Higher Inflammatory Status Research Articles

Association between airway microbiota and systemic inflammation markers in non-small cell lung cancer patients

Growing evidences have suggested the airway microbiota may participate in lung cancer progression. However, little was known about the relationship between airway microbiota and lung cancer associated systemic inflammation. Here we aimed to explore the association between sputum microbiota and systemic inflammation in lung cancer. The microbiota of spontaneous sputum samples from 51 non-small cell lung cancer (NSCLC) patients and 6 patients with lung benign nodules were sequenced via 16 S rRNA sequencing. Neutrophil-lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR) and C reactive protein (CRP) were used to represent systemic inflammation. Patients were divided into 2 groups based on level of inflammatory biomarkers respectively (CRP_low versus CRP_high; NLR_low versus NLR_high; PLR_low versus PLR_high). α-diversity was significantly decreased in CRP_high and NLR_high patients. β diversity analysis based on weighted unifrac distance indicated that microbial community structure differed significantly between patients with different inflammation status. Lefse identified genera Porphyromonas, Selenomonas, Moryella, Megasphaera, Corynebacterium were enriched in CRP_low group. Compared with NLR_high, genera Veillonella, Neisseria, Bulleidia, Moryella were enriched in NLR_low group. For patients with different PLR level, genera Veillonella, Prevotella, Moryella, Selenomonas were increased in PLR_ low patients. Function analysis identified propionate metabolism pathway was significantly enriched in CRP_low and PLR_low groups. Moreover, RDA analysis showed that compared with PLR, NLR and CRP had strongest association with microbial community. Airway microbial structure differed between lung cancer with different systemic inflammation status. Patients with relative high inflammation status were associated with alteration of specific airway genera and microbial metabolic function.

Development of a prediction model based on Hemoglobin, Albumin, Lymphocyte count, and Platelet-score for lymph node metastasis in rectal cancer.

This study aimed to evaluate the ability of the preoperative Hemoglobin, Albumin, Lymphocyte count, and Platelet (HALP) score to predict lymph node metastasis (LNM) in patients with rectal cancer (RC) and improve prediction accuracy by incorporating clinical parameters. Data from 263 patients with RC were analyzed. The receiver operating characteristic (ROC) curve was used to determine the optimal cutoff value (OCV) for the HALP score in predicting LNM. Based on this cutoff value, patients were divided into two groups. A baseline analysis was conducted to identify independent factors linked to LNM. A support vector machine (SVM) prediction model was developed, and its performance was evaluated using ROC, calibration curves, decision curve analysis, and Kolmogorov-Smirnov curve. The OCV for HALP score was 45.979. Patients were then classified into a low HALP group (n = 182) and a high HALP group (n = 81). The analysis found 21 clinical factors significantly associated with LNM. Among them, the key risk factors included high inflammatory status, poor nutritional condition, and a low HALP score. The SVM model incorporated these factors and showed robust predictive performance, with area under the curve values of 0.897, 0.813, and 0.750 for the training, validation, and testing datasets, respectively. The HALP score was significantly associated with LNM in RC patients. A machine learning model integrating the HALP score and inflammatory markers may be an effective tool for predicting LNM in RC.

Importance of younger age group and high inflammatory status in the association between periodontal disease and diabetes mellitus: results from the Korea National Health and Nutrition Examination Survey 2012-2018.

Although previous studies have demonstrated an association between periodontal disease (PD) and diabetes mellitus (DM), the influence of age and the mediating role of inflammation have seldom been explored. This study investigated this association while considering the modifying effects of age and inflammatory status. This study included 29,491 participants from the 2012-2018 Korea National Health and Nutrition Examination Survey. The community periodontal index (CPI) was assessed by trained dentists using the World Health Organization CPI probe. PD was defined as a CPI score of 3 or 4. Pre-existing and incident DM were identified based on serum glucose levels, a history of DM diagnosis, medication use, and insulin injections. Serum high-sensitivity C-reactive protein (hs-CRP) levels were utilized as an indicator of chronic inflammation. PD and DM exhibited a significant association, which was more pronounced with incident DM than with pre-existing DM, particularly in individuals younger than 65 years. Among those aged 20-44 years, the odds ratio of incident DM for CPI=4 versus CPI=0 was 2.61 (95% confidence interval, 1.16 to 6.09). High hs-CRP levels (>3 mg/L) were also associated with DM, especially in individuals with PD. This association was stronger with incident DM than with pre-existing DM. A notable joint effect was observed in younger individuals and those with PD. The association between PD and DM was more pronounced in younger age groups and those with higher levels of inflammation. Therefore, early interventions for PD in younger patients may be crucial for preventing DM.

