Time from Injury to Initial Operation May Be the Sole Risk Factor for Postoperative Leakage in AAST-OIS 2 and 3 Traumatic Duodenal Injury: A Retrospective Cohort Study.

Background and Objectives: Traumatic duodenal injury is a rare disease with limited evidence. We aimed to evaluate the risk factors for postoperative leakage and outcomes of pyloric exclusion after duodenal grade 2 and 3 injury. Materials and Methods: We reviewed a prospectively collected trauma database for the period January 2004-December 2020. Patients with grade 2 and 3 traumatic duodenal injury were included. To identify the risk factors for postoperative leakage, we used a stepwise multivariable logistic regression model and a least absolute shrinkage and selection operator (LASSO) logistic model. We constructed a receiver operator characteristic (ROC) curve to predict risk factors for postoperative leakage. Results: During the 17-year period, 179,887 trauma patients were admitted to a regional trauma center in Korea. Of these patients, 74 (0.04%) had duodenal injuries. A total of 49 consecutive patients had grade 2 and 3 traumatic duodenal injuries and underwent laparotomy. The incidence of postoperative leakage was 32.6% (16/49). Overall mortality was 18.4% (9/49). A stepwise multivariable logistic regression and LASSO logistic regression model showed that time from injury to initial operation was the sole statistically significant risk factor. The ROC curve at the optimal threshold of 15.77 h showed the following: area under ROC curve, 0.782; sensitivity, 68.8%; specificity, 87.9%; positive predictive value, 73.3%; and negative predictive value, 85.3%. There was no significant difference in outcomes between primary repair alone and pyloric exclusion. Conclusions: Time from injury to initial operation may be the sole significant risk factor for postoperative duodenal leakage. Pyloric exclusion may not be able to prevent postoperative leakage.

Different prognostic factors and strategies for early and late recurrence after adult living donor liver transplantation for hepatocellular carcinoma.

BACKGROUND: Some patients with hepatocellular carcinoma (HCC) recurrence after LT show good long-term survival. We aimed to determine the prognostic factors affecting survival after recurrence and to suggest treatment strategies. METHODS: Between January 2000 and December 2015, 532 patients underwent adult living donor liver transplantation (LDLT) for HCC. Among these, 92 (17.3%) who experienced recurrence were retrospectively reviewed. RESULTS: The 1-, 3-, and 5-year survival rates after recurrence were 59.5%, 23.0%, and 11.9%, respectively. In multivariate analysis, time to recurrence >6 months and surgical resection after recurrence were related to longer survival after recurrence, while multi-organ involvement at the time of primary recurrence was related to poorer survival. We classified patients into early (≤6 months) and late (>6 months) recurrence groups. In the early recurrence group, tumor size >5 cm in the explant liver, liver as the first detected site of recurrence, and multiple organ involvement at primary recurrence were related to survival on multivariate analysis. In the late recurrence group, mammalian target of rapamycin inhibitor (mTORi) usage and multi-organ involvement were significantly associated with the prognosis on multivariate analysis. CONCLUSIONS: Various therapeutic approaches are needed depending on the period of recurrence after LT and multiplicity of involved organs.

Memory T cells are significantly increased in rejected liver allografts of rhesus monkeys.

The rhesus monkey (RM) is an excellent preclinical model in kidney, heart, and islet transplantation that has provided the basis for new immunosuppressive protocols for clinical studies. However, there remain relatively few liver transplantation (LT) models in nonhuman primates. In this study, we analyzed the immune cell populations of peripheral blood mononuclear cells (PBMCs) and secondary lymphoid organs along with livers of normal RMs and compared them with those of rejected LT recipients following withdrawal of immunosuppression. We undertook 5 allogeneic ABO compatible orthotopic LTs in monkeys using 5 normal donor monkey livers. We collected tissues including lymph nodes, spleens, blood, and recipient livers, and we performed flow cytometric analysis using isolated immune cells. We found that CD4 or CD8 naïve T cells were normally seen at low levels, and memory T cells were seen at high levels in the liver rather than lymphoid organs or PBMC. However, regulatory cells such as CD4+ forkhead box P3+ T cells and CD8+ CD28- cells remained in high numbers in the liver, but not in the lymph nodes or PBMC. The comparison of CD4/8 T subpopulations in normal and rejected livers and the various tissues showed that naïve cells were dramatically decreased in the spleen, lymph node, and PBMCs of rejected LT monkeys, but rather, the memory CD4/8 T cells were increased in all tissues and PBMC. The normal liver has large numbers of CD4 regulatory T cells, CD8+ CD28-, and myeloid-derived suppressor cells, which are known immunosuppressive cells occurring at much higher levels than those seen in lymph node or peripheral blood. Memory T cells are dramatically increased in rejected liver allografts of RMs compared with those seen in normal RM tissues. Liver Transplantation 24 256-268 2018 AASLD.

