Inflachromene ameliorates Parkinson's disease by targeting Nrf2-binding Keap1.

Parkinson's disease (PD) is the most common neurodegenerative disease characterized by movement disorder. Despite current therapeutic efforts, PD progression and the loss of dopaminergic neurons in the substantia nigra remain challenging to prevent due to the complex and unclear molecular mechanism involved. We adopted a phenotype-based drug screening approach with neuronal cells to overcome these limitations. In this study, we successfully identified a small molecule with a promising therapeutic effect for PD treatment, called inflachromene (ICM), through our phenotypic screening strategy. Subsequent target identification using fluorescence difference in two-dimensional gel electrophoresis (FITGE) revealed that ICM ameliorates PD by targeting a specific form of Keap1. This interaction led to upregulating various antioxidants, including HO-1, NQO1, and glutathione, ultimately alleviating PD symptoms. Furthermore, ICM exhibited remarkable efficacy in inhibiting the loss of dopaminergic neurons and the activation of astrocytes and microglia, which are critical factors in PD pathology. Our findings suggest that the phenotypic approach employed in this study identified that ICM has potential for PD treatment, offering new hope for more effective therapeutic interventions in the future.

Predicting Safe Liver Resection Volume for Major Hepatectomy Using Artificial Intelligence.

(1) Background: Advancements in the field of liver surgery have led to a critical need for precise estimations of preoperative liver function to prevent post-hepatectomy liver failure (PHLF), a significant cause of morbidity and mortality. This study introduces a novel application of artificial intelligence (AI) in determining safe resection volumes according to a patient's liver function in major hepatectomies. (2) Methods: We incorporated a deep learning approach, incorporating a unique liver-specific loss function, to analyze patient characteristics, laboratory data, and liver volumetry from computed tomography scans of 52 patients. Our approach was evaluated against existing machine and deep learning techniques. (3) Results: Our approach achieved 68.8% accuracy in predicting safe resection volumes, demonstrating superior performance over traditional models. Furthermore, it significantly reduced the mean absolute error in under-predicted volumes to 23.72, indicating a more precise estimation of safe resection limits. These findings highlight the potential of integrating AI into surgical planning for liver resections. (4) Conclusion: By providing more accurate predictions of safe resection volumes, our method aims to minimize the risk of PHLF, thereby improving clinical outcomes for patients undergoing hepatectomy.

Surgical Outcomes of Laparoscopic versus Open Hepatectomy for Left Hepatocellular Carcinoma: Propensity Score Analyses Using Retrospective Japanese and Korean Individual Patient Data.

Introduction: This study aimed to compare the prognostic impact of laparoscopic left hepatectomy (LLH) with that of open left hepatectomy (OLH) on patient survival after resection of left hepatocellular carcinoma (HCC). Methods: Among the 953 patients who received initial treatment for primary HCC that was resectable by either LLH or OLH from 2013 to 2017 in Japan and Korea, 146 patients underwent LLH and 807 underwent OLH. The inverse probability of treatment weighting approach based on propensity scoring was used to address the potential selection bias inherent in the recurrence and survival outcomes between the LLH and OLH groups. Results: The occurrence rate of postoperative complications and hepatic decompensation was significantly lower in the LLH group than in the OLH group. Recurrence-free survival (RFS) was better in the LLH group than in the OLH group (hazard ratio, 1.33; 95% confidence interval, 1.03-1.71; p = 0.029), whereas overall survival (OS) was not significantly different. Subgroup analyses of RFS and OS revealed an almost consistent trend in favor of LLH over OLH. In patients with tumor sizes of ≥4.0 cm or those with single tumors, both RFS and OS were significantly better in the LLH group than in the OLH group. Conclusions: LLH decreases the risk of tumor recurrence and improves OS in patients with primary HCC located in the left liver.

Targeted Protein Upregulation of STING for Boosting the Efficacy of Immunotherapy.