Bioelectrical impedance analysis (BIA) phase angle in stroke patients: A systematic review

Background and AimsPhase angle (PhA), a raw variable of bioelectrical impedance analysis (BIA), is an index of muscle structure and quality and might have a potential role in the evaluation of nutritional status.The aim of this systematic review was to evaluate in stroke patients: baseline PhA and its changes during hospital stay; the association of PhA with clinical features of patients, comorbidities, nutritional status or sarcopenia, and clinical outcomes. MethodsSystematic research on electronic databases (PubMed, Scopus, and Web of Science) up to June 14th, 2024 was performed according to PRISMA checklist.Using PECOS strategy, “P” (patients)=stroke patients, “E” (exposure)=lowest PhA values, “C” (comparison)=versus greatest PhA values, “O” (outcome)=nutritional and clinical outcomes, and “S” (study design)=all study types.Methodological quality was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies (NIH). ResultsEighteen papers met the inclusion criteria, with a low risk of bias. In stroke patients, evidence suggests that PhA was associated with malnutrition, sarcopenia and sarcopenic obesity, as well as with physical function. In addition, patients with low PhA had a longer hospital stay, higher inflammatory status and higher incidence of urinary tract infections and hospital-acquired pneumonia. ConclusionsSelected papers, although not conclusive, show that in acute and subacute stroke patients PhA was inversely associated with malnutrition and poor physical function. PhA could be a marker of health status and disease progression. PhA may be useful in a more comprehensive evaluation of nutritional status to be used for diagnosis and implementing therapy.

Factors Involved in the Development of Diabetic Kidney Disease in Patients With Slowly Progressive Type 1 Diabetes Mellitus: A Retrospective Cohort Study.

Introduction The duration of diabetes mellitus (DM), blood pro-inflammatory markers, and dipeptidyl peptidase 4 (DPP4) activity are known predictors of diabetic kidney disease (DKD) progression in acute-onset type 1 DM (AT1DM) and type 2 DM. However, predictors of DKD progression in slowly progressive type 1insulin-dependent DM (SPIDDM) have been less frequently studied. Patients and methods This retrospective cohort study included 60 patients with SPIDDM (definite) (26 men/34 women). We utilized Cox proportional hazard analyses to determine whether characteristics and laboratory findings at the time of the SPIDDM diagnosis were associated with subsequent DKD progression. The urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) at the last outpatient clinic visit served as indicators of renal function. Also, to compare blood markers in patients with SPIDDM, we included 21 patients diagnosed with AT1DM at the same department during the same period and 50 healthy adult volunteers. Results In patients with SPIDDM (definite), the multivariate Cox proportional hazard analysis revealed that the body mass index (BMI), high-sensitivity C-reactive protein (hs-CRP) levels at diagnosis, and the duration of DM prior to SPIDDM diagnosis were associated with the new onset of albuminuria and systolic blood pressure (SBP) at diagnosis, and the duration of DM prior to SPIDDM diagnosis was associated with a decline in eGFR to less than 60 ml/min/1.73 m². Additionally, serum hs-CRP levels were significantly higher in the SPIDDM (definite) group compared to both the AT1DM patients and healthy controls, suggesting a higher inflammatory state in patients with SPIDDM at the time of diagnosis. In patients with SPIDDM (definite) who were not treated with a DPP4 inhibitor, plasma DPP4 activity was associated with the new onset of albuminuria. Conclusions BMI, SBP, hs-CRP levels, DPP4 activity at SPIDDM diagnosis, and the duration of DM prior to SPIDDM diagnosis are associated with subsequent progression of DKD in SPIDDM. Also, we found that the patients with SPIDDM are often already being treated as DM for a long period of time at the time of diagnosis, which may be linked to their already high inflammatory status at the time of SPIDDM diagnosis and contribute to DKD progression. These findings underscore the importance of early diagnosis and management in preventing DKD progression in this population.

Systemic Immune-inflammation Index in Evaluation of Inflammation in Rheumatoid Arthritis Patients.