Effect of PNPLA3 I148M polymorphism on histologically proven non-alcoholic fatty liver disease in liver transplant recipients.

AIM: PNPLA3 I148M polymorphism (rs738409 C>G) is the most important and best-known polymorphism for non-alcoholic fatty liver disease (NAFLD). However, little is known about the effect of this polymorphism on NAFLD after liver transplantation (LT). We aimed to evaluate the association between this polymorphism and post-LT NAFLD. METHODS: We designed a prospective case-control study. Among adult recipients who underwent LT between April 2014 and October 2015, those whose whole blood was preoperatively collected for genotyping in both recipients and coupled donors and those who underwent protocol biopsy at 1 year post-LT were enrolled. RESULTS: A total of 32 recipients were enrolled. Histologically proven steatosis (≥5%) was present in 28.1% of patients at a mean time of 12.7 ± 2.0 months after LT. Moderate and more severe steatosis (≥33%) was present in 9.4%. One year after LT, steatosis was present in 50.0% of homozygous recipients with the rs738409-G allele. It was present in 27.3% of heterozygous recipients with the rs738409-G allele, and in 9.1% (P = 0.041) of recipients with rs738409-CC. The genotype of the donor was not significantly (P = 0.647) associated with post-LT NAFLD. When both recipient and coupled donor showed heterogeneous or homozygous genotype of the rs738409-G allele, there was significantly more post-LT NAFLD compared to that in others (47.1% vs. 6.7%; P = 0.018). In univariate and multivariate analyses, only the presence of the rs738409-G risk allele in both donor and recipient was a significant risk factor for post-LT NALFD (relative risk, 26.95; P = 0.048). CONCLUSIONS: PNPLA3 I148M polymorphism can significantly affect histologically proven NAFLD at 1 year post-LT.

Tips and pitfalls in direct ligation of large spontaneous splenorenal shunt during liver transplantation.

Patients with large spontaneous splenorenal shunts (SRSs) prove challenging during liver transplantation (LT), regardless of organizing portal vein (PV) thrombosis. Here, we detail the clinical outcomes of 26 patients who underwent direct ligation of large SRSs during LT. Direct ligation of large SRS was applied in poor portal flow during LT. We performed temporary test clamping of the SRS before direct ligation and applied PV pressure monitoring in patients who showed signs of portal hypertension, such as bowel edema. We retrospectively reviewed and evaluated their clinical outcomes. Among 843 patients who underwent LT between 2010 and 2015, 26 (3.1%) underwent direct ligation of SRS without any intraoperative event. Mean preoperative Model for End-Stage Liver Disease score was 16.7 ± 9.0. The main PV diameter on preoperative computed tomography was 8.3 ± 3.4 mm (range, 3.0-14.0 mm). SRS was easily identified at just below the distal pancreas and beside the inferior mesenteric vein in all patients. Accompanying PV thrombectomy was done in 42.3% of patients. Among 26 patients, massive and prolonged ascites was evident in 15.4% (n = 4) postoperatively. They were all living donor LT recipients with a small PV diameter (4.0-6.7 mm). Except for 1 patient who underwent splenic artery embolization, ascites was tolerable and well controlled by conservative management. There was a 7.7% rate of major complications related to direct ligation, including reoperation due to combined ligation of SRS along with a left renal vein at the confluence. Except for 1 hospital mortality due to sepsis, 25 patients (96.2%) are alive with no evidence of further PV complications. In conclusion, direct ligation of large SRS during LT is a safe and feasible method to overcome the effects of a large SRS. Liver Transplantation 23 899-906 2017 AASLD.