Modulating target proteins via the ubiquitin-proteasome system has recently expanded the scope of pharmacological inventions. Stimulator of interferon genes (STING) is an auspicious target for immunotherapy. Seminal studies envisioned the importance of STING as well as the utility of its agonists in immunotherapy outcomes. Herein, we suggest UPPRIS (upregulation of target proteins by protein-protein interaction strategy) to pharmacologically increase cellular STING levels for improved immunotherapy. We discovered the small molecule SB24011 that inhibits STING-TRIM29 E3 ligase interaction, thus blocking TRIM29-induced degradation of STING. SB24011 enhanced STING immunity by upregulating STING protein levels, which robustly potentiated the immunotherapy efficacy of STING agonist and anti-PD-1 antibody via systemic anticancer immunity. Overall, we demonstrated that targeted protein upregulation of STING can be a promising approach for immuno-oncology.

The importance of muscle mass in predicting intradialytic hypotension in patients undergoing maintenance hemodialysis.

BACKGROUND: Patients undergoing hemodialysis are susceptible to sarcopenia. As intracellular reservoirs of water, skeletal muscles are important contributors to intradialytic hypotension. This study was designed to determine the role of skeletal muscle mass in intradialytic hypotension. METHODS: In a cross-sectional study, the body composition of 177 patients was measured immediately after hemodialysis using bioelectrical impedance analysis. The parameters measured were skeletal muscle mass, intracellular and extracellular water contents, total body water, and cell-membrane functionality (in phase angle at 50 kHz). Data from laboratory tests, chest radiography, measurements of handgrip strength and mid-arm circumference, and questionnaires were collected. The main outcome was intradialytic hypotension, defined as more than two episodes of hypotension (systolic blood pressure of <90 mmHg) with intervention over the 3 months following enrollment. Logistic regression models including each parameter related to sarcopenia were compared with a clinical model. RESULTS: Patients with a low ratio of skeletal muscle mass to dry body weight (SMM/WT) had a higher rate of intradialytic hypotension (40.7%). Most low-SMM/WT patients were female, obese, diabetic, and had a lower handgrip strength compared with the other patients. In the high-SMM/WT group, the risk of intradialytic hypotension was lower, with an odds ratio of 0.08 (95% confidence interval [CI], 0.02-0.28) and adjusted odds ratio of 0.06 (95% CI, 0.01-0.29). CONCLUSION: Measurement and maintenance of skeletal muscle can help prevent intradialytic hypotension in frail patients undergoing hemodialysis.

Outcomes of Pure Laparoscopic Living Donor Right Hepatectomy at a Small-Volume Center.

OBJECTIVES: Laparoscopic liver donor surgery is a technically difficult and demanding procedure. Our aim was toevaluate its feasibility at an established transplant center. Although our hospital is a small-volume center with <20 liver transplants per year, laparoscopic donor surgery has been performed regularly. In this study, we have reported our experiences with laparoscopic donor right hepa-tectomy and its outcomes. MATERIALS AND METHODS: Between May 2014 and March 2021, 26 deceased donor liver transplants and 37 living donor liver transplants, approved by the Korean Network for Organ Sharing, were performed at out center. From these, we reviewed the medical records, including clinical and demographic characteristics and operative outcomes, of 3 living donors who under-went pure laparoscopic donor right hepatectomy and their recipients. RESULTS: Each of the 3 laparoscopic donor right hepatectomies took over 10 hours with the prolonged Pringle maneuver time and warm ischemic time. However, there were no significant events during surgery or critical postoperative complications. In the recipients, posttransplant complications included middle hepatic vein obstruction, postoperative bleeding, bile leak, septic shock, and primary nonfunction of the graft. We managed and resolved these complications using various approaches, including retransplant, and all 3 recipients recovered and survived. CONCLUSIONS: Laparoscopic donor right hepatectomy had a relatively long operative time at our small-volume center. We believe that successful laparoscopic donor hepatectomy is possible if the donor is selected appropriately according to the center's experiences and there are constant efforts to overcome the learning curve.

De Novo Intrahepatic Cholangiocarcinoma After Deceased Donor Liver Transplant in an Adult Patient.

