inflammation parameters
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BackgroundHepatocellular carcinoma (HCC) is the most common pathological type of primary liver cancer. The lack of prognosis indicators is one of the challenges in HCC. In this study, we investigated the combination of tertiary lymphoid structure (TLS) and several systemic inflammation parameters as a prognosis indicator for HCC.Materials and MethodsWe retrospectively recruited 126 postoperative patients with primary HCC. The paraffin section was collected for TLS density assessment. In addition, we collected the systemic inflammation parameters from peripheral blood samples. We evaluated the prognostic values of those parameters on overall survival (OS) using Kaplan-Meier curves, univariate and multivariate Cox regression. Last, we plotted a nomogram to predict the survival of HCC patients.ResultsWe first found TLS density was positively correlated with HCC patients’ survival (HR=0.16, 95% CI: 0.06 − 0.39, p < 0.0001), but the power of TLS density for survival prediction was found to be limited (AUC=0.776, 95% CI:0.772 − 0.806). Thus, we further introduced several systemic inflammation parameters for survival analysis, we found neutrophil-to-lymphocyte ratio (NLR) was positively associated with OS in univariate Cox regression analysis. However, the combination of TLS density and NLR better predicts patient’s survival (AUC=0.800, 95% CI: 0.698-0.902, p < 0.001) compared with using any single indicator alone. Last, we incorporated TLS density, NLR, and other parameters into the nomogram to provide a reproducible approach for survival prediction in HCC clinical practice.ConclusionThe combination of TLS density and NLR was shown to be a good predictor of HCC patient survival. It also provides a novel direction for the evaluation of immunotherapies in HCC.

Background: The association between oral nutritional supplement use and nutritional parameters among patients with nondialysis chronic kidney disease (CKD-ND) with or at high risk of undernutrition/protein-energy wasting has not been previously studied. The definition of patient subgroups most likely to benefit from oral nutritional supplementation (ONS) is also an area where more research is needed. Objective: To assess nutritional parameter trajectories among patients with CKD-ND prescribed oral nutritional supplements in British Columbia, and to compare trajectories by nutritional phenotype. Design: Longitudinal cohort study, pre-post design. Setting: Multidisciplinary CKD clinics across British Columbia. Patients: A total of 3957 adult patients with CKD-ND, who entered multidisciplinary CKD clinics during 2010 to 2019, met criteria for oral nutritional supplement prescription based on dietitian assessment, and received ≥1 oral nutritional supplement prescription. Measurements: Longitudinal nutritional parameters, including body mass index (BMI), serum albumin, serum bicarbonate, serum phosphate, and neutrophil-to-lymphocyte ratio (NLR). Methods: Using linear mixed models, slopes for nutritional and inflammation parameters were assessed in the 2-year periods before and after the first oral nutritional supplement prescription. Hierarchical cluster analysis was applied to identify nutritional phenotypes using baseline data, and slope analysis was repeated by cluster. Results: In the pre-oral-nutritional-supplement period, declines in BMI (−0.87 kg/m2/year, 95% confidence interval [CI]: −0.99 to −0.75), albumin (−1.11 g/L/year, 95% CI: −1.27 to −0.95), and bicarbonate (−0.49 mmol/L/year; 95% CI: −0.59 to −0.39), and increases in NLR (+0.79/year; 95% CI: 0.60 to 0.98) and phosphate (+0.05 mmol/L/year; 95% CI: 0.04 to 0.06) were observed. Following oral nutritional supplement prescription, there were statistically significant increases in BMI slope (+0.91 kg/m2/year, P < .0001), albumin slope (+0.82 g/L/year, P < .0001), and phosphate slope (+0.02 mmol/L/year, P = .005), as well as a decline in NLR slope of −0.55/year ( P < .0001). There was no significant change in bicarbonate slope. Cluster analysis identified 5 distinct phenotypes. The cluster with the highest mean baseline NLR and lowest mean BMI demonstrated the greatest number of improvements in nutritional parameter slopes in the post-oral-nutritional-supplement period. Limitations: Possibility of residual confounding. Data on dietary intake, muscle mass, and nutritional scoring systems were not available in the registry. Conclusions: Among patients with CKD-ND prescribed oral nutritional supplements, there were improvements in nutrition/inflammation parameters over time following the first ONS prescription. The heterogeneity in response to ONS by cluster subgroup suggests an individualized approach to nutritional management may be beneficial.

