this study, we aimed to improve the properties and stability of natural antioxidants during in vitro digestion by synergistic combination and nanoencapsulation. RESULTS: Ten selected fruit and vegetable concentrates (acai berry, aronia, blackberry, cranberry, wild berry, raspberry, blueberry, red grape, cabbage, and spinach) were evaluated for their antioxidant capacity when combined via the oxygen radical absorbance capacity (ORAC) assay. Among the 45 combinations, the highest synergistic ORAC value was noted for the blueberry and cabbage concentrates (BUCA; 0.8 and 1.2 mg mL-1 ) at an antioxidant ratio of 5:5. Chitosan/carrageenan (CSCR) nanoparticles are physically more stable than chitosan/gum arabic nanoparticles during in vitro digestion and were selected for the oral delivery of BUCA. Under simulated intestinal conditions, BUCA-loaded CSCR nanoparticles showed significantly more stable antioxidant activity and total phenolic content than non-nanoencapsulated BUCA. The highest antioxidant stability was observed in the BUCA-loaded CSCR nanoparticles prepared with 0.2 mg mL-1 carrageenan, which showed two-times higher ORAC value and ten-times higher total phenolic content than non-nanoencapsulated BUCA after 12 h of in vitro digestion. CONCLUSION: CSCR nanoencapsulation of natural antioxidants could be an effective technique for improving antioxidant stability during digestion. © 2019 Society of Chemical Industry.

Inducing Transient Mixed Chimerism for Allograft Survival Without Maintenance Immunosuppression With Combined Kidney and Bone Marrow Transplantation: Protocol Optimization.

BACKGROUND: Tolerance induction is an important goal in the field of organ transplantation. We have sequentially modified our conditioning regimen for induction of donor-specific tolerance in recipients of major histocompatibility complex-mismatched combined kidney and bone marrow transplantation (CKBMT). METHODS: From December 2011 to May 2017, 8 major histocompatibility complex-mismatched patients received CKBMT. The initial conditioning regimen (protocol 1) consisted of cyclophosphamide (CP), rituximab, rabbit antithymocyte globulin, and thymic irradiation. Tacrolimus and steroids were used for the maintenance of immunosuppression (IS). RESULTS: This regimen was complicated by transient acute kidney injury, which has been the major clinical feature of engraftment syndrome and side effects of CP, although one of 2 subjects successfully discontinued his IS for 14 months. The conditioning regimen was modified by reducing the CP dose and adding fludarabine (protocol 2). The final modification was reducing the fludarabine and rabbit antithymocyte globulin doses (protocol 3). Mixed chimerism, detected by the short tandem repeat method, was achieved transiently in all subjects for 3-20 weeks. Among the 3 subjects treated with protocol 2, IS was successfully discontinued for >35 months in one subject, but the other 2 subjects suffered from severe BK virus-associated nephritis. All 3 subjects treated with protocol 3 tolerated the protocol well and have successfully discontinued IS for >4-41 months. Interestingly, de novo donor-specific antibody was not detected in any subject during all the follow-up periods. CONCLUSIONS: Our clinical trial has shown that long-term renal allograft survival without maintenance IS can be achieved by induction of mixed chimerism following CKBMT.

T-Cell Differentiation to T Helper 9 Phenotype is Elevated by Extremely Low-Frequency Electromagnetic Fields Via Induction of IL-2 Signaling.

Owing to the development of information technology and the electronics industry, and the increase in the use of electronic products, an increasing number of people are exposed to electromagnetic fields (EMFs) in daily life. There has been concern about the effects of EMFs on the human body. Th9 cells, which are characterized by the generation of interleukin-(IL-9), are a recently defined subset of T helper (Th) cells. In this study, we investigated the effect of extremely low-frequency (60 Hz) EMFs, such as those generated by household power sources, at 0.8 mT intensity on CD4+ T cells. The exposure of CD4+ T cells to such EMFs under Th9-polarizing conditions increased IL-9 secretion and gene expression of transcription factors that are important for Th9 development. The expression of GATA3 increased in the early stage, and the phosphorylation of STAT5 and STAT6, which regulate the expression of GATA3, increased. In addition, EMFs increased the expression of IL-2 by the T cells. In conclusion, the differentiation of CD4+ T cells to the Th9 phenotype was increased by exposure to extremely low-frequency EMFs, and this appeared to be dependent on the IL-2 signaling pathway. Furthermore, co-cultures of EMF-exposed Th9 cells and mast cells showed an increased expression of mast cell proteases, FcεR1α, and mast cell-derived inflammatory cytokines compared with co-cultures of non-EMF-exposed Th9 cells and mast cells. Our results suggest that EMFs enhance the differentiation of CD4+ T cells to the Th9 phenotype, resulting in mast cell activation and inflammation. Bioelectromagnetics. 2019;40:588-601. © 2019 Bioelectromagnetics Society.

Safety and Risk Factors of Pure Laparoscopic Living Donor Right Hepatectomy: Comparison to Open Technique in Propensity Score-matched Analysis.