Survival after liver transplant has progressively improved over recent decades. Recurrent or de novo malignancy, however, remains a major cause of patient death after transplant. Here, we have described a patient who developed de novo intrahepatic cholangiocarcinoma in the graft liver after orthotopic liver transplant. The 48-year-old male patient had end-stage liver disease from hepatitis B-related liver cirrhosis and a Model for End-Stage Liver Disease score of 26 and was listed for liver transplant. Recurrent esophageal variceal hemorrhage, severe ascites, and splenomegaly had complicated the liver disease. He underwent emergent whole organ, deceased donor liver transplant for liver cirrhosis. The donor liver was procured through the standard donation after brain death process from a 72-year-old man who died of intracranial hemorrhage. The graft weighted 1500 g and had normal color, and cold ischemia time was 5 hours upon arrival at our hospital. The patient's early postoperative course was uneventful. Two months posttransplant, the patient presented to the emergency department with fever, abdominal pain, and skin rash. Computed tomography revealed a focal biliary stricture in the right hepatic duct. Magnetic resonance cholangiopancreatography identified intrahepatic duct dilatations. Subsequent endoscopic retrograde cholangiography demonstrated marked intra- and extrahepatic biliary dilatation. We considered it to be a benign stricture and inserted plastic stents. He recovered from biliary stricture-related cholangitis. Approximately 10 months posttransplant, the patient was admitted with fever and skin rash. Marked dilatation of the intrahepatic bile duct was shown with a poorly enhancing tumor in the right lobe of the graft. Percutaneous transhepatic biliary drainage and tumor biopsy confirmed intrahepatic cholangiocarcinoma. We believe this to be the first case of de novo intrahepatic cholangiocarcinoma in a patient with hepatitis B-related end-stage liver disease after liver transplant without primary sclerosing cholangitis.

Usefulness of External Biliary Stent Buried Suture for Reducing Stent-Related Complications In Liver Transplantation.

BACKGROUND: External bile stents may be used to prevent biliary complications. However, the external biliary stent itself has a risk of complications. This study evaluated the frequency and treatment of complications associated with external bile stent. METHODS: From May 2015 to September 2019, 18 deceased donor liver transplantations (DDLTs) and 25 living donor liver transplantations (LDLTs) were performed. We retrospectively reviewed these patients' demographic profiles, type of transplantation and presence of biliary complications, external bile stent-related complications, and treatment results. RESULTS: Overall biliary complications occurred in 12 patients (27.9%): 3 strictures (6.9%), 2 leakages (4.6%), and 7 external bile stent-related complications (16.2%). Among the 7, 4 were self-removal or stent fractures at home, and 2 occurred after removal by a physician. One patient had ileus with peritonitis. Local peritonitis was controlled by antibiotics and fluid therapy, but 1 patient needed an operation because of intestinal obstruction with recurrent local peritonitis. All biliary complications occurred in LDLT, and external biliary stent-related complications also occurred only in LDLT, not in DDLT (P = .014). Interestingly, only 1 of 7 external bile stent-related complications occurred after we adopted the stent buried suture technique on the duodenum (P = .062). CONCLUSIONS: External bile stent-related complications were higher in LDLT than in DDLT. When performing external bile stent implantation, the stent buried suture technique will help reduce stent-related complications, especially in LDLT.

Inhibition of histone deacetylase 6 suppresses inflammatory responses and invasiveness of fibroblast-like-synoviocytes in inflammatory arthritis.

BACKGROUND: To investigate the effects of inhibiting histone deacetylase (HDAC) 6 on inflammatory responses and tissue-destructive functions of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). METHODS: FLS from RA patients were activated with interleukin (IL)-1ß in the presence of increasing concentrations of M808, a novel specific HDAC6 inhibitor. Production of ILs, chemokines, and metalloproteinases (MMPs) was measured in ELISAs. Acetylation of tubulin and expression of ICAM-1 and VCAM-1 were assessed by Western blotting. Wound healing and adhesion assays were performed. Cytoskeletal organization was visualized by immunofluorescence. Finally, the impact of HDAC6 inhibition on the severity of arthritis and joint histology was examined in a murine model of adjuvant-induced arthritis (AIA). RESULTS: HDAC6 was selectively inhibited by M808. The HDAC6 inhibitor suppressed the production of MMP-1, MMP-3, IL-6, CCL2, CXCL8, and CXCL10 by RA-FLS in response to IL-1ß. Increased acetylation of tubulin was associated with decreased migration of RA-FLS. Inhibiting HDAC6 induced cytoskeletal reorganization in RA-FLS by suppressing the formation of invadopodia following activation with IL-1ß. In addition, M808 tended to decrease the expression of ICAM-1 and VCAM-1. In the AIA arthritis model, M808 improved the clinical arthritis score in a dose-dependent manner. Also, HDAC6 inhibition was associated with less severe synovial inflammation and joint destruction. CONCLUSION: Inhibiting HDAC6 dampens the inflammatory and destructive activity of RA-FLS and reduces the severity of arthritis. Thus, targeting HDAC6 has therapeutic potential.

