The safety and effectiveness of clopidogrel versus aspirin in Kawasaki disease with mild-to-moderate liver injury.

Kawasaki disease can be combined with liver injury. As a mainstay treatment for Kawasaki disease, aspirin may cause liver injury. This study aimed to compare the safety and effectiveness of clopidogrel versus aspirin in Kawasaki disease with mild-to-moderate liver injury. This study retrospectively analysed 166 children with Kawasaki disease combined with mild-to-moderate liver injury. The children treated with clopidogrel were less likely to have aggravated liver injury than those treated with aspirin (n = 2/100 vs. n = 13/66, P < 0.001). The initial alanine aminotransferase value of the clopidogrel group was higher (131.5 [98.5, 167.5] vs. 96 [72, 133], P < 0.001), while the time of alanine aminotransferase recovery to normal was similar (5 [4, 7] vs. 4 [3, 7], P = 0.179). No significant fever differences observed between groups: 7.5 [6, 9] for aspirin vs. 7 [6, 8] for clopidogrel group, P = 0.064. The probability of nonresponse to intravenous immunoglobulin (n = 29/100 vs. n = 30/66, P = 0.030) and the days of hospitalization (n = 6 [4, 9] vs. n = 7 [5, 10], P = 0.007) in the clopidogrel group were less than those in the aspirin group. In conclusion, the application of clopidogrel is potentially superior to aspirin in Kawasaki disease combined with mild-to-moderate liver injury.

The activation of CaN/NFAT signaling pathway in macrophages aggravated Lactobacillus casei cell wall extract-induced Kawasaki disease vasculitis.

OBJECTIVES: By using GWAS(genome-wide association studies) and linkage disequilibrium analysis to investigate the susceptibility genes of KD(Kawasaki disease), previous studies have identified that the CaN(calcineurin)-NFAT(the nuclear factor of activated T cell) signal pathway were significantly associated with susceptibility to KD. However, little is known about the molecular basis of the CaN/NFAT pathway involved in KD. Therefore, in our study we investigate the role of Ca2+/CaN/NFAT signaling pathway in macrophages in vitro and in vivo on coronary artery lesions induced by LCWE (Lactobacillus casei cell wall extract). METHODS AND RESULTS: We observed that LCWE could increase the expression of NFAT1 and NFAT2 in macrophages in vitro, and also enhance the transcriptional activity of NFAT by promoting the nucleus translocation. Similarly, in LCWE-induced mice model, the expression of NFAT1 and NFAT2 and associated proinflammatory factors were increased significantly. In addition, by knocking down or overexpressing NFAT1 or NFAT2 in macrophages, the results indicated that NFAT signaling pathway mediated LCWE-induced immune responses in macrophages and regulated the synthesis of IL(interleukin)-6, IL-1ß and TNF(tumor necrosis factor)-α in LCWE-induced macrophage activation. As well, we found that this process could be suppressed by CaN inhibitor CsA(cyclosporinA). CONCLUSIONS: Therefore, the CaN/NFAT signaling pathway mediated LCWE-induced immune responses in macrophages, and also participated in the LCWE-induced CALs(coronary artery lesions). And also the inhibitory effect of CsA in LCWE-induced cell model towards a strategy to modulate the CaN/NFAT pathway during the acute course of KD might be helpful in alleviate KD-induced CALs.

The clinical impact of early recurrence and its recurrence patterns in patients with gallbladder carcinoma after radical resection.

BACKGROUND: It is common for patients with gallbladder carcinoma (GBC) to develop recurrence shortly after radical resection. We aimed to investigate the risk factors of early recurrence (ER) and its recurrence patterns and further analyze the effect of adjuvant chemotherapy (ACT) on ER and non-ER patients for decision-making in clinical practice. METHODS: A total of 276 patients who underwent radical resection for GBC were retrospectively analyzed. Factors associated with overall survival (OS) and recurrence free survival (RFS) were identified using the Cox proportional hazard regression model, whereas ER was investigated using univariate and multivariable logistic regression models. RESULTS: The results indicated that 23.2% (64/276) of GBC patients developed ER after radical resection. ER was determined to be an independent risk factor for OS in patients with GBC after resection (P < 0.05). CA125, liver invasion, T stage, and N stage were independently associated with ER (P < 0.05). N1/N2 stage disease was an independent risk factor for OS, RFS and ER, and had a better predictive value in identifying ER than the other three variables associated with ER (P < 0.05). The liver and lymph nodes were the main first recurrence sites, and ER patients had a higher proportion of multisite recurrence. The prognosis of GBC patients with ER after radical resection differed significantly depending on whether ACT was provided, with ACT demonstrated to improve their prognosis (P < 0.05). CONCLUSIONS: Early recurrence after radical resection indicates a very poor prognosis in GBC and can be used to identify those who will benefit from ACT.

