Systemic Inflammatory State Research Articles

Impact of Postoperative Naples Prognostic Score to Predict Survival in Patients with Stage II-III Colorectal Cancer.

The Naples prognostic score (NPS) is a scoring system that reflects a patient's systemic inflammatory and nutritional status. This study aimed to evaluate whether postoperative NPS is effective in assessing the prognosis of stage II-III colorectal cancer (CRC) patients compared with preoperative NPS. Between 2005 and 2012, a total of 164 patients diagnosed with stage II-III CRC, who underwent curative resection followed by adjuvant chemotherapy, were divided into two groups: Group 0-1 (NPS = 0-2) and Group 2 (NPS = 3 or 4). Preoperative NPS was calculated based on the results before surgeries, and postoperative NPS was assessed using the results obtained before adjuvant chemotherapy. The overall survival of Group 0-1 was higher than that of Group 2 in both pre- and postoperative NPS assessments. According to the ROC curve analysis, the Area Under the Curve (AUC) ratio for postoperative NPS was 0.64, compared with 0.57 for preoperative NPS, 0.52 for the preoperative neutrophil-lymphocyte ratio (p = 0.032), and 0.51 for the preoperative platelet-lymphocyte ratio (p = 0.027). Postoperative NPS is effective in predicting the prognosis of stage II-III CRC patients who underwent curative resection followed by adjuvant chemotherapy. The use of NPS could be beneficial in evaluating the prognosis of CRC patients after surgeries.

THU289 Hemichorea-Hemiballismus Syndrome Secondary To Steroid Induced Hyperglycemia In A Nondiabetic

Abstract Disclosure: E. Krishnaraju: None. K.N. Patolia: None. U.A. Ogar: None. S. Karki: None. A.G. Olafimihan: None. Introduction: Hemichorea-Hemiballismus syndrome (HCHB) associated with nonketotic hyperglycemia is a rare cause of acute to subacute acquired chorea. The syndrome is usually characterized by unilateral choreiform movements, poorly controlled diabetes mellitus, and striatal abnormalities on an MRI of the brain. Clinical Case: This is a case of a 70-year-old man with a history of congestive heart failure, hypertension, remote ischemic stroke, asymptomatic Paget's disease of the bone, chronic kidney disease, and statin-induced necrotizing myositis. Five months before his presentation, the patient was initiated on prednisone for myositis. On presenting to the ED, he had near resolution of his limb weakness from myositis but complained of one month of right-sided continuous involuntary tremors involving the right upper limb, lower limb, and face that resolved during his sleep. There was no family history of neurologic disorders or any history to suggest medication or illicit drug-induced movement disorders. On examination, the patient had normal cognitive functions and vital signs. Neurologic examination was remarkable for quick interspersed moderate amplitude choreiform movements of the right hand, forearm, proximal arm muscles, and right leg. Laboratory results revealed hyperglycemia and a newly elevated Hemoglobin A1c of 8.5, which was normal the year before. Infectious, hematologic, thyroid disease, and Wilson's disease workups were negative. Cerebrospinal fluid (CSF) analysis was remarkable for elevated glucose and identical oligoclonal bands in the serum and CSF, possibly suggestive of a nonspecific chronic systemic inflammatory state. Autoantibodies for paraneoplastic syndromes and autoimmune diseases, including autoimmune encephalitis were negative. There was also no evidence of occult malignancy on CT imaging of the chest, abdomen, and pelvis. MRI/MRA was significant for new small foci of susceptibility artifact in the bilateral basal ganglia, left cerebellar hemisphere, and cerebellar vermis, likely from chronic microvascular changes. The constellation of hemichorea and new onset hyperglycemia in the setting of a largely nondiagnostic workup raises suspicion for HBHC syndrome. Previous studies have found classic T1-weighted MRI hyperintensities in the basal ganglia, but normal imaging does not rule out a diagnosis of diabetic striatopathy. The patient was eventually discharged with mild improvement of his chorea after starting insulin and risperidone. Unfortunately, he was lost to follow-up and unexpectedly died of an unclear cause soon after. Conclusion: Metabolic complications of diabetes can manifest in complex ways. Non-ketotic hyperglycemic HCHB due to diabetic striatopathy is a rarely reported entity that is commonly misdiagnosed. This case is a unique presentation in a non-diabetic patient with steroid-induced hyperglycemia. Presentation: Thursday, June 15, 2023

A population-based study of children suggests blunted morning cortisol rhythms are associated with alterations of the systemic inflammatory state