Effectiveness of Albumin-bilirubin Score as a Predictor of Post-hepatectomy Liver Failure in Patients with Hepatocellular Carcinoma.

Backgrounds/Aims: Post-hepatectomy liver failure (PHLF) is a major concern for patients with hepatocellular carcinoma (HCC) who have undergone liver resection. The albumin-bilirubin (ALBI) score is a novel model for assessing liver function. We aimed to investigate the effectiveness of the ALBI score as a predictor of PHLF in HCC patients who have undergone hepatectomy in South Korea. Methods: Between January 2014 and November 2018, HCC patients who underwent hepatectomy and indocyanine retention rate at 15 min (ICG-R15) test were enrolled in this study. Results: A total of 101 patients diagnosed with HCC underwent hepatectomy. Thirty-two patients (31.7%) experienced PHLF. The ALBI score (OR 2.83; 95% CI 1.22-6.55; p=0.015), ICG-R15 (OR 1.07; 95% CI 1.02-1.12; p=0.007) and ALBI grade (OR 2,86; 95% CI 1.08-7.58; p=0.035) were identified as independent predictors of PHLF by multivariable analysis. The area under the receiver operating characteristic curve of the ALBI score and ICG-R15 were 0.676 (95% CI 0.566-0.785) and 0.632 (95% CI 0.513-0.752), respectively. The optimal cutoff value of the ALBI score in predicting PHLF was -2.62, with a sensitivity of 75.0% and a specificity of 56.5%. Conclusions: The ALBI score is an effective predictor of PHLF in patients with HCC, and its predictive ability is comparable to that of ICG-R15.

The usefulness of the totally intra-corporeal pringle maneuver with Penrose drain tube during laparoscopic left side liver resection.

BACKGROUNDS/AIMS: The Pringle maneuver is generally performed to reduce the amount of blood loss during hepatic resection. During laparoscopic liver resection, the Pringle maneuver can be used in several ways. We have developed a new Pringle maneuver (PM) with Penrose drain tube to sufficiently control blood loss during laparoscopic liver resection. This study was performed to determine the safety and outcome during laparoscopic left-sided hepatectomy performed using this new method. METHODS: We describe the technique and results of the left-sided liver resection with totally intracorporeal PM with Penrose drain tube. We performed 37 laparoscopic left-sided hepatic resections with (PM group) or without the Penrose PM (No PM group). We retrospectively compared the short-term operative outcome between the No PM group (n=12) and the PM group (n=25) during laparoscopic left-sided liver resection. RESULTS: Median PM duration was 34.3 min. The median duration of the surgery using the totally intracorporeal PM with Penrose drain tube was 174 min, while the surgical duration required for resection without the PM was 156 min. The median volume of operative blood loss was lower in the PM group than in the No PM group (No PM group (341 ml) vs. PM group (165 ml)). There was no postoperative mortality and no open conversion. CONCLUSIONS: The totally intracorporeal PM with Penrose drain tube for laparoscopic hepatectomy is safe, reproducible, and can facilitate liver dissection during left-sided liver resection.

Therapeutic potential of CKD-506, a novel selective histone deacetylase 6 inhibitor, in a murine model of rheumatoid arthritis.

