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The aim of our study was to investigate pre and intraoperative clinical factors, including platelet count, which could inform risk stratification of early acute kidney injury (AKI) after living donor liver transplantation (LDLT). Additionally, the impact of severe thrombocytopenia on AKI risk was assessed using a propensity score (PS)-matched analysis. In total, 591 adult patients who underwent LDLT between January 2009 and December 2018 at our hospital were retrospectively analyzed. Early postoperative AKI was determined based on the KDIGO criteria, and 149 patients (25.2%) developed AKI immediately after surgery. In a multivariate analysis, a lower preoperative platelet count was significantly associated with early postoperative AKI, together with diabetes mellitus, lower hourly urine output, and longer graft ischemic time; furthermore, a decrease in platelet count was correlated with AKI severity. After adjusting for the PS, the probability of AKI was significantly (1.9-fold) higher in patients with severe thrombocytopenia than in those without severe thrombocytopenia. Patients with thrombocytopenia showed a higher postoperative incidence of AKI and a higher requirement for dialysis than those without thrombocytopenia. The platelet count can easily be obtained via regular blood analysis of patients scheduled for LDLT and can be used to identify patients at risk for AKI.

Abstract Background Placenta-derived mesenchymal stem cells (PD-MSCs) have been highlighted as an alternative cell therapy agent that has become a next-generation stem cell treatment. Phosphatase of regenerating liver-1 (PRL-1), an immediate early gene, plays a critical role during liver regeneration. Here, we generated enhanced PRL-1 in PD-MSCs (PD-MSCsPRL-1, PRL-1+) using lentiviral and nonviral gene delivery systems and investigated mitochondrial functions by PD-MSCPRL-1 transplantation for hepatic functions in a rat bile duct ligation (BDL) model. Methods PD-MSCsPRL-1 were generated by lentiviral and nonviral AMAXA gene delivery systems and analyzed for their characteristics and mitochondrial metabolic functions. Liver cirrhosis was induced in Sprague-Dawley (SD) rats using common BDL for 10 days. PKH67+ naïve and PD-MSCsPRL-1 using a nonviral sysyem (2 × 106 cells/animal) were intravenously administered into cirrhotic rats. The animals were sacrificed at 1, 2, 3, and 5 weeks after transplantation and engraftment of stem cells, and histopathological analysis and hepatic mitochondrial functions were performed. Results PD-MSCsPRL-1 were successfully generated using lentiviral and nonviral AMAXA systems and maintained characteristics similar to those of naïve cells. Compared with naïve cells, PD-MSCsPRL-1 improved respirational metabolic states of mitochondria. In particular, mitochondria in PD-MSCsPRL-1 generated by the nonviral AMAXA system showed a significant increase in the respirational metabolic state, including ATP production and mitochondrial biogenesis (*p

Abstract Background Translational studies have explored the therapeutic potential and feasibility of mesenchymal stem cells (MSCs) in several degenerative diseases; however, mechanistic studies of the function of these cells have been insufficient. As ovarian failure causes anovulation as well as ovarian steroid hormonal imbalances, the specific aims of this study were to analyze the therapeutic role of placenta-derived MSCs (PD-MSCs) in an ovarian failure ovariectomy (OVX) rat model and evaluate whether PD-MSC transplantation (Tx) improved folliculogenesis and oocyte maturation in the injured ovary through PI3K/Akt and FOXO signaling. Methods Blood and ovary tissue were collected and analyzed after various PD-MSC Tx treatments in an ovariectomized rat model. Changes in the expression of folliculogenesis- and ovary regeneration-related genes induced by PD-MSC treatments were analyzed by qRT-PCR, Western blotting, and histological analysis. Results The levels of hormones related to ovary function were significantly increased in the PD-MSC Tx groups compared with those in the nontransplantation group (NTx). The follicle numbers in the ovarian tissues were increased along with the increased expression of genes related to folliculogenesis in the PD-MSC Tx groups compared with the NTx groups. Furthermore, Tx PD-MSCs induced follicle maturation by increasing the phosphorylation of GSK3 beta and FOXO3 (p

