Activin suppresses the expression of inflammatory genes and signaling proteins in human leukemia monocytic THP-1 cells.

Activin regulates inflammation, cell proliferation, immune response, wound repair, and endocrine function. In this study, we investigated the effect of activin on inflammatory genes in THP-1 cells and the involvement of NF-κB, AKT, and mitogen-activated protein kinase (MAPK) signaling. Cell viability was determined using a colorimetric assay with the MTS/PES solution. The mRNA levels were analyzed using reverse transcription-quantitative polymerase chain reaction. The expression of NF-κB, AKT, and MAPK signaling proteins was measured using immunoblot analysis. Activin A did not affect THP-1 cell viability at concentrations below 50 ng/ml. Activin decreased the mRNA expression of cytokines (interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α), toll-like receptor 4 (TLR4), and matrix metallo-proteinases (MMP)-9 proteins but did not affect IL-8 expression. Activin increased the expression of TLR2 and MMP-2. In addition, activin inhibited the phosphorylation of NF-κB p65, AKT, and MAPK (c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 MAPK) signaling proteins. Our results suggest that activin may be involved in anti-inflammation by inhibiting inflammatory gene expression and regulating NF-κB and AKT/MAPK signaling.

Benefit of living donor liver transplantation in graft survival for extremely high model for end-stage liver disease score ≥35.

BACKGROUND AND AIMS: Living liver donation with high model for end-stage liver disease (MELD) score was discouraged despite organ shortage. This study aimed to compare graft survival between living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) recipients with extremely high-MELD (score of ≥35). METHODS: Between 2008 and 2018, 359 patients who underwent liver transplantation with a MELD score ≥35 were enrolled. We compared graft survival between LDLT and DDLT after propensity score matching (PSM) and performed subgroup analysis according to donor type. RESULTS: After PSM, there was no statistical difference in graft survival between the LDLT and DDLT groups (p = .466). Old age, acute on chronic liver failure, re-transplantation, preoperative intensive care unit stay and red blood cell (RBC) transfusion during the operation were risk factors for graft failure (p = .046, .005, .032, .015 and .001, respectively). Biliary complications were more common in the LDLT group (p = .021), while viral infection, postoperative uncontrolled ascites, and postoperative hemodialysis were more common in the DDLT group (p = .002, .018, and .027, respectively). In the LDLT group, acute chronic liver failure, intraoperative RBC transfusion, and early postoperative complications were risk factors for graft failure (p = .007, <.001, and .001, respectively). CONCLUSION: Our study showed that LDLT is not inferior to DDLT in graft survival if appropriate risk evaluation is performed in cases of extremely high-MELD scores. This result will help overcome organ shortages in high-MELD liver transplantation.

Fibrosis-4 index, a predictor for prognosis of hepatocellular carcinoma patients after curative hepatectomy even in hepatitis B virus dominant populations.

Purpose: Liver fibrosis plays an important role in the development of hepatocellular carcinoma (HCC) and determining its prognosis. Although many staging systems and liver reserve models have been developed without the intention of predicting prognosis of HCC, some studies have investigated their prognostic values in HCC after curative liver resection (LR). The aim of this study is to evaluate prognostic value of non-invasive biomarkers after curative LR. Methods: Between 2006 and 2013, HCC patients underwent LR were included and total 962 patients were enrolled. All non-invasive biomarkers (fibrosis 4 index (FIB-4), aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), AAR-to-platelet ratio index (AARPRI), and albumin-bilirubin (ALBI) score) were measured at the time of HCC diagnosis. To binarize each biomarker, an optimal cut-off value for fibrosis stage was selected using the value of minimum distance from the left-upper corner of the receiver operating characteristic curve with a specificity >60%. We performed Cox regression analysis on 2-year recurrence-free survival (RFS) and overall survival (OS). Results: The area under curve values for FIB-4 and APRI were the largest for fibrosis stage compared to other biomarkers, 0.669 (95% confidential interval (CI), 0.610-0.719) and 0.748 (95% CI, 0.692-0.800), respectively. Between those two indices, FIB-4 is considered a statistically significant prognostic factor of RFS in HCC patients after LR. The HR for 2-year RFS and OS were 1.81 (95% CI, 1.18-2.77; P = 0.007) and 2.36 (95% CI, 0.99-5.65; P = 0.054), respectively. Conclusion: FIB-4 is identified as a statistically significant predictor of HCC prognosis after curative LR even in HBV dominant populations.