BackgroundIn children, digital media, lifestyle, and the COVID pandemic have impacted sunlight exposure, exercise, and diet patterns - cues that entrain the circadian clock. We hypothesized that low morning cortisol reflects a weak circadian clock, impacting the pro-inflammatory state. The primary objective was to test relationships between diurnal cortisol fluctuations and the inflammatory state in children as a means of providing indirect support for this hypothesis. MethodsThe Cardiovascular Health Intervention Program (CHIP) was a population-based cross-sectional and longitudinal study of circadian health in public elementary school children in Southern Maine, USA (recruitment period 2012–2017). Participants were 689 students in 4th grade (baseline; age=9.2 ± 0.4 years), and 647 students in 5th grade (age=10.5 ± 0.5 years). Nine salivary cortisol measures per child (2 awakening and 1 prior to bed for 3 sequential days) (n = 1336 child phenotype days; n = 7987 cortisol assays), 10 cytokines measured in morning and evening saliva samples (n = 202 child phenotype days), and lipids were measured. Clinical outcomes were blood pressure, weight and height (body mass index [BMI]; BMI = kg/m2), among others. FindingsUpon-waking cortisol levels were 0.28 ± 0.13 µg/dL, 30-minute post-waking 0.33 ± 0.15 µg/dL, and evening 0.08 ± 0.10 µg/dL. Salivary cytokine levels (n = 202) showed interleukins (IL) IL-1β and IL-8 were highest in early morning (upon awakening; AM), and IL-6 and tumor necrosis factor (TNF) TNF-α highest before bed (PM) (IL-1β AM > PM [−4.02 fold; p < 0.001]; IL-8 AM > PM [−1.36 fold; p < 0.001]; IL-6 AM < PM [+1.49 fold; p < 0.001]; TNF-α AM < PM [+1.73 fold; p = 0.03]. Regression modeling showed high morning cortisol was associated with high morning IL-1β (p = 3.82 ×10−6), but low evening IL-1β (p = 6.27 ×10−4). Regression modeling of BMI z-score as the response variable showed the expected significant relationships to high density lipoprotein (HDL) (negative; p < 0.001), mean arterial pressure (positive; p < 0.001), and morning cortisol (negative; p = 0.01) but only weak relationships to either evening cortisol (p = 0.1) or cytokine (positive; p = 0.02; from the model with smallest Rsquared) levels. InterpretationWe provide preliminary data on diurnal fluctuations of inflammatory cytokines in saliva in a population-based cohort of children. Correlation of morning and evening cortisol levels with inflammatory cytokines in the same saliva samples showed that high morning cortisol was associated with high morning IL-1β and low evening IL-1β. Future studies may test the hypothesis that strong diurnal cycling of IL-1β may serve as a homeostatic mechanism keeping the immune system in check, and that low morning cortisol (possible circadian misalignment) may lead to less stringent control of inflammatory networks.

Prognostic Value of Inflammation Biomarkers in Penile Squamous Cell Carcinoma Patients Without Distant Metastasis.

To investigate the value of the presurgical inflammatory biomarkers including C-reactive protein (CRP), albumin (ALB), C-reactive protein to albumin ratio (CAR), Glasgow prognostic score (GPS), the modified GPS (mGPS), and the high-sensitivity modified GPS (Hs-mGPS) in penile squamous cell carcinoma (PSCC) without distant metastasis and develop a tool to predict the overall survival (OS) of PSCC patients. We retrospectively enrolled 271 PSCC patients without distant metastasis from 2006 to 2021. Patients were divided into 2 cohorts by a 7:3 ratio-a training cohort (n=191) and a validation cohort (n=80). We performed cox regression analyses on the training cohort and constructed a nomogram to predict OS over 1, 3, and 5 years. Data from the validation cohort was used to validate the nomogram's predictive power. According to Kaplan-Meier analysis, elevated CRP (P < .001), hypoalbuminemia (P=.008), higher CAR (P < .001), higher GPS score (P < .001), higher mGPS score (P < .001), and higher Hs-mGPS score (P=.015) were associated with a decreased overall survival. GPS score, along with age, pathology N stage, and grade, was found to be an independent risk factor for poor prognosis in the multivariate analysis. We constructed a nomogram based on the prespecified variables predicting 1-, 3- and 5-year OS. The C-indexes of the nomogram in the training and validation cohorts were 0.871 and 0.869, respectively. The decision curve analysis showed that the nomogram had a larger net benefit. The Kaplan-Meier curves showed significant differences between the risk groups categorized according to the nomogram (P < .001). Inflammation biomarkers of systemic inflammation and nutritional status play an important role in individual OS predictions for PSCC patients without distant monitoring. The establishment of the nomogram provided a tool to predict the survival of 1-, 3-, and 5-year OS in PSCC patients without distant metastasis.

