The risk factors and clinical outcomes in hepatitis B seropositive and seronegative renal transplant patients.

INTRODUCTION: Hepatitis B virus (HBV) infection is prevalent in Asia including Taiwan. We retrospectively evaluated the risk of HBV reactivation and clinical outcomes in HBV+ and HBV- kidney transplant recipients. METHODS: Patients who underwent kidney transplantation between January 2004 and December 2021 were reviewed. The outcomes of interest included risks of HBV reactivation and patient/graft survival. RESULTS: We identified 337 patients (47.5 ± 12 years) were enrolled in our final cohort. Fifty-two (15.4%) had HBsAg positive at the time of transplantation. Seventeen developed viral reactivations, with 41.2% of them accompanied by active hepatitis. The graft survival, acute rejection rate, and cancer development after kidney transplantation did not differ in terms of HBsAg status. The Cox multivariate analysis indicated the HBV reactivation risk was increased by a lack of pre-transplant anti-HBV medication [hazard ratio (HR), 5.95; 95% confidence interval (CI), 1.31-27.02; P = 0.021 or an absence of lifelong antiviral therapy [HR, 3.14; 95% CI, 1.01-9.74; P = 0.047] Conclusion: Individuals, independent of HBsAg status, had similar prognosis in terms of patient and graft survival, acute rejection rate, and cancer development. The absence of either pre-transplant anti-HBV medication or lifelong antiviral therapy was significantly associated with an increased risk of HBV reactivation.

Functional analysis of auxin derived from a symbiotic mycobiont.

The biosynthesis of auxin or indole-3-acetic acid by microorganisms has a major impact on plant-microbe interactions. Several beneficial microbiota are known to produce auxin, which largely influences root development and growth in the host plants. Akin to findings in rhizobacteria, recent studies have confirmed the production of auxin by plant growth-promoting fungi too. Here, we show that Penicillium citrinum isolate B9 produces auxin as deduced by liquid chromatography tandem-mass spectrometry analysis. Such fungal auxin is secreted and contributes directly to enhanced root and shoot development and overall plant growth in Arabidopsis thaliana. Furthermore, auxin production by P. citrinum likely involves more than one tryptophan-dependent pathway. Using auxin biosynthesis inhibitor L-Kynurenine, we show that the indole-3-pyruvate pathway might be one of the key biosynthetic routes involved in such auxin production. Confocal microscopy of the DR5rev:GFP Arabidopsis reporter line helped demonstrate that P. citrunum B9-derived auxin is biologically active and is able to significantly enhance auxin signaling in roots during such improved root growth and plant development. Furthermore, the phenotypic growth defects arising from impaired auxin signaling in Arabidopsis taa1 mutant or upon L-Kynurenine treatment of wild-type Arabidopsis seedlings could be significantly alleviated by fungus B9-derived auxin, thus suggesting its positive role in plant growth promotion. Collectively, our results provide clear evidence that the production of auxin is one of the main mechanisms involved in induction of the beneficial plant growth by P. citrinum.

Arterial blood pressure waveform in liver transplant surgery possesses variability of morphology reflecting recipients' acuity and predicting short term outcomes.

We investigated clinical information underneath the beat-to-beat fluctuation of the arterial blood pressure (ABP) waveform morphology. We proposed the Dynamical Diffusion Map algorithm (DDMap) to quantify the variability of morphology.  The underlying physiology could be the compensatory mechanisms involving complex interactions between various physiological mechanisms to regulate the cardiovascular system. As a liver transplant surgery contains distinct periods, we investigated its clinical behavior in different surgical steps. Our study used DDmap algorithm, based on unsupervised manifold learning, to obtain a quantitative index for the beat-to-beat variability of morphology. We examined the correlation between the variability of ABP morphology and disease acuity as indicated by Model for End-Stage Liver Disease (MELD) scores, the postoperative laboratory data, and 4 early allograft failure (EAF) scores. Among the 85 enrolled patients, the variability of morphology obtained during the presurgical phase was best correlated with MELD-Na scores. The neohepatic phase variability of morphology was associated with EAF scores as well as postoperative bilirubin levels, international normalized ratio, aspartate aminotransferase levels, and platelet count. Furthermore, variability of morphology presents more associations with the above clinical conditions than the common BP measures and their BP variability indices. The variability of morphology obtained during the presurgical phase is indicative of patient acuity, whereas those during the neohepatic phase are indicative of short-term surgical outcomes.

