Search Results (204)

Background and Objectives: Accurately diagnosing acute appendicitis (AA) in children remains clinically challenging due to overlapping symptoms with other pediatric conditions and limitations in conventional diagnostic tools. The systemic immune-inflammation index (SII) has emerged as a promising biomarker in adult populations; however, its utility in pediatrics is still unclear. This study aimed to evaluate the diagnostic accuracy of SII in distinguishing pediatric acute appendicitis from elective non-inflammatory surgical procedures and to assess its predictive value in identifying complicated cases. Materials and Methods: This retrospective, single-center study included 397 pediatric patients (5–15 years), comprising 297 histopathologically confirmed appendicitis cases and 100 controls. Demographic and laboratory data were recorded at admission. Inflammatory indices including SII, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were calculated. ROC curve analysis was performed to evaluate diagnostic performance. Results: SII values were significantly higher in the appendicitis group (median: 2218.4 vs. 356.3; p < 0.001). SII demonstrated excellent diagnostic accuracy for AA (AUROC = 0.95, 95% CI: 0.92–0.97), with 91% sensitivity and 88% specificity at a cut-off > 624. In predicting complicated appendicitis, SII showed moderate discriminative ability (AUROC = 0.66, 95% CI: 0.60–0.73), with 83% sensitivity but limited specificity (43%). Conclusions: SII is a reliable and easily obtainable biomarker for diagnosing pediatric acute appendicitis and may aid in early detection of complicated cases. Its integration into clinical workflows may enhance diagnostic precision, particularly in resource-limited settings. Age-specific validation studies are warranted to confirm its broader applicability. Full article

Background/Objectives: Acne vulgaris is a widespread, chronic inflammatory skin condition that significantly impacts patients’ quality of life. Although oral isotretinoin remains the most effective treatment, recent evidence suggests that H₁-antihistamines such as desloratadine and levocetirizine may enhance acne therapy. This study assesses whether combining H₁-antihistamines to isotretinoin enhances treatment efficacy in acne vulgaris compared to isotretinoin alone. Methods: Our analysis included 10 randomized controlled trials involving 675 patients collectively, predominantly from Asia and the Middle East. Data were extracted by two independent reviewers, with discrepancies resolved by a third. Risk of bias was assessed using the Cochrane RoB 2 tool. Analyses were performed using RevMan 5.4 with random-effects models, and heterogeneity was evaluated via I² and Q tests. Sensitivity analyses were conducted to assess result robustness. Results: Combination therapy with isotretinoin and desloratadine showed a significantly greater reduction in GAGS (Global Acne Grading Scale) score by week 12 (p < 0.00001; MD 2.68, 95% CI 1.60 to 3.75; I² = 0%) while earlier timepoints showed non-significant or borderline results. For inflammatory lesions, significant improvements with desloratadine emerged at weeks 4, 8, and 12 after excluding an influential outlier, with low heterogeneity and consistent direction of effect. Non-inflammatory lesions did not differ significantly at weeks 4 or 8. At week 12, a significant reduction was seen in the desloratadine subgroup (OR 2.61, p = 0.003, I² = 11%) and in overall pooled analysis (OR 2.77, p < 0.0001, I² = 2%). Among side effects, acne flare-ups, pruritus, and cheilitis were significantly reduced in the desloratadine group, as well as in pooled analysis. Xerosis did not consistently differ between groups. Overall, desloratadine improved tolerability and reduced mucocutaneous adverse events more than levocetirizine. Conclusions: Current evidence suggests that combining oral antihistamines with isotretinoin may offer therapeutic benefits in acne management, particularly in enhancing tolerability and potentially improving clinical outcomes, as reflected by significant reductions in GAGS scores and mucocutaneous adverse effects such as cheilitis, pruritus, and acne flare-ups. Full article