Abstract Background This study investigated perioperative clinical risk factors for early post-transplant bacteremia in patients undergoing living donor liver transplantation (LDLT). Additionally, postoperative outcomes were compared between patients with and without early post-transplant bacteremia. Methods Clinical data of 610 adult patients who underwent elective LDLT between January 2009 and December 2018 at Seoul St. Mary’s Hospital were retrospectively collected. The exclusion criteria included overt signs of infection within 1 month before surgery. A total of 596 adult patients were enrolled in this study. Based on the occurrence of a systemic bacterial infection after surgery, patients were classified into non-infected and infected groups. Results The incidence of bacteremia at 1 month after LDLT was 9.7% (57 patients) and Enterococcus faecium (31.6%) was the most commonly cultured bacterium in the blood samples. Univariate analysis showed that preoperative psoas muscle index (PMI), model for end-stage disease score, utility of continuous renal replacement therapy (CRRT), ascites, C-reactive protein to albumin ratio, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio, and sodium level, as well as intraoperative post-reperfusion syndrome, mean central venous pressure, requirement for packed red blood cells and fresh frozen plasma, hourly fluid infusion and urine output, and short-term postoperative early allograft dysfunction (EAD) were associated with the risk of early post-transplant bacteremia. Multivariate analysis revealed that PMI, the CRRT requirement, the NLR, and EAD were independently associated with the risk of early post-transplant bacteremia (area under the curve: 0.707; 95% confidence interval: 0.667–0.745; p

Abstract Background Early extubation after liver transplantation is safe and accelerates patient recovery. Patients with end-stage liver disease undergo sarcopenic changes, and sarcopenia is associated with postoperative morbidity and mortality. We investigated the impact of core muscle mass on the feasibility of immediate extubation in the operating room (OR) after living donor liver transplantation (LDLT). Methods A total of 295 male adult LDLT patients were retrospectively reviewed between January 2011 and December 2017. In total, 40 patients were excluded due to emergency surgery or severe encephalopathy. A total of 255 male LDLT patients were analyzed in this study. According to the OR extubation criteria, the study population was classified into immediate and conventional extubation groups (39.6 vs. 60.4%). Psoas muscle area was estimated using abdominal computed tomography and normalized by height squared (psoas muscle index [PMI]). Results There were no significant differences in OR extubation rates among the five attending transplant anesthesiologists. The preoperative PMI correlated with respiratory performance. The preoperative PMI was higher in the immediate extubation group than in the conventional extubation group. Potentially significant perioperative factors in the univariate analysis were entered into a multivariate analysis, in which preoperative PMI and intraoperative factors (i.e., continuous renal replacement therapy, significant post-reperfusion syndrome, and fresh frozen plasma transfusion) were associated with OR extubation. The duration of ventilator support and length of intensive care unit stay were shorter in the immediate extubation group than in the conventional extubation group, and the incidence of pneumonia and early allograft dysfunction were also lower in the immediate extubation group. Conclusions Our study could improve the accuracy of predictions concerning immediate post-transplant extubation in the OR by introducing preoperative PMI into predictive models for patients who underwent elective LDLT.

BackgroundThis study investigated the association between the fibrinogen level and the risk of acute kidney injury (AKI) in patients who have undergone living donor liver transplantation (LDLT).Patients and methodsA total of 676 patients who underwent LDLT were analyzed retrospectively. Exclusion criteria included a history of severe kidney dysfunction, emergency operation, deceased donor, ABO-incompatible transplantation, and missing data. The study population was divided into low and normal fibrinogen groups. A 1:1 propensity score (PS) matching analysis was used to evaluate the association between a low fibrinogen level (< 160 mg/dL) and postoperative development of AKI.ResultsIn total, 142 patients (23.1%) developed AKI after LDLT. The PS matching analysis showed that the probability of AKI was two-fold higher in the low fibrinogen group than in the normal fibrinogen group. In addition, patients with AKI had poorer postoperative outcomes such as longer hospitalization, longer ICU stay, and higher mortality than patients without AKI.ConclusionsThe preoperative fibrinogen level may be useful for risk stratification of patients undergoing LDLT in terms postoperative development of AKI.