Optimizing the Safe Washout Period for Liver Transplantation Following Immune Checkpoint Inhibitors with Atezolizumab, Nivolumab, or Pembrolizumab.

BACKGROUND: Using immune checkpoint inhibitors (ICIs) as a downstaging therapy for liver transplantation (LT) has improved outcomes for patients with advanced hepatocellular carcinoma (HCC). However, this therapy carries a risk of post-transplant graft rejection. The washout (WO) period between the last ICI dose and LT seems critical in preventing postoperative rejection. This study aimed to optimize the WO period by balancing tumor burden suppression and rejection prevention using ICIs before LT. METHODS: We reviewed published case reports or series from March 2020 to December 2022 regarding LT for HCC after downstaging or bridge therapy with ICIs and included 4 of our cases. Most patients received atezolizumab, nivolumab, or pembrolizumab; these ICIs shared a half-life of around 28 days. Therefore, we excluded cases without definite WO period data and those using non-atezolizumab/nivolumab/pembrolizumab ICIs and ultimately enrolled 22 patients for analysis. We compared their clinical outcomes and estimated the rejection-free survival for every 0.5 half-life interval. RESULTS: Most study subjects received nivolumab (n = 25). Six patients had severe rejections (nivolumab group, n = 5) and needed rescue management. Of the 6 cases, 1 patient died after rejection, and 2 underwent re-transplantation. The median WO period in these 6 patients was 22 days (IQR: 9-35 days). In addition, we found that a 1.5 half-life (42 days) was the shortest safe WO period associated with significant rejection-free survival (P = .005). CONCLUSIONS: Our results showed that 42 days was the safest WO period before LT for HCC after ICI with atezolizumab, nivolumab, or pembrolizumab.

Long-term outcomes of liver transplantation for alcohol-related liver disease.

BACKGROUND: Liver transplantation (LT) is being increasingly performed for alcohol-related liver disease (ALD). It is unclear whether the increasing frequency of LTs in ALD patients has a negative impact on deceased-donor (DDLT) allocation and whether the current policy of 6 months of abstinence before transplantation effectively prevents recidivism after transplantation or improves long-term outcomes. METHODS: A total of 506 adult LT recipients, including 97 ALD patients, were enrolled. The outcomes of ALD patients were compared with those of non-ALD patients. The 97 ALD patients were further divided into group A (6-month abstinence) and group N (nonabstinence) based on the pretransplant alcohol withdrawal period. The incidence of relapsed drinking and the long-term outcomes were compared between the two groups. RESULTS: The prevalence of LT for ALD significantly increased after 2016 (27.0% vs 14.0%; p < 0.01), but the frequency of DDLT for ALD remained unchanged (22.6% vs 34.1%, p = 0.210). After a median follow-up of 56.9 months, patient survival was comparable between the ALD and non-ALD patients (1, 3, and 5 years posttransplant: 87.6%, 84.3%, and 79.5% vs 82.8%, 76.6%, and 72.2%, respectively; p = 0.396). The results were consistent irrespective of the transplant type and disease severity. In ALD patients, 22 of the 70 (31.4%) patients reported relapsed drinking after transplantation, and the prevalence in group A had a higher tendency than that in group N (38.3% vs 17.4%, p = 0.077). Six months of abstinence or nonabstinence did not result in a survival difference, and de novo malignancies were the leading cause of late patient death in ALD patients. CONCLUSION: LT achieves favorable outcomes for ALD patients. Six months of abstinence pretransplant did not predict the risk of recidivism after transplantation. The high incidence of de novo malignancies in these patients warrants a more comprehensive physical evaluation and better lifestyle modifications to improve long-term outcomes.

Hybrid Method for Peritoneal Dialysis Catheter Insertion: A New Technique for Improved Outcomes and Reduced Costs.