Macrovascular invasion is not an absolute contraindication for living donor liver transplantation.

The indication of liver transplantation (LT) for the treatment of advanced hepatocellular carcinoma (HCC) is expanding. However, portal vein tumor thrombus (PVTT) has been still accepted as an absolute contraindication. We experienced an unexpectedly good prognosis in selected patients. Therefore, we tried to identify the prognostic factors after LT for HCC with major PVTT. Among 282 patients who underwent living donor liver transplantation (LDLT) for HCC from January 2009 to December 2013, 11 (3.9%) patients with major PVTT that was preoperatively diagnosed were investigated. The 1-, 3-, and 5-year recurrence-free survival rates were 63.6%, 45.5%, and 45.5%, respectively, and all recurrent cases showed intrahepatic and extrahepatic recurrence. The 1-, 3-, and 5-year overall survival rates were 72.7%, 63.6%, and 63.6%, respectively, and 2 patients with delayed recurrence survived approximately 5 years after LT. Main portal vein (PV) invasion (P < 0.01), high alpha-fetoprotein × protein induced by vitamin K absence/antagonist-II (AP) score (≥20,000; P < 0.01), high standardized uptake value (SUV) ratio (tumor/background liver) in positron emission tomography (≥2.1; P < 0.01), and a large original tumor (≥7 cm; P = 0.03) were significant risk factors for recurrence. In conclusion, if the PVTT has not expanded to the main PV and the AP score is not high, we can consider LDLT as a curative treatment option. Liver Transplantation 23:19-27 2017 AASLD.

Evaluation of donor workups and exclusions in a single-center experience of living donor liver transplantation.

The process of evaluating potential donors in liver transplantation is important to ensure donor safety and provide optimal recipient outcomes. However, there has been no report about donor exclusion rates and reasons for such exclusion in Korea. In this study, we aimed to elucidate the outcomes of potential living liver donor evaluation in a major living donor liver transplantation center. From July 2011 to June 2015, prospectively collected data of 726 potential donors for 588 matched recipients were subsequently evaluated. Among 726 potential donors, 374 potential donors (51.5%) finally reached donation; 352 potential donors (48.5%) were excluded for various reasons. Donor reasons were 29.8%, including medical problems, withdrawal of consent, graft volume issues, and identification of a better suitable donor. Recipient reasons were 20.7%, including recipient death or recovery, allocation to deceased donor, and progressions of hepatocellular carcinoma. A total of 38 (5.2%) potential donors had a fatty liver. Among them, 15 (39.5%) potential donors tried short-term weight reduction and eventually were able to donate. In conclusion, the main reasons for donor exclusion were medical problems and withdrawal of consent. Therefore, thorough medical screening and careful examination for donor voluntarism are important in the donor evaluation process. Liver Transplantation 23 614-624 2017 AASLD.

Split liver transplantation for retroperitoneal immature teratoma masquerading as hepatoblastoma.

Extragonadal teratoma originating from the retroperitoneum represents less than 5% of all teratomas and accounts for less than 10% of all pediatric retroperitoneal neoplasms. To date, there has been no report of teratoma managed with LT. This study reports an infant aged 3 months with retroperitoneal immature teratoma involving the hepatic hilum, refractory to chemotherapy and treated with LT. The patient was referred to our hospital for management of a growing abdominal mass. Histopathology of a fine needle biopsy of the lesion suggested the possibility of a hepatoblastoma with teratoid features. Cisplatin-based chemotherapy was initiated, but rapid growth of the tumor encasing the hepatic artery proper was detected, even after two cycles of chemotherapy. A split LT was carried out, and pathological examination of the explanted liver revealed the involvement of numerous neuroepithelial components, confirming the diagnosis of a Norris grade 3 immature teratoma. The patient recovered well and was discharged on day 19 post-LT. As on date, on postoperative day 240, he has completed seven cycles of a 12-cycle vinblastine and doxorubicin-based adjuvant chemotherapy.