Textbook outcome in gallbladder carcinoma after curative-intent resection: a 10-year retrospective single-center study.

BACKGROUND: Textbook outcome (TO) can guide decision-making among patients and clinicians during preoperative patient selection and postoperative quality improvement. We explored the factors associated with achieving a TO for gallbladder carcinoma (GBC) after curative-intent resection and analyzed the effect of adjuvant chemotherapy (ACT) on TO and non-TO patients. METHODS: A total of 540 patients who underwent curative-intent resection for GBC at the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2020 were retrospectively analyzed. Multivariable logistic regression was used to investigate the factors associated with TO. RESULTS: Among 540 patients with GBC who underwent curative-intent resection, 223 patients (41.3%) achieved a TO. The incidence of TO ranged from 19.0% to 51.0% across the study period, with a slightly increasing trend over the study period. The multivariate analysis showed that non-TO was an independent risk factor for prognosis among GBC patients after resection ( P = 0.003). Age ≤60 years ( P = 0.016), total bilirubin (TBIL) level ≤34.1 µmol/L ( P <0.001), well-differentiated tumor ( P = 0.008), no liver involvement ( P <0.001), and T1-2 stage disease ( P = 0.006) were independently associated with achieving a TO for GBC after resection. Before and after propensity score matching (PSM), the overall survival outcomes of non-TO GBC patients who received ACT and those who did not were statistically significant; ACT improved the prognosis of patients in the non-TO group ( P <0.05). CONCLUSION: Achieving a TO is associated with a better long-term prognosis among GBC patients after curative-intent resection, and ACT can improve the prognosis of those with non-TO.

A Bayesian network model to predict neoplastic risk for patients with gallbladder polyps larger than 10 mm based on preoperative ultrasound features.

BACKGROUND: Polyp size of 10 mm is insufficient to discriminate neoplastic and non-neoplastic risk in patients with gallbladder polyps (GPs). The aim of the study is to develop a Bayesian network (BN) prediction model to identify neoplastic polyps and create more precise criteria for surgical indications in patients with GPs lager than 10 mm based on preoperative ultrasound features. METHODS: A BN prediction model was established and validated based on the independent risk variables using data from 759 patients with GPs who underwent cholecystectomy from January 2015 to August 2022 at 11 tertiary hospitals in China. The area under receiver operating characteristic curves (AUCs) were used to evaluate the predictive ability of the BN model and current guidelines, and Delong test was used to compare the AUCs. RESULTS: The mean values of polyp cross-sectional area (CSA), long, and short diameter of neoplastic polyps were higher than those of non-neoplastic polyps (P < 0.0001). Independent neoplastic risk factors for GPs included single polyp, polyp CSA ≥ 85 mm 2, fundus with broad base, and medium echogenicity. The accuracy of the BN model established based on the above independent variables was 81.88% and 82.35% in the training and testing sets, respectively. Delong test also showed that the AUCs of the BN model was better than that of JSHBPS, ESGAR, US-reported, and CCBS in training and testing sets, respectively (P < 0.05). CONCLUSION: A Bayesian network model was accurate and practical for predicting neoplastic risk in patients with gallbladder polyps larger than 10 mm based on preoperative ultrasound features.

The optimal number of examined lymph nodes for accurate staging of intrahepatic cholangiocarcinoma: A multi-institutional analysis using the nodal staging score model.