INTRODUCTION: Peritoneal dialysis (PD) is a well-established treatment choice for end-stage kidney disease (ESKD). While there are several methods for PD catheter insertion, they each have limitations. In this study, we present a new hybrid method for PD catheter insertion and compare it to the conventional laparoscopic method. METHODS: This retrospective study included 171 patients who were undergoing their first PD catheter insertion, and a total of 20% of the enrolled patients had a past medical history of abdominal surgery. Out of these, 101 patients underwent the laparoscopic method and 70 underwent a new invented hybrid method. The study aimed to compare the surgical outcomes, incidence of early and late complications, hospital stay, and medical expenses between the two groups. RESULTS: There were no notable differences in basic demographic features and comorbid conditions between the two groups. The results of our data revealed that the hybrid group had a significantly shorter break-in period and did not require temporary hemodialysis. Additionally, length of hospital stay and medical costs were significantly lower in the hybrid group (all p < 0.05). The incidence of early complications was lower in the hybrid group, while the incidence of late complications was comparable between the two groups. CONCLUSION: Our study demonstrates that the hybrid method of PD catheter insertion provides a safe and efficient alternative to the traditional laparoscopic method, enabling urgent-start PD and reducing hospital stays and medical expenses. Our findings support the use of the hybrid method as a new standard of care for ESKD patients undergoing PD catheter insertion.

Single-Center Experience in Managing Right Liver Grafts From Trifurcation or Independent Right Posterior Portal Vein in Adult Living Donor Liver Transplantation.

BACKGROUND: The right liver graft has sometimes been from the trifurcation portal vein (TPV) or independent right posterior portal vein (IRPPV). Managing these PV anatomies to increase the recipient's survival rate remains challenging. Many published techniques could overcome this problem, such as simple unification venoplasty (SUV), autologous portal Y-graft interposition, conjoined unification venoplasty (CUV) with a baseball-like conduit, and SUV plus circumferential fence-like vein extension. This study reviewed our strategy for managing the right liver grafts from TPV or IRPPV in adult living donor liver transplantation (aLDLT). METHODS: We enrolled the study population who underwent aLDLT using the grafts with TPV or IRPPV at our institute from October 2004 to October 2022. We analyzed the reconstruction methods for these grafts and postoperative PV complications in donors and recipients. RESULTS: During the study period, of 528 aLDLT recipients, we identified 26 donors with TPV (n = 10) or IRPPV (n = 16). Eight grafts from TPV had a single PV orifice. The other 18 grafts had dual right PVs that underwent initial PV management, including SUV (n = 13), recipient's right and left portal veins to graft's dual PVs (n = 2), Y-graft interposition (n = 1), CUV (n = 1) and SUV with fence-like vein extension (n = 1). One SUV graft changed to fence venoplasty due to significant tension for PV anastomosis. The acute right posterior PV thrombus and anterior PV stenosis happened in 2 cases with Y-graft interposition and native PVs direct anastomosis. One donor with TPV had portal vein thrombosis and needed thrombectomy with vein patch repair. CONCLUSIONS: The graft from TPV should be carefully planned. A single PV orifice may be feasible but not always possible. An SUV could cover most IRPPVs, but if the distance between the right anterior and posterior PVs is a problem, CUV would be an alternative method. In addition, SUVs with fence venoplasty could relieve PV anastomosis tension.

Penicillium citrinum Provides Transkingdom Growth Benefits in Choy Sum (Brassica rapa var. parachinensis).