Objectives We examine the association between vitamin B12 level and risk for acute kidney injury (AKI) in patients undergoing living donor liver transplantation (LDLT).Design Retrospective observational cohort study.Setting University hospital, from January 2009 to December 2018.Participants A total of 591 patients who underwent elective LDLT were analysed in this study. Those with a preoperative history of kidney dysfunction, vitamin B12 supplementation due to alcoholism, low vitamin B12 (900 pg/mL) and postoperative AKI was evaluated.Results Preoperative vitamin B12 was higher in the AKI group. Potentially significant perioperative factors from univariate analyses were entered into multivariate analyses, including preoperative factors (vitamin B12, diabetes), intraoperative factors (hourly urine output) and donor graft fatty change in LDLT patients. PS matching analyses with adjustment using PS revealed that high serum vitamin B12 (>900 pg/mL) was associated with risk for AKI, and the risk was 2.8-fold higher in patients with high vitamin B12 than in those with normal vitamin B12. Higher vitamin B12 was also related to a higher AKI stage. In addition, inflammatory factors (C reactive protein, white blood cells and albumin) were associated with vitamin B12 level.Conclusions Our study may improve the accuracy of predicting postoperative AKI by introducing preoperative vitamin B12 into risk assessments for patients undergoing LDLT.

Phosphatase of regenerating liver-1 (PRL-1) controls various cellular processes and liver regeneration. However, the roles of PRL-1 in liver regeneration induced by chorionic-plate-derived mesenchymal stem cells (CP-MSCs) transplantation remain unknown. Here, we found that increased PRL-1 expression by CP-MSC transplantation enhanced liver regeneration in a bile duct ligation (BDL) rat model by promoting the migration and proliferation of hepatocytes. Engrafted CP-MSCs promoted liver function via enhanced hepatocyte proliferation through increased PRL-1 expression in vivo and in vitro. Moreover, higher increased expression of PRL-1 regulated CP-MSC migration into BDL-injured rat liver through enhancement of migration-related signals by increasing Rho family proteins. The dual effects of PRL-1 on proliferation of hepatocytes and migration of CP-MSCs were substantially reduced when PRL-1 was silenced with siRNA-PRL-1 treatment. These findings suggest that PRL-1 may serve as a multifunctional enhancer for therapeutic applications of CP-MSC transplantation.

BackgroundWe investigated the impact of postreperfusion syndrome (PRS) on hyperglycemia occurrence and connecting (C) peptide release, which acts as a surrogate marker for insulin resistance, during the intraoperative period after graft reperfusion in patients undergoing living donor liver transplantation (LDLT) using propensity score (PS)-matching analysis.Patients and methodsMedical records from 324 adult patients who underwent elective LDLT were retrospectively reviewed, and their data were analyzed according to PRS occurrence (PRS vs. non-PRS groups) using the PS-matching method. Intraoperative levels of blood glucose and C-peptide were measured through the arterial or venous line at each surgical phase. Hyperglycemia was defined as a peak glucose level >200 mg/dL, and normal plasma concentrations of C-peptide in the fasting state were taken to range between 0.5 and 2.0 ng/mL.ResultsAfter PS matching, there were no significant differences in pre- and intra-operative recipient findings and donor-graft findings between groups. Although glucose and C-peptide levels continuously increased through the surgical phases in both groups, glucose and C-peptide levels during the neohepatic phase were significantly higher in the PRS group than in the non-PRS group, and larger changes in levels were observed between the preanhepatic and neohepatic phases. There were higher incidences of C-peptide levels >2.0 ng/mL and peak glucose levels >200 mg/dL in the neohepatic phase in patients with PRS than in those without. PRS adjusted for PS with or without exogenous insulin infusion was significantly associated with hyperglycemia occurrence during the neohepatic phase.ConclusionsElucidating the association between PRS and hyperglycemia occurrence will help with establishing a standard protocol for intraoperative glycemic control in patients undergoing LDLT.