BACKGROUND: This study aims to develop a nodal staging score (NSS) to determine the optimal number of lymph nodes (LNs) examined in intrahepatic cholangiocarcinoma (iCCA) patients. METHODS: Clinicopathologic data were collected from the SEER database (development cohort, n = 2782) and seven Chinese tertiary hospitals (validation cohort, n = 363). NSS was constructed based on a binomial distribution to indicate the probability of nodal disease absence. In addition, its prognostic value was examined by survival analysis and multivariable modeling on pN0 patients. RESULTS: A model fit was performed in node-positive patients and a subgroup analysis was performed according to clinical characteristics. Statistically significant differences were only found in the subgroups when divided by the tumor size of 3 cm. As the number of examined lymph nodes (ELNs) increased, the likelihood of missing a metastatic LN decreased. NSS escalated as ELNs increased in groups with different tumor sizes, with plateaus at 7 and 11 LNs ensuring an NSS of 90.0% for ≤3 cm and >3 cm tumors, respectively. For pN0 patients, multivariate analysis revealed that NSS was an independent prognostic factor for overall survival (OS) and recurrence-free survival (RFS). CONCLUSIONS: For accurate staging of iCCA, the optimal number of ELNs was related to tumor size. We recommend that at least 7 and 11 LNs should be examined for tumor size ≤3 cm and >3 cm, respectively. Therefore, the NSS model could be helpful to make clinical decisions for pN0 iCCA.

Preoperative Fibrinogen Albumin Ratio is an Effective Biomarker for Prognostic Evaluation of Gallbladder Carcinoma After Radical Resection: A 10-Year Retrospective Study at a Single Center.

Background: To explore and screen preoperative serum immune response level-related biomarkers with better prognostic ability and developed a prognostic model for decision-making in clinical practice for gallbladder carcinoma (GBC) patients. Methods: A total of 427 patients who underwent radical resection for GBC in the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2020 were retrospectively analyzed. Time-dependent receiver operating characteristic (time-ROC) was performed to determine the prognostic predictive power of preoperative biomarkers. A nomogram survival model was established and validated. Results: Time-ROC indicated that the preoperative fibrinogen-to-albumin ratio (FAR) had a better predictive ability for overall survival among preoperative serum immune response level-related biomarkers. Multivariate analysis indicated that FAR was an independent risk factor (P<0.05). The proportion of clinicopathological characteristics of poor prognosis (such as advanced T stage, and N1-2 stage) was significantly higher in high FAR group (P<0.05). Subgroup analyses indicate the prognostic discrimination ability of FAR depended on CA19-9, CA125, liver involvement, major vascular invasion, perineural invasion, T stage, N stage, and TNM stage (all P <0.05). A nomogram model was established based on the prognostic independent risk factors with the C-index of 0.803 (95% CI:0.771~0.835) and 0.774 (95% CI:0.696~0.852) in the training and testing sets, respectively. The decision curve analysis indicated the nomogram model had a better predictive ability than the FAR and TNM staging system in the training and testing sets. Conclusion: Preoperative serum FAR has a better predictive ability for overall survival among preoperative serum immune response level-related biomarkers, and it can be used for survival assessment of GBC and guide clinical decision-making.

A Bayesian Network Prediction Model for Microvascular Invasion in Patients with Intrahepatic Cholangiocarcinoma: A Multi-institutional Study.

BACKGROUND: Microvascular invasion (MVI) has been reported to be an independent prognostic factor of recurrence and poor overall survival in patients with intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the preoperative independent risk factors of MVI and establish a Bayesian network (BN) prediction model to provide a reference for surgical diagnosis and treatment. METHODS: A total of 531 patients with ICC who underwent radical resection between 2010 and 2018 were used to establish and validate a BN model for MVI. The BN model was established based on the preoperative independent variables. The ROC curves and confusion matrix were used to assess the performance of the model. RESULTS: MVI was an independent risk factor for relapse-free survival (RFS) (P < 0.05). MVI has a correlation with postoperative recurrence, early recurrence (< 6 months), median RFS and median overall survival (all P < 0.05). The preoperative independent risk variables of MVI included obstructive jaundice, prognostic nutritional index, CA19-9, tumor size, and major vascular invasion, which were used to establish the BN model. The AUC of the BN model was 78.92% and 83.01%, and the accuracy was 70.85% and 77.06% in the training set and testing set, respectively. CONCLUSION: The BN model established based on five independent risk variables for MVI is an effective and practical model for predicting MVI in patients with ICC.

Magnetic anchor technique in laparoscopic cholecystectomy: a single-center, prospective, randomized controlled trial.

