Iron oxide nanoparticles for treatment and diagnosis of chronic inflammatory diseases: A systematic review.

Chronic inflammatory conditions are among the most prevalent diseases worldwide. Several debilitating diseases such as atherosclerosis, inflammatory bowel disease, rheumatoid arthritis, and Alzheimer's are linked to chronic inflammation. These conditions often develop into complex and fatal conditions, making early detection and treatment of chronic inflammation crucial. Current diagnostic methods show high variability and do not account for disease heterogeneity and disease-specific proinflammatory markers, often delaying the disease detection until later stages. Furthermore, existing treatment strategies, including high-dose anti-inflammatory and immunosuppressive drugs, have significant side effects and an increased risk of infections. In recent years, superparamagnetic iron oxide nanoparticles (SPIONs) have shown tremendous biomedical potential. SPIONs can function as imaging modalities for magnetic resonance imaging, and as therapeutic agents due to their magnetic hyperthermia capability. Furthermore, the surface functionalization of SPIONs allows the detection of specific disease biomarkers and targeted drug delivery. This systematic review explores the utility of SPIONs against chronic inflammatory disorders, focusing on their dual role as diagnostic and therapeutic agents. We extracted studies indexed in the Web of Science database from the last 10 years (2013-2023), and applied systematic inclusion criteria. This resulted in a final selection of 38 articles, which were analyzed for nanoparticle characteristics, targeted diseases, in vivo and in vitro models used, and the efficacy of the therapeutic or diagnostic modalities. The results revealed that ultrasmall SPIONs are excellent for imaging arterial and neuronal inflammation. Furthermore, novel therapies using SPIONs loaded with chemotherapeutic drugs show promise in the treatment of inflammatory diseases. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Sodium-glucose cotransporter 2 inhibitors, inflammation, and heart failure: a two-sample Mendelian randomization study.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are increasingly recognized for their role in reducing the risk and improving the prognosis of heart failure (HF). However, the precise mechanisms involved remain to be fully delineated. Evidence points to their potential anti-inflammatory pathway in mitigating the risk of HF. METHODS: A two-sample, two-step Mendelian Randomization (MR) approach was employed to assess the correlation between SGLT-2 inhibition and HF, along with the mediating effects of inflammatory biomarkers in this relationship. MR is an analytical methodology that leverages single nucleotide polymorphisms as instrumental variables to infer potential causal inferences between exposures and outcomes within observational data frameworks. Genetic variants correlated with the expression of the SLC5A2 gene and glycated hemoglobin levels (HbA1c) were selected using datasets from the Genotype-Tissue Expression project and the eQTLGen consortium. The Genome-wide association study (GWAS) data for 92 inflammatory biomarkers were obtained from two datasets, which included 14,824 and 575,531 individuals of European ancestry, respectively. GWAS data for HF was derived from a meta-analysis that combined 26 cohorts, including 47,309 HF cases and 930,014 controls. Odds ratios (ORs) and 95% confidence interval (CI) for HF were calculated per 1 unit change of HbA1c. RESULTS: Genetically predicted SGLT-2 inhibition was associated with a reduced risk of HF (OR 0.42 [95% CI 0.30-0.59], P < 0.0001). Of the 92 inflammatory biomarkers studied, two inflammatory biomarkers (C-X-C motif chemokine ligand 10 [CXCL10] and leukemia inhibitory factor) were associated with both SGLT-2 inhibition and HF. Multivariable MR analysis revealed that CXCL10 was the primary inflammatory cytokine related to HF (MIP = 0.861, MACE = 0.224, FDR-adjusted P = 0.0844). The effect of SGLT-2 inhibition on HF was mediated by CXCL10 by 17.85% of the total effect (95% CI [3.03%-32.68%], P = 0.0183). CONCLUSIONS: This study provides genetic evidence supporting the anti-inflammatory effects of SGLT-2 inhibitors and their beneficial impact in reducing the risk of HF. CXCL10 emerged as a potential mediator, offering a novel intervention pathway for HF treatment.

Systemic inflammation indices as hematological biomarkers of inflammatory response in non-silicotic workers exposed to respirable silica dust.

