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Obesity is a global health concern and independent risk factor for cancers including hepatocellular carcinoma (HCC). However, evidence on the causal links between obesity and HCC is limited and inconclusive. This study aimed to investigate the causal relationship between obesity-related traits and HCC risk and explore underlying mechanisms using bioinformatics approaches. Two-sample Mendelian randomization analysis was conducted leveraging publicly available genome-wide association study summary data on obesity traits (body mass index, body fat percentage, waist circumference, waist-to-hip ratio, visceral adipose tissue volume) and HCC. Associations of obesity with primary mechanisms (insulin resistance, adipokines, inflammation) and their effects on HCC were examined. Differentially expressed genes in obesity and HCC were identified and functional enrichment analyses were performed. Correlations with tumor microenvironment (TME) and immunotherapy markers were analyzed. Genetically predicted higher body mass index and body fat percentage showed significant causal relationships with increased HCC risk. Overall obesity also demonstrated causal links with insulin resistance, circulating leptin levels, C-reactive protein levels and risk of severe insulin resistant type 2 diabetes. Four differentially expressed genes (ESR1, GCDH, FAHD2A, DCXR) were common in obesity and HCC. Enrichment analyses indicated their roles in processes like RNA capping, viral transcription, IL-17 signaling and endocrine resistance. They exhibited negative correlations with immune cell infiltration and immunotherapy markers in HCC. Overall obesity likely has a causal effect on HCC risk in Europeans, possibly via influencing primary mechanisms. The identified differentially expressed genes may be implicated in obesity-induced hepatocarcinogenesis through regulating cell cycle, inflammation and immune evasion. Further research on precise mechanisms is warranted. [ABSTRACT FROM AUTHOR]

Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).Results: In this study, treatment with a combination of anti-PD-1 antibody and GnP regimen for pancreatic cancer resulted in partial response (PR) for 10 out of 27 (37.04%) patients, stable disease (SD) for 10 (37.04%) patients, and progressive disease (PD) for 7 (25.92%) patients. The study found that the median OS (mOS) for these patients was 16.4 months [standard error (SE) = 1.117, 95% confidence interval (CI) 14.211– 18.589], while the median PFS (mPFS) was 6.4 months (SE = 1.217, 95% CI 3.981– 8.752). Subgroup analysis revealed that pancreatic cancer patients' Eastern Cooperative Oncology Group (ECOG) performance status (PS) (0 vs 1) and treatment cycles (≤ 6 cycles vs > 6 cycles) significantly affected OS and PFS. Patients experienced mostly grade 1– 2 adverse events (AEs), which were relieved through clinical treatment.Conclusion: The combination of GnP with anti-PD-1 antibodies shows promise as a potential treatment option for advanced pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background: ABO-incompatible liver transplantation (ABOi LT) under the desensitization protocol with rituximab had excellent survival outcomes comparable to those of ABO-compatible liver transplantation (ABOc LT). In this work, we explored the effect of ABOi LT on recipients from the perspective of biliary microbiota and metabonomics. Methods: Liver transplant (LT) recipients treated at our center were enrolled in the study. In total, 6 ABOi LT recipients and 12 ABOc LT recipients were enrolled, and we collected their bile five times (during LT and at 2 days, 1 week, 2 weeks and 1 month after LT). The collected samples were used for 16S ribosomal RNA sequencing and liquid chromatography mass spectrometry analysis. Results: We obtained 90 bile samples. Whether in group ABOi LT or ABOc LT, the most common phyla in all of the samples were Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria. The most common genera were Lactobacillus, Weissella, Klebsiella, Pantoea and Lactococcus. There was no significant difference in the diversity between the two groups at 1 week, 2 weeks and 1 month after LT. However, the biggest disparities between the ABOi LT recipients and ABOc LT recipients were observed 2 days after LT, including increased biodiversity with a higher ACE, Chao1, OBS and Shannon index (p < 0.05), and more Staphylococcus in ABOi LT and binary–Jaccard dissimilarity, which indicated varying β-diversity (p = 0.046). These differences were not observed at 1 week, 2 weeks and 1 month after LT. The principal coordinate analysis (PCoA) revealed that the composition of the bile microbiota did not change significantly within 1 month after LT by longitudinal comparison. In an analysis of the bile components, the metabolites were not significantly different every time. However, four enrichment KEGG pathways were observed among the groups. Conclusion: These findings suggest that ABOi LT under the desensitization protocol with rituximab did not significantly affect the biliary microbiota and metabolites of recipients. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to assess how pre‐transplant dialysis duration affects transplant outcomes after simultaneous pancreas‐kidney transplant (SPK) in patients with type 1 diabetes mellitus (T1DM). Methods: Data of 6887 T1DM patients who underwent SPK transplantation between 2008 and 2018 were obtained from the Scientific Registry of Transplant Recipients database. According to pre‐transplant dialysis duration, the patients were divided into the preemptive SPK, 0‐2 years, 2‐5 years, and >5 years dialysis groups. Kaplan‐Meier survival analysis was performed to compare patient and graft survival among the groups. Univariate and multivariate Cox regression analyses were used to identify predictors of transplant outcomes. Results: The mean follow‐up period was 56.7 ± 34.7 months. Compared with no dialysis or preemptive SPK, dialysis for 0‐2 years was not significantly associated with patient or kidney graft survival, while long‐term dialysis of 2‐5 years and >5 years was significantly associated with increased risk of death and kidney graft failure. However, the duration of dialysis was not associated with pancreas graft survival. Conclusion: Long‐term dialysis duration before SPK transplant is an independent predictor of patient death and kidney graft failure in T1DM patients. [ABSTRACT FROM AUTHOR]