Systemic Inflammatory Status of Patients with Obstructive Sleep Apnea Syndrome and the Predictive Value of Heparin-Binding Protein.

Objective: To investigate the alteration of the systemic inflammatory status of patients with obstructive sleep apnea syndrome (OSAS) and the predictive value of heparin-binding protein (HBP) for OSAS. Methods: Patients with OSAS who were hospitalized in our hospital from 2020 January to 2022 December and diagnosed by polysomnography (PSG) (OSAS group, n = 79) were retrospectively studied and their relevant examination findings and demographic characteristics were recorded. Sex- and age-matched non-OSAS patients hospitalized at the same time were selected as the control group (control group, n = 28). Differences in peripheral blood neutrophil counts, lymphocyte counts, neutrophil-to-lymphocyte ratio (NLR), procalcitonin (PCT), and HBP were compared between the 2 groups. The predictive value of these markers for OSAS was analyzed using the receiver operating characteristic curve, and independent risk factors for OSAS were determined using logistic regression analysis. Peripheral blood was drawn from all patients in the fasting state of the morning. Results: The number of peripheral blood neutrophils, lymphocytes, and HBP was higher in the OSAS group than in the control group, and the differences were statistically significant (P all <.05), while the differences in NLR and PCT between the 2 groups were not statistically significant (P all >.05). Plasma HBP level had an area under the curve (AUC) of 0.79 (P < .0001) in determining OSAS, with a sensitivity of 80.49% and a specificity of 70.83% and the best cutoff value was >10.73 ng/ml. Combining body mass index (BMI), neutrophil, lymphocyte, and HBP improved the predictive value of OSAS with an AUC of 0.89 (P < .0001), a sensitivity of 80.49%, and a specificity of 87.50%. Logistic regression analysis showed that both BMI and HBP were independent risk factors for OSAS (PBMI < .001, PHBP < .01), while neutrophils and lymphocytes were not (P all >.05). Conclusions: This is the first study to objectively examine HBP in OSAS patients, and HBP is an independent risk factor that may serve as a diagnostic biomarker in OSAS. Patients with OSAS have an altered systemic inflammatory state and may be more prone to severe bacterial infections.

Threshold effect of systemic immune inflammatory index on hypertension in American adults (NHANES 2017-2020).

Research reports on the relationship between systemic immune-inflammation index (SII) and hypertension are limited. We aim to evaluate the possible relationship between SII and hypertension. We conducted a cross-sectional analysis of adults from the National Nutrition and Health Database from 2017 to 2020. In this study, 13 742 participants were included. The exposure variable in this study was the systemic inflammatory state as defined by SII and an outcome was hypertension. There is a nonlinear association between SII and hypertension. Two piecewise logistic regression models were used to analyze the relationship between them and calculated the cut-off point of SII to be 501.2. We found that SII on the left side of the cut-off point has nothing to do with the prevalence of hypertension. However, in patients with SII at least 501.2, the prevalence of hypertension increased with the increase of SII (odds ratio, 3.13; 95% confidence interval, 2.04-4.81). The nonlinear association between LgSII and hypertension still existed stably in the subgroups of sex, age, BMI, diabetes, and cardiovascular disease (P for interaction > 0.05). A cross-sectional analysis reported the threshold effect of SII on and hypertension and calculated the turning point of SII to be 501.2.Graphical Abstract, http://links.lww.com/HJH/C283.

Assessment of inflammatory status and oxidative stress in readymade garment manufacturing workers of Garden Reach-Metiabruz area of Kolkata

Objectives: The textile industry including readymade garment manufacturing contributes substantially to the foreign exchange earned by India. More than 45 million people are employed in this industry. Our previous study revealed a compromised lung function (obstructive and mixed) in readymade garment manufacturing workers in the Garden Reach-Metiabruz region of Kolkata. The present study was undertaken to evaluate the impact of the work environment on the immune health at the local and systemic levels of the workers of this region. Oxidative stress encountered by the workers was also assessed. Materials and Methods: Male workers of age group 18–35 years (n = 80) from readymade garment manufacturing units of Garden Reach-Metiabruz region of Kolkata, India were selected for the study. The control group was selected from the same region unexposed to the factory environment. Blood samples were collected from both groups for estimation of cytokines, C-reactive protein (CRP), cortisol and anti-oxidants of the subjects. Sputum samples from dust-exposed workers were studied for alveolar macrophages. Results: Accumulation of alveolar macrophages in the sputum was noted in the workers which indicated a local inflammation. A systemic inflammatory state was revealed by elevated proinflammatory cytokines and CRP. Reduction in antioxidants noted is an indicator of oxidative stress in the workers. Conclusion: A chronic proinflammatory condition exists in these workers and may be the underlying cause of the compromised respiratory status noted in the workers of this region. The inflammatory condition may lead to the pathogenesis of cardiovascular disorders, autoimmune disorders, etc., later in life. This might also influence the outcome of various respiratory infections like the current COVID-19.