Background/Objectives: Given the multifaceted role of estrogen hormones in skeletal muscle pathophysiology and their well-established immunomodulatory properties, this study aimed to characterize the expression of the G-protein-coupled estrogen receptor (GPER) in patients with inflammatory myopathies (IM). Methods: Immunohistochemical analysis was performed on muscle biopsies from 13 patients with IM, 11 with non-inflammatory myopathies (N.IM), and 5control subjects. Intergroup differences in GPER score were statistically evaluated. We performed an analysis based on the Visual Analog Scale (VAS). The scoring system evaluates overall pathology (VAS score) based on four distinct components: inflammation, vascular involvement, myopathic changes, and connective tissue alterations. Results: Immunolocalization analysis demonstrated that GPER is constitutively expressed in human skeletal muscle and is upregulated in IM. Enhanced expression included both sarcolemmal and intracellular membrane localization. Notably, GPER upregulation showed a positive correlation with the severity of tissue inflammation. The IM group had significantly higher VAS scores compared to both the N.IM and control groups. Conclusions: We provide the first histopathological characterization of GPER expression in human skeletal muscle. In IM, GPER upregulation may play a protective role by negatively modulating the release of inflammatory mediators, as suggested by experimental evidence from other models of inflammation. The emerging therapeutic development of GPER agonists may represent a promising avenue for the treatment of inflammatory myopathies. Full article

This article reviews the multifaceted roles of itaconate in immune regulation and inflammatory metabolism. Itaconic acid is a dicarboxylic acid with anti-inflammatory, antioxidant, and anti-tumor properties. It is initially produced by the heating decomposition of citric acid and is closely related to the tricarboxylic acid cycle. In immune regulation, itaconate regulates macrophage function through a variety of mechanisms, including metabolic reprogramming, polarization regulation, inhibition of cytokine production, and regulation of oxidative stress. It can also affect the function of T cells and B cells. In terms of inflammatory metabolism, itaconate can regulate the production of inflammatory factors, inhibit the activity of succinate dehydrogenase, and affect cellular energy metabolism and lipid metabolism. Its mechanism of action involves the inhibition of succinate dehydrogenase, covalent modification of proteins, influence on epigenetic modification, and playing a role through the G protein-coupled receptor OXGR1 (Oxoglutarate Receptor 1). Itaconic acid derivatives have shown good effects in anti-inflammation and anti-oxidation and have broad application prospects in clinical treatment, including the treatment of inflammatory diseases, anti-tumor and anti-microbial infection. However, the long-term safety and side effects of itaconic acid as a therapeutic agent still need to be further studied. Future studies will further explore the synthesis and function of itaconic acid in different cell types, its physiological effects in non-inflammatory conditions, and its potential application in clinical treatment in order to develop new therapeutic strategies and improve the treatment effect of chronic inflammatory and metabolism-related diseases. Full article

Keratoconus (KC) is a progressive non-inflammatory disorder characterized by significant changes in the corneal structure, leading to severe vision loss. Risk factors include eye rubbing, a positive family history, and allergic reactions. There is growing evidence suggesting that sex hormones may influence the development and progression of KC, but the exact mechanisms and extent of their impact remain unclear and controversial. This review aims to examine the current literature on the association between KC and sex hormones and to evaluate the potential of these hormones as clinical markers for diagnosing, prognosticating, and managing KC. Full article

Background: While keratoconus (KC) has traditionally been classified as a non-inflammatory corneal disorder, emerging evidence suggests that inflammatory processes may be involved in its pathogenesis. This study investigated whether systemic inflammation contributes to KC development by measuring serum levels of key pro-inflammatory cytokines in KC patients compared to healthy controls. Methods: This cross-sectional comparative study included 60 participants aged 18–30 and was divided into three equal groups: healthy controls, progressive KC, and stable KC. The levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) in the serum were measured through an enzyme-linked immunosorbent assay. KC severity was classified based on mean keratometry values. Results: There were no significant differences detected in serum IL-6, TNF-α, and IL-1β levels across groups (p > 0.05). Moreover, no significant correlations were found between systemic cytokine levels and KC severity categories (p > 0.05). Conclusions: Systemic levels of IL-1β, IL-6, and TNF-α do not significantly differ between KC patients and controls nor do they correlate with disease severity, reinforcing the hypothesis that KC involves primarily local inflammatory processes. Full article