Pure 3D laparoscopic living donor right hemihepatectomy in a donor with separate right posterior and right anterior hepatic ducts and portal veins.

BACKGROUND: Despite increases in the performance of pure laparoscopic living donor hepatectomy, variations in the bile duct or portal vein have been regarded as relative contraindications to this technique [1-3]. This report describes a donor with separate right posterior and right anterior hepatic ducts and portal veins who underwent pure laparoscopic living donor right hemihepatectomy, integrated with 3D laparoscopy and indocyanine green (ICG) near-infrared fluorescence cholangiography [1, 4, 5]. METHODS: A 50-year-old man offered to donate part of his liver to his older brother, who required a transplant for hepatitis B-associated liver cirrhosis and hepatocellular carcinoma. Donor height was 178.0 cm, body weight was 82.7 kg, and body mass index was 26.1 kg/m2. Preoperative computed tomography and magnetic resonance cholangiopancreatography showed that the donor had separate right posterior and right anterior hepatic ducts and portal veins. The entire procedure was performed under 3D laparoscopic view. Following intravenous injections of 0.05 mg/kg ICG, ICG near-infrared fluorescence camera was used to demarcate the exact transection line and determine the optimal bile duct division point. RESULTS: The total operation time was 443 min; the donor required no transfusions and experienced no intraoperative complications. The graft weighed 1146 g with a graft-to-recipient weight ratio of 1.88%. The optimal bile duct division point was identified using ICG fluorescence cholangiography, and the bile duct was divided with good patency without any stricture. The right anterior and posterior portal veins were transected with endostaplers without any torsion. The patient was discharged on postoperative day 8, with no complications. CONCLUSION: Using a 3D view and ICG fluorescence cholangiography, pure 3D laparoscopic living donor right hemihepatectomy is feasible in a donor with separate right posterior and right anterior hepatic ducts and portal veins.

Korean Patients Undergoing Deceased Donor Liver Transplantation for Alcoholic Liver Disease Have Non-Inferior Survival Outcomes than for Hepatitis B Virus: a Real-World Experience without Minimum Abstinence before Transplantation.

Few studies have compared outcomes in patients undergoing liver transplantation (LT) for hepatitis B virus (HBV) and alcoholic liver disease (ALD) in Asian countries in which living donor LT (LDLT) is dominant, where HBV is endemic and where there are no strict regulations on pre-transplant abstinence for ALD. This study compared post-LT outcomes of deceased donor LT (DDLT) in patients with ALD and HBV. Data from 220 patients who underwent primary DDLT at Seoul National University Hospital from January 2010 to December 2014, including 107 with HBV and 38 with ALD, were retrospectively analyzed. Seventy-four patients (69.2%) in the HBV group and 30 (78.9%) in the ALD group had United Network for Organ Sharing (UNOS) status 2A (P = 0.250). There were no significant differences in their 1-year (90.7% vs. 92.1%) and 3-year (82.1% vs. 82.3%) overall survival rates (P = 1.000). Multivariate analysis showed that high serum gamma glutamyltransferase concentration (≥ 70 IU/L) was independently prognostic of 1-year post-LT overall survival. Survival outcomes following DDLT were similar in Korean patients with ALD and HBV, even in the absence of strict pre-transplant abstinence from alcohol as a selection criterion.

Sirolimus and Metformin Synergistically Inhibits Colon Cancer In Vitro and In Vivo.