Although the liver has a regenerative capacity, hepatic failure is a severe and irreversible chronic disease. Placenta-derived mesenchymal stem cells (PD-MSCs) have distinctive features, such as recycling of the placenta waste after birth, ease of accessibility, abundant cell numbers, and strong immunosuppressive properties. Previously, we reported that PD-MSCs can regenerate the liver in hepatic failure through antifibrotic and autophagic mechanisms. Many reports have investigated whether exosomes, which are formed by the budding of vesicular bodies and are emitted into the blood, from stem cells have therapeutic potential in various diseases. C-reactive protein (CRP) is produced in hepatocytes and secreted via vessels. Therefore, the objectives of this study were to compare the expression of CRP in exosomes of a hepatic failure rat model (bile duct ligation, BDL) and to evaluate the therapeutic effect by their correlation between CRP and angiogenesis depending on PD-MSC transplantation. The exosomes were analyzed in a BDL rat model with transplantation of PD-MSCs through LC-MS analysis and precipitation solution. The exosomes, CRP, and factors related to these molecules were evaluated and quantified in exosomes as well as investigated by real-time PCR, Western blot, and immunofluorescence (IF) in vivo and in vitro. CRP was present in exosomes from serum of a rat model and increased by PD-MSC transplantation. In the exosomes, CRP upregulated the factors related to the Wnt signaling pathway and angiogenesis in the BDL rat liver-transplanted PD-MSCs. Also, CRP regulated the Wnt pathway and vascularization in rat hepatocytes by interacting with endothelial cells. Therefore, our findings indicate that CRP in exosomes excreted by PD-MSCs functions in angiogenesis via the Wnt signaling pathway.

Background/Aims Chronic liver disease leads to liver fibrosis, and although the liver does have a certain regenerative capacity, this disease is associated with dysfunction of the liver vessels. C-reactive protein (CRP) is produced in the liver and circulated from there for metabolism. CRP was recently shown to inhibit angiogenesis by inducing endothelial cell dysfunction. The objective of this study was to determine the effect of CRP levels on angiogenesis in a rat model of liver dysfunction induced by bile duct ligation (BDL). Methods The diameter of the hepatic vein was analyzed in rat liver tissues using hematoxylin and eosin (H&E) staining. The expression levels of angiogenic factors, albumin, and CRP were analyzed by real-time PCR and Western blotting. A tube formation assay was performed to confirm the effect of CRP on angiogenesis in human umbilical vein endothelial cells (HUVECs) treated with lithocholic acid (LCA) and siRNA-CRP. Results The diameter of the hepatic portal vein increased significantly with the progression of cirrhosis. The expression levels of angiogenic factors were increased in the cirrhotic liver. In contrast, the expression levels of albumin and CRP were significantly lower in the liver tissue obtained from the BDL rat model than in the normal liver. The CRP level was correlated with the expression of albumin in hepatocytes treated with LCA and siRNA-CRP. Tube formation was significantly decreased in HUVECs when they were treated with LCA or a combination of LCA and siRNA-CRP. Conclusion CRP seems to be involved in the abnormal formation of vessels in hepatic disease, and so it could be a useful diagnostic marker for hepatic disease.

Oxidative stress is one of the major etiologies of ovarian dysfunction, including premature ovarian failure (POF). Previous reports have demonstrated the therapeutic effects of human placenta-derived mesenchymal stem cells (PD-MSCs) in an ovariectomized rat model (OVX). However, their therapeutic mechanism in oxidative stress has not been reported. Therefore, we investigated to profile the exosome of serum and demonstrate the therapeutic effect of PD-MSCs transplantation for the ovary function. We established an OVX model by ovariectomy and PD-MSCs transplantation was conducted by intravenous injection. Additionally, various factors in the exosome were profiled by LC-MS analysis. As a result, the transplanted PD-MSCs were engrafted into the ovary and the existence of antioxidant factors in the exosome. A decreased expression of oxidative stress markers and increased expression of antioxidant markers were shown in the transplantation (Tx) in comparison to the non-transplantation group (NTx) (* p < 0.05). The apoptosis factors were decreased, and ovary function was improved in Tx in comparison to NTx (* p < 0.05). These results suggest that transplanted PD-MSCs restore the ovarian function in an OVX model via upregulated antioxidant factors. These findings offer new insights for further understanding of stem cell therapy for reproductive systems.