OBJECTIVES: Histone deacetylase (HDAC) 6 promotes inflammation. We investigated the anti-arthritic effects of CKD-506, a novel HDAC6 inhibitor, in vitro and in a murine model of arthritis as a novel treatment option for rheumatoid arthritis (RA). METHODS: HDAC6 was overexpressed in mouse peritoneal macrophages and RAW 264.7 cells, and the effects of a HDAC6 inhibitor CKD-506 on cytokine production and activity of NF-κB and AP-1 signaling were examined. Peripheral blood mononuclear cells (PBMCs) from RA patients and fibroblast-like synoviocytes (FLS) were activated in the presence of CKD-506. Next, regulatory T cells (Tregs) were induced from RA patients and co-cultured with healthy effector T cells (Teffs) and cell proliferation was analyzed by flow cytometry. Finally, the effects of the inhibitor on the severity of arthritis were assessed in a murine model of adjuvant-induced arthritis (AIA). RESULTS: Overexpression of HDAC6 induced macrophages to produce TNF-α and IL-6. The inhibitory effect of CKD-506 was mediated via blockade of NF-κB and AP-1 activation. HDAC6 inhibition reduced TNF-α and IL-6 production by activated RA PBMCs. CKD-506 inhibited production of MMP-1, MMP-3, IL-6, and IL-8 by activated FLS. In addition, CKD-506 inhibited proliferation of Teffs directly and indirectly by improving iTreg function. In AIA rats, oral CKD-506 improved clinical arthritis in a dose-dependent manner. A combination of sub-therapeutic CKD-506 and methotrexate exerted a synergistic effect. CONCLUSION: The novel HDAC6 inhibitor CKD-506 suppresses inflammatory responses by monocytes/macrophages, improves Treg function, and ameliorates arthritis severity in a murine model of RA. Thus, CKD-506 might be a novel and effective treatment option for RA.

A novel histone deacetylase 6 inhibitor improves myelination of Schwann cells in a model of Charcot-Marie-Tooth disease type 1A.

BACKGROUND AND PURPOSE: Charcot-Marie-Tooth (CMT) disease is the most common hereditary peripheral neuropathy. CMT type 1A (CMT1A) accounts for approximately 50% of CMT patients and is linked to PMP22 gene duplication. Histone deacetylase-6 (HDAC6) has pleiotropic effects, such as regulating lipid homeostasis and cellular stress. Although HDAC6 has been regarded as a promising drug target for neurodegenerative diseases, its inhibition has not yet been tested in CMT1A. Here we have tested the therapeutic potential of CKD-504, a clinical stage HDAC6 inhibitor, in a mouse model of CMT1A EXPERIMENTAL APPROACH: The potency and selectivity of CKD-504 was evaluated, using a HDAC enzyme panel assay and western blots. The therapeutic potential of CKD-504 was evaluated using behavioural testing and electrophysiological assessments in the C22 mouse model of CMT1A. PMP22 protein expression and aggregation were analysed in mesenchymal stem cell-derived Schwann cells from CMT1A patients and sciatic nerves from C22 mice. KEY RESULTS: The HDAC6 inhibitor, CKD-504, modulated molecular chaperon proteins such as HSP90 and HSP70, which are involved in the folding/refolding of proteins such as PMP22. CKD-504 treatment restored myelination in both mesenchymal stem cell-derived Schwann cells from CMT1A patients and sciatic nerves of C22 mice and improved the axonal integrity of the sciatic nerve, leading to behavioural, electrophysiological, and histological improvements in C22 mice. CONCLUSION AND IMPLICATIONS: A novel HDAC6 inhibitor, CKD-504, has potent therapeutic efficacy for CMT1A.

Liver transplantation for azithromycin-induced severe liver injury.

Drug-induced liver injury is the most common cause of acute liver failure in Western countries by prescription drugs and herbal medications. Liver injury due to azithromycin has rarely been reported. This is a brief report of a patient administered azithromycin and who developed acute liver failure leading to liver transplantation. We report the case of a 68-year-old woman who developed jaundice 1 week after she started taking a azithromycin. On the 3rd day of hospitalization, her hepatic function rapidly deteriorated and level of consciousness decreased to drowsiness. The model for end-stage liver disease score was confirmed to be 33, and liver transplantation was considered. On the 8th day of hospitalization, she underwent emergency living donor liver transplantation, receiving a right lobe liver graft from a 35-year-old male donor, the patient's son. Currently, she is alive with good liver function after 25 months of transplant. This case suggests that azithromycin may cause rare hepatitis with liver failure. Therefore, at the beginning of the azithromycin treatment, patients should visit the hospital immediately if symptoms such as jaundice and abdominal pain are experienced.

Poor preoperative enteral nutrition would be a risk factor for readmission due to infection after liver transplantation.