This cross-sectional study was performed to assess whether systemic inflammatory indices, including systemic inflammation response index (SIRI), systemic immune­inflammation index (SII), and aggregate index of systemic inflammation (AISI), can be considered as possible inflammatory markers in silica-exposed workers with no diagnosis of silicosis. We studied 371 non-silicotic workers exposed to respirable silica dust (RSD) and 1422 reference workers. The workers' exposure to RSD were assessed and the inflammatory indices were compared between subgroups of the exposed workers based on the severity and duration of exposure. Correlations between inflammatory indices and the pulmonary function parameters were investigated. Also, the receiver operating characteristic (ROC) curve and Youden index were used to determine the cut-off values of the SII, SIRI, and AISI. Significant dose-response relationships were observed between duration of exposure and all indices except monocytes and LMR. No significant interaction was observed between duration of exposure to RSD and smoking. Borderline significant correlations were observed between AISI and SIRI with forced expiratory volume (FEV1) and FEV1 to forced vital capacity (FVC) ratio. Higher AUCs were obtained for SII and AISI, respectively. The cut-off values for these biomarkers to be considered abnormal were > 348.48 for SII, > 183.78 for AISI, and > 0.768 for SIRI. Overall, the present study showed for the first time, that SII, AISI, and SIRI might be considered as available, easy-to-obtain, and non-expensive markers of inflammation in non-silicotic workers with a long duration of exposure to RSD who are at risk of developing silicosis in subsequent years.

[Biomarkers of Inflammation in Predicting the Outcomes of Heart Failure of Ischemic Etiology: the Results of Factor Analysis].

AIM: To study the prognostic significance of inflammatory biomarkers in patients with chronic heart failure (CHF) and stenotic multivessel coronary atherosclerosis, with determination of the biomarker separate set that reflects subclinical inflammation and is associated with the development of cardiovascular complications during prospective observation. MATERIAL AND METHODS: A prospective observational study was conducted that included 80 patients with CHF and ischemic heart disease who were scheduled for coronary artery bypass grafting (CABG) during their current hospitalization. In addition to routine clinical laboratory tests, coagulation parameters were evaluated and the following inflammatory biomarkers were determined: neutrophil gelatinase-associated lipocalin (NGAL), growth/differentiation factor 15 (GDF-15), fibroblast growth factor 23 (FGF-23), transforming growth factor beta-1 (TGF-ß1), and high-sensitivity C-reactive protein. Also, the calculated neutrophil-to-lymphocyte ratio (N LR) was included in the analysis. Follow-up duration was at least 12 months (median 16 [13, 22] months). Statistical analysis of the data was performed with the IBM SPSS Statistics 21 software. RESULTS: The study presented results of a factor analysis of 10 inflammatory biomarkers in patients who were scheduled for CABG. One of the factors identified by the analysis included the levels of NGAL and GDF-15, N LR, and the level of fibrinogen in the blood in CHF patients with stenotic coronary atherosclerosis and was significantly associated with the death rate during prospective observation. Furthermore, this association remained significant even after adjustments for age, glomerular filtration rate, severity of heart and coronary insufficiency, and the presence of diabetes mellitus. CONCLUSION: In patients with CHF and stenotic coronary atherosclerosis, a set of inflammatory markers, including blood NGAL, GDF-15, N LR, and fibrinogen, can be combined into one factor reflecting subclinical inflammation. The value of this factor can be used to predict cardiovascular death in the long term after surgical myocardial revascularization.

The predictive value of miR-377 and phospholipase A2 in the early diagnosis of diabetic kidney disease and their relationship with inflammatory factors.

OBJECTIVE: The value of novel biomarkers for DKD has received increasing attention, and there is an urgent need for novel biomarkers with sensitivity, specificity and ability to detect kidney damage.miR-377 regulates many basic biological processes, plays a key role in tumor cell proliferation, migration and inflammation, and can also increase the expression of matrix proteins and fibronectin, leading to renal tubulointerstitial inflammation and renal fibrosis. Lipoprotein-associated phospholipase A2, as an inflammatory marker, is involved in the pathological process of microalbuminuria production and renal function decline, and is a predictive factor of microalbuminuria production and renal function decline, and can be used as an indicator to evaluate the progression of DKD.The aim of this study was to investigate the effects of miR-377 and phospholipase A2 on the development of diabetic kidney disease through regulation of inflammatory factors and the mechanism of action. METHODS: 80 diabetic patients were divided into two groups according to urinary albumin-to-creatinine ratio (UACR): diabetic normal proteinuria group (n = 42) and diabetic proteinuria group (n = 38). Forty-three healthy people were selected as the normal control group. The serum levels of TGF-ß, IL-6, and IL-18 were measured by ELISA, miR-377 was detected by qPCR, and the serum levels of phospholipase A2 were detected by electrochemiluminescence. Analyze the correlation of study group indicators, ROC curve was used to evaluate the diagnostic efficacy of miR-377 and phospholipase A2 in diabetic kidney disease. RESULTS: The average levels of serum TGF-ß, IL-6, IL-18, miR-377 and phospholipase A2 in diabetic proteinuria group were significantly higher than those in normal control group and diabetic proteinuria normal group(P < 0.05). miR-377, phospholipase A2 were significantly correlated with inflammatory factors such as glomerular filtration rate and TGF-ß. miR-377 and phospholipase A2 are independent predictors of diabetic kidney disease. The area under the curve of miR-377 and phospholipase A2 in the normal diabetic proteinuria group and the diabetic proteinuria group were 0.731 and 0.744, respectively. CONCLUSION: miR-377 and phospholipase A2 have good diagnostic efficiency for the early diagnosis of diabetic kidney disease. They can be used as early biomarkers.miR-377 and phospholipase A2 were positively correlated with inflammatory factors and involved in the occurrence and development of diabetic kidney disease.