We estimated the effect of various immunosuppressants (ISs) and metformin (M) to provide theoretical background of optimal therapeutic strategy for de novo colon cancer after liver transplantation (LT). Three colon cancer cell lines (HT29, SW620, and HCT116) were used in in vitro studies. HT29 was also used in BALB/c-nude mice animal models. Following groups were used in both in vitro and in vivo studies: sirolimus (S), tacrolimus (T), cyclosporin A (CsA), M, metformin/sirolimus (Met/S), metformin/tacrolimus (Met/T), and metformin/cyclosporin A (Met/CsA). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed and western blot analyses were performed for mTOR pathway proteins, apoptosis proteins, and epithelial-mesenchymal-transition (EMT) proteins. Tumor volume was measured for 4 weeks after inoculation. MTT-assay revealed significant cell viability inhibition in all 3 colon cancer cell lines in groups of S, M, and Met/S. Of note, group Met/S showed synergistic effect compare to M or S group. Western blot analysis showed significant low levels of all investigated proteins in groups of S and Met/S in both in vitro and in vivo experiment. Tumor growth was significantly inhibited only in the Met/S group. Combination of Met and S showed the most potent inhibition in all colon cancer cell lines. This finding might have application for de novo colon cancer.

False Positive Diagnosis of Hepatocellular Carcinoma in Liver Resection Patients.

The diagnosis of hepatocellular carcinoma (HCC) is based on imaging studies particularly in high-risk patients without histologic confirmation. This study evaluated the prevalence and characteristics of false-positively diagnosed HCC in a liver resection cohort for HCC. A retrospective review was performed of 837 liver resection cases for clinically diagnosed HCC between 2005 and 2010 at our institute. High-risk patients with tumors > 1 cm with one or two image findings consistent with HCC and tumors < 1 cm with two or more image findings consistent with HCC with persistently increased serum alpha-fetoprotein (AFP) levels above the normal range with underlying inhibited hepatitis activity underwent liver resection. The false-positive rate was 2.2% (n = 18). Of the 18 patients, 7 patients (0.8%) were diagnosed with benign conditions (one each of hemangioma, inflammation, cortical adenoma, dysplastic nodule, angiomyolipoma, bile duct adenoma, and non-neoplastic liver parenchyme) and 11 patients (1.3%) were diagnosed with malignancies (cholangiocarcinoma [n = 6], hepatoblastoma [n = 2], and one each of lymphoepithelioma-like carcinoma, ovarian cystadenocarcinoma, and nasopharynx carcinoma metastasis). The clinical characteristics of pathologically diagnosed HCC patients were similar (P > 0.05) compared to non-HCC patients except for higher rate of history of alcoholism (P < 0.05) observed in non-HCC patients. Four of 18 non-HCC patients (22.2%) showed diagnostic discordance on the dynamic imaging study. Despite the recent progression in diagnostic imaging techniques, 2.2% of cases were false-positively diagnosed as HCC in a liver resection patient cohort; and the final diagnosis was benign disease in 0.8% of liver resection patients clinically diagnosed with HCC.

Evaluation of female overactive bladder using urodynamics: relationship with female voiding dysfunction.

PURPOSE: To investigate the role of urodynamic study (UDS) in female patients with overactive bladder (OAB) analyzing the relationship between OAB symptoms and female voiding dysfunction (FVD). MATERIALS AND METHODS: We analyzed the clinical and urodynamic data of 163 women with OAB symptoms. OAB symptoms were categorized as dry and wet. FVD was described as detrusor underactivity (DUA), which was defined as a maximum flow rate (Qmax) of ≤ 15 mL/s associated with a detrusor pressure at Qmax (PdetQ max) of ≤ 20 cmH2O, along with bladder outlet obstruction (BOO), which was defined as a Qmax of ≤ 15 mL/s with a PdetQ max of > 20 cmH2O. Clinical and urodynamic results were compared between patients with dry and wet symptoms and between those with and without FVD. RESULTS: 78 (47.9%) had dry, and 85 (52.1%) had wet symptoms. The entire group had a relatively low Qmax (15.1 ± 6.6 mL/s) and relatively high number of BOO (42.9%, 70/163) and DUA (8.6%, 14/163). A significantly higher number of patients with wet symptoms had detrusor overactivity compared to those with dry, as detected by the UDS (p < 0.05). No significant differences were found in BOO and DUA number between dry and wet groups. Further, the international prostate symptom score did not different significantly between patients with and without FVD. CONCLUSION: A significant number of women with OAB had voiding dysfunction. However, the OAB symptoms themselves were not useful for predicting the presence of FVD. Therefore, UDS may be necessary for accurate diagnosis in women with OAB symptoms.