To evaluate the systemic immune-inflammation (SII) index in patients with rheumatoid arthritis (RA) stratified by systemic inflammatory status. Seropositive patients with RA (n=58) were divided into two groups based on serum hs-C-reactive protein (hs-CRP) levels: RA patients with hs-CRP levels of at or 3 mg/L or above (high systemic inflammatory status; n=38) and RA patients with hs-CRP levels of less than 3 mg/L (low systemic inflammatory status; n=20). The control group comprised 31 healthy individuals. Blood samples were tested for the next parameters: leukocytes, neutrophilic granulocytes, lymphocytes, thrombocytes [platelet (PLT)], high-sensitivity hs-CRP, sed rate [erythrocyte sedimentation rate (ESR)], neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR). The SII index was derived as Neu x PLT/Lym. In patients with RA, the SII index was elevated compared with that of healthy individuals and positively correlated with hs-CRP, erythrocyte sedimentation rate, NLR, MLR, PLR, tender joint count, and swollen-to-tender joint count ratio. Patients with RA who had hs-CRP levels of 3 mg/L above exhibited a statistically significant increase in the SII compared with those with hs-CRP levels below 3 mg/L. Additionally, within the cohort of RA patients with hs-CRP levels at or above 3 mg/L, a positive correlation was found between the SII index and both NLR and PLR. The SII index was positively correlated with NLR, MLR, and PLR in RA patients with hs-CRP levels below 3 mg/L. The cut-off point of the SII index for distinguishing between RA cases with hs-CRP levels 3 mg/L and those with hs-CRP levels 3 mg/L or higher was ≥323.4, with a sensitivity of 77.6% and a specificity of 54.8%. The serum SII index can be a potentially useful marker for evaluating the inflammatory process and clinical progression of RA.

Baseline and early dynamic changes in inflammatory and nutritional status can predict survival in patients with advanced biliary tract carcinoma receiving immunotherapy: A retrospective cohort study

Abstract Background Inflammatory and nutritional indicators are established prognostic factors in patients with various types of solid tumors. However, it remains unclear whether differences in the baseline and early dynamic changes in these factors can predict the prognosis of immunotherapy in patients with advanced biliary tract carcinoma (aBTC). Methods Data were retrospectively collected from 74 consecutive patients who were diagnosed with aBTC and received immunotherapy. Peripheral blood cell counts and other laboratory tests were performed at baseline and after two cycles of immunotherapy. The skeletal muscle index was measured using computed tomography/magnetic resonance imaging scans. Analyses of the relationship between clinicopathological characteristics and survival outcomes were conducted using Kaplan-Meier curves and Cox regression models. Results Seventy-four patients were enrolled in the study, with 42 (56.8%) being male. The median age at diagnosis for all participants was 61 years (range, 35–77 years). In the univariate analysis, six baseline indices were associated with survival, namely, lactate dehydrogenase (LDH), carbohydrate antigen 199, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, Prognostic Nutritional Index, and Controlling Nutritional Status score. In the multivariable analysis, an elevated baseline NLR (HR: 3.363, 95% CI: 1.600–7.070, P = 0.001) and elevated baseline LDH (HR: 2.030, 95% CI: 1.122–3.670, P = 0.019) were independent risk factors for a shorter overall survival. Sarcopenia was not correlated with the overall survival (P > 0.05). A persistently high NLR, platelet-to-lymphocyte ratio, and Controlling Nutritional Status score and low Prognostic Nutritional Index indicated a worse prognosis. Conclusions Elevated baseline NLR and LDH values are independent negative prognostic factors in patients with aBTC receiving immunotherapy. Patients with persistently high inflammation and poor nutritional status experience a poorer prognosis.

Unraveling the Interaction between Inflammation and the Cardiometabolic Index in Older Men: A Pilot Study.

Both cardiometabolic and chronic inflammatory diseases pose a significant challenge to global public health, particularly among older adults. Here, we investigated the interplay between systemic inflammatory status and the cardiometabolic index (CMI) in older men with adequate weight or obesity. In this observational cross-sectional study, older men (71.79 ± 7.35 years) were separated into groups with normal weight (NW, n = 34) and obesity (O, n = 32) to assess circulating levels of pro- and anti-inflammatory cytokines and CMI. Overall, the O group showed not only a higher inflammatory status but also increased CMI (p < 0.0001) compared with the NW group. Interestingly, only positive correlations were found between pro- and anti-inflammatory cytokines in both groups. Through multivariate regression analysis, IL-6 (β = -0.2276, p = 0.0003) and IL-10 (β = 0.2023, p = 0.0030) significantly influenced CMI in the NW group. No significant results were found in the O group. Our findings reinforce the effects of obesity in inflammaging, as well as suggesting that the influence of cytokines in CMI occurs in older men with normal weight, since the elevated pro-inflammatory profile observed in older men with obesity can interfere in this effect.

Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, Systemic Immune Inflammation Index and Efficacy of Remote Ischemic Conditioning in Acute Ischemic Stroke: A Post Hoc Exploratory Analysis of the RICAMIS Study.

We conducted a post-hoc analysis of the RICAMIS trial to investigate the effect of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) on the efficacy of remote ischemic conditioning treatment. In this post-hoc analysis, NLR, PLR, and SII were measured before randomization. Patients were divided into two groups based on their cut-off values: high vs low NLR, high vs low PLR, and high vs low SII groups. Each group was further subdivided into RIC and control groups. The primary endpoint was a poor outcome (mRS 2-6 at 90 days). Differences in the primary endpoint between the RIC and control subgroups were compared, and the interactions of treatment assignment with NLR, PLR, and SII were evaluated. A total of 1679 patients were included in the final analysis. Compared with the control group, RIC significantly improved functional outcomes regardless of the inflammation status. The improved probability of poor outcome in the RIC vs control group was numerically greater in the high vs low inflammation group (NLR, 7.8% vs 5.1%; PLR, 7% vs 6.5%; SII, 9% vs 5.3%). However, we did not find an interaction effect of an intervention (RIC or control) with different NLR, PLR, or SII on clinical outcomes (P > 0.05). In addition, the NLR and SII were independently associated with functional outcomes in all patients, regardless of whether they received RIC. Inflammation may not affect the efficacy of RIC in patients with acute moderate ischemic stroke, although a lower probability of poor outcome at 90 days was identified in patients with a high vs low inflammatory status.

Gut microbiome and inflammation among athletes in wheelchair in a crossover randomized pilot trial of probiotic and prebiotic interventions

Disorders related to gut health are a significant cause of morbidity among athletes in wheelchair. This pilot feasibility trial aims to investigate whether probiotics compared to prebiotics can improve inflammatory status and gut microbiome composition in elite athletes in wheelchair. We conducted a 12-week, randomized, cross-over controlled trial involving 14 elite Swiss athletes in wheelchair. Participants were given a multispecies-multistrain probiotic or prebiotic (oat bran) daily for 4 weeks (Clinical trials.gov NCT04659408 09/12/2020). This was followed by a 4-week washout and then crossed over. Thirty inflammatory markers were assessed using bead-based multiplex immunoassays (LegendPlex) from serum samples. The gut microbiome was characterized via 16S rRNA sequencing of stool DNA samples. Statistical analyses were conducted using linear mixed-effect models (LMM). At baseline, most athletes (10/14) exhibited low levels of inflammation which associated with higher gut microbiome alpha diversity indices compared to those with high inflammation levels. The use of probiotic had higher decrease in 25 (83%) inflammatory markers measured compared to prebiotic use. Probiotic has the potential in lowering inflammation status and improving the gut microbiome diversity. The future trial should focus on having sufficient sample sizes, population with higher inflammation status, longer intervention exposure and use of differential abundance analysis.

Concerns about the application of resistance exercise with blood-flow restriction and thrombosis risk in hemodialysis patients

BackgroundHemodialysis (HD) per se is a risk factor for thrombosis. Considering the growing body of evidence on blood-flow restriction (BFR) exercise in HD patients, identification of possible risk factors related to the prothrombotic agent D-dimer is required for the safety and feasibility of this training model. The aim of the present study was to identify risk factors associated with higher D-dimer levels and to determine the acute effect of resistance exercise (RE) with BFR on this molecule. MethodsTwo hundred and six HD patients volunteered for this study (all with a glomerular filtration rate of <15 mL/min/1.73 m2). The RE + BFR session consisted of 50% arterial occlusion pressure during 50 min sessions of HD (intradialytic exercise). RE repetitions included concentric and eccentric lifting phases (each lasting 2 s) and were supervised by a strength and conditioning specialist. ResultsSeveral variables were associated with elevated levels of D-dimer, including higher blood glucose, citrate use, recent cardiovascular events, recent intercurrents, higher inflammatory status, catheter as vascular access, older patients (>70 years old), and HD vintage. Furthermore, RE + BFR significantly increases D-dimer after 4 h. Patients with borderline baseline D-dimer levels (400–490 ng/mL) displayed increased risk of elevating D-dimer over the normal range (≥500 ng/mL). ConclusionThese results identified factors associated with a heightened prothrombotic state and may assist in the screening process for HD patients who wish to undergo RE + BFR. D-dimer and/or other fibrinolysis factors should be assessed at baseline and throughout the protocol as a precautionary measure to maximize safety during RE + BFR.