Abstract The postmenopausal period is characterized by a decrease in the hormonal supply which is associated with Alzheimer's Disease (AD). Vitamin D is neuroprotective and can be used in combination with pre-existing medications to improve its effects. The objective was to evaluate the effect of vitamin D associated with memantine and donepezil in female mice submitted to ovariectomy (OVX) for 5 months and subjected to an AD-induced dementia model. Animals were divided into 5 groups who received 17 days of treatment and were subjected to behavioral tests. The animals underwent euthanasia at 18th day. OVX groups exhibit reduced levels of E2 and triple treatment group had high levels of vitamin D. The induction of dementia with OVX induced short- and long-term spatial and habituation memories damage. Also, induced reduction of BDNF and IL-4 levels in hippocampus, and increasing levels of TNFα in hippocampus and of IL-1β in hippocampus and frontal cortex of animals, as well as a significant increase on GFAP immunoreactivity. Triple-association treatment reversed the effects of long-term spatial and habituation memories damage, as well as reversed changes in TNFα, IL-1β, IL-4 and GFAP immunoreactivity levels in hippocampus of treated animals. Therapeutic association has beneficial effects on memory and inflammation parameters in female mice subjected to OVX and the AD animal model of dementia.

Chronic rhinosinusitis (CRS) is a characteristic feature of cystic fibrosis (CF) multiorgan disease and develops early in the life of patients with CF. The study aimed to correlate the inflammatory markers and the presence of structural abnormalities detected by MRI in the paranasal sinuses of patients with CF. Methods: Nasal lavage and MRI of the paranasal sinuses was performed in a cohort of 30 CF patients (median age 14 y; range 7–20 y). Morphological abnormalities characteristic of CF were evaluated with a dedicated CRS MRI scoring system and correlated with different inflammation parameters measured in nasal lavage. Inflammation of the paranasal sinuses was positively associated with structural abnormalities in MRI. The concentration of the pro-inflammatory markers neutrophil elastase (NE) and the neutrophil elastase/alpha1-antitrypsin (NE/A1AT) complex correlated significantly with CRS-MRI sum score (p < 0.05, r = 0.416 and p < 0.05, r = 0.366, respectively). S. aureus infection was associated with the increased pro-inflammatory cytokine activity of IL-6 and IL-8, and increased levels of NE/A1AT complex in our patients (p < 0.05, respectively). CRS-MRI sum score and individual sinus MRI scores were positively associated with inflammatory activity as a sign of CRS pathology present in CF.

Abstract Background Human intestinal spirochetosis (HIS) is an infectious disease of large intestines caused by Brachyspira species, and most HIS cases are asymptomatic or exhibit mild intestinal symptoms. The host reaction to HIS remains unclear, and we examined HIS-related mucosal inflammatory features histologically. Methods From the archival HIS cases in a single medical center, 24 endoscopically taken specimens from 14 HIS cases (male:female = 10:4; 28–73 yrs) were selected as not containing polypoid or neoplastic lesions. Stromal neutrophils, eosinophils, and mast cells, and intraepithelial neutrophils and eosinophils, (sNeu, sEo, sMast, iNeu, and iEo, respectively) were counted, and the presence or absence of lymphoid follicles/aggregates (LFs) was also examined. Association of the above inflammation parameters and spirochetal infection parameters (such as degrees of characteristic fringe distribution, of spirochetal cryptal invasion, and of spirochetal intraepithelial invasion) were also analysed. Results iNeu was observed in 29.2%, iEo in 58.3%, and LFs in 50.0% of the specimens. Maximal counts of sNeu, sEo, sMast, iNeu, and iEo averaged 8.4, 21.5, 6.0, 0.5 and 1.5, respectively. Strong correlation between the maximum counts of iNeu and iEo (p < 0.001, r = 0.81), and correlations between those of iEo and sNeu (p = 0.0012, r = 0.62) and between those of iEo and sEo (p = 0.026, r = 0.45) were observed. iNeu was influenced by fringe formation (p < 0.05) and spirochetal crypt involvement (p < 0.05). Conclusions HIS was accompanied by inflammatory reactions, and among these, mucosal eosinophilic infiltration may be a central indicator and host reaction of HIS.

Older age and comorbidities in hemodialysis patients determines the use of tunneled catheters as vascular access despite their reported clinical and mortality disadvantages. This prospective matched study analyzes the impact of permanent catheters on inflammation and mortality in hemodialysis patients; We studied 108 patients, 54 with AV-fistula (AVF) and 54 with indwelling hemodialysis catheters (HDC) matched by sex, age, diabetes and time under renal-replacement therapy comparing dialysis efficacy, inflammation and micro-inflammation parameters as well as mortality. Cox-regression analysis was applied to determine predictors of mortality, HDC patients presented higher C-reactive-protein (CRP) blood levels and percentage of pro-inflammatory lymphocytes CD14+/CD16+ with worse dialysis-efficacy parameters. Thirty-six-months mortality appeared higher in the HDC group although statistical significance was not reached. Age with a Hazard Ratio (HR) = 1.06, hypoalbuminemia (HR = 0.43), hypophosphatemia (HR = 0.75) and the increase in CD14+/CD16+ monocyte count (HR = 1.02) were predictors of mortality; elder patients dialyzing through HDC show increased inflammation parameters as compared with nAVF bearing patients, although they do not present a significant increase in mortality when matched by covariates. Increasing age and percentage of pro-inflammatory monocytes as well as decreased phosphate and serum-albumin were predictors of mortality and indicate the main conclusions or interpretations.