The rising incidence of chronic autoimmune and autoinflammatory diseases has been increasingly associated with environmental and lifestyle factors, including Western dietary patterns, intestinal dysbiosis, and reduced production of short-chain fatty acids (SCFAs). Reduced production of acetate, propionate, and butyrate has been associated with impaired epithelial barrier function, altered peripheral immune tolerance, and low-grade systemic inflammation. This article integrates and systematizes current knowledge in the field of immunometabolism, focusing on the role of the microbiota–metabolism–immunity axis. The molecular mechanisms by which these bacterial metabolites modulate immune function—both through the activation of specific surface receptors and direct epigenetic regulation—are analyzed in detail. SCFAs have been shown to actively reprogram the metabolic and transcriptional profiles of effector cells, stimulating anti-inflammatory macrophage polarization, suppressing cellular inflammatory cascades, and inducing the differentiation of protective regulatory T cells. To address the pharmacokinetic limitations of natural fatty acids, this study critically evaluates modern translational strategies. The clinical potential of synthetic receptor agonists, selective epigenetic modulators, and advanced next-generation bacterial consortia is analyzed. The presented data synthesis not only organizes the pathophysiological foundations but, above all, points to promising new directions for personalized non-pharmacological immunomodulation in the treatment of inflammatory diseases.

Chronic wounds remain a major global health challenge despite substantial advances in biomaterials, regenerative medicine, and wound-care technologies. Current therapeutic strategies are largely based on the assumption that chronic wounds represent impaired or incomplete healing responses and therefore require augmentation of regenerative processes. This paradigm has driven the development of increasingly sophisticated wound dressings incorporating extracellular matrix analogs, growth factors, stem cells, extracellular vesicles, biosensors, and bioelectronic components. However, the clinical impact of these innovations has often fallen short of expectations. In this review, we propose a conceptual framework intended to generate experimentally testable hypotheses rather than provide a definitive mechanistic model. Persistent alterations in immune, stromal, vascular, extracellular matrix, metabolic, mechanical, and microbial networks create interconnected feedback systems that resist transition toward regeneration. From this perspective, successful therapy requires not only stimulation of repair mechanisms but also disruption of the processes that stabilize chronicity. We discuss how advances in systems biology, immunomodulatory biomaterials, bioelectronics, artificial intelligence, and precision medicine support the emergence of adaptive therapeutic interfaces capable of sensing, interpreting, and reprogramming pathological tissue behavior. Unlike previous reviews that primarily summarize emerging wound dressings or regenerative biomaterials, this Review proposes a systems-level conceptual framework in which chronic wounds are interpreted as stable pathological tissue states maintained by multiscale biological memory. This perspective integrates biomaterials, systems biology, artificial intelligence, and tissue-state dynamics into a unified translational model that has not previously been presented in the wound-healing literature. Previous reviews have predominantly focused on the design, biological activity, or clinical performance of individual biomaterials. In contrast, the present Review proposes a systems-level framework that integrates wound biology, biological memory, tissue-state dynamics, artificial intelligence, and adaptive biomaterials into a unified conceptual model for precision wound medicine. This state-based model reframes advanced wound dressings as tools for biological state engineering and provides a translational framework for the future of chronic wound management.

Postoperative wound complications remain a major cause of morbidity, prolonged hospitalization, increased healthcare costs, and reduced quality of life. While traditional wound dressings functioned primarily as passive barriers against contamination and exudate, advances in wound biology have transformed surgical wound management. Tissue repair is now recognized as a dynamic immunometabolic process involving coordinated interactions among immune cells, stromal populations, extracellular matrix remodeling, mechanotransduction, mitochondrial function, redox balance, microbial ecology, and bioelectrical signaling. Consequently, modern wound dressings are increasingly designed as bioactive systems capable of actively modulating the wound microenvironment. Recent developments in biomaterials science, immunoengineering, nanotechnology, extracellular vesicle biology, bioelectronics, and artificial intelligence have enabled the creation of advanced wound platforms, including stimuli-responsive hydrogels, immunomodulatory biomaterials, nanozyme-based dressings, conductive scaffolds, oxygen-generating matrices, extracellular vesicle-loaded systems, and biosensor-integrated interfaces. Therapeutic strategies are progressively shifting from antimicrobial-focused approaches toward immune-regenerative modulation targeting chronic inflammation, mitochondrial dysfunction, ferroptosis, cellular senescence, and impaired mechanobiological signaling. This review examines emerging surgical wound dressings from mechanistic, translational, and biomaterial perspectives, highlighting current innovations, translational challenges, and future directions. Collectively, these technologies may enable intelligent therapeutic systems capable of sensing and directing tissue regeneration in real time.