Association between C10X polymorphism in the CARD8 gene and inflammatory markers in young healthy individuals in the LBA study.

BACKGROUND: The Caspase activation and recruitment domain 8 (CARD8) protein is a component of innate immunity as a negative regulator of NF- ĸB, and has been associated with regulation of proteins involved in inflammation. Expression of CARD8 mRNA and protein has been identified in human atherosclerotic lesions, and the truncated T30A variant (rs2043211) of CARD8 has been associated with lower C-reactive (CRP) and MCP-1 levels in myocardial infarction patients. The present study examines the role of a genetic variation in the CARD8 gene in relation to a selection of markers of inflammation. METHODS: In a cross-sectional study of young healthy individuals (18.0-25.9 yrs, n = 744) the association between the rs2043211 variant in the CARD8 gene and protein markers of inflammation was assessed. Genotyping of the CARD8 C10X (rs2043211) polymorphism was performed with TaqMan real time PCR on DNA from blood samples. Protein levels were studied via Olink inflammation panel ( https://olink.com/ ). Using linear models, we analyzed men and two groups of women with and without estrogen containing contraceptives separately, due to previous findings indicating differences between estrogen users and non-estrogen using women. Genotypes were analyzed by additive, recessive and dominant models. RESULTS: The minor (A) allele of the rs2043211 polymorphism in the CARD8 gene was associated with lower levels of CCL20 and IL-6 in men (CCL20, Additive model: p = 0.023; Dominant model: p = 0.016. IL-6, Additive model: p = 0.042; Dominant model: p = 0.039). The associations remained significant also after adjustment for age and potential intermediate variables. CONCLUSIONS: Our data indicate that CARD8 may be involved in the regulation of CCL20 and IL-6 in men. No such association was observed in women. These findings strengthen and support previous in vitro data on IL-6 and CCL20 and highlight the importance of CARD8 as a factor in the regulation of inflammatory proteins. The reason to the difference between sexes is however not clear, and the influence of estrogen as a possible factor important for the inflammatory response needs to be further explored.

Value of markers of systemic inflammation for the prediction of postoperative progression in patients with pancreatic neuroendocrine tumors.

Background: Non-invasive prognostic predictors for rare pancreatic neuroendocrine tumors (PNETs) are lacking. We aimed to approach the prognostic value of preoperative systemic inflammatory markers in patients with PNETs. Methods: The clinical data of 174 patients with PNETs undergoing surgical treatment were retrospectively analyzed to explore the correlation of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), and platelet to white blood cell ratio (PWR) with clinicopathological parameters and the progression of tumor after the operation. The optimal cutoff values for predictors and the area under the curve (AUC) of the receiver operating characteristic (ROC) were estimated. Univariate and multivariate Cox proportional hazards models were used to assess the relation between NLR, LMR, PLR, and progression-free survival (PFS), examined by the Kaplan-Meier and log-rank tests. Results: The scores of the NLR (P = 0.039) and PLR (P = 0.011) in the progression group were significantly higher than those in the progression-free group, and the LMR was significantly lower than those in the progression-free group (P = 0.001). The best cutoff values of NLR, LMR, and PLR before operation were 2.28, 4.36, and 120.91. The proportions of tumor progression in the high NLR group (P = 0.007) and high PLR group (P = 0.013) obviously increased, and the proportion of tumor development in the low LMR group was higher than that in the high LMR group (P < 0.001). The K-M survival curve showed that the progression-free survival rate was lower in the high NLR group (P = 0.004), the low LMR group (P < 0.001), and the high PLR group (P = 0.018). The results of the multivariate Cox proportional hazards model suggested that preoperative LMR (HR = 3.128, 95% CI: 1.107~8.836, P = 0.031) was an independent predictor of PFS. Conclusion: The markers of systemic inflammation, especially LMR, can predict the postoperative progression of PNETs.