Association of DNA methylation/demethylation with the functional outcome of stroke in a hyperinflammatory state.

JOURNAL/nrgr/04.03/01300535-202410000-00024/figure1/v/2024-02-06T055622Z/r/image-tiff Inflammation is closely related to stroke prognosis, and high inflammation status leads to poor functional outcome in stroke. DNA methylation is involved in the pathogenesis and prognosis of stroke. However, the effect of DNA methylation on stroke at high levels of inflammation is unclear. In this study, we constructed a hyperinflammatory cerebral ischemia mouse model and investigated the effect of hypomethylation and hypermethylation on the functional outcome. We constructed a mouse model of transient middle cerebral artery occlusion and treated the mice with lipopolysaccharide to induce a hyperinflammatory state. To investigate the effect of DNA methylation on stroke, we used small molecule inhibitors to restrain the function of key DNA methylation and demethylation enzymes. 2,3,5-Triphenyltetrazolium chloride staining, neurological function scores, neurobehavioral tests, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR and western blot assay were used to evaluate the effects after stroke in mice. We assessed changes in the global methylation status by measuring DNA 5-mc and DNA 5-hmc levels in peripheral blood after the use of the inhibitor. In the group treated with the DNA methylation inhibitor, brain tissue 2,3,5-triphenyltetrazolium chloride staining showed an increase in infarct volume, which was accompanied by a decrease in neurological scores and worsening of neurobehavioral performance. The levels of inflammatory factors interleukin 6 and interleukin-1 beta in ischemic brain tissue and plasma were elevated, indicating increased inflammation. Related inflammatory pathway exploration showed significant overactivation of nuclear factor kappa B. These results suggested that inhibiting DNA methylation led to poor functional outcome in mice with high inflammation following stroke. Further, the effects were reversed by inhibition of DNA demethylation. Our findings suggest that DNA methylation regulates the inflammatory response in stroke and has an important role in the functional outcome of hyperinflammatory stroke.

A survival nomogram involving nutritional-inflammatory indicators for cervical cancer patients receiving adjuvant radiotherapy.

Objective: The combined impact of nutritional and inflammatory status on survival of cervical cancer patients remained unclear. This study aimed to construct a survival nomogram involving both nutritional and inflammatory indicators and evaluate their potential correlation. Methods: This retrospective study included 325 cervical cancer patients who received adjuvant radiotherapy between September 2010 and September 2020. Baseline nutritional indicators such as body mass index (BMI), controlling nutritional status (CONUT) and serum albumin were assessed. Inflammatory indicators of platelet/lymphocyte ratio (PLR), neutrophil/lymphocyte ratio (NLR), systemic immune inflammation index (SII) and system inflammation response index (SIRI) were evaluated respectively. The LASSO regression and Cox regression models were applied for variable selection and nomogram building. The predictive accuracy and superiority of prognostic model were assessed by area under curve (AUC), C-index, decision curve analysis (DCA), integrated discrimination improvement (IDI) and net reclassification improvement (NRI). Results: Patients with high inflammatory indicators (PLR, NLR and SII) and poor nutritional status (CONUT scores > 2) suffered poorer prognosis compared to these with well nutritional status and lower inflammation levels. Our study unveiled a positive correlation between malnutrition and hyperinflammation. Even after accounting for baseline inflammatory level, malnutrition remained a significant risk factor for patients. Notably, the inflammatory level and nutritional status were further modulated by the clinical features of patients. Patients with poorer nutritional status exhibited higher levels of PLR, NLR, SII and SIRI, particularly for those in advanced clinical stages and with non-squamous cell carcinoma. In addition, our study found elevated levels of circulating basophil and serum carbohydrate antigen 125 (CA125) were associated with the poor prognosis. The prognostic nomogram which incorporated the nutritional-inflammatory indicators of PLR and CONUT showed a favorable performance with the AUC value of 0.76 at 5-year survival prediction. The DCA, IDI and NRI consistently demonstrated the favorable superiority of the model. Moreover, the nomogram-based risk stratification system could effectively classify patients into three mortality risks subgroups. Conclusions: Poorer nutritional and high inflammatory status collectively contributed to the poorer prognosis. The prognostic nomogram which incorporated nutritional-inflammatory indicators significantly improved the prediction of long-term outcomes of cervical cancer patients undergoing adjuvant radiotherapy.