BackgroundThe aim of this study was to compare the prevalence of diastolic dysfunction between the 2016 American Society of Echocardiography (ASE)/European Association of Cardiovascular Imaging and 2009 ASE/European Association of Echocardiography recommendations in patients undergoing living-donor liver transplantation (LDLT).Patients and methodsA total of 312 adult patients who underwent LDLT at our hospital from January 2010 to December 2017 were retrospectively analyzed. Exclusion criteria were systolic dysfunction, arrhythmia, myocardial ischemia, and mitral or aortic valvular insufficiency.ResultsThe study population was largely male (68.3%), and the median age was 54 (49-59) years. The median model for end-stage liver disease score was 12 (6-22) points. A predominant difference in the prevalence rates of diastolic dysfunction was observed between the two recommendations. The prevalence rates of diastolic dysfunction and indeterminate diastolic function were lower according to the 2016 recommendations than the 2009 recommendations. The level of concordance between the two recommendations was poor. The proportion of patients with a high brain natriuretic peptide level (> 100 pg/mL) decreased significantly during surgery in the normal and indeterminate groups according to the 2009 recommendations; however, only the normal group showed an intraoperative decrease in the proportion according to the 2016 recommendations. Patients with diastolic dysfunction showed a poorer overall-survival rate than those with normal function according to both recommendations. However, there was a difference in the survival rate in the indeterminate group between the two recommendations. A significant difference in patient survival rate was observed between the dysfunction and indeterminate groups according to the 2009 recommendations; however, the difference was not significant in the 2016 recommendations.ConclusionsThe 2016 classification may be better able to identify patients with a risk for diastolic dysfunction. Particularly, patients in the 2016 indeterminate group seemed to require a cardiac diastolic functional evaluation more frequently during and after surgery than those in the 2009 indeterminate group.

BACKGROUND:This study was performed to determine the association between the ratio of C-reactive protein to albumin (CRP/ALB) and the risk of early allograft dysfunction (EAD) in patients undergoing living donor liver transplantation (LDLT). PATIENTS AND METHODS:A total of 588 adult patients undergoing LDLT were retrospectively investigated, after 22 were excluded because of signs of overt infection or history of ALB infusion. The study population was classified into high and low CRP/ALB ratio groups according to EAD. All laboratory variables, including CRP and ALB, had been collected on the day before surgery. A percentage value for the CRP/ALB ratio (%) was calculated as CRP/ALB × 100. RESULTS:After LDLT, 83 patients (14.1%) suffered EAD occurrence. A higher CRP/ALB ratio was independently associated with risk of EAD, Model for End-stage Liver Disease score, fresh frozen plasma transfusion, and donor age. Based on a cutoff CRP/ALB ratio (i.e., > 20%), the probability of EAD was significantly (2-fold) higher in the high versus low CRP/ALB group. The predictive utility of CRP/ALB ratio for EAD was greater than those of other inflammatory markers. In addition, patients with a high CRP/ALB ratio had poorer survival than those with a low CRP/ALB ratio during the follow-up period. CONCLUSIONS:The easily calculated CRP/ALB ratio may allow estimation of the risk of EAD after LDLT and can provide additional information that may facilitate the estimation of a patient's overall condition.

Liver graft regeneration is orchestrated by specific and sequential stimuli, including hepatocyte growth factors, cytokines, and catecholamines. We evaluated the association between preoperative serum cytokines and early liver graft regeneration in human living donor liver transplantation (LDLT).We retrospectively reviewed the data of adult patients who underwent LDLT from January 2010 to December 2014. Serum cytokines, including interleukin (IL)-2, 6, 10, 12, 17, interferon (IFN)-γ and tumor necrosis factor (TNF)-α were measured in the recipients 1 day before surgery and on postoperative day (POD) 7. Liver graft volume was estimated using abdominal computed tomography images of the donors and recipients.In total, 226 patients were analyzed in this study. Median preoperative levels of serum cytokines were as follows: IL-2, 0.1 (0.1-1.6) pg/mL; IL-6, 7.3 (0.1-30.2) pg/mL; IL-10, 0.5 (0.1-11.0) pg/mL; IL-12, 0.1 (0.1-0.1) pg/mL; IL-17, 2.0 (0.1-16.4) pg/mL; IFN-γ, 3.2 (0.1-16.0) pg/mL; and TNF-α, 9.8 (5.4-17.9) pg/mL. Higher preoperative serum levels of IL-6, IL-10, and TNF-α, dichotomized at the median, were associated with increased relative liver volumes by POD 7. Multivariate analysis revealed that higher levels of serum IL-6 and TNF-α were independently associated with increased graft volume during the first 1 week after LDLT, based on the lower levels of those cytokines.IL-6 and TNF-α were important mediators of the success of early graft regeneration in patients who underwent LDLT.