BACKGROUND: There have been no prospective randomized controlled clinical trials evaluating the advantages of the magnetic anchor technique (MAT) used in reduced-port laparoscopic cholecystectomy (LC). The present study evaluated a novel magnetic anchor device designed by the authors. METHODS: Between April 2019 and June 2020, 60 patients with gallbladder diseases participated in a single-center, prospective, randomized controlled clinical trial. The patients were randomly apportioned to undergo either 2-port LC assisted by the novel MAT (MAT-2P-LC, experimental group) or conventional 3-port LC (3P-LC, control). The groups were compared regarding operative time, postoperative complications, surgical incision pain score (Wong-Baker), and other indicators. The patients were followed for 2 years. RESULTS: The test and control groups were comparable in age, gender, body mass index, and primary disease. No patient in the MAT-2P-LC group was converted to 3P-LC. No patients were converted to laparotomy. On the first postoperative day, the Wong-Baker pain score of the experimental group (1.60 ± 0.67) was significantly lower than that of the control (2.20 ± 0.76; P = 0.002). The groups were statistically similar regarding intraoperative blood loss; operative time; time to leave bed; hospital stay; postoperative pain scores at 1 and 4 weeks; and complications. CONCLUSIONS: This rigorous clinical trial shows that the novel MAT used to assist reduced-port LC significantly reduced postoperative pain, but has no obvious advantages in other terms. Clinical Trails.gov. number, ChiCTR1800019464.

A Bayesian network prediction model for gallbladder polyps with malignant potential based on preoperative ultrasound.

BACKGROUND: It is important to identify gallbladder polyps (GPs) with malignant potential and avoid unnecessary cholecystectomy by constructing prediction model. The aim of the study is to develop a Bayesian network (BN) prediction model for GPs with malignant potential in a long diameter of 8-15 mm based on preoperative ultrasound. METHODS: The independent risk factors for GPs with malignant potential were screened by χ2 test and Logistic regression model. Prediction model was established and validated using data from 1296 patients with GPs who underwent cholecystectomy from January 2015 to December 2019 at 11 tertiary hospitals in China. A BN model was established based on the independent risk variables. RESULTS: Independent risk factors for GPs with malignant potential included age, number of polyps, polyp size (long diameter), polyp size (short diameter), and fundus. The BN prediction model identified relationships between polyp size (long diameter) and three other variables [polyp size (short diameter), fundus and number of polyps]. Each variable was assigned scores under different status and the probabilities of GPs with malignant potential were classified as [0-0.2), [0.2-0.5), [0.5-0.8) and [0.8-1] according to the total points of [- 337, - 234], [- 197, - 145], [- 123, - 108], and [- 62,500], respectively. The AUC was 77.38% and 75.13%, and the model accuracy was 75.58% and 80.47% for the BN model in the training set and testing set, respectively. CONCLUSION: A BN prediction model was accurate and practical for predicting GPs with malignant potential patients in a long diameter of 8-15 mm undergoing cholecystectomy based on preoperative ultrasound.

Prognostic value of lymphadenectomy in node-negative intrahepatic cholangiocarcinoma: A multicenter, retrospectively study.

BACKGROUND: This study aimed to evaluate the prognostic value of lymph node dissection (LND) in node-negative intrahepatic cholangiocarcinoma (ICC) and identify the appropriately total number of lymph nodes examined (TNLE). METHODS: Data from node-negative ICC patients who underwent curative intent resection in ten Chinese hepatobiliary centers from January 2010 to December 2018 were collected. Overall survival (OS), relapse-free survival (RFS) and postoperative complications were analyzed. Propensity score matching (PSM) was performed to reduce the bias due to confounding variables in LND group and non-lymph node dissection (NLND) group. The optimal TNLE was determined by survival analysis performed by the X-tile program using the enumeration method. RESULTS: A total of 637 clinically node-negative ICC patients were included in this study, 74 cases were found lymph node (LN) positive after operation. Among the remaining 563 node-negative ICC patients, LND was associated with longer OS but not RFS before PSM (OS: 35.4 vs 26.0 months, p = 0.047; RFS: 15.0 vs 15.4 months, p = 0.992). After PSM, patients in LND group had better prognosis on both OS and RFS (OS: 38.0 vs 23.0 months, p < 0.001; RFS: 15.0 vs 13.0 months, p = 0.029). There were no statistically differences in postoperative complications. When TNLE was greater than 8, OS (48.5 vs 31.1 months, p = 0.025) and RFS (21.0 vs 13.0 months, p = 0.043) were longer in the group with more dissected LNs. CONCLUSION: Routinely LND for node-negative ICC patients is recommended for it helps accurate tumor staging and associates with better prognosis. The optimal TNLE is more than 8.