Associations of dietary inflammatory index with low estimated glomerular filtration rate, albuminuria and chronic kidney disease in U.S adults: Results from the NHANES 2011–2018

Background and AimsChronic Kidney Disease (CKD) is characterized by a high inflammation status with ever-increasing prevalence, and defined as low estimated glomerular filtration rate (eGFR) or albuminuria. Both low eGFR and albuminuria can have independent effects on the body. The dietary inflammatory index (DII) is a validated tool used to assess the inflammatory potential of the diet. We aim to explore not only the association between DII and CKD, but also the associations of DII with low eGFR and albuminuria, respectively. In addition, their associations in different subgroups remain to be explored. Methods and Results18,070 participants from the 2011-2018 NHANES with complete data of dietary intake and laboratory data were involved in our study. The data of 24-hour dietary recall interview was used to calculate DII, CKD could be reflected by laboratory data of creatinine and albumin. Then weighted multivariate logistic regression models and subgroup analyses were performed. The prevalence of low eGFR, albuminuria and CKD were 6.8%, 9.8% and 14.5%, respectively. A positive association between DII and low eGFR was observed (OR=1.12, 95%CI: 1.05-1.21), Q2, Q3 and Q4 are positively associated with a significant 39%, 65% and 71% increased risk of low eGFR compared with Q1 (P for trend<0.05). DII was also associated with CKD (OR=1.06, 95%CI: 1.01-1.11). ConclusionSignificant positive associations of DII with CKD and low eGFR were observed. But we didn’t find such association between DII and albuminuria.

Association between short-term air pollution exposure and perturbation in thyrotropin levels in 1.38 million Chinese women: A national longitudinal analysis, 2014–2019

Prevalence of subclinical hypothyroidism substantially increased during the last decade in China, which has been commonly/clinically diagnosed as elevation in thyrotropin (thyroid-stimulating hormone [TSH]). Tobacco smoke containing toxic substances has been linked to thyroid dysfunction; however, data on perturbation of TSH following air pollution exposure in human has not been assessed at nationwide population level. We investigated the longitudinal impact of daily ambient air pollution estimated at residential level on serum TSH in 1.38 million women from China’s 29 mainland provinces between 2014 and 2019. We observed that particulate matter with aerodynamic diameter ≤ 10 and ≤ 2.5 µm (PM10, PM2.5) and nitrogen dioxide (NO2) at cumulative lag 0–7 days of exposure were associated with percent elevations in TSH (0.88% [95% CI: 0.71, 1.05] per [interquartile range, IQR: 54.8 μg/m3] of PM10; 0.89% [95% CI, 0.71, 1.07] per IQR [40.3 μg/m3] of PM2.5; 2.01% [95% CI: 1.81, 2.22] per IQR [27.4 μg/m3] of NO2). Greater associations were observed in participants living in areas with ≥adequate iodine intake and those with low BMI levels and high inflammation status. Our results suggest that increased concentrations of recent ambient air pollutants at exposure ranges commonly encountered in Asia were associated with increases in TSH, supporting disturbing role of short-term air pollution exposure on the regulation of thyroid hormone homeostasis.