BACKGROUND:Patients with end-stage liver disease frequently experience acute kidney injury (AKI) after living donor liver transplantation (LDLT). Serum levels of brain natriuretic peptide (BNP) have increasingly been accepted as a predictor of AKI in clinical settings. This study investigated the predictive role of intraoperative BNP levels in the early development of AKI after LDLT. PATIENTS AND METHODS:Adult patients (≥19 years old) who had undergone elective LDLT from January 2011 to December 2017 were classified into the non-AKI and AKI groups according to the Kidney Disease: Improving Global Outcomes criteria. Serum levels of BNP were measured three times in the preanhepatic, anhepatic, and neohepatic phases. Perioperative data in recipients and donors were analyzed retrospectively. RESULTS:Sixty-one patients (22.4%) suffered from AKI immediately after LDLT. Severity according to AKI stage was as follows: 28 patients in stage 1 (10.3%), 18 patients in stage 2 (6.6%), and 15 patients in stage 3 (5.5%). In the neohepatic phase, both BNP levels and proportions of patients with high BNP levels (≥100 pg/mL) were higher in the AKI group than in the non-AKI group. Only BNP levels in the non-AKI and AKI stage 1 groups significantly decreased from the preanhepatic phase to the neohepatic phase; those in AKI stages 2 and 3 groups did not. In particular, BNP levels of all AKI stage 3 patients increased to more than 100 pg/mL, and the proportion of patients with high levels also increased significantly through the surgical phases in the AKI stage 3 group. In multivariate analyses, BNP levels in the neohepatic phase were significantly associated with early development of AKI after LDLT, as well as the total amount of packed red blood cells in transfusions and total duration of graft ischemia. CONCLUSIONS:Monitoring serum levels of BNP is useful for predicting the early development of AKI after LDLT.

Introduction. Previous studies have shown that a higher serum interleukin- (IL-) 6 level is associated with a higher risk of acute kidney injury (AKI) development after major nontransplant surgery. Our study investigated the potential association of preoperative serum cytokine profiles with new AKI development in patients who underwent living donor liver transplantation (LDLT). Methods. Serum levels of cytokines IL-2, IL-6, IL-10, IL-12, and IL-17, interferon-γ, and tumor necrosis factor- (TNF-) α were measured in 226 LDLT recipients preoperatively and analyzed retrospectively. Recipients with a preoperative functional impairment of the kidney were excluded. AKI was defined according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Results. In a univariate regression model, IL-6, IL-17, and TNF-α levels showed an association with AKI development after LDLT. Multivariate analysis showed an independent association of the preoperative serum IL-6 level with AKI development after LDLT and a significant relationship between higher serum IL-6 levels and a greater likelihood of developing AKI. Serum IL-6 levels were higher in patients with stage 3 AKI than in patients who did not develop AKI. Conclusions. Our results support the need for further investigations of IL-6 as a predictor of AKI development in patients undergoing LDLT.