Impact of preoperative ultrasonography for predicting the prognosis of deceased donor kidney transplantation.

PURPOSE: This study evaluated the role of donor kidney ultrasonography (US) for predicting functional kidney volume and identifying ideal kidney grafts in deceased donor kidney transplantation. METHODS: In total, 272 patients who underwent deceased donor kidney transplantation from 2000 to 2020 at Samsung Medical Center were enrolled. Donor kidney information (i.e., right or left) was provided to the radiologist who performed US image re-analysis. To binarize each kidney's ultrasound parameters, an optimal cutoff value for estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73 m2 within 1 year after kidney transplantation was selected using the receiver operating characteristic curve with a specificity >60%. Cox regression analysis was performed for an eGFR less than 30 mL/min/1.73 m2 within 1 year after kidney transplantation and graft failure within 2 years after kidney transplantation. RESULTS: The product of renal length and cortical thickness was a statistically significant predictor of graft function. The odds ratios of an eGFR less than 30 mL/min/1.73 m2 within a year after kidney transplantation and the hazard ratio of graft failure within 2 years after kidney transplantation were 5.91 (P=0.003) and 5.76 (P=0.022), respectively. CONCLUSION: Preoperative US of the donor kidney can be used to evaluate donor kidney function and can predict short-term graft survival. An imaging modality such as US should be included in the donor selection criteria as an additional recommendation. However, the purpose of this study was not to narrow the expanded criteria but to avoid catastrophic consequences by identifying ideal donor kidneys using preoperative US.

Primary non-function in a deceased donor kidney transplant even with a Kidney Donor Risk Index less than 1.0: a case report.

Donations from deceased donors have been increasing since the introduction of expanded criteria for donor kidney selection. Several studies have shown that patients receiving deceased donor kidneys using these expanded criteria have improved survival compared to those remaining on the waiting list during hemodialysis. It is important, however, to consider that some of the kidneys classed as usable under the expanded criteria may in fact be unacceptable. To address this concern, preoperative biopsy and imaging of deceased donor kidneys are increasingly being used to assess candidate kidneys. We present the case of a 44-year-old female patient who underwent deceased donor kidney transplantation with negative complement-dependent cytotoxicity and flow cytometry crossmatch. Hours after graft reperfusion, given clinical evidence of primary nonfunction in the kidney, the patient underwent nephrectomy. Despite negative tests for blood type difference and crossmatch, and although the main artery and vein were well perfused, the kidney graft was never functional, and pathologic findings showed thrombotic microangiopathy and diffuse acute tubular necrosis. We conclude that further work on ideal criteria for identifying acceptable donor kidneys is needed.

Clinical Significance of Signet-Ring-Cell Colorectal Cancer as a Prognostic Factor.

PURPOSE: The aim of this study is to evaluate the prognosis for patients with a signet-ring-cell carcinoma (SRCC) who undergo curative surgery by comparing them to patients with an adenocarcinoma (ADC), excluding a mucinous ADC. METHODS: Between September 1994 and December 2013, 14,110 patients with colorectal cancer underwent surgery and among them, 12,631 patients were enrolled in this study. 71 patients with a SRCC and 12,570 patients with a ADC were identified. We analyzed the disease-free survival and the overall survival rates before and after a 1:2 propensity score matching and evaluated those rates after stage stratification. RESULTS: The median follow-up durations were 48.5 months for the SRC group and 48.6 months for the ADC group. The disease-free survival rates and the overall survival rates were significantly lower in the SRC group before and after propensity score matching (P < 0.001). After stratification by stage, no differences were observed between the SRC and the ADC groups for the disease-free survival (DFS) and the overall survival (OS) rates for patients with cancer in its early stages (P = 0.913 and P = 0.380 for the DFS and the OS, respectively, in stages 0 and I, and P = 0.223 and P = 0.991 for the DFS and the OS, respectively, in stage II), but those rates were significantly lower in the SRC group for cancer in its later stages (P < 0.001, respectively in stages III and IV). CONCLUSION: For cancer in advanced stages, patients with a resectable colorectal SRCC had a poorer prognosis after propensity score matching than those with an ADC did. Therefore, more intensive surveillance and closer observation should be offered to such patients.