Background: Most patients who undergo liver transplantation (LT) have advanced cirrhosis and poor nutritional status. The aim of this study was to investigate the effect of enteral nutrition (EN) on the clinical outcomes after LT. Methods: From 2015 to 2019, the medical records of recipient of LT at Kosin University Gospel Hospital were retrospectively reviewed. Results: Thirty-seven patients underwent LT. Nineteen patients underwent living donor liver transplantation (LDLT) and 18 patients underwent deceased donor liver transplantation (DDLT). One LDLT patient was excluded because transplantation was done within 1 month. Five DDLT patients were excluded either because they died within 1 month (n=4) or received transplantation within 1 month. (n=1). Therefore, 31 patients were analyzed. Psoas-muscle index (P=0.715) and serum albumin (P=0.111) were not statistically different between the LDLT and DDLT groups. Four patients (4/31) were readmitted because of infection. One LDLT patient was diagnosed with genitourinary infection. The three DDLT patients were diagnosed with pulmonary tuberculosis (n=1), diverticulitis (n=1), and sepsis (n=1). Readmission caused by infection was not statistically different between LDLD and DDLT patients (P=0.284). Preoperative EN <25% of the recommended amount (P=0.016) was significantly associated with readmission related to infection. In multivariate analyses, preoperative EN <25% was an independent risk factor for readmission due to infection after LT regardless of psoas-muscle index, baseline Model for End-Stage Liver Disease score, or LT type. Conclusions: Preoperative poor EN is significantly associated with readmission risk due to infection within 3 months of LT.

Clinical implication of tumor site in terms of node metastasis for intrahepatic cholangiocarcinoma.

BACKGROUND: The clinical implication of lymph node (LN) dissection of intrahepatic cholangiocarcinoma (ICCA) is still controversial, and LN metastasis (LNM) based on tumor site has not been confirmed yet. METHODS: Patients who underwent curative-intent surgery at 10 tertiary referral centers were identified and divided into peripheral (PP) and near second confluence level tumor (NC) groups on the basis of the distance from the second confluence and oncological outcomes were compared. RESULTS: Of 179 patients, 121 patients with LND were divided into the NC (n = 89) and PP groups (n = 32) on the basis of 4.5 cm from the second confluence. NC group showed higher LNM rate than PP group (46.1 vs 21.9%, p = 0.016) and NC was a risk factor for LNM (odds ratio: 4.367; 95% confidence interval: 1.234-15.453, p = 0.022). The 5-year overall survival (OS) rate (38.0% vs. 27.8%, p = 0.777) and recurrence-free survival (RFS) rates (22.8% vs. 25.8%, p = 0.742) showed no differences between the PP and NC groups. In the NC group, N1 patients showed worse 5-year OS (12.7% vs 39.0%, p = 0.004) and RFS (8.8% vs 28.6%, p = 0.004) than the N0 patients. In the PP group, discordant results in 5-year OS (48.9% vs. 50.0%, p = 0.462) and RFS (41.3% vs. 0%, p = 0.056) were found between the N0 and N1 patients. CONCLUSION: The NC group was an independent risk factor for LNM and LNM worsened prognosis in NC group for ICCA. In the PP group, LND should not be omitted because of high LNM rate and insufficient oncologic evidence.

Acetylation changes tau interactome to degrade tau in Alzheimer's disease animal and organoid models.

Alzheimer's disease (AD) is an age-related neurodegenerative disease. The most common pathological hallmarks are amyloid plaques and neurofibrillary tangles in the brain. In the brains of patients with AD, pathological tau is abnormally accumulated causing neuronal loss, synaptic dysfunction, and cognitive decline. We found a histone deacetylase 6 (HDAC6) inhibitor, CKD-504, changed the tau interactome dramatically to degrade pathological tau not only in AD animal model (ADLPAPT ) brains containing both amyloid plaques and neurofibrillary tangles but also in AD patient-derived brain organoids. Acetylated tau recruited chaperone proteins such as Hsp40, Hsp70, and Hsp110, and this complex bound to novel tau E3 ligases including UBE2O and RNF14. This complex degraded pathological tau through proteasomal pathway. We also identified the responsible acetylation sites on tau. These dramatic tau-interactome changes may result in tau degradation, leading to the recovery of synaptic pathology and cognitive decline in the ADLPAPT mice.