BackgroundAcute liver failure (ALF) is a rapidly progressing and fatal disease for which liver transplantation (LT) is the only treatment. Posttransplant mechanical ventilation tends to be more prolonged in patients with ALF than in other LT patients. The present study examined the clinical effects of prolonged posttransplant mechanical ventilation (PMV), and identified risk factors for PMV following LT for ALF.MethodsWe reviewed data of patients undergoing LT for ALF between January 2005 and June 2011. After grouping patients according to administration of PMV (≥ 24 h), donor and recipient perioperative variables were compared between the groups with and without PMV. Potentially significant factors (P < 0.1) from the univariate intergroup comparison were entered into a multivariate logistic regression to establish a predictive model for PMV.ResultsTwenty-four (25.3%) of 95 patients with ALF who received PMV had a higher mortality rate (29.2% vs 11.3%, P = 0.038) and longer intensive care unit stay (12.9 ± 10.4 vs 7.1 ± 2.7 days, P = 0.012) than patients without PMV. The intergroup comparisons revealed worse preoperative hepatic conditions, more supportive therapy, and more intraoperative fluctuations in vital signs and less urine output in the with- compared with the without-PMV group. The multivariate analysis revealed that preoperative hepatic encephalopathy (≥ grade III), intraoperative blood pressure fluctuation, and oliguria (< 0.5 ml/kg/h) were independent risk factors for PMV.ConclusionsPMV was associated with deleterious outcomes. Besides care for known risk factors including hepatic encephalopathy, meticulous attention to managing intraoperative hemodynamic circulatory status is required to avoid PMV and improve the posttransplant prognosis in ALF patients.

In cholestatic liver diseases, impaired bile excretion disrupts lipid homeostasis. We investigated changes of lipid metabolism, including mitochondrial β-oxidation, in a rat model of bile duct ligation (BDL) in which chorionic plate-derived mesenchymal stem cells (CP-MSCs) were transplanted. Serum cholesterol level, which was elevated after BDL, was significantly decreased following CP-MSC transplantation. The expression levels of genes involved in intracellular lipid uptake, including long-chain fatty acyl-CoA synthetases and fatty acid transport proteins, were decreased in rats after BDL; however, they were not significantly changed by subsequent CP-MSC transplantation. Carnitine palmitoyltransferase 1A (CPT1A), a rate-limiting enzyme in mitochondrial β-oxidation, was upregulated after BDL and then was downregulated after CP-MSC transplantation. CPT1A expression was changed via microRNA-33—a posttranscriptional regulator of CPT1A—in a peroxisome proliferator-activated receptor α-independent manner. Cellular adenosine triphosphate production—an indicator of mitochondrial function—was reduced after BDL and was restored by CP-MSC transplantation. Expression levels of heme oxygenases also were significantly affected following BDL and CP-MSC transplantation. Lipid metabolism is altered in response to chronic cholestatic liver injury and can be restored by CP-MSC transplantation. Our study findings support the therapeutic potential of CP-MSCs in cholestatic liver diseases and help in understanding the fundamental mechanisms by which CP-MSCs affect energy metabolism.

BackgroundBody posture, as a gravitational factor, has a clear impact on pulmonary ventilation and perfusion. In lung units with mismatched ventilation and perfusion, gas exchange and/or elimination of carbon dioxide can be impaired. In this situation, differences in the value of arterial and end-tidal carbon dioxide tension [Δ(PaCO2 - PETCO2)] are expected to increase. This study was conducted to observe how Δ(PaCO2 - PETCO2) changed according to the 3 different surgical positions, and to determine whether Δ(PaCO2 - PETCO2) is a reliable predictor of ventilation/perfusion mismatch when a patient is in different postural positions.MethodsFifty-nine patients were divided into either the chronic obstructive pulmonary disease (COPD) group (n = 29) or the non-COPD group (n = 30). PaCO2 and PETCO2 were measured during surgery in the supine, prone, and lateral decubitus positions after a 10 minute stabilization period. The Δ(PaCO2 - PETCO2) were calculated and compared among positions.ResultsThe Δ(PaCO2 - PETCO2) decreased slightly in the prone position and increased significantly in the lateral decubitus position compared with the supine position in both groups. These patterns almost corresponded with the degree of ventilation/perfusion mismatch from the results of the radiological studies. The Δ(PaCO2 - PETCO2) in the COPD group was significantly greater than that in the non-COPD group at all surgical positions.ConclusionsLateral decubitus position is associated with marked increase in Δ(PaCO2 - PETCO2), especially in patients with COPD. The Δ(PaCO2 - PETCO2) is a simple and reliable indicator to predict ventilation/perfusion mismatch at different surgical positions in patients with or without COPD.