Inflammatory markers and frailty in home-dwelling elderly, a cross-sectional study.

BACKGROUND: Low-grade, chronic inflammation during ageing, ("inflammageing"), is suggested to be involved in the development of frailty in older age. However, studies on the association between frailty, using the frailty index definition, and inflammatory markers are limited. The aim of this study was to investigate the relationship between inflammatory markers and frailty index (FI) in older, home-dwelling adults. METHOD: Home-dwelling men and women aged ≥ 70 years old, living in South-East Norway were recruited and included in a cross-sectional study. The FI used in the current study was developed according to Rockwood's frailty index and included 38 variables, resulting in an FI score between 0 and 1 for each participant. Circulating inflammatory markers (IL-6, CRP, IGF-1, cystatin C, cathepsin S, and glycoprotein Acetyls) were analyzed from non-fasting blood samples using ELISA. Whole-genome PBMC transcriptomics was used to study the association between FI score and inflammation. RESULTS: The study population comprised 403 elderly (52% women), with a median age of 74 years and a mean BMI of 26.2 kg/m2. The mean FI score for the total group was 0.15 (range 0.005-0.56). The group was divided into a frail group (FI score ≥ 0.25) and non-frail group. After adjusting for BMI, age, sex, and smoking in the whole group, IL-6, cathepsin S, cystatin C, and Gp-acetyls remained significant associated to FI score (IL-6: 0.002, 95% CI: 0.001, 0.002, cathepsin S: 6.7e-06, 95% CI 2.44e-06, 0.00001, cystatin C: 0.004, 95% CI: 0.002, 0.006, Gp- Acetyls: 0.09, 95% CI: 0.05, 0.13, p < 0.01 for all), while CRP and IGF-1 were not (0.0003, 95% CI: -00001, 0.0007, p = 0.13, (-1.27e-06), 95% CI: (-0.0003), 0.0003, p = 0.99). There was a significant association between FI score and inflammatory markers, and FI score and monocyte-specific gene expression. CONCLUSIONS: We found an association between FI score and inflammatory markers, and between FI score and monocyte-specific gene expression among elderly subjects above 70 years of age. Whether inflammation is a cause or consequence of frailty and whether the progression of frailty can be attenuated by reducing inflammation remains to be clarified.

Soluble ST2 as a possible biomarker for inflammation in patients with acute heart failure.

AIM: The aim of this study was to explore the relationship between peripheral circulating serum soluble suppression of tumorigenicity-2 (sST2) levels and inflammatory biomarkers in patients with acute heart failure (AHF). METHODS: One hundred and eleven consecutive AHF patients with NYHA class II-IV were enrolled, and peripheral blood was collected within 24 h of admission for the detection of NT-ProBNP, sST2, hypersensitive troponin I, cytokines, precalcitoninogen, C-reactive protein, in addition to routine standard of care blood tests. RESULTS: The median sST2 of 111 patients was 47.50 ng/ml (24.25-86.15 IQR), of whom 43 patients (38.7%) had sST2 35 ng/ml or less; linear correlation analysis showed that serum sST2 correlated with NT-ProBNP ( r2  = 0.32), NEU% ( r2  = 0.41), NLR ( r2  = 0.36), CRP ( r2  = 0.50), IL-18 ( r2  = 0.43) ( P  < 0.001), and correlated with Hs-cTnI ( r2  = 0.19), NUE ( r2  = 0.25), LYM ( r2  = -0.23), IL-2RA ( r2  = 0.29) ( P  < 0.05). Multiple linear regression analysis depicted that CRP (ß = 0.318), IL-18 (ß = 0.368), NEU% (ß = 0.346), NLR (ß = -0.304), and NT-ProBNP (ß = 0.324) significantly correlated with sST2 values, respectively ( P  < 0.05). ST2 levels have a linear association with length of hospitalization. CONCLUSION: Peripheral blood inflammatory markers (CRP, IL-18, NEU%, NLR) in patients with AHF had a close relationship with sST2 levels, and the mechanism of action of sST2 may be related to the inflammatory response.