Soil-borne beneficial microbes establish symbioses with plant hosts and play key roles during growth and development therein. In this study, two fungal strains, FLP7 and B9, were isolated from the rhizosphere microbiome associated with Choy Sum (Brassica rapa var. parachinensis) and barley (Hordeum vulgare), respectively. Sequence analyses of the internal transcribed spacer and 18S ribosomal RNA genes combined with colony and conidial morphology identified FLP7 and B9 to be Penicillium citrinum strains/isolates. Plant-fungus interaction assays revealed that isolate B9 showed significant growth promotion effects in Choy Sum plants cultivated in normal soil, as well as under phosphate-limiting conditions. In comparison to the mock control, B9-inoculated plants showed a 34% increase in growth in aerial parts and an 85% upsurge in the fresh weight of roots when cultivated in sterilized soil. The dry biomass of such fungus-inoculated Choy Sum increased by 39% and 74% for the shoots and roots, respectively. Root colonization assays showed that P. citrinum associates directly with the root surface but does not enter or invade the root cortex of the inoculated Choy Sum plants. Preliminary results also indicated that P. citrinum can promote growth in Choy Sum via volatile metabolites too. Interestingly, we detected relatively higher amounts of gibberellins and cytokinins in axenic P. citrinum culture filtrates through liquid chromatography-mass spectrometry analyses. This could plausibly explain the overall growth induction in P. citrinum-inoculated Choy Sum plants. Furthermore, the phenotypic growth defects associated with the Arabidopsis ga1 mutant could be chemically complemented by the exogenous application of P. citrinum culture filtrate, which also showed accumulation of fungus-derived active gibberellins. Our study underscores the importance of transkingdom beneficial effects of such mycobiome-assisted nutrient assimilation and beneficial fungus-derived phytohormone-like metabolites in the induction of robust growth in urban farmed crops.

The strategy of diminishing age gap effect on different donor-recipient combinations in living donor kidney transplantation.

BACKGROUND: The disparity between kidney donation and the number of uremic patients on the waiting list has increased the demand for older live-donor kidneys (OLK). However, the donor-recipient age gap may have an impact on the recipient's outcome. METHODS: Patients who underwent living donor kidney transplantation at our institute between 2005 and 2019 were enrolled and categorized into four donor-recipient groups according to age (≥50 years and <50 years). The Estimated Post-Transplant Survival (EPTS) score was used to quantify the recipient's condition. Adjusted models analyzed recipient outcomes and related risks among the four groups. RESULTS: Of the 154 pairs of live donors and recipients, OLK did not influence overall or death-censored graft survival. The four donor-recipient combinations had similar recipient outcomes, except it slightly worsened in the "old donor to young recipient" group. The EPTS score (adjusted HR, 1.02; 95% CI, 1.01-1.04; p = 0.014) and rejection (adjusted HR, 4.26; 95% CI, 1.36-13.37; p = 0.013) were significant risk factors for overall and death-censored graft survival, respectively. Recipients with pretransplant diabetes or prior solid organ transplantation could have amplified risk effects. The main causes of graft loss were death in older recipients and chronic rejection in younger recipients. CONCLUSION: OLK is safe for young recipients. Nevertheless, adequate immunosuppression should be maintained to prevent rejection and subsequent graft loss, especially for those receiving second kidney transplantation. In contrast, older recipients should avoid overt immunosuppression and control their comorbidities, such as diabetes-related complications to improve their long-term outcomes.

High-Throughput Sequencing of Complementarity Determining Region 3 in the Heavy Chain of B-Cell Receptor in Renal Transplant Recipients: A Preliminary Report.

BACKGROUND: Graft failure resulting from rejection or any other adverse event usually originates from an aberrant and/or exaggerated immune response and is often catastrophic in renal transplantation. So, it is essential to monitor patients' immune status for detecting a rejection/graft failure early on. METHODS: We monitored the sequence change of complementary determining region 3 (CDR3) in B-cell receptor (BCR) immunoglobulin heavy-chain (IGH) immune repertoire (iR) in 14 renal transplant patients using next-generation sequencing (NGS), correlating its diversity to various clinical events occurring after transplantation. BCR-IGH-CDR3 in peripheral blood mononuclear cells was sequenced along the post-transplantation course by NGS using the iRweb server. RESULTS: Datasets covering VDJ regions of BCR-IGH-CDR3 indicated clonal diversity (D50) variations along the post-transplant course. Furthermore, principal component analysis showed the clustering of these sequence variations. A total of 544 shared sequences were identified before transplantation. D50 remained low in three patients receiving rituximab. Among them, one's D50 resumed after 3 m, indicating graft tolerance. The D50 rapidly increased after grafting and decreased thereafter in four patients without rejection, decreased in two patients with T-cell-mediated rejection (TCMR) and exhibited a sharp down-sliding after 3 m in two patients receiving donations after cardiac death (DCD). In another two patients with TCMR, D50 was low just before individual episodes, but either became persistently low or returned to a plateau, depending on the failure or success of the immunosuppressive treatments. Shared CDR3 clonal expansions correlated to D50 changes. Agglomerative hierarchical clustering showed a commonly shared CDR3 sequence and at least two different clusters in five patients. CONCLUSIONS: Clonal diversity in BCR-IGH-CDR3 varied depending on clinical courses of 14 renal transplant patients, including B-cell suppression therapy, TCMR, DCD, and graft tolerance. Adverse events on renal graft failure might lead to different clustering of BCR iR. However, these preliminary data need further verification in further studies for the possible applications of iR changes as genetic expression biomarkers or laboratory parameters to detect renal graft failure/rejection earlier.