Acne vulgaris is a dermatological condition characterized by the hyperkeratinization of sebaceous follicles, which can further lead to post-inflammatory hyperpigmentation. Considering the intricate pathophysiology of acne, it is essential to develop novel topical therapies that are capable of targeting multiple underlying mechanisms of acne. The objective of this study was to study the effect of products containing retinol, niacinamide, ceramides, and dipotassium glycyrriszinate on acne-related markers. A total of 43 women with acne skin (including sensitive skin) were enrolled. To evaluate the effect of test products on acne-related indicators following 4 weeks of use, this study combined clinical assessments of skin condition (acne lesion counts), instrumental assessments (skin gloss), and photo tracking using VISIA-CR and Primos CR systems, which encompass metrics such as a*, ITA°, skin area (%) covered by sebum spots, and the presence of sebum spots. Adverse reactions were also assessed. After 4 weeks of treatment, significant reductions were observed in both the inflammatory acne lesion count and non-inflammatory acne lesion count, while there was also a significant decrease in skin redness a* and skin area (%) covered by sebum spots and a significant increase in skin brightness ITA° and gloss. No adverse events occurred during the entire testing process. In summary, the daily application of products containing retinol, niacinamide, and ceramides not only improves acne-related symptoms but also alleviates post-inflammatory hyperpigmentation caused by acne, which suggests that such products have the potential to meet the dual needs of brightening and acne care. Full article

Background: Crystal arthritides represent the most common inflammatory rheumatologic condition. While the prevalence of gouty arthritis by monosodium urate (MSU) is well established, the prevalences of calciumpyrophosphat (CPP) and basic calcium pyrophosphate (ARP) arthritis are less clear. We herein sought to assess the prevalence and inflammatory characteristics of crystal arthritides at our institution, the biggest tertiary center in Switzerland. Methods: A total of 5036 synovial fluid (SF) samples were analyzed with regard to crystal positivity as well as joint, age, and sex distribution in affected patients. We furthermore compared inflammatory and non-inflammatory SF samples for yields of their Polymorphonuclear (PMN) fractions. Results: About half of all samples were derived from knee joints, a male/female ratio up to 10.1:1 among the MSU-positive, and a clear shift towards elder patients with CPP–arthritis was seen. These findings were in line with previous studies and suggest good comparability of our cohort. Of note, 21.9% of all samples were CPP positive, whereas 15.3% and 9.5% were positive for MSU and ARP/alizarin-red positive, respectively. Importantly, CPP crystals were predominant in inflammatory (58.9%) and non-inflammatory (65.7%) samples. By contrast, MSU crystals were significantly more often associated with synovitis (p < 0.001). Interestingly, higher PMN fractions were found in non-inflammatory MSU-positive samples (p < 0.01), whereas a similar trend was seen in CPP-positive samples. Conclusions: CPP arthritis represented the most frequent crystal arthritis form at our center. Higher PMN fractions in non-inflammatory samples with CPP and MSU crystals suggest subclinical inflammation and provide further arguments for earlier anti-inflammatory and uric acid-lowering therapies in patients with crystal deposits. Full article

Background/Objectives: Inflammatory sarcopenia, characterized by muscle weakness exacerbated by chronic systemic inflammation, has emerged as a critical factor in fall risk among older adults. While previous studies have examined sarcopenia and inflammation independently, few have investigated their combined impact on mobility impairments and fall susceptibility, particularly in immunocompromised individuals. This study aimed to assess the role of inflammatory sarcopenia in increasing fall risk by comparing functional performance, muscle strength, and inflammatory biomarkers across three groups: healthy older adults, individuals with non-inflammatory sarcopenia, and those with inflammatory sarcopenia. A secondary objective was to evaluate fall incidence in immunocompromised versus non-immunocompromised individuals. Methods: A prospective observational study was conducted on 250 adults aged ≥65 years, categorized based on inflammatory status and muscle health. Functional assessments included handgrip strength, the Timed Up and Go (TUG) test, and fall frequency analysis. Inflammatory status was determined by measuring C-reactive protein (CRP) and interleukin-6 (IL-6) levels. Multivariate regression models were used to identify predictors of fall risk. Results: Participants with inflammatory sarcopenia exhibited significantly higher CRP and IL-6 levels, greater muscle weakness, poorer mobility performance, and a fourfold increase in fall incidence compared to controls (p < 0.001). Immunocompromised individuals had nearly double the fall risk of their non-immunocompromised counterparts (p < 0.001). TUG test performance was the strongest fall predictor. Conclusions: Our findings highlight the importance of integrating fall prevention strategies that not only focus on muscle-strengthening programs but also include regular screening for inflammatory markers. Given the strong association between systemic inflammation, muscle weakness, and fall risk, identifying and managing chronic inflammation may play a crucial role in reducing mobility impairments and improving outcomes in older adults. Full article