BACKGROUND: The innovative pure laparoscopic living donor right hepatectomy (LLDRH) procedure for liver transplantation has never been fully compared to open living donor right hepatectomy (OLDRH). We aimed to compare the donor safety and graft results of pure LLDRH to those of OLDRH. METHODS: From May 2013 to July 2017, 288 consecutive donors underwent either OLDRH (n = 197) or pure LLDRH (n = 91). After propensity score matching, 72 donors were included in each group. The primary outcome was postoperative complications during a 90-day follow-up period. Comprehensive complication index, duration of hospital stay, need for additional pain control, readmission, and donor outcomes were also compared. RESULTS: The incidence of major complication during the 90-day follow-up was higher in the LLDRH group than the OLDRH group (6.6% vs 15.4%, P = 0.017) but was not statistically significant in propensity-matched analysis (11.1% vs 13.9%, odds ratio [OR], 1.29; 95% confidence interval [CI], 0.47-3.51; P = 0.62). A right hepatic duct <1 cm was independently associated with complication in the pure LLDRH group (odds ratio, 4.01; 95% confidence interval, 1.08-14.99; P = 0.04). CONCLUSIONS: In the initial 91 pure LLDRH cases, incidence of major complication was higher than in the OLDRH group, but the difference was not significant in propensity-matched analysis. A right hepatic duct verified as <1 cm may be related to increased frequency of complications in pure LLDRH donors. Further analysis is needed.

One-Year Recipient Morbidity of Liver Transplantation Using Pure Laparoscopic Versus Open Living Donor Right Hepatectomy: Propensity Score Analysis.

Donor safety and graft results of pure laparoscopic living donor right hepatectomy (LLDRH) have previously been compared with those of open living donor right hepatectomy (OLDRH). However, the clinical outcomes of recipients at 1-year follow-up have never been accurately compared. We aimed to compare 1-year outcomes of recipients of living donor right liver transplantation (LRLT) using pure LLDRH and OLDRH. From May 2013 to May 2017, 197 consecutive recipients underwent LRLT. Donor hepatectomies were performed either by OLDRH (n = 127) or pure LLDRH (n = 70). After propensity score matching, 53 recipients were included in each group for analysis. The clinical outcomes at 1-year follow-up were compared between the 2 groups. The primary outcome was recipient death or graft failure during the 1-year follow-up period. In the propensity-matched analysis, the incidence of death or graft failure during the 1-year follow-up period was not different between the 2 groups (3.8% versus 5.7%; odds ratio [OR], 1.45; 95% confidence interval [CI], 0.24-8.95; P = 0.69). However, the composite of Clavien-Dindo 3b-5 complications was more frequent in the pure LLDRH group (OR, 2.62; 95% CI, 1.15-5.96; P = 0.02). In conclusion, although pure LLDRH affords a comparable incidence of fatal complications in recipients, operative complications may increase at the beginning of the program. The safety of the recipients should be confirmed to accept pure LLDRH as a feasible option.

Mucoadhesive Chitosan-Gum Arabic Nanoparticles Enhance the Absorption and Antioxidant Activity of Quercetin in the Intestinal Cellular Environment.

Quercetin (QUE)-loaded nanoparticles (QCG-NPs) were fabricated by ionic gelation between chitosan (CS) and gum arabic (GA) at pH 3.5. At constant CS (0.5 mg/mL) and QUE (60 µM) concentrations, QCG-NPs (260-490 nm) were prepared uniformly with 0.8-2.2 mg/mL GA and exhibited high QUE encapsulation efficiency (94.8-98.0%) and sustained QUE release (4.42-8.89% after 8 h). Because of the electrostatic interaction between QCG-NPs and the mucin layer, in vitro mucin and cell adhesion of QUE were significantly (p < 0.05) enhanced in QCG-NPs (0.44-0.48 mg/mL and 31.7-78.5%), respectively, and the adhesiveness was significantly (p < 0.05) increased with an increase of GA. Because particle size and adhesion properties affect the surface area and retention time of QCG-NPs at the absorption site, cell permeation of QUE through simple diffusion by QCG-NPs exhibited the same tendency as the adhesion results. These data were verified in cellular antioxidant and in vivo ferric reducing abilities of plasma assays that evaluated the antioxidant activities of QUE absorbed into an intestinal cell model and rat blood, respectively. The results provide a better understanding of QCG-NP absorption and indicate that QCG-NPs with mucoadhesion properties can be an effective delivery system for improving QUE absorption.

Tablet or capsule form of generic mycophenolate mofetil (My-Rept®) after liver transplantation: a prospective randomized trial.

BACKGROUND: Tablet and capsule forms have advantages and disadvantages in the market. Generally, the tablet form (500 mg) of mycophenolate mofetil (MMF) is more convenient for drug ingestion and more cost-effective than the capsule form (250 mg). We examined the efficacy and safety of MMF in its different forms combined with tacrolimus in liver transplant recipients. METHODS: A randomized controlled trial was performed to compare the efficacy and safety between the tablet form of MMF (tablet group) and the capsule form of MMF (capsule group) in liver transplant patients. One hundred sixteen patients were enrolled in the present study from 2014 to 2017. Fifty-six patients in the full-analysis set (FAS) population were in the capsule group and 60 were in the tablet group. The primary endpoint was incidence of biopsy-proven acute rejection (BPAR) by 24 weeks after liver transplantation (LT). Secondary endpoints were patient survival, serum creatinine level, and adverse events (AEs). RESULTS: In the per-protocol population, 45 patients were in the tablet group and 49 were in the capsule group. There were no statistically significant differences in MMF dose, mycophenolic acid trough level, and tacrolimus trough level between the two groups. The incidence of BPAR at 24 weeks after randomization was 6.7% in the tablet group and 6.1% in the capsule group (P=0.627). All patients with BPAR responded well to steroid pulse therapy and increased tacrolimus. Serum creatine level and eGFR were not different between the two groups. The incidence of serious AEs was 7.2% in the tablet group and 7.6% in the capsule group, and none were related to formulation. There was no significant difference in incidence of discontinuations or serious AEs between the two groups. CONCLUSION: The present study suggests that the new tablet formulation can be a useful treatment option to maintain a consistent systemic exposure level of MMF, which may help reduce graft failure in liver transplant patients.