Similarities and differences between MIS-C and KD: a systematic review and meta-analysis.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a new syndrome with some clinical manifestations similar to Kawasaki disease (KD), which is difficult to distinguish. OBJECTIVE: The study aimed to characterize the demographic characteristics, clinical characteristics, laboratory features, cardiac complications, and treatment of MIS-C compared with KD. STUDY DESIGN: Studies were selected by searching the PubMed, EMBASE and so on before February 28, 2022. Statistical analyses were performed using Review Manager 5.4 software and STATA 14.0. RESULTS: Fourteen studies with 2928 participants were included. MIS-C patients tended to be older and there was no significant difference in the sex ratio. In terms of clinical characteristics, MIS-C patients were more frequently represented with respiratory, gastrointestinal symptoms and shock. At the same time, they had a lower incidence of conjunctivitis than KD patients. MIS-C patients had lower lymphocyte counts, platelet (PLT) counts, erythrocyte sedimentation rates (ESRs), alanine transaminase (ALT), and albumin levels and had higher levels of aspartate transaminase (AST), N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), troponin, C-reactive protein (CRP), D-dimer, fibrinogen, ferritin, and creatinine. MIS-C patients had a higher incidence of left ventricle (LV) dysfunction, valvular regurgitation, pericardial effusion, myocarditis, and pericarditis. The incidence of coronary artery lesion (CAL) was lower in MIS-C patients [OR (95% CI): 0.52 (0.29, 0.93), p =0.03], while it was similar in the acute period. MIS-C patients had higher utilization of glucocorticoids (GCs) and lower utilization of intravenous immune globulin (IVIG). CONCLUSIONS: There were specific differences between MIS-C and KD, which might assist clinicians with the accurate recognition of MIS-C and further mechanistic research.

A Nomogram Model to Predict Early Recurrence of Patients With Intrahepatic Cholangiocarcinoma for Adjuvant Chemotherapy Guidance: A Multi-Institutional Analysis.

Background: The influence of different postoperative recurrence times on the efficacy of adjuvant chemotherapy (ACT) for intrahepatic cholangiocarcinoma (ICC) remains unclear. This study aimed to investigate the independent risk factors and establish a nomogram prediction model of early recurrence (recurrence within 1 year) to screen patients with ICC for ACT. Methods: Data from 310 ICC patients who underwent radical resection between 2010 and 2018 at eight Chinese tertiary hospitals were used to analyze the risk factors and establish a nomogram model to predict early recurrence. External validation was conducted on 134 patients at the other two Chinese tertiary hospitals. Overall survival (OS) and relapse-free survival (RFS) were estimated by the Kaplan-Meier method. Multivariate analysis was conducted to identify independent risk factors for prognosis. A logistic regression model was used to screen independent risk variables for early recurrence. A nomogram model was established based on the above independent risk variables to predict early recurrence. Results: ACT was a prognostic factor and an independent affecting factor for OS and RFS of patients with ICC after radical resection (p < 0.01). The median OS of ICC patients with non-ACT and ACT was 14.0 and 15.0 months, and the median RFS was 6.0 and 8.0 months for the early recurrence group, respectively (p > 0.05). While the median OS of ICC patients with non-ACT and ACT was 41.0 and 84.0 months, the median RFS was 20.0 and 45.0 months for the late recurrence group, respectively (p < 0.01). CA19-9, tumor size, major vascular invasion, microvascular invasion, and N stage were the independent risk factors of early recurrence for ICC patients after radical resection. The C-index of the nomogram was 0.777 (95% CI: 0.713~0.841) and 0.716 (95%CI: 0.604~0.828) in the training and testing sets, respectively. Conclusion: The nomogram model established based on the independent risk variables of early recurrence for curatively resected ICC patients has a good prediction ability and can be used to screen patients who benefited from ACT.

Recurrence and prognosis in intrahepatic cholangiocarcinoma patients with different etiology after radical resection: a multi-institutional study.