Background/Objectives: Obstruction of the biliary duct may be caused by various conditions ranging from chronic inflammation to neoplasia, including cholangiocarcinoma (CCA). While the definite histological diagnosis of intrahepatic lesions is relatively straightforward, the diagnostic workup of biliary duct stenosis can be challenging, despite the availability of novel tools for intraductal diagnosis. This proof-of-principle study aimed to investigate whether microRNAs (miRNAs) from bile duct stents may be used as biomarkers to differentiate between various bile duct diseases. Methods: For this purpose, we included 100 patients with one or more bile duct stents for various reasons, including malignant disease (n = 40), stenosis due to liver transplantation or surgery (n = 60), and cholangitis (n = 42). During endoscopic retrograde cholangiography, the stents were collected, and miRNA analyses were performed to evaluate miR-16, miR-21, and miR-223. Results: All studied miRNAs were successfully detected from the specimens obtained from the bile duct stents and were comparable in different stents from the same subjects. Following normalization, significant increases in miR-16, -21, and -223 levels were identified in patients with cholangitis compared to specimens from a non-inflammatory cohort. However, when comparing the data from patients in the malignant and non-malignant cohorts, the individual levels of miR-16, miR-21, and miR-223 showed high variation, without reaching a statistically significant difference. Conclusions: In summary, bile duct stents can be considered as potential sources of intraductal biomarkers, specifically miRNAs. Further profiling and validation analyses are necessary to identify the most appropriate miRNA targets for differentiating bile duct diseases. Full article

A biopsy involves the removal of a piece or an entire organ from a living patient. The former began with open heart surgery (surgical pathology) and the latter with the recipient heart in cardiac transplantation. Transvenous or transarterial catheterization is the current procedure to performed endomyocardial biopsy with bioptome from the ventricles. This manoeuvre was first carried out by Werner Forssmann through a urological catheter in 1929, which he introduced into his radial left vein until it reached the RV. Then, in London in 1974, Richardson invented a new technique with a catheter via the right femoral vein, which he applied with success in patients with multiple myocardial diseases, both inflammatory and non-inflammatory. Subsequently, a transjugular endomyocardial biopsy was accomplished by Margaret Billingham to monitor heart rejection during cardiac transplantation. In the beginning, only histology for a light microscope, and rarely during electron microscopy, was employed. With the advent of molecular techniques and the discovery of polymerase chain reaction (PCR), molecular investigation became part of the gold standard for diagnosis involving EMB: histology, immunohistochemistry and molecular investigation, the latter in search of a viral cause. Nowadays, EMB is frequently employed in infiltrative (amyloidosis) and storage diseases (e.g., hemochromatosis and Fabry diseases). Diagnosis of myocarditis is now possible through Magnetic Cardiac Resonance (MCR), in place of BEM histology, thanks to oedema. With the help of ECMO, it is possible to allow the heart to rest, supporting its recovery from ejection fraction even in fulminant myocarditis. Cardiac transplantation with the pathological study of the recipient heart offers the opportunity to discover and study new diseases, like restrictive cardiomyopathy and a non-compacted left ventricle. Full article

This study purpose was to determine the gene expression as well as serum profile of acute phase proteins (APPs) and hormonal indicators linked to Barki sheep’s susceptibility to postpartum issues. Three equal-sized groups (each with fifty ewes) were created from the blood of 150 adult Barki ewes: the control group (CG), the inflammatory postpartum disorders group (IPG), and the non-inflammatory postpartum disorders group (NIPG). The expression levels of the oxidative stress (PGC-1α, SIRT1, GCLC, GCLM, and EPAS1) and metabolic (FBXL12, KPNA7, and LRRK1) genes were significantly higher in postpartum disorders sheep than in resistant ones. Ewes with inflammatory postpartum illnesses showed significantly higher levels of the examined markers than did the non-inflammatory and control groups. The serum profile analysis also revealed that the levels of Fb, Cp, Hp, SAA, cortisol, TIBC, UIBC, and ferritin were significantly higher in the IPG than in the NIPG and CG. Serum insulin, iron, transferrin, and Tf Sat.% levels, however, were all markedly lower. On the basis of the variance in the genes being studied and the modulation in the serum indicators being studied, it should be possible to monitor the health status in postpartum problems of sheep. Full article