Expression of transient receptor potential vanilloid 4 and effects of ruthenium red on detrusor overactivity associated with bladder outlet obstruction in rats.

PURPOSE: To investigate transient receptor potential vanilloid 4 (TRPV4) expression and the effects of ruthenium red (RR)-TRPV antagonist-on detrusor overactivity (DO) associated with bladder outlet obstruction (BOO). METHODS: Rats were randomly assigned to 3 groups. The control group (n = 10) included sham-operated rats. The BOO-group without RR (n = 15) and BOO-group with RR (n = 15) underwent partial BOO surgery. Three weeks postoperatively, cystometrography was performed in all rats. After confirming DO, RR was instilled intravesically in the BOO-group with RR. Urodynamic parameters were investigated, including contraction interval (CI) and contraction pressure (CP). TRPV4 expression was evaluated through immunofluorescence staining and western blotting. RESULTS: The BOO-group without RR had significantly shorter CI and significantly higher CP compared to the control. In the BOO-group with RR, CI was significantly longer compared to the BOO-group without RR. However, change in CP between BOO-group without and with RR was not significantly different. Immunofluorescence staining showed that TRPV4 was localized in the urothelium and detrusor muscles. TRPV4 immunofluorescence signals were increased in the urothelium and detrusor muscle in BOO-group without RR, compared with the control. In western blot analysis, immunoreactive bands indicating expression of TRPV4 were detected in the urothelium and detrusor muscle, and those were significantly increased in the BOO-group without RR compared with the control in the urothelium and detrusor muscle. CONCLUSIONS: TRPV4 plays an important role in the pathophysiology of DO, and RR has a beneficial effect on DO associated with BOO.

Changes in urinary nerve growth factor and prostaglandin E2 in women with overactive bladder after anticholinergics.

INTRODUCTION AND HYPOTHESIS: The aim of this study is to investigate changes in urinary nerve growth factor (NGF) and prostaglandin E(2) (PGE(2)) in women with overactive bladder (OAB) following anticholinergic treatment. METHODS: A total of 30 female patients with OAB were enrolled and the control group included 15 healthy women who did not present any bladder symptoms. All subjects with OAB recorded voiding diaries, underwent urodynamic study, and were evaluated for urgency grade. They received anticholinergic treatment for 4 weeks, after which they were again evaluated for urinary urgency grade and voiding diaries. OAB patients were classified into three groups according to the change on the 5-point Urinary Sensation Scale after the treatment: group 1 (no change in urgency grade), group 2 (1 point of improvement), and, group 3 (more than 2 points of improvement). Urinary NGF and PGE(2) levels between controls and OAB patients (before and after treatment in groups 1, 2, and 3) were compared. RESULTS: Urinary NGF and PGE(2) levels were significantly higher in OAB patients than in the controls. NGF levels were not significantly different between pre- and post-treatment in groups 1 and 2. However, in group 3, NGF levels were significantly decreased after treatment. PGE(2) levels were not significantly different between pre- and post-treatment in either group. CONCLUSIONS: NGF and PGE(2) have important roles in the development of OAB symptoms in women. Initial reduction of urgency severity after anticholinergic treatment in women with OAB could be associated with decreasing urinary NGF levels.

Proper position of single and large (≥5 cm) hepatocellular carcinoma in Barcelona Clinic Liver Cancer classification.

The purpose of this study was to evaluate the proper position of single large hepatocellular carcinoma (HCC) in the Barcelona Clinic Liver Cancer (BCLC) staging system. The data were collected from the nationwide multicentre database of the Korean Liver Cancer Association. Patients with single large (≥5 cm) HCC were separated from BCLC stage A patients and designated as Group X. The remaining BCLC stage A and stage B patients were classified as Group A and Group B, respectively. The survival outcomes of propensity score-matched groups were compared. Among the 3965 randomly selected patients, the number of patients in Group X, Group A, and Group B was 414, 2787, and 760, respectively. TriMatch analysis allowed us to obtain 116 well-balanced triplets. The 1-, 3-, and 5-year overall survival rates in Group X were worse than in Group A (91%, 71%, and 48% vs 90%, 78%, and 64%, respectively; P < .000). However, the rates were not different compared with those in Group B (91%, 71%, and 48% vs 90%, 69%, and 48%, respectively; P < .09). In multivariate analysis, Group X, Group B, age over 60 years, prothrombin time-international normalized ratio, and creatinine level were independent predictors of worse overall survival. Our findings suggest that Group X should be relocated to BCLC stage B rather than BCLC stage A.