Anterior chamber flare and choroidal vascular index as inflammatory markers after uncomplicated phacoemulsification surgery.

PURPOSE: To determine the effect of phacoemulsification surgery, which is one of the types of cataract surgery by using ultrasonic power to break up the crystalline lens and clean it with vacuum, on anterior chamber flare (ACF) and choroidal vascular index (CVI). METHODS: For this cross-sectional study, patients were included if they had cataract with nucleus hardness grade 2 or 3, no systemic inflammatory disease, and not use of anti-inflammatory drugs/prostaglandins preoperatively. ACF using a laser flare meter and CVI in patients underwent uncomplicated phacoemulsification was recorded preoperatively, on the postoperative 1st day, 1st week, and 1st month. RESULTS: Fifty-six eyes were included. ACF was 9.00 ± 2.90 ph/ms preoperatively. Although ACF increased significantly on postoperative day-1 (39.38 ± 23.31ph/ms) and decreased gradually until the 1st month (14.03 ± 6.03ph/ms) after the operation, it was still significantly higher at the 1st month (p < 0.001). Macular and peripapillary CVI increased significantly on postoperative day-1 (0.64 ± 0.03/0.63 ± 0.05) and week-1 (0.64 ± 0.04/0.62 ± 0.04) (p = 0.01, p < 0.001); the postoperative 1st month was similar to the preoperative one (0.59 ± 0.06/0.58 ± 0.06). The relationship between the change in ACF and the change in CVI was not significant. CONCLUSION: Phacoemulsification causes raises in ACF and CVI due to increased intraocular inflammation. The fact that ACF was significantly higher in postoperative month-1 and CVI returned to its preoperative value suggests that the effect of uncomplicated phacoemulsification surgery on the increase in inflammation in the anterior segment lasts longer than in the posterior segment. These results suggest that ACF and CVI follow-up may be clinically important in the follow-up of postoperative inflammation.

Nonspecific Orbital Inflammation (NSOI): Unraveling the Molecular Pathogenesis, Diagnostic Modalities, and Therapeutic Interventions.

Nonspecific orbital inflammation (NSOI), colloquially known as orbital pseudotumor, sometimes presents a diagnostic and therapeutic challenge in ophthalmology. This review aims to dissect NSOI through a molecular lens, offering a comprehensive overview of its pathogenesis, clinical presentation, diagnostic methods, and management strategies. The article delves into the underpinnings of NSOI, examining immunological and environmental factors alongside intricate molecular mechanisms involving signaling pathways, cytokines, and mediators. Special emphasis is placed on emerging molecular discoveries and approaches, highlighting the significance of understanding molecular mechanisms in NSOI for the development of novel diagnostic and therapeutic tools. Various diagnostic modalities are scrutinized for their utility and limitations. Therapeutic interventions encompass medical treatments with corticosteroids and immunomodulatory agents, all discussed in light of current molecular understanding. More importantly, this review offers a novel molecular perspective on NSOI, dissecting its pathogenesis and management with an emphasis on the latest molecular discoveries. It introduces an integrated approach combining advanced molecular diagnostics with current clinical assessments and explores emerging targeted therapies. By synthesizing these facets, the review aims to inform clinicians and researchers alike, paving the way for molecularly informed, precision-based strategies for managing NSOI.

Systematic review of the significance of neutrophil to lymphocyte ratio in anastomotic leak after gastrointestinal surgeries.