The management of inflammatory bowel disease (IBD), which is characterized by immunodeficiency, has attracted increasing attention, highlighting the necessity for more precise and streamlined diagnostic approaches in clinics. Calprotectin, an immune cell-derived protein with inherent anti-inflammatory and antimicrobial properties, plays a pivotal role in immune regulation and intestinal homeostasis. Its expression levels are intricately linked to IBD activity, enabling differentiation between inflammatory and non-inflammatory states while predicting recurrence risks. As a non-invasive biomarker, fecal calprotectin (FC) and serum calprotectin (SC) analysis offers high reproducibility and clinical utility, facilitating both IBD diagnosis and real-time disease monitoring. Beyond its diagnostic specificity in distinguishing IBD from other gastrointestinal disorders, calprotectin also emerges as a promising therapeutic target, due to its dual role in modulating inflammatory pathways and interacting with the gut microbiota. With collaborative advancements in standardized detection protocols and innovative research methodologies, it is anticipated that calprotectin-based strategies will be integrated into mainstream clinical practice for IBD. Full article

Objectives: This retrospective study examines midkine, an inflammatory cytokine, as a potential serological biomarker to distinguish dilated cardiomyopathy (DCM) and inflammatory dilated cardiomyopathy (DCMi). Identifying such a biomarker is crucial for effective treatment of these two entities. Methods: The study included 54 patients with heart failure, reduced left ventricular systolic function, and suspected cardiac inflammation. Endomyocardial biopsies were obtained from all 54 patients to differentiate between DCM and DCMi. Blood sera were collected from these patients the same day the endomyocardial biopsy was performed and compared with those of 13 age-matched healthy individuals for different measurements such as midkine and NT-proBNP. Patients were followed up to a median of 194 days after the baseline visit. Results: Endomyocardial biopsies from patients with DCMi were associated with more infiltrating immune cells such as CD68⁺ macrophages and CD3⁺ T cells and a more frequent presence of a viral genome than those from patients with DCM. Both groups showed similar improvements in LV function and dimensions over time. MK serum levels were significantly higher in DCM/ DCMi patients than in healthy individuals but did not differ significantly between DCM and DCMi. MK levels did not significantly correlate with NYHA class, NT-proBNP, LVEDD, or LVEF, except for a weak correlation with LVEF at follow-up. Conclusions: Midkine serum levels were significantly higher in patients with a DCM phenotype and severely reduced systolic function. However, these levels could not distinguish between DCM and DCMi and showed no correlation with baseline or follow-up parameters. Therefore, midkine cannot be used as a biomarker to distinguish between DCM and DCMi. Full article

Background: IgG4 is the least immunogenic subclass of IgG. Immunization with mRNA vaccines against SARS-CoV-2, unlike other vaccines, induces an increase in IgG4 against the spike protein in healthy populations. This study investigated whether immunosuppressive therapy affects the immune response, focusing on IgG subclass changes, to four doses of mRNA vaccine in kidney transplant recipients (KTRs). Methods: This study includes 146 KTRs and 23 dialysis patients (DPs) who received three mRNA-1273 vaccine doses and a BNT162b2 booster. We evaluated anti-spike IgG titers and subclasses, T-CD4+ and T-CD8+ cellular responses, and serum neutralizing activity (SNA). Results: At the fourth dose, 75.8% of COVID-19 naïve KTRs developed humoral and cellular responses (vs. 95.7% in DPs). There was a correlation between anti-spike IgG titers/subclasses and SNA (p < 0.001). IgG subclass kinetics after the third/fourth dose differed between COVID-19 naïve KTRs and DPs. Immunosuppressive therapy influenced IgG subclasses: mTOR inhibitors (mTORi) positively influenced IgG1 and IgG3 (p < 0.05), while mycophenolic acid negatively affected IgG1, IgG3, and IgG4 (p < 0.05). SNA is correlated with breakthrough infections after four doses of vaccine in KTRs. mTORi was the only factor associated with SNA > 65% in naïve KTRs [4.29 (1.21–15.17), p = 0.024]. Conclusions: KTRs show weaker cellular and humoral immune responses to mRNA vaccines and a class shift towards non-inflammatory anti-S IgG4 upon booster doses. IgG subclasses show a positive correlation with SNA and are influenced by immunosuppression. Increased SNA after four doses of vaccine is protective against infection. mTORi may benefit non-responding KTRs. Full article