Minimal invasive treatment for post-liver and renal transplant lymphatic leaks.

INTRODUCTION: Persistent lymphatic leakage from the surgical drain is a troubling complication occasionally encountered postoperatively. This study investigated lymphatic leaks after renal or liver transplantation, comparing the treatment efficacy of traditional catheter drainage vs. minimally invasive lymphatic interventions. We also discuss access and treatment targets considering the physiology of lymphatic flow. METHODS: Between September 2018 and September 2020, 13 patients with lymphatic leakage were treated with minimally invasive lymphatic interventions; 11 had received a renal transplant, and two received a liver transplant. The control group included 10 patients with postrenal transplant lymphatic leakage treated with catheter drainage. The treatment efficacy of catheter drainage, lymphatic interventions, and different targets of embolization were compared. RESULTS: The technical success rate for lymphatic intervention was 100%, and the clinical success rate was 92%, with an 82.9% reduction in drain volume on the first day after treatment. The duration to reach clinical success was 5.9 days with lymphatic intervention, and 33.9 days with conservative catheter drainage. CONCLUSION: Lymphangiography and embolization are minimally invasive and efficient procedures for treating persistent lymphatic leaks after renal or liver transplantation. We suggest prompt diagnosis and embolization at upstream lymphatics to reduce the duration of drain retention, days of hospitalization, and associated comorbidities.

Advanced preoperative three-dimensional planning decreases the surgical complications of using large-for-size grafts in pediatric living donor liver transplantation.

BACKGROUND: Using "large-for-size" liver graft, graft-to-recipient weight ratio (GRWR) ≥4%, has been debated in pediatric liver transplantation due to possible graft compartment after abdomen closure. Meticulous preoperative evaluation with three-dimensional (3D) techniques may prevent these problems. This study compared the safety of large-for-size grafts in pediatric living donor liver transplantation (PLDLT) during the eras with or without 3D planning. METHODS: We defined the 3D era was after November 2017 due to our first implication of 3D printing for surgical planning and subsequently developing a 3D simulation implanting model. From November 2004 to July 2021, we enrolled 30 PLDLT patients with body weight (BW) < 10 kg and categorized them into conventional group: GRWR ≥4% before the 3D era (n = 9), 3D group: GRWR ≥4% in the 3D era (n = 8), and control group: GRWR <4% (n = 13). We followed and compared their clinical outcomes. RESULTS: The 3D group had the lowest BW and the highest graft volume reduction rate, with all receiving modified left lateral segments (LLS), such as reduced LLS (n = 2), hyperreduced LLS (n = 5), and segment 2 monosegment (n = 1). Overall postoperative complications were similar in conventional and control groups but significantly lower in the 3D group (OR 0.06, 95% CI 0.006-0.70, p = 0.025). However, all groups had similar graft and patient survival at 1, 2, and 4 years. CONCLUSION: Advanced preoperative 3D planning can decrease post-transplant complications and increase the safety of large-for-size grafts in PLDLT. LEVEL OF EVIDENCE: Type of study: Retrospective comparative study; Evidence level: Level III.

Identification and Characterization of Auxin/IAA Biosynthesis Pathway in the Rice Blast Fungus Magnaporthe oryzae.