OBJECTIVE: We aimed to evaluate the prognosis and adjuvant chemotherapy (ACT) in intrahepatic cholangiocarcinoma (ICC) patients with different etiology after radical resection. METHODS: A total of 448 patients with ICC who underwent radical resection between 2010 and 2018 at ten Chinese tertiary hospitals were analyzed in the study. These patients were divided into conventional ICC (Con-ICC, n = 261, 58.2%), hepatitis B virus ICC (HBV-ICC, n = 102, 22.8%) and hepatolithiasis (Stone-ICC, n = 85,19.0%) subtypes according to different etiology. Propensity score matching (PSM) was conducted to mitigate the baseline differences between Con-ICC and HBV-ICC, Con-ICC and Stone-ICC, HBV-ICC and Stone-ICC subtypes. RESULTS: Univariate and multivariate analysis showed that different etiology was a prognostic factor for overall survival and relapse-free survival, and different etiology was an independent risk factor for overall survival in ICC patients, respectively (P < 0.05). In addition, there was a statistical difference for overall survival in early recurrence patients among the three etiological subtypes (P < 0.05). After PSM, the overall survival of patients with Stone-ICC was worse than those of Con-ICC and HBV-ICC subtypes (P < 0.05), while the relapse-free survival of patients with Stone-ICC was equivalent to patients with Con-ICC and HBV-ICC (P > 0.05). In Stone-ICC patients, the median overall survival was 16.0 months and 29.7 months, and the median relapse-free survival was 9.0 months and 20.0 months for non-ACT and ACT patients, respectively (P < 0.05). CONCLUSION: The prognosis of Stone-ICC patients was significantly worse than those of Con-ICC and HBV-ICC patients. Interestingly, postoperative adjuvant chemotherapy can improve the prognosis of Stone-ICC patients effectively.

Prediction Efficacy of Prognostic Nutritional Index and Albumin-Bilirubin Grade in Patients With Intrahepatic Cholangiocarcinoma After Radical Resection: A Multi-Institutional Analysis of 535 Patients.

BACKGROUND: The preoperative nutritional status and the immunological status have been reported to be independent prognostic factors of patients with intrahepatic cholangiocarcinoma (ICC). This study aimed to investigate whether prognostic nutritional index (PNI) + albumin-bilirubin (ALBI) could be a better predictor than PNI and ALBI alone in patients with ICC after radical resection. METHODS: The prognostic prediction evaluation of the PNI, ALBI, and the PNI+ALBI grade was performed in 373 patients with ICC who underwent radical resection between 2010 and 2018 at six Chinese tertiary hospitals, and external validation was conducted in 162 patients at four other Chinese tertiary hospitals. Overall survival (OS) and relapse-free survival (RFS) were estimated using the Kaplan-Meier method. Multivariate analysis was conducted to identify independent prognostic factors. A time-dependent receiver operating characteristic (ROC) curve and a nomogram prediction model were further constructed to assess the predictive ability of PNI, ALBI, and the PNI+ALBI grade. The C-index and a calibration plot were used to assess the performance of the nomogram models. RESULTS: Univariate analysis showed that PNI, ALBI, and the PNI+ALBI grade were prognostic factors for the OS and RFS of patients with ICC after radical resection in the training and testing sets (p < 0.001). Multivariate analysis showed that the PNI+ALBI grade was an independent risk factor for OS and RFS in the training and testing sets (p < 0.001). Analysis of the relationship between the PNI+ALBI grade and clinicopathological characteristics showed that the PNI+ALBI grade correlated with obstructive jaundice, alpha-fetoprotein (AFP), cancer antigen 19-9 (CA19-9), cancer antigen 125 (CA125), PNI, ALBI, Child-Pugh grade, type of resection, tumor size, major vascular invasion, microvascular invasion, T stage, and N stage (p < 0.05). The time-dependent ROC curves showed that the PNI+ALBI grade had better prognostic predictive ability than the PNI, ALBI, and the Child-Pugh grade in the training and testing sets. CONCLUSION: Preoperative PNI+ALBI grade is an effective and practical predictor for the OS and RFS of patients with ICC after radical resection.

External Validation of Six Liver Functional Reserve Models to predict Posthepatectomy Liver Failure after Major Resection for Hepatocellular Carcinoma.