Prognostic Impact of Tumor-Infiltrating Lymphocytes, Tertiary Lymphoid Structures, and Neutrophil-to-Lymphocyte Ratio in Pulmonary Metastases from Uterine Leiomyosarcoma

BackgroundThe presence of tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) in tumor tissue has been related to the prognosis in various malignancies. Meanwhile, neutrophil-to-lymphocyte ratio (NLR) as a systemic inflammation marker also has been associated with the prognosis in them. However, few reports have investigated the relationship between pulmonary metastases from sarcoma and these biomarkers.MethodsWe retrospectively recruited 102 patients undergoing metastasectomy for pulmonary metastases from uterine leiomyosarcoma at Okayama University Hospital from January 2006 to December 2019. TILs and TLSs were evaluated by immunohistochemical staining of surgically resected specimens of pulmonary metastases using anti-CD3/CD8/CD103/Foxp3/CD20 antibodies. NLR was calculated from the blood examination immediately before the most recent pulmonary metastasectomy. We elucidated the relationship between the prognosis and these factors. Because we considered that the status of tumor tissue and systemic inflammation were equally valuable, we also assessed the impact of the combination of TILs or TLSs and NLR on the prognosis.ResultsAs for TILs, CD3-positive cells and CD8-positive cells were correlated with the prognosis. The prognosis was significantly better in patients with CD3-high group, CD8-high group, TLSs-high group, and NLR-low group, respectively. The prognosis of CD8-high/NLR-low group and TLSs-high/NLR-low group was significantly better than that of CD8-low/NLR-high group and TLSs-low/NLR-high group, respectively.ConclusionsCD3-positive TILs, CD8-positive TILs, TLSs, and NLR are correlated with the prognosis, respectively. The combination of CD8-positive TILs or TLSs and NLR may be the indicators to predict the prognosis of patients with pulmonary metastases from uterine leiomyosarcoma.

The associations between dietary fibers intake and systemic immune and inflammatory biomarkers, a multi-cycle study of NHANES 2015-2020.

In recent years, there has been considerable growth in abnormal inflammatory reactions and immune system dysfunction, which are implicated in chronic inflammatory illnesses and a variety of other conditions. Dietary fibers have emerged as potential regulators of the human immune and inflammatory response. Therefore, this study aims to investigate the associations between dietary fibers intake and systemic immune and inflammatory biomarkers. This cross-sectional study used data from the National Health and Nutrition Examination Survey (2015-2020). Dietary fibers intake was defined as the mean of two 24-h dietary recall interviews. The systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), red blood cell distribution width-to-albumin ratio (RA), ferritin, high-sensitivity C-reactive protein (hs-CRP), and white blood cell (WBC) count were measured to evaluate systemic immune and inflammatory states of the body. The statistical software packages R and EmpowerStats were used to examine the associations between dietary fibers intake and systemic immune and inflammatory biomarkers. Overall, 14,392 participants were included in this study. After adjusting for age, gender, race, family monthly poverty level index, alcohol consumption, smoking status, vigorous recreational activity, body mass index, hyperlipidemia, hypertension, diabetes, and dietary inflammatory index, dietary fibers intake was inversely associated with SII (β = -2.19885, 95% CI: -3.21476 to -1.18294, p = 0.000248), SIRI (β = -0.00642, 95% CI: -0.01021 to -0.00263, p = 0.001738), NLR (β = -0.00803, 95% CI: -0.01179 to -0.00427, p = 0.000284), RA (β = -0.00266, 95% CI: -0.00401 to -0.00131, p = 0.000644), ferritin (β = -0.73086, 95% CI: -1.31385 to -0.14787, p = 0.020716), hs-CRP (β = -0.04629, 95% CI: -0.0743 to -0.01829, p = 0.002119), WBC (β = -0.01624, 95% CI: -0.02685 to -0.00563, p = 0.004066), neutrophils (β = -0.01346, 95% CI: -0.01929 to -0.00764, p = 0.000064). An inverse association between dietary fibers and PLR was observed in the middle (β = -3.11979, 95% CI: -5.74119 to -0.4984, p = 0.028014) and the highest tertile (β = -4.48801, 95% CI: -7.92369 to -1.05234, p = 0.016881) and the trend test (βtrend = -2.2626, 95% CI: -3.9648 to -0.5604, Ptrend = 0.0150). The observed associations between dietary fibers intake and SII, SIRI, NLR, RA, ferritin, hs-CRP, WBC, and neutrophils remained robust and consistent in the sensitivity analysis. No significant interaction by race was found. Dietary fibers intake is associated with the improvement of the parameters of the immune response and inflammatory biomarkers, supporting recommendations to increase dietary fibers intake for enhanced immune health.