The rice blast fungus Magnaporthe oryzae has been known to produce the phytohormone auxin/IAA from its hyphae and conidia, but the detailed biological function and biosynthesis pathway is largely unknown. By sequence homology, we identified a complete indole-3-pyruvic acid (IPA)-based IAA biosynthesis pathway in M. oryzae, consisting of the tryptophan aminotransferase (MoTam1) and the indole-3-pyruvate decarboxylase (MoIpd1). In comparison to the wild type, IAA production was significantly reduced in the motam1Δ mutant, and further reduced in the moipd1Δ mutant. Correspondingly, mycelial growth, conidiation, and pathogenicity were defective in the motam1Δ and the moipd1Δ mutants to various degrees. Targeted metabolomics analysis further confirmed the presence of a functional IPA pathway, catalyzed by MoIpd1, which contributes to IAA/auxin production in M. oryzae. Furthermore, the well-established IAA biosynthesis inhibitor, yucasin, suppressed mycelial growth, conidiation, and pathogenicity in M. oryzae. Overall, this study identified an IPA-dependent IAA synthesis pathway crucial for M. oryzae mycelial growth and pathogenic development.

Safety and long-term outcomes of early liver transplantation for pediatric methylmalonic acidemia patients.

BACKGROUND: LT is a treatment option for MMA patients, but renal function impairment is one of the long-term concerns. The aim of this study was to evaluate the outcomes of early LT in these patients. METHODS: A total of 11 MMA mut-type patients (including 10 mut0 cases and 1 mut-case) who received LT in our institute were reviewed. Their metabolic profiles were compared between the pre/post-transplant periods. Their immunosuppressant and renal function changes after transplantation were assessed. RESULTS: After a mean follow-up of 97.5 ± 38.4 months, there were two deaths, and the actual survival rate was 81.8%. Their metabolic profiles had improved (mean blood ammonia level 366.8 ± 105.5 vs. 53.1 ± 17.4 µg/dl, p < .001; C3/C2 ratio 2.68 ± 0.87 vs. 0.73 ± 0.22, p = .003; mean urine MMA level 920.5 ± 376.6 vs. 196.2 ± 85.4, p = .067), and hospital stays were decreased (78.8 ± 74.5 vs. 7.4 ± 7.0 days/year, p = .009) after transplantation. The mean age at transplant was 1.81 ± 2.02 years old, and nine of these patients received LT before the age of 1.5 years old (early LT). Under prospective immunosuppressant dose reduction, three of these early LT patients discontinued the drug and were sustained for more than 5 years. Most of the patients had a preserved renal function, and no patient is currently on dialysis. CONCLUSIONS: In addition to the improvement in the metabolic parameters, early LT in MMA patients may allow for a dose reduction of the immunosuppressant, and the patient's renal function could be preserved in the long term.

Repeated loco-regional therapies for hepatocellular carcinoma is associated with inferior outcome after living donor liver transplantation in cirrhotic patients.

BACKGROUND: Liver transplantation is the definitive treatment for defined stage hepatocellular carcinoma (HCC) in cirrhotic patients. Loco-regional therapy (LRT) may be considered before transplantation to prevent the disease progression and the patient from dropping out of the waiting list. This study aims to evaluate the impact of repeated pretransplant LRTs on the long-term outcomes in HCC liver transplant recipients. METHODS: Between 2004 and 2019, living donor liver transplantation (LDLT) recipients with viable HCC on the explant livers were enrolled. Uni- and multivariate analysis was performed with the Cox regression model to stratify the risk factors associated with HCC recurrence and patent survival after LDLT. RESULTS: A total of 124 patients were enrolled, in which 65.3% (n = 81) were Barcelona Clinic Liver Cancer classification stage B or D and 89% (n = 110) had advanced fibrosis or cirrhosis on the explanted livers. After a median follow-up of 41 months (IQR: 24-86.5), there were 18 cases (13.7%) of HCC recurrence. Univariate analysis showed that the model of end-stage liver disease and Child-Turcotte-Pugh score, pretransplant alpha-fetoprotein value (>500 ng/ml), repeated pretransplant LRTs (N > 4), increased tumor numbers and maximal size, presence of microvascular invasion, and the histological grading of the tumors are risk factors of inferior outcomes. In multivariate analysis, only repeated pretransplant LRTs (N > 4) had a significant impact on both the overall- and recurrence-free survival. The impact of pretransplant LRT was consistently significant among subgroups based on their LRT episodes (N = 0, 1-4, >4 respectively). CONCLUSION: Repeated LRT for HCC can be associated with the risk of tumor recurrence and inferior patient survival after LDLT in cirrhotic patients. Early referral of those eligible for transplantation may improve the treatment outcomes in these patients.