Background: Primary hyperoxaluria (PH) is an inherited disease lacking of hepatic oxalic acid metabolic enzymes which could lead to irreverisible renal damage. Currently, liver-kidney transplantation is a curative but highly invasive therapy used to treat patients with PH. However, limited studies have focused on combined liver-kidney transplantation (CLKT) and sequential liver and kidney transplantation (SLKT) in patients with PH.Methods: The present study included 201 patients with PH who received both liver and kidney transplants and who were listed on the Scientific Registry of Transplant Recipients from 1987 to 2018. According to the liver-kidney transplant procedure, patients were separated into a CLKT group and a SLKT group. Patient demographics and transplant outcomes were assessed in each group.Results: Compared with the SLKT group, The CLKT group got a worse pretransplant dialysis condition in both the proportion of patients under pretransplant dialysis (p = 0.048) and the duration of the pretransplant dialysis (p < 0.001). The SLKT group got higher human leukocyte antigen mismatch score of kidney donor (p < 0.001) and liver donor (p = 0.003). The CLKT group utilized higher proportion (98.9%) of organs from a single deceased donor, while the SLKT group utilized 75.0% of organs from deceased liver donors and only 35.0% of organs from deceased kidney donors (p < 0.001). Kidney function measured by serum creatinine concentration before liver transplantation (LT) or CLKT was similar (p = 0.305) between groups. Patient survival was not significantly different between the two groups (p = 0.717) and liver (p = 0.685) and kidney (p = 0.464) graft outcomes were comparable between the two groups.Conclusions: SLKT seems to be an alternative option with strict condition for CLKT, further exploration about the SLKT is still required. [ABSTRACT FROM AUTHOR]

Background: There are no multicenter studies on the influence of diabetes duration on pancreatic transplant outcomes. Our study aimed to determine how type 1 diabetes duration influenced survival of pancreatic grafts. Methods: The data of 8,139 patients who received pancreas transplants during 2006–2015 were extracted from the Scientific Registry of Transplant Recipients database. Patients were separated into two groups according to duration of diabetes: S group (diabetes ≤20 years) and L group (>20 years). Results: Compared to S group, L group were older and prone to be male, to have higher body mass index, to receive pancreas after kidney transplantation (PAK), and to be White. Patient survival was not significantly different between the two groups, but pancreatic survival was better in the L group (hazard ratio 0.88; P = 0.012). Pancreatic survival of L group was better than S group in pancreas transplant alone and simultaneous pancreas‐kidney transplantation (SPK). Graft survival was not significant different between the two groups in PAK. Diabetes duration was an independent predictor of graft survival in SPK patients (hazard ratio 0.86; P = 0.012). Conclusions: Diabetes duration has no influence on patient survival. However, long duration of type 1 diabetes mellitus appears to be protective against pancreatic graft loss. [ABSTRACT FROM AUTHOR]