Inflammation o'clock: interactions of circadian rhythms with inflammation-induced skeletal muscle atrophy.

Circadian rhythms are ∼24 h cycles evident in behaviour, physiology and metabolism. The molecular mechanism directing circadian rhythms is the circadian clock, which is composed of an interactive network of transcription-translation feedback loops. The core clock genes include Bmal1, Clock, Rev-erbα/β, Per and Cry. In addition to keeping time, the core clock regulates a daily programme of gene expression that is important for overall cell homeostasis. The circadian clock mechanism is present in all cells, including skeletal muscle fibres, and disruption of the muscle clock is associated with changes in muscle phenotype and function. Skeletal muscle atrophy is largely associated with a lower quality of life, frailty and reduced lifespan. Physiological and genetic modification of the core clock mechanism yields immune dysfunction, alters inflammatory factor expression and secretion and is associated with skeletal muscle atrophy in multiple conditions, such as ageing and cancer cachexia. Here, we summarize the possible interplay between the circadian clock modulation of immune cells, systemic inflammatory status and skeletal muscle atrophy in chronic inflammatory conditions. Although there is a clear disruption of circadian clocks in various models of atrophy, the mechanism behind such alterations remains unknown. Understanding the modulatory potential of muscle and immune circadian clocks in inflammation and skeletal muscle health is essential for the development of therapeutic strategies to protect skeletal muscle mass and function of patients with chronic inflammation.

Abstract P2084: Adipose Tissues Thermogenesis Provides Cardioprotection Against Diastolic Dysfunction Developed In An Obesity-Induced HFpEF Model

Background: Heart failure with preserved ejection fraction (HFpEF) is a major source of morbidity/ mortality in the United States. A systemic inflammatory state established through underlying comorbidities, such as obesity, is thought to develop cardiac dysfunction in HFpEF. Clinical observations associate adiposity with diastolic dysfunction. Herein we demonstrate that adipose tissue is a direct source of diastolic dysfunction and reveal a cardioprotective role of adipose tissue thermogenesis in obesity related HFpEF. Methods and Results: Mice were treated with a β3-AR agonist, CL-316243 (CL), to induce thermogenesis, followed by HFpEF treatment consisting of HFD and L-NAME. Echocardiography revealed that this protected against HFpEF-induced diastolic dysfunction. Whole heart extracts and AT were then evaluated for the signature of β3-AR signaling. In the heart, no signature of β3-AR signaling was observed. In AT, though, various aspects of β3-AR induced thermogenesis were observed. Histological analysis revelated that CL treatment conferred resistance against obesity-induced whitening of interscapular brown adipose tissue (iBAT). Gene and protein expression changes of thermogenic regulators and lipid metabolism enzymes suggested greater thermogenic activity in CL-treated mice. Accordingly, indirect calorimetry showed enhanced energy expenditure, while regression analysis revealed that AT uniquely contributed to this. Transplantation experiments involving CL-treated donor AT and wild-type donors followed by echocardiographic measurements confirmed that the effects of CL were mediated through AT. This approach was complemented with a genetic model we previously used ( Ucp1 -Cre ERT2 ; Cdkn2a fl/fl ) to promote the expansion of beige AT. Here, beige AT expansion protected against diastolic dysfunction and cardiomyocyte hypertrophy developed during HFpEF. Conclusion: Our study indicates enhanced energy expenditure in AT is cardioprotective in obesity related HFpEF. Furthermore, identifying obese AT as a direct source of diastolic dysfunction highlights the therapeutic potential of targeting AT metabolism as a relevant source of diastolic dysfunction.

Enteric nervous system as a target and source of SARS-CoV-2 and other viral infections.