The feasibility of medial segment graft in pediatric liver transplantation revisited by three-dimensional printing.

BACKGROUND: The medial segment as a mono-segmental graft was proposed to increase the donor pool for pediatric liver transplantation, but to date, there has been no published case. This study aims to revisit the feasibility of procuring the medial segment graft (MSG) by three-dimensional (3D) printing and ex vivo procedures performed on explanted diseased livers to overcome the gap between theory and clinical implementation. METHODS: From October 2004 to December 2016, we retrospectively analyzed preoperative computed tomography, magnetic resonance cholangiopancreatography, and intraoperative cholangiography images of our previous live liver donors and identified the indicated anatomy for the MSG, then materialized by 3D printing models to simulate the engraftment. Furthermore, we practiced the procurement procedures on selected explanted diseased livers. RESULTS: Among 291 analyzed livers, 96 livers (33%) met the arterial criteria for MSG, and two-thirds of them had ideal portal branches for reconstruction. The proposed right border of the MSG was the Cantlie's line, and the left edge was the right side of the umbilical fissure. The mean estimated volume of the MSG was 234 ± 54 ml. Besides, we suggest implanting the MSG as an auxiliary partial graft in an inverted vertical position or a standalone graft with right-side rotation in the right subphrenic space. CONCLUSION: The procurement of the MSG is feasible based on our results. However, due to the novelty of the procedure, we suggest that the first attempted case of MSG should be implanted as an auxiliary partial graft to maximize patient safety. LEVEL OF EVIDENCE: Type of study: Case series with no comparison groups EVIDENCE LEVEL: Level IV.

Living donor liver transplantation for small infants aged less than 6 months: The experience of a single institute.

PURPOSE: Liver transplantation (LT) for small infants < 6 months old is rare but becoming common as perioperative care improves. In Taiwan, living donor LT (LDLT) has expanded indications but is rarely performed for this age group because of unfavorable outcomes in the literature. We evaluated LDLT outcomes of patients <6 months old. METHODS: We identified infants < 6 months old undergoing LDLT between 2004 and 2019 at our hospital. Variables related to recipients, donors, surgeries, and outcomes were analyzed. RESULTS: Nine patients were identified. Indications for LT were biliary atresia (n = 2), Alagille syndrome (n = 1), protein C deficiency (n = 1), and acute liver failure (n = 5), including two patients with neonatal hemochromatosis, one with herpes simplex hepatitis, one with giant cell hepatitis with autoimmune hemolytic anemia, and one with hemophagocytic lymphohistiocytosis. Median age and weight at LT were 129 days and 4.8 kg, respectively. Graft types included left lateral segment (LLS, n = 4), hyper-reduced LLS (n = 4), and monosegment (n = 1). The median graft-to-recipient weight ratio was 4%. The median follow-up period was 14 months (range, 8 days to 127 months) with two mortalities, and two patients were totally weaned off immunosuppressants. Adjuvant therapies were required for patients with giant cell hepatitis and hemophagocytosis. Preoperative reconstructive imaging for estimating graft thickness facilitated surgical planning. CONCLUSION: Although LDLT is difficult to perform for small infants, outcomes are favorable and mainly dependent on underlying causes in addition to technical innovations.

Demethoxycurcumin Suppresses Proliferation, Migration, and Invasion of Human Brain Glioblastoma Multiforme GBM 8401 Cells via PI3K/Akt Pathway.