Clinical Course of Renal Disease in Recipients of Liver Transplant Who Required Peritransplant Dialysis.

PURPOSE: Renal dysfunction is a common complication and one of the factors that affects the outcomes of liver transplantation (LT). The aim of this study was to review the clinical course of recipients of LT who needed peritransplant dialysis at our center. METHODS: We compared the clinical demographics, morbidity, and mortality between patients who required and those who did not require peritransplant dialysis among 26 recipients of LT from May 2015 to February 2018 at our center. RESULTS: Among the recipients, 9 had pretransplant or posttransplant dialysis and 17 did not. The patients who underwent dialysis had a higher pretransplant Model for End-Stage Liver Disease score (42 vs 13; P < .001), older donor age (41 vs 24 years; P < .001), and longer post-LT hospital stay (37 vs 20 days; P < .001). However, there was no significant difference in the serum creatinine level between the 2 groups (1.36 vs 0.93 mg/dL; P = .187) at 2 weeks (1.10 vs 0.96 mg/dL; P = .341), 1 month (1.06 vs 0.86 mg/dL; P = .105), and 3 months after LT (0.92 vs 0.94 vs 0.89 mg/dL; P = .825). Mortality was higher in the peritransplant dialysis group (P = .043). The pre-LT dialysis duration was significantly related to post-LT dialysis (P = .028) and mortality (P = .011). CONCLUSIONS: The pre-LT dialysis duration is considered an important factor in the survival and recovery of kidney function after LT. Therefore, if the patient has started dialysis, it may be beneficial to proceed to LT as soon as possible.

Validation of the prognostic performance in various nodal staging systems for gallbladder cancer: results of a multicenter study.

BACKGROUND: Although the current nodal staging system for gallbladder cancer (GBC) was changed based on the number of positive lymph nodes (PLN), it needs to be evaluated in various situations. METHODS: We reviewed the clinical data for 398 patients with resected GBC and compared nodal staging systems based on the number of PLNs, the positive/retrieved LN ratio (LNR), and the log odds of positive LN (LODDS). Prognostic performance was evaluated using the C-index. RESULTS: Subgroups were formed on the basis of an restricted cubic spline plot as follows: PLN 3 (PLN = 0, 1-2, ≥ 3); PLN 4 (PLN = 0, 1-3, ≥ 4); LNR (LNR = 0, 0-0.269, ≥ 0.27); and LODDS (LODDS < - 0.8, - 0.8-0, ≥ 0). The oncological outcome differed significantly between subgroups in each system. In all patients with GBC, PLN 4 (C-index 0.730) and PLN 3 (C-index 0.734) were the best prognostic discriminators of survival and recurrence, respectively. However, for retrieved LN (RLN) ≥ 6, LODDS was the best discriminator for survival (C-index 0.852). CONCLUSION: The nodal staging system based on PLN was the optimal prognostic discriminator in patients with RLN < 6, whereas the LODDS system is adequate for RLN ≥ 6. The following nodal staging system considers applying different systems according to the RLN.

Effect of patient solicitation on mortality among patients receiving hemodialysis in Korea.

BACKGROUND: There is concern that overcompetition and illegal activities such as patient solicitation by some dialysis units may threaten patients' health in Korea. Therefore, we investigated the effect of nephrologists' patient-soliciting activity on hemodialysis practices and patients' survival using the Korean Health Insurance Review and Assessment Service database. METHODS: We selected 19 soliciting hemodialysis facilities and matched them with 19 non-soliciting facilities located nearby to eliminate location bias. Soliciting behavior was defined as the reduction of medical fees or providing money to attract dialysis patients. RESULTS: A total of 2,231 incident dialysis patients were included and followed for a median of 37.2 months. Soliciting facilities had a lower percentage of nephrologists, a higher average daily number of hemodialysis patients per physician, and a higher number of hemodialysis patients per nurse compared with non-soliciting facilities. Survival analysis showed that the crude mortality was significantly higher in patients treated in soliciting facilities than in those treated in non-soliciting facilities, even after adjustment for the effects of many other independently predictive covariates. CONCLUSIONS: This study demonstrated that in Korea, the overall mortality rate in incident dialysis patients was higher in those attending soliciting facilities than in those attending non-soliciting facilities.