Coronavirus disease 2019 (COVID-19) has been demonstrated to affect several systems of the human body, including the gastrointestinal and nervous systems. The enteric nervous system (ENS) is a division of the autonomic nervous system that extends throughout the gut, regulates gastrointestinal function, and is therefore involved in most gut dysfunctions, including those resulting from many viral infections. Growing evidence highlights enteric neural cells and microbiota as important players in gut inflammation and dysfunction. Furthermore, the ENS and gastrointestinal immune system work together establishing relevant neuroimmune interactions during both health and disease. In recent years, gut-driven processes have also been implicated as players in systemic inflammation and in the initiation and propagation of several central nervous system pathologies, which seem to be hallmarks of COVID-19. In this review, we aim to describe evidence of the gastrointestinal and ENS infection with a focus on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We discuss here viral-induced mechanisms, neuroplasticity, and neuroinflammation to call attention to the enteric neuroglial network as a nervous system with a sensitive and crucial position to be not only a target of the new coronavirus but also a way in and trigger of COVID-19-related symptoms.

Association among inflammaging, body composition, physical activity, and physical function tests in physically active women.

Inflammaging is a phenomenon that has been associated with the development and progression of sarcopenia and frailty syndrome. According to the literature, on the one side, the increase in body fat is associated with a systemic pro-inflammatory status, which consequently favors inflammaging, and on the other side, the regular practice of physical exercise can mitigate the development of this scenario. Therefore, here, we aimed to evaluate the association between inflammaging and physical factors, both body and functional, in a group of physically active older women. Seventy older women (mean age 72.66 ± 6.17 years) participated in this observational cross-sectional and were separated into the eutrophic, overweight, and obese groups. It was assessed: by bioimpedance-body fat percentage (Fat%) and total (Fat kg), skeletal muscle mass (muscle), and free fat mass both in percentage (FFM%) and total (FFMkg); by the International Physical Activity Questionnaire (IPAQ)-the time of moderate-intensity physical activity per week; by physical tests-handgrip (HG), sit-up-stand-on-the-chair in 5 repetitions (Sit-up) and vertical squat jump test (SJ); in addition to the determination of serum cytokine concentration (IL-6, TNF-α, IL-10, and IL-8), and also body mass index (BMI) and calf circumference (Calf). Higher FFM% and lower body fat (both kg and %) were found in the eutrophic group than in the other groups. The eutrophic group also performed more weekly physical activity, jumped higher, and presented not only higher serum IL-6 concentration but also an increased ratio of IL-10/IL-6, IL-10/TNF-α, IL-10/IL-8 as compared to the values found in the overweight group. The obese group presented higher body fat (kg and %) and lower FFM% than the other groups and also higher serum IL-6 concentration than the overweight group. Interestingly, several significant negative and positive correlations between body composition, physical tests, and serum cytokine concentrations were found in the eutrophic and obese groups. While the eutrophic older women group showed a remarkable regulation of the systemic inflammatory status with positive associations in the physical parameters assessed, the overweight and obese groups presented impairment regulations of the inflammaging, which could be related to less weekly physical activity and higher body fat.

Are CT-Derived Muscle Measurements Prognostic, Independ-ent of Systemic Inflammation, in Good Performance Status Pa-tients with Advanced Cancer?

The present study examined the relationships between CT-derived muscle measurements, systemic inflammation, and survival in advanced cancer patients with good performance status (ECOG-PS 0/1). Data was collected prospectively from patients with advanced cancer undergoing anti-cancer therapy with palliative intent. The CT Sarcopenia score (CT-SS) was calculated by combining the CT-derived skeletal muscle index (SMI) and density (SMD). The systemic inflammatory status was determined using the modified Glasgow Prognostic Score (mGPS). The primary outcome of interest was overall survival (OS). Univariate and multivariate Cox regressions were used for survival analysis. Three hundred and seven patients met the inclusion criteria, out of which 62% (n = 109) were male and 47% (n = 144) were ≥65 years of age, while 38% (n = 118) were CT-SS ≥ 1 and 47% (n = 112) of patients with pre-study blood were inflamed (mGPS ≥ 1). The median survival from entry to the study was 11.1 months (1–68.1). On univariate analysis, cancer type (p &lt; 0.05) and mGPS (p &lt; 0.001) were significantly associated with OS. On multivariate analysis, only mGPS (p &lt; 0.001) remained significantly associated with OS. In patients who were ECOG-PS 0, mGPS was significantly associated with CT-SS (p &lt; 0.05). mGPS may dominate the prognostic value of CT-derived sarcopenia in good-performance-status patients with advanced cancer.