BACKGROUND/AIM: Demethoxycurcumin (DMC), one of the derivatives of curcumin, has been shown to induce apoptotic cell death in many human cancer cell lines. However, there is no available information on whether DMC inhibits metastatic activity in human glioblastoma cancer cells in vitro. MATERIALS AND METHODS: DMC at 1.0-3.0 µM significantly decreased the proliferation of GBM 8401 cells; thus, we used 2.0 µM for further investigation regarding anti-metastatic activity in human glioblastoma GBM 8401 cells. RESULTS: The internalized amount of DMC has reached the highest level in GBM 8401 cells after 3 h treatment. Wound healing assay was used to determine cell mobility and results indicated that DMC suppressed cell movement of GBM 8401 cells. The transwell chamber assays were used for measuring cell migration and invasion and results indicated that DMC suppressed cell migration and invasion in GBM 8401 cells. Gelatin zymography assay was used to examine gelatinolytic activity (MMP-2) in conditioned media of GBM 8401 cells treated by DMC and results demonstrated that DMC significantly reduced MMP-2 activity. Western blotting showed that DMC reduced the levels of p-EGFR(Tyr1068), GRB2, Sos1, p-Raf, MEK, p-ERK1/2, PI3K, p-Akt/PKBα(Thr308), p-PDK1, NF-κB, TIMP-1, MMP-9, MMP-2, GSK3α/ß, ß-catenin, N-cadherin, and vimentin, but it elevated Ras and E-cadherin at 24 h treatment. CONCLUSION: DMC inhibited cancer cell migration and invasion through inhibition of PI3K/Akt and NF-κB signaling pathways in GBM 8401 cells. We suggest that DMC may be used as a novel anti-metastasis agent for the treatment of human glioblastoma cancer in the future.

Effect of referral systems on costs and outcomes after hip fracture surgery in Taiwan.

OBJECTIVE: To explore the economic burdens of hip fracture surgery in patients referred to lower-level medical institutions and to evaluate how referral systems affect costs and outcomes of hip fracture surgery. DESIGN: A nationwide population-based retrospective cohort study. SETTING: All hospitals in Taiwan. PARTICIPANTS: A total of 7500 patients who had received hip fracture surgery (International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM) diagnostic codes 820.0 ∼ 820.9 and procedure codes 79.15, 79.35, 81.52, 81.53) performed in 1997 to 2013. MAIN OUTCOME MEASURES: Total costs including outpatient costs, inpatient costs and total medical costs and medical outcomes including 30-day readmission, 90-day readmission, infection, dislocation, revision and mortality. RESULTS: The patients were referred to a lower medical institution after hip fracture surgery (downward referral group) and 3034 patients continued treatment at the same medical institution (non-referral group). Demographic characteristics, clinical characteristics and institutional characteristics were significantly associated with postoperative costs and outcomes (P < 0.05). On average, the annual healthcare cost was New Taiwan Dollars (NT$)2262 per patient lower in the downward referral group compared with the non-referral group. The annual economic burdens of the downward referral group approximated NT$241 million (2019 exchange rate, NT$30.5 = US$1). CONCLUSIONS: Postoperative costs and outcomes of hip fracture surgery are related not only to demographic and clinical characteristics, but also to institutional characteristics. The advantages of downward referral after hip fracture surgery can save huge medical costs and provide a useful reference for healthcare authorities when drafting policies for the referral system.

Artificial Neural Network and Cox Regression Models for Predicting Mortality after Hip Fracture Surgery: A Population-Based Comparison.

This study purposed to validate the accuracy of an artificial neural network (ANN) model for predicting the mortality after hip fracture surgery during the study period, and to compare performance indices between the ANN model and a Cox regression model. A total of 10,534 hip fracture surgery patients during 1996-2010 were recruited in the study. Three datasets were used: a training dataset (n = 7,374) was used for model development, a testing dataset (n = 1,580) was used for internal validation, and a validation dataset (1580) was used for external validation. Global sensitivity analysis also was performed to evaluate the relative importances of input predictors in the ANN model. Mortality after hip fracture surgery was significantly associated with referral system, age, gender, urbanization of residence area, socioeconomic status, Charlson comorbidity index (CCI) score, intracapsular fracture, hospital volume, and surgeon volume (p < 0.05). For predicting mortality after hip fracture surgery, the ANN model had higher prediction accuracy and overall performance indices compared to the Cox model. Global sensitivity analysis of the ANN model showed that the referral to lower-level medical institutions was the most important variable affecting mortality, followed by surgeon volume, hospital volume, and CCI score. Compared with the Cox regression model, the ANN model was more accurate in predicting postoperative mortality after a hip fracture. The forecasting predictors associated with postoperative mortality identified in this study can also bae used to educate candidates for hip fracture surgery with respect to the course of recovery and health outcomes.