INTRODUCTION: The inflammatory response is thought to be a critical initiator of epigenetic alterations. The neutrophil to lymphocyte ratio (NLR), a biomarker of inflammation, is computed by dividing the number of neutrophils by the number of lymphocytes. The primary goal of this systematic review and meta-analysis was to evaluate the pre-operative NLR of gastrointestinal surgery patients who had an anastomotic leak (AL) in comparison to those who did not AL. METHODS: We performed a comprehensive search for relevant papers published before May 4, 2022, using PubMed, Scopus, and Web of Science. Standardized mean difference (SMD) with a 95% confidence interval (CI) was pooled in meta-analysis to yield a summary estimate. We utilized the random-effects model to create pooled effects since we discovered a substantial heterogeneity level. For evaluating quality, the Newcastle-Ottawa scale (NOS) was implemented. RESULTS: The research comprised 12 studies with a total of 2940 individuals who had GI operations, 353 of whom went on to develop AL. We discovered that patients who had GI surgeries and acquired AL had significantly higher NLR levels than those who did not (random-effects model: SMD = 0.75, 95% CI = 0.11-1.38, p = 0.02). Patients with AL showed significantly higher NLR levels than control group in retrospective studies (SMD = 0.93, 95% CI = 0.20-1.66, p=0.01) but not in prospective studies (SMD = - 0.11, 95% CI = - 0.65-0.43, p = 0.69), according to the subgroup analysis based on research design. Subgroup analysis based on ethnicity yielded that white patients with AL exhibited significantly higher NLR values than the control group (SMD = 1.35, 95% CI = 0.01-2.68, p = 0.04) but this result was not applied to East Asian patients (SMD = 0.14, 95% CI = -0.13-0.41, p = 0.29). CONCLUSION: Our research suggests a potential association between preoperative NLR and postoperative AL. However, it is essential to acknowledge the variability in the findings, with significantly higher NLR levels observed in retrospective studies and among white patients, but not consistently replicated in prospective studies and among East Asian patients. Further investigations with larger and more diverse cohorts are warranted to validate these findings and explore potential factors contributing to the observed discrepancies.

Pretransplantation Inflammatory and Nutritional Status in Elderly Allogeneic Hematopoietic Stem Cell Transplantation: Prognostic Value of C-Reactive Protein-to-Albumin Ratio.

There are no clear criteria for selecting elderly patients with hematologic malignancies eligible for allogeneic hematopoietic stem cell transplantation (HSCT). This study aimed to evaluate inflammatory and nutritional status biomarkers as prognostic indicators of allogeneic HSCT in elderly patients. We compared the prognostic effects of 4 representative pretransplantation biomarkers: C-reactive protein-to-albumin ratio (CAR), Glasgow Prognostic Score (GPS), prognostic nutritional index (PNI), and albumin-to-globulin ratio (AGR). A total of 143 patients age ≥60 years who underwent their first allogeneic HSCT for a hematologic malignancy were enrolled between 2010 and 2020 in our single-center cohort. The median patient age was 65 years (range, 60 to 72 years). Pretransplantation high CAR, high GPS, and low PNI scores were associated with poor overall survival (OS), but the AGR was not associated with OS. Among the 4 biomarkers, CAR stratified OS most significantly (P < .001). Multivariate analyses identified only high CAR as an independent prognostic factor associated with OS (hazard ratio [HR], 1.98; P = .031) and showed that a Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) score ≥3 also was associated with OS (HR, 2.04; P = .012). High CAR was correlated with poor performance status, male sex, and high Disease Risk Index, but not with high HCT-CI score. When the patients were stratified into 3 groups according to a composite risk assessment using CAR and HCT-CI, the 3-year OS decreased significantly with increasing scores (82.8%, 50.3%, and 27.0%, respectively; P < .0001). In conclusion, CAR is the most useful prognostic indicator among the inflammatory and nutritional status biomarkers for allogeneic HSCT in elderly patients. Inflammatory and nutritional status in the elderly may be important prognostic factors for allogeneic HSCT independent of HCT-CI score.

Biomarkers of peripheral blood neutrophil extracellular traps in the diagnosis and progression of malignant tumors.

BACKGROUND AND AIMS: The mortality rate associated with malignant tumors remains high and there is a lack of effective diagnostic and tumor progression markers. Neutrophil extracellular traps (NETs) can promote tumor-associated thrombosis, invasive metastasis, and inflammatory responses, but there is a lack of research on the value of measuring NETs in the peripheral blood of patients with malignancies. METHODS: We included 263 patients with malignancies (55 gliomas, 101 ovarian, 64 colorectal, and 43 lung cancers) and 75 healthy controls in this study. We compared the levels of citrullinated histone H3 (citH3), cell-free DNA (cfDNA), and systemic inflammation-related parameters, including neutrophils, lymphocytes, monocytes, platelets, neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune inflammation index, and systemic inflammation response index. We assessed the value of changes in NETs in peripheral blood to determine the diagnosis, venous thromboembolism, clinical staging, and systemic inflammatory response in patients with malignancy. RESULTS: The levels of citH3 and cfDNA in peripheral blood can distinguish between healthy controls and tumor patients. The levels of citH3 and cfDNA before clinical intervention did not predict the risk of combined venous thromboembolism in oncology patients in the short-term after clinical intervention. The levels of citH3, cfDNA, and systemic inflammation-related parameters in the peripheral blood of tumor patients increased with the clinical stage. There was a correlation between cfDNA levels in peripheral blood and systemic inflammation-related parameters in tumor patients, and this correlation was more significant in patients with advanced tumors. CONCLUSIONS: Changes in NETs in the peripheral blood differ between healthy controls and patients with malignant tumors. NETs may be involved in tumor-induced systemic inflammatory responses through interaction with circulating inflammatory cells, thus promoting tumor progression. NETs may be used as markers to assist in the diagnosis and progression of tumor malignancy.