Objective: To validate and compare the predictive ability of albumin-bilirubin model (ALBI) with other 5 liver functional reserve models (APRI, FIB4, MELD, PALBI, King's score) for posthepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC) who underwent major hepatectomy. Methods: Data of patients undergoing major hepatectomy for HCC from 4 hospitals between January 01, 2008 and December 31, 2019 were retrospectively analyzed. PHLF was evaluated according to the definition of the 50-50 criteria. Performances of six liver functional reserve models were determined by the area under the receiver operating characteristic curve (AUC), calibration plot and decision curve analysis. Results: A total of 745 patients with 103 (13.8%) experienced PHLF were finally included in this study. Among six liver functional reserve models, ALBI showed the highest AUC (0.64, 95% CI: 0.58-0.69) for PHLF. All models showed good calibration and greater net benefit than treating all patients at a limit range of threshold probabilities, but the ALBI demonstrated net benefit across the largest range of threshold probabilities. Subgroup analysis also showed ALBI had good predictive performance in cirrhotic (AUC=0.63) or non-cirrhotic (AUC=0.62) patients. Conclusion: Among the six models, the ALBI model shows more accurate predictive ability for PHLF in HCC patients undergoing major hepatectomy, regardless of having cirrhosis or not.

Establishment of a nomogram prediction model for long diameter 10-15 mm gallbladder polyps with malignant tendency.

BACKGROUND: Surgical indications for the treatment of gallbladder polyps are controversial. Evaluation of gallbladder polyps with malignant tendency and indications for cholecystectomy in patients with long diameter polyps of 10 to 15 mm require further analysis and discussion. In this study, our objective was to re-evaluate indications for the surgical resection of gallbladder polyps and construct a nomogram model for the prediction of gallbladder polyps with malignant tendency. METHODS: Clinicopathologic data of 2,272 patients who had undergone cholecystectomy for gallbladder polyps were collected from 11 medical centers in China. Risk factor analyses and nomogram prediction model for gallbladder polyps with malignant tendency were conducted. RESULTS: Excluding 311 patients with cholelithiasis and 488 patients with long diameter polyps ≤5 and >15 mm, factors that differed significantly among patients with gallbladder polyps having a long diameter of 6 to 9 mm (885 cases) and 10 to 15 mm (588 cases) were polyp detection time, CEA and CA19-9 levels, number of polyps, fundus, echogenicity, gallbladder wall thickness and postoperative pathologic features (P < .05). Among 588 patients with gallbladder polyps with a long diameter of 10 of 15 mm, multivariate analysis indicated the following independent risk factors of gallbladder polyps with malignant tendency: single polyps (OR = 0.286/P < .001), polyps with broad base (OR = 2.644/P = .001), polyps with medium/low echogenicity (OR = 2.387/P = .003), and polyps with short diameter of 7 to 9 or 10 to 15 mm (OR = 3.820/P = .005; OR = 2.220/P = .048, respectively). The C-index of the nomogram model and internal validation were .778 and .768, respectively. In addition, a sample online calculator for the nomogram prediction model had been created (https://docliqi.shinyapps.io/dynnom/). CONCLUSION: Indications for cholecystectomy in patients with gallbladder polyps with a long diameter of 10 to 15 mm should be assessed by combining the information on short diameter, number of polyps, fundus, and echogenicity. The nomogram model can be used to predict the risk for the development of gallbladder polyps with malignant tendency.

Altered Monocyte Subsets in Kawasaki Disease Revealed by Single-cell RNA-Sequencing.

BACKGROUND: Kawasaki disease (KD) is characterized by a disorder of immune response, and its etiology remains unknown. Monocyte is an important member of the body's innate immune system; however its role in KD is still elusive due to its ambiguous heterogeneity and complex functions. We aim to comprehensively delineate monocyte heterogeneity in healthy and KD infants and to reveal the underlying mechanism for KD. METHODS: Peripheral monocytes were enriched from peripheral blood samples of two healthy infants and two KD infants. scRNA-seq was performed to acquire the transcriptomic atlas of monocytes. Bio-information analysis was utilized to identify monocyte subsets and explore their functions and differentiation states. SELL+CD14+CD16- monocytes were validated using flow cytometry. RESULTS: Three monocyte subsets were identified in healthy infants, including CD14+CD16- monocytes, CD14+CD16+ monocytes, and CD14LowCD16+ monocytes. Cell trajectory analysis revealed that the three monocyte subsets represent a linear differentiation, and possess different biological functions. Furthermore, SELL+CD14+CD16- monocytes, which were poorly differentiated and relating to neutrophil activation, were found to be expanded in KD. CONCLUSION: Our findings provide a valuable resource for deciphering the monocyte heterogeneity in healthy infants and uncover the altered monocyte subsets in KD patients, suggesting potential biomarkers for KD diagnosis and treatment.

