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Background It remains unclear whether intensification of the chemotherapy backbone in tandem with an anti-EGFR can confer superior clinical outcomes in a cohort of RAS/BRAF wild-type colorectal cancer (CRC) patients with initially unresectable colorectal liver metastases (CRLM). To that end, we sought to comparatively evaluate the efficacy and safety of cetuximab plus FOLFOXIRI (triplet arm) versus cetuximab plus FOLFOX (doublet arm) as a conversion regimen (i.e., unresectable to resectable) in CRC patients with unresectable CRLM. Methods and findings This open-label, randomized clinical trial was conducted from April 2018 to December 2022 in 7 medical centers across China, enrolling 146 RAS/BRAF wild-type CRC patients with initially unresectable CRLM. A stratified blocked randomization method was utilized to assign patients (1:1) to either the cetuximab plus FOLFOXIRI (n = 72) or cetuximab plus FOLFOX (n = 74) treatment arms. Stratification factors were tumor location (left versus right) and resectability (technically unresectable versus [greater than or equal to]5 metastases). The primary outcome was the objective response rate (ORR). Secondary outcomes included the median depth of tumor response (DpR), early tumor shrinkage (ETS), R0 resection rate, progression-free survival (PFS), overall survival (not mature at the time of analysis), and safety profile. Radiological tumor evaluations were conducted by radiologists blinded to the group allocation. Primary efficacy analyses were conducted based on the intention-to-treat population, while safety analyses were performed on patients who received at least 1 line of chemotherapy. A total of 14 patients (9.6%) were lost to follow-up (9 in the doublet arm and 5 in the triplet arm). The ORR was comparable following adjustment for stratification factors, with 84.7% versus 79.7% in the triplet and doublet arms, respectively (odds ratio [OR] 0.70; 95% confidence intervals [CI] [0.30, 1.67], Chi-square p = 0.42). Moreover, the ETS rate showed no significant difference between the triplet and doublet arms (80.6% (58/72) versus 77.0% (57/74), OR 0.82, 95% CI [0.37, 1.83], Chi-square p = 0.63). Although median DpR was higher in the triplet therapy group (59.6%, interquartile range [IQR], [50.0, 69.7] versus 55.0%, IQR [42.8, 63.8], Mann-Whitney p = 0.039), the R0/R1 resection rate with or without radiofrequency ablation/stereotactic body radiation therapy was comparable with 54.2% (39/72) of patients in the triplet arm versus 52.7% (39/74) in the doublet arm. At a median follow-up of 26.2 months (IQR [12.8, 40.5]), the median PFS was 11.8 months in the triplet arm versus 13.4 months in the doublet arm (hazard ratio [HR] 0.74, 95% CI [0.50, 1.11], Log-rank p = 0.14). Grade [greater than or equal to] 3 events were reported in 47.2% (35/74) of patients in the doublet arm and 55.9% (38/68) of patients in the triplet arm. The triplet arm was associated with a higher incidence of grade [greater than or equal to] 3 neutropenia (44.1% versus 27.0%, p = 0.03) and diarrhea (5.9% versus 0%, p = 0.03). The primary limitations of the study encompass the inherent bias in subjective surgical decisions regarding resection feasibility, as well as the lack of a centralized assessment for ORR and resection. Conclusions The combination of cetuximab with FOLFOXIRI did not significantly improve ORR compared to cetuximab plus FOLFOX. Despite achieving an enhanced DpR, this improvement did not translate into improved R0 resection rates or PFS. Moreover, the triplet arm was associated with an increase in treatment-related toxicity. Trial Registration ClinicalTrials.gov Identifier: NCT03493048., Author(s): De-Shen Wang 1, Chao Ren 1, Shan-Shan Li 2, William Pat Fong 1, Xiao-Jun Wu 3, Jian Xiao 2,4, Bin-Kui Li 5, Yun Zheng 5, Pei-Rong Ding 3, Gong [...]

C21H16I N3O2, monoclinic, P21/c (no. 14), a = 12.7439(9) Å, b = 11.8391(8) Å, c = 13.4459(7) Å, β = 99.803(5)°, V = 1999.0(2) Å3, Z = 4, R gt(F) = 0.0365, wR ref(F 2) = 0.0905, T = 293(2) K.

Objective: The study aimed to investigate the correlation between metabolic dysfunctionassociated fatty liver disease and liver fibrosis based on Fibrotouch. Methods: During the years 2015-2018, a total of 401 patients with fatty liver diagnosed by imaging and met the diagnostic criteria of MAFLD, examined by transient elastography (TE) were enrolled in the Department of Hepatology of the Traditional Chinese Medical Hospital Affiliated to Xinjiang Medical University. The patients were classified into 4 MAFLD subgroups: MAFLD lean/normal weight group (n=25), MAFLD overweight group (n=52), MAFLD obese group (n=249) and MAFLD diabetic (MAFLD-DM) group (n=75), according to their body mass index (BMI) with or without diabetes mellitus (DM). Fasting plasma glucose (FPG), glycated hemoglobin A1c (HbA1c), liver and kidney function, blood lipid, routine blood test, liver stiffness value (LSM), controlled attenuation parameter (CAP) and so on, were collected. A variety of noninvasive hepatic fibrosis indexes such as NAFLD fibrosis score (NFS), aspartate aminotransferase (AST) to platelet (PLT) ratio index (APRI), diabetes score (BARD) and fibros-4 index (FIB-4) were used to evaluate the risk of hepatic fibrosis, comparing the general information, biochemical indicators and non-invasive liver fibrosis indicators among them. Whether accompanied with liver fibrosis or not. The patients were divided into MAFLD group and MAFLD liver fibrosis group Univariate analysis and multivariate Logsitics regression analysis were performed to analyze the correlation between MAFLD and liver fibrosis. Results: Systolic blood pressure (SBP), diastolic blood pressure (DBP), PLT, AST, alanyl aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), albumin (A lb), APRI, FIB-4, hyperlipidemia, history of lipid-regulating drugs, and history of viral hepatitis (hepatitis B and hepatitis C) were not statistically significant. Age, sex, body mass index (BMI), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), creatinine (Cr), uric acid (UA), FPG, HbA1c, NFS score, BARD score, LSM, CAP, diabetes mellitus, hypoglycemic or antihypertensive drug use history, drinking history, smoking history were statistically significant. The proportion of significant and advanced liver fibrosis in MAFLDobese group and MAFLD-DM group was significantly higher than other two groups. Increased BMI, CAP, and APRI scores were associated with an increased risk of liver fibrosis in MAFLD by univariate and multivariate analyses. Conclusion: BMI, CAP and APRI score are risk factors for the progression of liver fibrosis in MAFLD. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the diagnostic efficacy of chronic viral hepatitis B (CHB) with significant liver fibrosis (S2) in patients with nonalcoholic fatty liver disease (NAFLD) by using noninvasive diagnosis and their combined models, and to explore their clinical features. Methods: A total of 104 inpatients with CHB diagnosed and complicated with NAFLD (hepatic steatosis suggested by liver biopsy) were retrospectively collected from January 2018 to January 2023 in the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University. Liver biopsy was performed in all patients. General data, laboratory test results, liver hardness (LSM), FIB-4, APRI, GGT/PLT, AST/PLT and other results of patients were collected and grouped according to different fibrosis stages (S) to explore the clinical and pathological characteristics of patients with