Iron status in Swiss adolescents with paediatric major depressive disorder and healthy controls: a matched case-control study.

PURPOSE: Depression is associated with low-grade systemic inflammation and impaired intestinal function, both of which may reduce dietary iron absorption. Low iron status has been associated with depression in adults and adolescents. In Swiss adolescents, we determined the associations between paediatric major depressive disorder (pMDD), inflammation, intestinal permeability and iron status. METHODS: This is a matched case-control study in 95 adolescents with diagnosed pMDD and 95 healthy controls aged 13-17 years. We assessed depression severity using the Children's Depression Rating Scale-Revised. We measured iron status (serum ferritin (SF) and soluble transferrin receptor (sTfR)), inflammation (C-reactive protein (CRP) and alpha-1-acid-glycoprotein (AGP)), and intestinal permeability (intestinal fatty acid binding protein (I-FABP)). We assessed history of ID diagnosis and treatment with a self-reported questionnaire. RESULTS: SF concentrations did not differ between adolescents with pMDD (median (IQR) SF: 31.2 (20.2, 57.0) µg/L) and controls (32.5 (22.6, 48.3) µg/L, p = 0.4). sTfR was lower among cases than controls (4.50 (4.00, 5.50) mg/L vs 5.20 (4.75, 6.10) mg/L, p < 0.001). CRP, AGP and I-FABP were higher among cases than controls (CRP: 0.16 (0.03, 0.43) mg/L vs 0.04 (0.02, 0.30) mg/L, p = 0.003; AGP: 0.57 (0.44, 0.70) g/L vs 0.52 (0.41, 0.67) g/L, p = 0.024); I-FABP: 307 (17, 515) pg/mL vs 232 (163, 357) pg/mL, p = 0.047). Of cases, 44% reported having a history of ID diagnosis compared to 26% among controls (p = 0.020). Finally, 28% of cases had iron treatment at/close to study inclusion compared to 14% among controls. CONCLUSION: Cases had significantly higher systemic inflammation and intestinal permeability than controls but did not have lower iron status. Whether this is related to the higher rate of ID diagnosis and iron treatment in adolescents with depression is uncertain.

When inflammation is not just inflammation-A review of systemic diseases of the nose and sinuses part 1: IgG4-related disease and sarcoidosis.

BACKGROUND: Chronic rhinosinusitis is a very common condition. IgG4-related disease (IgG4-RD) and sarcoidosis are systemic diseases which can contribute to the development of chronic rhinosinusitis in select patients. OBJECTIVE: Characterize the presenting features, diagnostic criteria, workup, and management of sinonasal IgG4-RD and sarcoidosis as they are encountered in otolaryngology clinics. METHODS: Full length manuscripts published 2000 or later were reviewed. A separate search was conducted for each disease. Pertinent clinical features related to sinonasal manifestations of IgG4-RD and sarcoidosis were collected and reported in this review. RESULTS: 404 references were discovered during literature review process. In total, 42 references for IgG4-RD and 34 references for sarcoidosis were included in this review. CONCLUSION: IgG4-RD and sarcoidosis are autoimmune inflammatory conditions that can affect many systems of the body. For both disease entities, sinonasal disease is a less common presentation which can lead to delayed diagnosis. Sinonasal IgG4-RD commonly presents in the setting of multisystem disease. All with other clinical features, biopsy plays a key role in the diagnosis for both diseases. Treatment for IgG4-RD consists primarily of steroids and rituximab which can lead to excellent and durable remission. A variety of immunosuppressive agents are used in the management of sarcoidosis. Surgery for IgG4-RD is primarily utilized for tissue biopsy, although resection or debulking may be considered. For sarcoidosis, surgery can be used for tissue biopsy and functional sinus surgery can offer symptomatic relief in many patients.