Coronary artery disease (CAD) is increasingly recognized as a thromboinflammatory disorder in which innate immune activation and coagulation are tightly coupled within the plaque microenvironment. Emerging single-cell and spatial technologies have refined this paradigm by demonstrating that these processes are not diffusely distributed but instead concentrated within discrete cellular niches. This narrative review critically evaluates mechanistic and translational studies integrating single-cell RNA sequencing, spatial transcriptomics, and ligand-receptor modeling to characterize cell-cell communication networks driving immunothrombosis in CAD. Converging evidence from single-cell and spatial studies indicates substantial heterogeneity among macrophages, neutrophils, and smooth muscle cells, with functionally distinct subpopulations contributing differentially to inflammation, matrix remodeling, and thrombogenicity. Spatial analyses further demonstrate that procoagulant and inflammatory programs converge in anatomically defined high-risk regions, particularly at the plaque shoulder and sites of endothelial dysfunction. However, whether these transcriptional states represent causal drivers or epiphenomena remains unresolved. Many insights are derived from murine models or dissociated tissues, raising concerns regarding translational relevance and loss of spatial context. Additionally, computational inference of intercellular communication remains indirect and requires functional validation. In conclusion, immunothrombosis in CAD should be interpreted as an emergent property of spatially organized cellular networks rather than a uniform inflammatory state. While these approaches identify candidate therapeutic nodes, their clinical translation and the central challenge is to distinguish causal regulatory nodes from transcriptional correlates generated by high-dimensional profiling.

Vulvar Lichen Sclerosus (VLS) is a chronic inflammatory dermatosis of unknown etiology affecting the external genitalia. In pediatric patients, it can lead to significant discomfort and progressive structural changes in tissues. In recent years, there has been increasing interest in the participation of immune checkpoints and inflammatory mediators in the pathogenesis of chronic diseases, including VLS. Immune checkpoints, such as PD-1, PD-L1, CTLA-4, CD200, and CD200R, play a crucial role in modulating the immune response and may serve as potential diagnostic markers and therapeutic targets. This study aimed to evaluate the expression of PD-1, PD-L1, CTLA-4, CD200, and CD200R molecules on CD4+ T cells, CD8+ T cells, and CD19+ B lymphocytes in prepubertal girls diagnosed with VLS. Additionally, the concentrations of their soluble forms and the levels of proinflammatory cytokines, including IL-2, IL-6, and TNF-α, in serum were determined to assess their potential as diagnostic biomarkers. The study included patients with VLS (study group) and healthy children (control group). The expression of checkpoints was analyzed using flow cytometry, while the concentrations of soluble forms and cytokines were determined using the enzyme-linked immunosorbent assay (ELISA) technique. Statistical significance tests and Spearman’s rank correlation analysis were used. Patients with VLS showed markedly higher serum C-reactive protein (CRP) levels compared with healthy controls (49.99 ± 6.09 mg/L vs. 2.70 ± 0.96 mg/L, p < 0.001). A significant increase in checkpoint expression was observed on lymphocyte subsets, including CD4+ T cells expressing PD-1 (4.90 ± 1.67% vs. 0.85 ± 0.56%, p < 0.001) and CTLA-4 (11.58 ± 4.70% vs. 0.96 ± 0.48%, p < 0.001), as well as CD8+ T cells expressing PD-1 (17.31 ± 4.81% vs. 0.76 ± 0.67%, p < 0.001) and CD19+ B cells expressing PD-L1 (16.10 ± 9.50% vs. 1.41 ± 0.45%, p < 0.001). Soluble checkpoint molecules were consistently elevated, for example, sPD-1 (26.69 ± 3.88 pg/mL vs. 4.40 ± 0.75 pg/mL, p < 0.001) and sCTLA-4 (43.96 ± 3.77 pg/mL vs. 5.09 ± 1.09 pg/mL, p < 0.001). Similarly, cytokine levels were significantly increased in VLS patients, including interleukin-2 (28.80 ± 6.36 pg/mL vs. 4.32 ± 1.33 pg/mL, p < 0.001), interleukin-6 (25.35 ± 7.52 pg/mL vs. 2.35 ± 0.78 pg/mL, p < 0.001), and tumor necrosis factor alpha (31.26 ± 3.10 pg/mL vs. 12.80 ± 1.30 pg/mL, p < 0.001). Correlation analyses confirmed significant positive associations between cytokine concentrations and checkpoint expression, highlighting their interdependence in VLS immunopathogenesis. The obtained results confirm an increased immunoactivation profile in children with VLS, characterized by elevated checkpoint expression and increased levels of proinflammatory cytokines. The studied parameters show potential as diagnostic and prognostic biomarkers, which may constitute the basis for the development of new diagnostic tools and targeted therapeutic strategies in VLS in pediatric patients.