BackgroundIschemia reperfusion (IR) injury is a complex phenomenon that leads to organ dysfunction and causes primary liver failure following liver transplantation. We investigated whether an intravenous administration of magnesium before reperfusion can prevent or reduce IR injury.MethodsFifty-nine living donor liver transplant recipients were randomly assigned to an MG group (n = 31) or an NS group (n = 28). Each group was also divided in two groups based on the preoperative magnesium levels (normal: ≥ 0.70 mmol/L, low: < 0.70 mmol/L). The MG groups received 25 mg/kg of MgSO4 mixed in 100 ml normal saline intravenously before reperfusion and the NS groups received an equal volume of normal saline. The levels of lactate, pH, arterial oxygen tension, and base excess were measured to assess reperfusion injury at five specific times, which were 10 min after the beginning of anhepatic phase, and 10, 30, 60 and 120 min after reperfusion. To evaluate postoperative organ function, the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin and creatinine levels were measured at preoperative day 1, postoperative day 1 and 5.ResultsThe blood lactate levels were significantly lower at 10, 30, 60 and 120 min after reperfusion in the MG groups compared to the NS groups. In addition, significantly higher blood lactate levels were observed in the NS group with preoperative hypomagnesemia than in MG groups.ConclusionsMagnesium administration before reperfusion of liver transplantation significantly reduces blood lactate levels. These findings suggest that magnesium treatment may have protective effects on IR injury during living donor liver transplantation.

BackgroundSince 2009, database construction of anesthesia-related adverse events has been initiated through the legislation committee of the Korean Society of Anesthesiologists (KSA), based on expert consultation referrals provided by police departments, civil courts, and criminal courts.MethodsThis study was a retrospective descriptive analysis of expert consultation referrals on surgical anesthesia-related cases between December 2008 and July 2010.ResultsDuring the given period, 46 surgical anesthesia-related cases were referred to the KSA legislation committee for expert consultation. Because six cases were excluded due to insufficient data, 40 cases were included in the final analysis. Of 40 cases, 29 (72.5%) resulted in death. Respiratory events were most common in both surviving/disabled and dead patients (36.4 vs. 51.7%, respectively; P > 0.05). Overall, respiratory depression due to the drugs used for monitored anesthesia care (MAC) was the most common specific mechanism (25%), in which all but one case (profound brain damage) resulted in death. In all of these cases, surgeons or physicians provided MAC without the help of anesthesiologists.ConclusionsOverall, the most common damaging mechanism was related to respiratory depression due to sedatives or anesthetics used for MAC. Almost all MAC injury cases are believed to be preventable with the use of additional or better monitoring and an effective response to initial physiological derangement. Thus, it is essential to establish practical MAC guidelines and adhere to these guidelines strictly to reduce the occurrence of severe anesthesia-related adverse outcomes.

Although hypoxic environments have been known to regulate the migratory ability of bone marrow-derived mesenchymal stem cells (BM-MSCs), which is a critical factor for maximizing the therapeutic effect, the underlying mechanisms remain unclear. Therefore, we aimed to confirm the effect of hypoxia-inducible factor-1α (HIF-1α) on the migration of BM-MSCs and to analyze the interaction between HIF-1α and integrin-mediated signals. Hypoxia-activated HIF-1α significantly increased BM-MSC migration. The expression of integrin α4 was decreased in BM-MSCs by increased HIF-1α under hypoxia, whereas the expression of Rho-associated kinase 1 (ROCK1) and Rac1/2/3 was increased. After downregulation of HIF-1α by YC-1, which is an inhibitor of HIF-1α, BM-MSC migration was decreased via upregulation of integrin α4 and downregulation of ROCK1 and Rac1/2/3. Knockdown of integrin α4 by integrin α4 siRNA (siITGA4) treatment increased BM-MSC migration by upregulation of ROCK1, Rac1/2/3, and matrix metalloproteinase-2 regardless of oxygen tension. Moreover, siITGA4 treatment increased HIF-1α expression and augmented the translocation of HIF-1α into the nucleus under hypoxia. Taken together, the alternative expression of HIF-1α induced by microenvironment factors, such as hypoxia and integrin α4, may regulate the migration of BM-MSCs. These findings may provide insights to the underlying mechanisms of BM-MSC migration for successful stem cell-based therapy.