Age-and Gender-Specific Reference Intervals for Systemic Inflammatory Indicators in Healthy Moroccan Adults.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and the systemic immune inflammation index (SII) are effective prognostic markers of patients in various clinical situations such as cancer, cardiovascular diseases and inflammatory diseases. This study aims to explore the reference values based on gender and age for NLR, PLR, LMR and SII in the Moroccan population. METHODS: From January 2018 to February 2020, data of ostensibly healthy adults were collected retrospectively from the laboratory information system (LIS) of the Laboratory for Research and Medical Analysis of the Fraternal Royal Gendarmerie, Rabat (Morocco). A total of 5,898 men and 10,172 women aged between 18 and 90 years were included. RIs of each parameter were established and validated in accordance with the Clinical and Laboratory Standards Institute (CLSI) document C28-A3. RESULTS: NLR was significantly different between men and women (p < 0.05), while PLR, LMR and SII were not. The values of NLR, PLR, LMR and SII differed significantly between different age groups of both genders (p < 0.05). Therefore, RI of PLR, LMR, and SII had to be divided into groups based on age, but not on gender, while establishing the NLR reference intervals took into account both factors; age and gender. CONCLUSIONS: This paper provides Reference Intervals for NLR, PLR, LMR, and SII according to age and gender in healthy Moroccan adults. This can improve assessment and potentially widen the use of these biomarkers in Moroccan clinical context.

SuPAR, biomarkers of inflammation, and severe outcomes in patients hospitalized for COVID-19: The International Study of Inflammation in COVID-19.

Severe coronavirus disease 2019 (COVID-19) is a hyperinflammatory syndrome. The biomarkers of inflammation best suited to triage patients with COVID-19 are unknown. We conducted a prospective multicenter observational study of adult patients hospitalized specifically for COVID-19 from February 1, 2020 to October 19, 2022. Biomarkers measured included soluble urokinase plasminogen activator receptor (suPAR), C-reactive protein, interleukin-6, procalcitonin, ferritin, and D-dimer. In-hospital outcomes examined include death and the need for mechanical ventilation. Patients admitted in the United States (US, n = 1962) were used to compute area under the curves (AUCs) and identify biomarker cutoffs. The combined European cohorts (n = 1137) were used to validate the biomarker cutoffs. In the US cohort, 356 patients met the composite outcome of death (n = 197) or need for mechanical ventilation (n = 290). SuPAR was the most important predictor of the composite outcome and had the highest AUC (0.712) followed by CRP (0.642), ferritin (0.619), IL-6 (0.614), D-dimer (0.606), and lastly procalcitonin (0.596). Inclusion of other biomarkers did not improve discrimination. A suPAR cutoff of 4.0 ng/mL demonstrated a sensitivity of 95.4% (95% CI: 92.4%-98.0%) and negative predictive value (NPV) of 92.5% (95% CI: 87.5%-96.9%) for the composite outcome. Patients with suPAR < 4.0 ng/mL comprised 10.6% of the cohort and had a 0.8% probability of the composite outcome. Applying this cutoff to the validation cohort yielded a sensitivity of 93.8% (90.4%-96.7%) and NPV of 95.5% (93.1%-97.8%) for the composite outcome. Among commonly measured biomarkers, suPAR offered stronger discriminatory ability and may be useful in triaging low-risk patients with COVID-19.

Evaluation of Dry Eye Severity and Ocular Surface Inflammation in Patients with Pemphigus and Pemphigoid.

PURPOSE: To evaluate ocular surface involvement, tear cytokine levels, and histopathological changes in pemphigus and pemphigoid patients. METHODS: A total of 22 patients (15 pemphigus and 7 pemphigoids) and 21 non-diseased controls were enrolled in our study. All participants underwent ocular surface evaluation, which included ocular surface disease index test, slit lamp observation, dry eye-related examination, tear multicytokine analysis, and conjunctival impression cytology. RESULTS: Pemphigus and pemphigoid patients presented much more severe conjunctivochalasis, corneal epithelial defects, corneal opacity, symblepharon   and dry eye. Severe ocular surface squamous metaplasia and a significant increase of tear macrophage inflammatory protein-1beta, tumor necrosis factor-alpha, interleukin (IL)-1ß, IL -6, and IL-8 occurred in pemphigus and pemphigoid patients. CONCLUSIONS: Our results revealed that ocular surface inflammation and dry eye persist in most pemphigus and pemphigoid patients, and do not occur in parallel with the systemic course. Regular ophthalmological examinations and local anti-inflammatory should be provided for pemphigus and pemphigoid patients.