The signature and predictive value of immune parameters in patients with secondary hemophagocytic lymphohistiocytosis

BackgroundSecondary hemophagocytic lymphohistiocytosis (sHLH) is a rare but fatal clinical syndrome, characterized by severe immune dysfunction and overwhelming inflammatory response. However, the host immune signature and also its role in predicting the clinical outcome are not fully described. ObjectiveThe present study aims to investigate the host immune status of sHLH patients in the early stage of the disease, including lymphocyte subsets, phenotypes and cytokines, and also to explore its clinical value in prognosis. MethodsSixty-four patients with sHLH admitted to a tertiary hospital in central China between 2018 and 2022 were enrolled, of which 21 were deceased. The subsets and phenotypes of lymphocytes, and the levels of cytokines in serum were analyzed. ResultsIn patients with sHLH, the percentages of total T cells, CD8+ T cells, HLA-DR+ T cells, HLA-DR+CD8+ T cells, CD45RO+CD4+ T cells, and the levels of IL-1β, IL-2R, IL-6, IL-8, IL-10 and TNF-α were significantly increased, while the percentages of CD4+ T cells, NK cells, CD45RA+CD4+ T cells, CD45RA+ regulatory T (Treg) cells, the counts of total T cells, total B cells, CD4+ T cells, CD8+ T cells, NK cells, and the ratio of CD4+ T/CD8+ T cells were significantly decreased, compared with healthy controls (HC). In addition, dysregulation of host immune response and high inflammatory status were more obvious in deceased patients than that of survivors. Kaplan-Meier survival analysis and multivariate logistic regression analysis demonstrated that lower levels of CD4+ T cells count and CD28+CD4+ T cells percentage, but higher levels of NK cells percentage and IL-1β were poor prognostic indicators of sHLH. ConclusionThe evaluation of immunological markers has critical value for selecting prognostic markers and potential treatment target among adults with sHLH.

Association between the dietary inflammatory index and markers of endothelial and systemic inflammation in hemodialysis patients.

The current survey aimed to investigate the link between energy-adjusted dietary inflammatory index (E-DII) and risk factors for CVD including markers of endothelial and systemic inflammation in Iranian hemodialysis patients. Patients on hemodialysis for at least 6 months prior to enrollment were considered eligible in this cross-sectional study. The usual dietary intakes of the hemodialysis individuals were examined through 4 non-consecutive days including 2 dialysis days and 2 non-dialysis days using a 24-h recall approach to calculate E-DII. Multiple linear regression analysis was utilized to investigate the link between E-DII and selected biomarkers of inflammation and oxidative stress including high-sensitive C reactive protein (hs-CRP), serum intercellular adhesion molecule (sICAM), serum vascular cell adhesion molecule (sVCAM), malondialdehyde, and nitric oxide (NO), sE-selectin, and endothelin-1, and beta (β) and 95% confidence interval (CI) was reported. Value of p < 0.05 was considered statistically significant. Overall, 291 hemodialysis patients make up our study population. In the crude model, the E-DII score was positively associated with a higher sVCAM-1 (β = 177.39; 95% CI: 60.51, 294.26; ptrend = 0.003). Further adjustment for potential confounders attenuated the findings in a way that an increase of 128.72 in the sVCAM-1 was observed when the E-DII score increased from -2.68 to -1.14 (95% CI: 13.50, 243.94). After controlling for potential confounders, E-DII was associated with sE-selectin in hemodialysis patients in the highest category of E-DII as compared to the lowest category (β = 4.11; 95% CI: 0.22, 8.00; ptrend = 0.039). The present findings suggest that adherence to a pro-inflammatory diet among hemodialysis patients is associated with a higher inflammatory status as evidenced by sVCAM-1 and sE-selectin; however, bidirectionality may exist and the role of residual confounders should be taken into account. Therefore, more longitudinal investigations are needed to elucidate the role of diet on the inflammatory status of hemodialysis patients.

Hypoosmolar and hyperosmolar COVID-19 patients are predisposed to dismal clinical outcomes

We aimed to investigate the associations of hypo- and hyperosmolarity at hospital admission with clinical characteristics and outcomes in 5645 consecutive hospitalized COVID-19 patients treated at a tertiary-level institution. Serum osmolarity was calculated as 2x Na (mmol/L) + urea (mmol/L) + glucose (mmol/L), with normal range from 275 to 295 mOsm/L. Median serum osmolarity was 292.9 mOsm/L with 51.8% normoosmolar, 5.3% hypoosmolar and 42.9% hyperosmolar patients present at the time of hospital admission. Hypoosmolarity was driven by hyponatremia, and was associated with the presence of chronic liver disease, liver cirrhosis, active malignancy and epilepsy. Hyperosmolarity was driven by an increase in urea and glucose and was associated with the presence of chronic metabolic and cardiovascular comorbidities. Both hypo- and hyperosmolar patients presented with more severe COVID-19 symptoms, higher inflammatory status, and experienced higher mortality in comparison to normoosmolar patients. In multivariate analysis, hypoosmolarity (adjusted odds ratio (aOR)=1.39, p = 0.024) and hyperosmolarity (aOR = 1.9, p < 0.001) remained significantly associated with higher mortality independently of older age, male sex, higher Charlson Comorbidity Index and more severe COVID-19. Disruptions in serum osmolarity are frequent in COVID-19 patients, may be easy to detect and target therapeutically, and thus potentially moderate associateds poor prognosis.