Factors associated with failure to start consolidation durvalumab after definitive chemoradiation for locally advanced NSCLC.

The introduction of consolidation immunotherapy after chemoradiotherapy has improved outcome for patients with locally advanced non-small cell lung cancer. However, not all patients receive this treatment. This study identifies factors associated with failure to start durvalumab as consolidation therapy with the aim of optimizing treatment, supportive care and prehabilitation to ensure that more patients complete the planned treatment. Patients from two clinical trials and a named patient use program, were included in this study. All patients received platinum-doublet chemotherapy concomitant with radiotherapy to a total dose of 60-66 gray. Patient characteristics, cancer treatment, toxicity, performance status and laboratory data before and after chemoradiotherapy were recorded and patients who never started durvalumab were compared with those who did. A total of 101 patients were included, of which 83 started treatments with durvalumab after chemoradiotherapy. The 18 patients who did not start durvalumab had significantly higher lactate dehydrogenase at baseline and a worse performance status, cumulative toxicity and higher c-reactive protein after completed chemoradiotherapy. Data also suggest that pre-treatment diabetes and reduced hemoglobin and/or diffusion capacity of the lungs for carbon monoxide contribute to the risk of treatment abruption. Treatment plan disruption rate was 18%. Systemic inflammation and performance status were associated with failure to receive durvalumab after chemoradiation. Further studies are needed to confirm findings and prospective trials should investigate whether prehabilitation and supportive treatment could help more patients finishing the planned treatment. clinicaltrials.gov, identifier NCT03798535; NCT04392505.

A localizing nanocarrier formulation enables multi-target immune responses to multivalent replicating RNA with limited systemic inflammation

RNA vaccines possess significant clinical promise in counteracting human diseases caused by infectious or cancerous threats. Self-amplifying replicon RNA (repRNA) has been thought to offer the potential for enhanced potency and dose sparing. However, repRNA is a potent trigger of innate immune responses invivo, which can cause reduced transgene expression and dose-limiting reactogenicity, as highlighted by recent clinical trials. Here, we report that multivalent repRNA vaccination, necessitating higher doses of total RNA, could be safely achieved in mice by delivering multiple repRNAs with a localizing cationic nanocarrier formulation (LION). Intramuscular delivery of multivalent repRNA by LION resulted in localized biodistribution accompanied by significantly upregulated local innate immune responses and the induction of antigen-specific adaptive immune responses in the absence of systemic inflammatory responses. In contrast, repRNA delivered by lipid nanoparticles (LNPs) showed generalized biodistribution, a systemic inflammatory state, an increased body weight loss, and failed to induce neutralizing antibody responses in a multivalent composition. These findings suggest that invivo delivery of repRNA by LION is a platform technology for safe and effective multivalent vaccination through mechanisms distinct from LNP-formulated repRNA vaccines.

Predictive Value of Systemic Inflammation Score for Contrast-Associated Acute Kidney Injury and Adverse Outcomes Among Patients Undergoing Elective Percutaneous Coronary Intervention.

Prior research has demonstrated a key role of systemic inflammatory state in the pathogenesis and progression of contrast-associated acute kidney injury (CA-AKI). Recently, the systemic inflammation score (SIS) has been introduced to evaluate the inflammatory status, utilizing the lymphocyte-to-monocyte ratio (LMR) and albumin. The primary objective of this study was to determine whether the SIS can predict CA-AKI and long-term prognosis in patients undergoing elective percutaneous coronary intervention (PCI). A total of 5726 patients who underwent elective PCI were included from January 2012 to December 2018. The primary outcome was CA-AKI, defined as an increase in serum creatinine (SCr) ≥0.3 mg/dl or ≥50% than baseline SCr within 48 h after the PCI procedure. The secondary outcome was long-term mortality. All patients were classified into low- and high-SIS groups. During hospitalization, 349 (6.1%) patients developed CA-AKI. Multivariate logistic regression analysis showed that patients in the high SIS group had a 1.47-fold higher risk of developing CA-AKI than those in the low SIS group [odds ratio (OR): 1.50, 95% confidence interval (CI): 1.12-2.01, P =0.006]. Furthermore, the SIS showed the greatest prediction performance for CA-AKI compared with other inflammatory hematological ratios. In the multivariate Cox regression analysis, the high SIS group was found to be closely associated with long-term mortality [hazard ratio (HR): 1.58, 95% CI: 1.26-1.97, P <0.001, vs low SIS group]. The Kaplan-Meier curve analysis also demonstrated a difference in long-term mortality between the two groups (Log rank test, P <0.001). The SIS was closely associated with CA-AKI and long-term mortality in patients after elective PCI. Thus, more attention should be paid to exploring the potential benefits of anti-inflammatory strategies in preventing CA-AKI and improving the prognosis of patients undergoing PCI.