Accidental ABO-incompatible pediatric liver transplantation with blood group antigen immune and operational tolerance: a case report with 21 years of follow-up.

Liver transplantation is a critical procedure for patients with end-stage liver disease, but it is often hindered by ABO-incompatibility between the donor and recipient, which can lead to immediate humoral rejection. We present a unique case involving a 10-month-old patient who, by accident, received an ABO-incompatible partial liver transplant from a type A mother without undergoing desensitization. Remarkably, during a 21-year follow-up period, the patient exhibited no signs of humoral or graft rejection, despite nonadherence to medication. This case highlights the possibility of dual tolerance in pediatric ABO-incompatible liver transplantation and provides insights into immune tolerance mechanisms, with implications for enhancing patient care and reducing healthcare costs. Further research is necessary to clarify these mechanisms and to evaluate the long-term durability of tolerance in pediatric transplant recipients.

Altered Frequency, Activation, and Clinical Relevance of Circulating Innate and Innate-Like Lymphocytes in Patients With Alcoholic Liver Cirrhosis.

Alcoholic liver cirrhosis (ALC) is caused by chronic alcohol overconsumption and might be linked to dysregulated immune responses in the gut-liver axis. However, there is a lack of comprehensive research on levels and functions of innate lymphocytes including mucosal-associated invariant T (MAIT) cells, NKT cells, and NK (NK) cells in ALC patients. Thus, the aim of this study was to examine the levels and function of these cells, evaluate their clinical relevance, and explore their immunologic roles in the pathogenesis of ALC. Peripheral blood samples from ALC patients (n = 31) and healthy controls (HCs, n = 31) were collected. MAIT cells, NKT cells, NK cells, cytokines, CD69, PD-1, and lymphocyte-activation gene 3 (LAG-3) levels were measured by flow cytometry. Percentages and numbers of circulating MAIT cells, NKT cells, and NK cells were significantly reduced in ALC patients than in HCs. MAIT cell exhibited increased production of IL-17 and expression levels of CD69, PD-1, and LAG-3. NKT cells displayed decreased production of IFN-γ and IL-4. NK cells showed elevated CD69 expression. Absolute MAIT cell levels were positively correlated with lymphocyte count but negatively correlated with C-reactive protein. In addition, NKT cell levels were negatively correlated with hemoglobin levels. Furthermore, log-transformed absolute MAIT cell levels were negatively correlated with the Age, Bilirubin, INR, and Creatinine score. This study demonstrates that circulating MAIT cells, NKT cells, and NK cells are numerically deficient in ALC patients, and the degree of cytokine production and activation status also changed. Besides, some of their deficiencies are related to several clinical parameters. These findings provide important information about immune responses of ALC patients.

Rat Model of Normothermic Ex-Situ Perfused Heterotopic Heart Transplantation.

Heart transplantation is the most effective therapy for end-stage heart failure. Despite the improvements in therapeutic approaches and interventions, the number of heart failure patients waiting for transplantation is still increasing. The normothermic ex situ preservation technique has been established as a comparable method to the conventional static cold storage technique. The main advantage of this technique is that donor hearts can be preserved for up to 12 h in a physiologic condition. Moreover, this technique allows resuscitation of the donor hearts after circulatory death and applies required pharmacologic interventions to improve donor function after implantation. Numerous animal models have been established to improve normothermic ex situ preservation techniques and eliminate preservation-related complications. Although large animal models are easy to handle compared to small animal models, it is costly and challenging. We present a rat model of normothermic ex situ donor heart preservation followed by heterotopic abdominal transplantation. This model is relatively cheap and can be accomplished by a single experimenter.