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Funder: Università degli Studi di Trieste, PURPOSE: The aim of this study is to evaluate the prognostic value of pre-treatment advanced lung cancer inflammation index (ALI) in patients with HPV-negative HNSCC undergoing up-front surgical treatment. METHODS: The present multi-centre, retrospective study was performed in a consecutive cohort of patients who underwent upfront surgery with or without adjuvant (chemo)-radiotherapy for head and neck squamous cell carcinoma (HNSCC). Patients were stratified by ALI, and survival outcomes were compared between groups. In addition, the prognostic value of ALI was compared with two other indices, the prognostic nutritional index (PNI) and systemic inflammatory index (SIM). RESULTS: Two hundred twenty-three patients met the inclusion criteria (151 male and 72 female). Overall and progression-free survival were significantly predicted by ALI < 20.4 (HR 3.23, CI 1.51-6.90 for PFS and HR 3.41, CI 1.47-7.91 for OS). Similarly, PNI < 40.5 (HR = 2.43, 95% CI: 1.31-4.51 for PFS and HR = 2.40, 95% CI: 1.19-4.82 for OS) and SIM > 2.5 (HR = 2.51, 95% CI: 1.23-5.10 for PFS and HR = 2.60, 95% CI: 1.19-5.67 for OS) were found to be significant predictors. Among the three indices, ALI < 20.4 identified the patients with the worst 5-year outcomes. Moreover, patients with a combination of low PNI and low ALI resulted to be a better predictor of progression (HR = 5.26, 95% CI: 2.01-13.73) and death (HR = 5.68, 95% CI: 1.92-16.79) than low ALI and low PNI considered alone. CONCLUSIONS: Our results support the use of pre-treatment ALI, an easily measurable inflammatory/nutritional index, in daily clinical practice to improve prognostic stratification in surgically treated HPV-negative HNSCC.

Background Inflammatory indexes (platelet-to-lymphocyte ratio [PLR], neutrophil-to-lymphocyte ratio [NLR], and lymphocyte-to-monocyte ratio [LMR]) are recently supposed to be the biomarkers of sarcopenia. We aimed to validate the association between these inflammatory indexes and sarcopenia in Chinese community-dwelling older people. Methods We consecutively recruited community-dwelling older adults aged 60 years or older. The neutrophil, lymphocyte, monocyte, and platelet counts, and C-reactive protein (CRP) were tested using standard methods. Sarcopenia was defined according to different criteria: the Asian Working Group for Sarcopenia (AWGS), the updated version of AWGS (AWGS 2019), the European Working Group on Sarcopenia in Older People (EWGSOP), the updated version of EWGSOP (EWGSOP2), the International Working Group on Sarcopenia (IWGS), and the Foundation for the National Institutes of Health Sarcopenia Project (FNIH). Multiple logistic regression analysis was performed. Results We included 384 participants. A total of 61 participants (15.9%) were diagnosed with sarcopenia according to the AWGS criteria. There was no significant difference in PLR, NLR, LMR, and CRP between the sarcopenia group and the non-sarcopenia group regardless of the diagnostic criteria. No significant association between PLR, NLR, LMR, and AWGS-defined sarcopenia was found (PLR per 1- standard deviation [SD]: adjusted odds ratio [OR] 1.09, 95% confidence interval [CI] 0.82 to 1.45; NLR per 1-SD: adjusted OR 0.96, 95% CI 0.71 to 1.30; LMR per 1-SD: adjusted OR 1.01, 95% CI 0.74 to 1.38). Similar results were found when sarcopenia was defined by different criteria and when PLR, NLR, LMR were treated as categorical variables. Conclusions Our study did not support the utility of the inflammatory indexes (NLR, PLR, and LMR) as the biomarkers of sarcopenia in Chinese community-dwelling older people. However, considering the inflammatory indexes can be simply calculated from a routine blood test, further studies in different populations remain warranted.

Background: μ opioid receptors (μORs) are expressed by neurons and inflammatory cells, and mediate immune response. We tested whether activation of peripheral μORs ameliorates the acute and delayed phase of colitis. Methods: C57BL/6J mice were treated with 3% dextran sodium sulfate (DSS) in water, 5 days with or without the peripherally acting μOR agonist, [D-Ala2, N-Me-Phe4, Gly5-ol]-Enkephalin (DAMGO) or with DAMGO+μOR antagonist at day 2-5, then euthanized. Other mice received DSS followed by water for 4 weeks, or DSS with DAMGO starting at day 2 of DSS for 2 or 3 weeks followed by water, then euthanized at 4 weeks. Disease activity index (DAI), histological damage, and myeloperoxidase assay (MPO), as index of neutrophil infiltration, were evaluated. Cytokines and μOR mRNAs were measured with RT-PCR, and nuclear factor-kB (NF-kB), the antiapoptotic factor Bcl-xL, and caspase 3 and 7 with Western blot. Key Results: DSS induced acute colitis with elevated DAI, tissue damage, apoptosis and increased MPO, cytokines, μOR mRNA, and NF-kB. DAMGO significantly reduced DAI, inflammatory indexes, cytokines, caspases, and NF-kB, and upregulated Bcl-xL, effects prevented by μOR antagonist. In DSS mice plus 4 weeks of water, DAI, NF-kB, and μOR were normal, whereas MPO, histological damage, and cytokines were still elevated; DAMGO did not reduce inflammation, and did not upregulate Bcl-xL. Conclusions & Inferences: μOR activation ameliorated the acute but not the delayed phase of DSS colitis by reducing cytokines, likely through activation of the antiapoptotic factor, Bcl-xL, and suppression of NF-kB, a potentiator of inflammation. μ opioid receptors (μORs) mediate a variety of biological processes, including gastrointestinal functions and immune response. This study showed that activation of peripheral μOR with DAMGO, a selective μOR agonist, reduces the inflammatory response and disease activity index in acute experimental colitis through a mechanism involving the activation of the antiapoptotic factor, Bcl-xL, a member of the Bcl-2 family of apoptosis regulator proteins, and the suppression of the transcription nuclear factor-kB (shown here), which in turns reduces the release of pro-inflammatory cytokines and immune cells infiltration. By contrast, the delayed phase of colitis, which is characterized by lower level of inflammation, does not appear to benefit for additional treatment with peripherally acting μOR agonists as indicated by the lack of effect of DAMGO on the expression of Bcl-xL and NF-kB.