Comprehensive analysis of the association between inflammation indexes and complications in patients undergoing pancreaticoduodenectomy

BackgroundDuring clinical practice, routine blood tests are commonly performed following pancreaticoduodenectomy (PD). However, the relationship between blood cell counts, inflammation-related indices, and postoperative complications remains unclear.MethodWe conducted a retrospective study, including patients who underwent PD from October 2018 to July 2023 at the First Hospital of Chongqing Medical University, and compared baseline characteristics and clinical outcomes among different groups. Neutrophil count (NC), platelet count (PLT), lymphocyte count (LC), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and the product of platelet count and neutrophil count (PPN) were derived from postoperative blood test results. We investigated the association between these indicators and outcomes using multivariable logistic regression and restricted cubic spline analysis. The predictive performance of these indicators was assessed by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve and decision curve analysis (DCA).ResultA total of 232 patients were included in this study. Multivariate logistic regression and restricted cubic spline analysis showed that all indicators, except for PLT, were associated with clinical postoperative pancreatic fistula (POPF). SII, NLR, and NC were linked to surgical site infection (SSI), while SII, NLR, and PLR were correlated with CD3 complication. PLT levels were related to postoperative hemorrhage. SII (AUC: 0.729), NLR (AUC: 0.713), and NC (AUC: 0.706) effectively predicted clinical POPF.ConclusionIn patients undergoing PD, postoperative inflammation-related indices and blood cell counts are associated with various complications. NLR and PLT can serve as primary indicators post-surgery for monitoring complications

PPM1G regulates hepatic ischemia/reperfusion injury through STING‐mediated inflammatory pathways in macrophages

Abstract Background Ischemia/reperfusion injury (IRI) is generally unavoidable following liver transplantation. Here, we investigated the role of protein phosphatase, Mg2+/Mn2+ dependent 1G (PPM1G) in hepatic IRI. Methods Hepatic IRI was mimicked by employing a hypoxia/reperfusion (H/R) model in RAW 264.7 cells and a 70% warm ischemia model in C57BL/6 mice, respectively. In vitro, expression changes of tumor necrosis factor‐α and interleukin were detected by quantitative real‐time polymerase chain reaction (qRT‐PCR), western blot analysis, and enzyme‐linked immunosorbent assay. The protein expressions of PPM1G and the stimulator of interferon genes (STING) pathway components were analyzed by western blot. Interaction between PPM1G and STING was verified by coimmunoprecipitation (CO‐IP). Immunofluorescence was applied for detection of p‐IRF3. Flow cytometry, qRT‐PCR and western blot were utilized to analyze markers of macrophage polarization. In vivo, histological analyses of mice liver were carried out by TUNEL and H&E staining. Changes in serum aminotransferases were also detected. Results Following H/R intervention, a steady decline in PPM1G along with an increase in inflammatory cytokines in vitro was observed. Addition of plasmid with PPM1G sequence limited the release of inflammatory cytokines and downregulated phosphorylation of STING. CO‐IP validated the interaction between PPM1G and STING. Furthermore, inhibition of PPM1G with lentivirus enhanced phosphorylation of STING and its downstream components; meanwhile, p65, p38, and Jnk were also surged to phosphorylation. Expression of INOS and CD86 was surged, while CD206, Arg‐1, and IL‐10 were inhibited. In vivo, PPM1G inhibition further promoted liver damage, hepatocyte apoptosis, and transaminases release. Selective inhibition of STING with C‐176 partially reversed the activation of STING pathway and inflammatory cytokines in vitro. M1 markers were also suppressed by C‐176. In vivo, C‐176 rescued liver damage and transaminase release caused by PPM1G inhibition. Conclusion PPM1G suppresses hepatic IRI and macrophage M1 phenotype by repressing STING‐mediated inflammatory pathways

Table_1_Malnutrition diagnosed by the Global Leadership Initiative on Malnutrition criteria predicting survival and clinical outcomes of patients with cancer: A systematic review and meta-analysis.DOCX

ObjectivesRecently, some cohorts have looked into the use of Global Leadership Initiative on Malnutrition (GLIM) criteria in cancer patients. The objective of the current meta-analysis was to determine its utility in predicting clinical and survival outcomes for cancer patients.MethodSearching and screening literature from PubMed, Web of Science and Embase until September 13, 2022 was performed by two researchers independently. According to the exclusion and inclusion criteria, articles reporting the impact of malnutrition diagnosed by GLIM on long-term survival and clinical outcomes were included. Data of interest were also extracted from the included papers. The stability of the pooled results was evaluated using sensitivity analysis. With the aid of subgroup analysis, heterogeneity was revealed. To assess publication bias, Egger’s and Begg’s tests were conducted. The influence of publication bias on the pooling risk estimate was examined using a trim-and-fill analysis.Results15 studies that qualified for our study were identified. Pooled hazard ratio (HR) from both multivariate and univariate regression analysis showed a worse overall survival in GLIM-defined malnourished cancer patients than those in well-nourished status. Meanwhile, disease-free survival was also poorer in malnourished patients. Moreover, pooled odds ratio (OR) demonstrated that malnourished cancer patients were more likely to develop overall postoperative complications, complications ≥ Clavien-Dindo grade IIa and complications ≥ Clavien-Dindo grade IIIa. Two articles reported negative relation between GLIM-defined malnutrition and 30-day readmission/mortality.ConclusionGLIM-defined malnutrition possesses value in predicting poorer survival and clinical outcomes for cancer patients.Systematic review registration[https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=321094], identifier [CRD42022321094].</p