Effects of Exercise on Inflammatory Markers in Individuals with Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

Individuals with chronic kidney disease (CKD) have a systemic inflammatory state. We assessed the effects of exercise on inflammatory markers in individuals with CKD. An electronic search was conducted, including MEDLINE. Experimental clinical trials that investigated the effects of exercise on inflammatory markers in individuals with CKD at all stages were included. Meta-analyses were conducted using the random-effects model and standard mean difference (SMD). Subgroup analyses were performed for resistance, aerobic, and combined exercise interventions. Twenty-nine studies were included in the meta-analyses. Exercise interventions showed significant reductions in C-reactive protein (CRP) (SMD: -0.23; 95% CI: -0.39 to -0.06), interleukin (IL)-6 (SMD: -0.35; 95% CI: -0.57, -0.14), and tumor necrosis factor-alpha (TNF-α) (SMD: -0.63, 95% CI: -1.01, -0.25) when compared with the controls. IL-10 levels significantly increased (SMD: 0.66, 95% CI: 0.09, 1.23) with exercise interventions. Resistance interventions significantly decreased CRP (SMD: -0.39, 95% CI: -0.69, -0.09) and TNF-α (SMD: -0.72, 95% CI: -1.20, -0.23) levels, while increasing IL-10 levels (SMD: 0.57, 95% CI: 0.04, 1.09). Aerobic interventions only significantly reduced IL-6 levels (SMD: -0.26, 95% CI: -0.51, -0.01). No significant changes in any inflammatory markers were observed with combined exercise interventions. Exercise interventions are effective as an anti-inflammatory therapy in individuals with CKD compared to usual care control groups. Resistance interventions seem to promote greater anti-inflammatory effects.

Association between Proinflammatory Cytokines and Anxiety and Depression Symptoms in Rheumatoid Arthritis Patients: A Cross-sectional Study.

Rheumatoid arthritis (RA) patients have a greater prevalence of anxiety and depression. Proinflammatory cytokines are elevated in RA. We aim to evaluate the association between systemic inflammation in RA and anxiety and depression. There were 31 RA patients, 16 with active disease activity and 15 in remission state; they were assessed using the Hospital Anxiety and Depression Scale and for RA disease activity using Disease Activity Score of 28 joints (DAS28) - CRP (C-reactive protein). Serum proinflammatory cytokines were measured, including interleukin (IL)-6, IL-17, and Tumour Necrosis Factor-alpha (TNF-α). Among 31 patients, ten patients showed anxiety symptoms, 19 patients showed depression symptoms, and two displayed mixed symptoms. Serum TNF-α levels were significantly higher in active disease than in the remission group (p-value 0.006). There was no association or correlation between proinflammatory cytokines to anxiety and depression symptoms in the active disease and remission groups. This suggests that other factors besides disease activity and state of systemic inflammation may cause anxiety and depression in RA patients.

A novel insight into the key gene signature associated with the immune landscape in the progression of sarcopenia

Sarcopenia is an age-related skeletal muscle disorder that causes falls, disability and death in the elderly, but its exact mechanism remains unknown. In this study, we merged three GEO datasets into the expression profiles of 118 samples and screened 22 differentially expressed genes (DEGs) as candidate genes. Pathway analysis demonstrated that the functional enrichment of DEGs is mainly in the cellular response to insulin stimulus, PPAR signaling pathway and other metabolism-related pathways. Then, we identified six key genes by machine learning, which were confirmed to be closely associated with sarcopenia by bioinformatics analysis. It was experimentally verified that SCD1 exhibits the most substantial alterations in the progression of sarcopenia with disturbed lipid metabolism and myosteatosis. In addition, the immune microenvironment of sarcopenia was found to be affected by these key genes, with Th17 cells down-regulated and NK cells up-regulated. Sarcopenic patients consequently presented a more significant systemic inflammatory state with higher CAR (p = 0.028) and PAR (p = 0.018). For the first time, we identified key genes in sarcopenia with high-throughput data and demonstrated that key genes can regulate the progression of sarcopenia by affecting the immune microenvironment. Among them, SCD1 may influence lipid metabolism and myosteatosis process. Screening of key genes and analyzing of immune microenvironment provide a more accurate target for treating sarcopenia.