Stress, immune mechanisms, and mental illness: from etiology to treatment

It is now well-established that a strong relationship exists between psychiatric disorders and disturbances of immune mechanisms at different stages of life. Indeed, a derangement in the expression and function of specific immune elements may predispose and contribute to the development of different psychopathologic conditions and could also represent an important component that must be targeted by therapeutic intervention. The proposed symposium will summarize authoritatively the important recent advances on the immune mechanisms contributing to the etiology of psychiatric disorders, with a specific focus on the role of stress, and it will discuss if and how the effectiveness of therapeutic intervention may depend on the ability to regulate immune mechanisms that are altered under pathologic conditions. The symposium will unfold upon the discussion of preclinical and clinical studies addressing different aspects related to psychiatric disorders. Prof. A. Pillai (University of Texas, U.S.A.) will specifically discuss the roles of neuroinflammation and synapse loss in IFN-I signaling-mediated social deficits under chronic stress conditions. He will discuss how peripheral blockade of IFN-I signaling attenuated stress-induced neuroimmune alterations and social behavioral deficits and also the key role of complement component 3a receptor 1 (C3ar1) in these mechanisms. Along this line, Prof. M.A. Riva (University of Milan, Italy) will show how immune mechanisms and dysregulation of microglial function may contribute to the vulnerability to stress at different life stages, from adolescence to adulthood. Moreover, he will discuss how the normalization of some of these mechanisms following pharmacological intervention may contribute to therapeutic effectiveness in the treatment of different psychiatric disorders characterized, particularly in patients characterized by a higher inflammatory status. At the clinical level, Dr. G. Scaini (University of Texas, U.S.A.) will discuss the interplay between inflammation, stress, and mitochondria in bipolar disorder patients. She will highlight the significant correlation between alterations in mitochondrial proteins and inflammatory markers with a decrease in functional status and an increase in the severity of symptoms. Lastly, Prof. J. Felger (Emory Univ.) will discuss how depressed patients with increased inflammation show altered functional connectivity within the ventral striatum to ventromedial prefrontal cortex reward circuitry in relation to symptoms of anhedonia. These changes can be improved by pharmacological intervention aimed to increase dopamine levels suggesting that functional connectivity in reward circuitry may also serve as a modifiable imaging biomarker for the efficacy of pharmacological and/or behavioral interventions to reverse the impact of inflammation on the brain of depressed subjects.

A Comprehensive Summary of the Current Understanding of the Relationship between Severe Obesity, Metabolic Syndrome, and Inflammatory Status.

At present, obesity, as a part of metabolic syndrome, represents the leading factor for disability, and is correlated with higher inflammation status, morbidity, and mortality. The purpose of our study is to add new insights to the present body of knowledge regarding the correlations between chronic systemic inflammation and severe obesity, which cannot be treated without considering other metabolic syndrome conditions. Biomarkers of high-level chronic inflammation are recognized as important predictors of pro-inflammatory disease. Besides the well-known pro-inflammatory cytokines, such as WBCs (white blood cells), IL-1 (interleukin-1), IL-6 (interleukin-6), TNF-alpha (tumor necrosis factor-alpha), and hsCRP (high-sensitivity C-reactive protein), as well as anti-inflammatory markers, such as adiponectin and systemic inflammation, can be determined by a variety of blood tests as a largely available and inexpensive inflammatory biomarker tool. A few parameters, such as the neutrophil-to-lymphocyte ratio; the level of cholesterol 25-hydroxylase, which is part of the macrophage-enriched metabolic network in adipose tissue; or levels of glutamine, an immune-metabolic regulator in white adipose tissue, are markers that link obesity to inflammation. Through this narrative review, we try to emphasize the influence of the weight-loss process in reducing obesity-related pro-inflammatory status and associated comorbidities. All data from the presented studies report positive results following weight-loss procedures while improving overall health, an effect that lasts over time, as far as the existing research data show.