KCa3.1 Inhibition of Macrophages Suppresses Inflammatory Response Leading to Endothelial Damage in a Cell Model of Kawasaki Disease.

PURPOSE: Macrophages-mediated inflammation is linked with endothelial damage of Kawasaki disease (KD). KCa3.1, a calcium-activated potassium channel, modulates inflammation of macrophages. However, little is known about the role of KCa3.1 in inflammation by macrophages involved in KD. Hence, this study is aimed to explore the potential role of KCa3.1 in regulating inflammatory response by macrophages and subsequent vascular injury in an in vitro model of KD. METHODS: RAW264.7 cells were stimulated with Lactobacillus casei cell wall extract (LCWE) with or without TRAM-34 or PDTC or AG490. Subsequently, mouse coronary artery endothelial cells (MCAECs) were incubated with RAW264.7 cells-conditioned medium to mimic local inflammatory lesions in KD. CCKi8 assay was used to evaluate cell viability. The mRNA levels of inflammatory mediators were detected by qRT-PCR. Expressions of KCa3.1, MCAECs injury-associated molecules, proteins involved in signal pathways of nuclear factor-κB (NF-κB), signal transducers and activators of transcription (STAT) 3 and p38 were evaluated by Western blot. RESULTS: Our study showed that LCWE increased KCa3.1 protein level in RAW264.7 macrophages and KCa3.1 inhibition by TRAM-34 notably suppressed the expression of pro-inflammatory molecules in LCWE-treated macrophages via blocking the activation of NF-κB and STAT3 pathways. Besides, the inflammation and damage of MCAECs were attenuated in the TRAM-34-treated group compared with the KD model group. This vascular protective role was dependent on the down-regulation of NF-κB and STAT3 signal pathways, which was confirmed by using inhibitors of NF-κB and STAT3. CONCLUSION: This study demonstrates that KCa3.1 blockade of macrophages suppresses inflammatory reaction leading to mouse coronary artery endothelial cell injury in a cell model of KD by hampering the activation of NF-κB and STAT3 signaling pathway. These findings imply that KCa3.1 may be a potential therapeutic target for KD.

Comprehensive analysis of genomic mutation signature and tumor mutation burden for prognosis of intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal malignancy of the biliary tract. Analysis of somatic mutational profiling can reveal new prognostic markers and actionable treatment targets. In this study, we explored the utility of genomic mutation signature and tumor mutation burden (TMB) in predicting prognosis in iCCA patients. METHODS: Whole-exome sequencing and corresponding clinical data were collected from the ICGC portal and cBioPortal database to detect the prognostic mutated genes and determine TMB values. To identify the hub prognostic mutant signature, we used Cox regression and Lasso feature selection. Mutation-related signature (MRS) was constructed using multivariate Cox regression. The predictive performances of MRS and TMB were assessed using Kaplan-Meier (KM) analysis and receiver operating characteristic (ROC). We performed a functional enrichment pathway analysis using gene set enrichment analysis (GSEA) for mutated genes. Based on the MRS, TMB, and the TNM stage, a nomogram was constructed to visualize prognosis in iCCA patients. RESULTS: The mutation landscape illustrated distributions of mutation frequencies and types in iCCA, and generated a list of most frequently mutated genes (such as Tp53, KRAS, ARID1A, and IDH1). Thirty-two mutated genes associated with overall survival (OS) were identified in iCCA patients. We obtained a six-gene signature using the Lasso and Cox method. AUCs for the MRS in the prediction of 1-, 3-, and 5-year OS were 0.759, 0.732, and 0.728, respectively. Kaplan-Meier analysis showed a significant difference in prognosis for patients with iCCA having a high and low MRS score (P < 0.001). GSEA was used to show that several signaling pathways, including MAPK, PI3K-AKT, and proteoglycan, were involved in cancer. Conversely, survival analysis indicated that TMB was significantly associated with prognosis. GSEA indicated that samples with high MRS or TMB also showed an upregulated expression of pathways involved in tumor signaling and the immune response. Finally, the predictive nomogram (that included MRS, TMB, and the TNM stage) demonstrated satisfactory performance in predicting survival in patients with iCCA. CONCLUSIONS: Mutation-related signature and TMB were associated with prognosis in patients with iCCA. Our study provides a valuable prognostic predictor for determining outcomes in patients with iCCA.