BACKGROUND:Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and is characterized by dysregulated apoptosis and metabolic reprogramming, including alterations in lipid metabolism. However, the plasma lipidome of newly diagnosed, treatment-naïve CLL patients remains insufficiently characterized. This study aimed to define disease-specific plasma lipidomic alterations, identify discriminatory lipid species, and investigate associated metabolic pathways. METHODS:The study cohort consisted of 41 participants (median age 75 years, range: 40-86), including 30 newly diagnosed, treatment-naïve CLL patients (median age 75 years, range: 40-86) and 11 age- and sex-matched healthy controls (median age 75 years, range: 41-85). Targeted lipidomic profiling was performed on plasma samples using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Data processing was conducted in R using LipidSigR. Statistical analyses employed the Wilcoxon-Mann-Whitney test with Benjamini-Hochberg correction. To address data dimensionality, Boruta machine learning and pathway enrichment analyses were applied. Gene-lipid associations were further explored using GATOm, followed by Metascape analysis to identify enriched biological processes. RESULTS:A total of 124 lipid species from five major classes (phosphatidylcholines, lysophosphatidylcholines, sphingomyelins, ether-linked phosphatidylcholines, and acylcarnitines) were quantified. CLL patients exhibited significant enrichment of acylcarnitines, saturated phosphatidylcholines, and sphingolipids compared with controls. Principal component analysis showed partial separation by disease status. Machine learning identified carnitines and ether-linked phospholipids as key discriminators. Integrated gene-lipid analyses revealed significant enrichment of lipid metabolism-related pathways, particularly glycerolipid and phosphatidylcholine metabolism, as well as lipid catabolism, ether lipid metabolism, and fatty acid metabolism. CONCLUSIONS:Treatment-naïve CLL patients display distinct plasma lipidomic signatures indicative of disease-specific metabolic reprogramming. Integrated lipidomic and predictive pathway analyses suggest disruptions in lipid metabolic pathways and highlight carnitines and ether-linked phospholipids as biological markers warranting further investigation as potential CLL biomarkers.

Coronary artery disease remains an epidemiological challenge as global morbidity is not declining despite the fact that the risk factors are well known. Metabolomic derivatives of atherosclerosis formation have recently gained attention as a possible non-traditional risk factor. The aim of this study was to find potential differences in acetyl-carnitine chain serum concentrations between epicardial artery disease patients and a control group. There were 41 patients (25 men and 16 women), with a median (Q1–Q3) age of 69 (63–73) years, enrolled in the prospective metabolomic analysis. They were divided into two groups based on cine angiography results confirming epicardial artery disease (group 1, n = 25 (61%)) or showing characteristics corresponding to normal angiograms (group 2, n = 16 (39%)). The quantitation of metabolites was performed based on the coronary angiograms. Significant differences related to the plasma concentration of L-Acetyl-carnitine (7.49 (4.79–9.23) µM vs. 9.36 (8.57–10.23) µM (p = 0.009)), Decanoyl-carnitine (0.00 (0.00–0.37) µM vs. 0.36 (0.19–0.44) µM (p = 0.040)), C12:1-carnitine (0.17 (0.14–0.20) µM vs. 0.22 (0.18–0.24) µM (p = 0.008)), trans-2-Dodecenoyl-carnitine (0.10 (0.07–0.13) µM vs. 0.13 (0.10–0.15) µM (p = 0.002)), cis-5-Tetradecenoyl-carnitine (0.03 (0.02–0.04) µM vs. 0.04 (0.03–0.05) µM (p = 0.043)), and 3,5-Tetradecadien-carnitine (0.16 (0.14–0.18) µM vs. 0.18 (0.17–0.27) µM (p = 0.007)) in group 1 vs. group 2 were noted. Increased plasma levels of acetyl-carnitine may be characteristic of patients with normal coronary angiograms.

Oxidative stress (OS), defined as an imbalance between pro-oxidant and antioxidant mechanisms, contributes to DNA and protein oxidation as well as cellular injury, and plays a pivotal role in the pathogenesis of chronic kidney disease (CKD). Peroxiredoxins (PRDXs) are key antioxidant enzymes that regulate intracellular peroxide levels and maintain redox homeostasis. Beyond its renal implications, OS is closely intertwined with hypertension and atherosclerosis, both common comorbidities that accelerate CKD progression. As previously reported, serum concentrations of PRDXs 1-5 may help to differentiate between IgA nephropathy (IgAN), membranous nephropathy (MN), and lupus nephritis (LN). This study aimed to assess the utility of baseline serum PRDX levels in predicting longitudinal changes in kidney function and proteinuria in patients with IgAN, MN, and LN. We analyzed data from 80 patients (IgAN, n = 36; MN, n = 23; LN, n = 21) drawn from an initial cohort of 108 in whom baseline serum concentrations of PRDX 1-5 were measured. Patients were stratified into low, medium, and high PRDX level groups at baseline, and associations between these strata and longitudinal changes in eGFR and proteinuria were assessed over a follow-up period of up to five years. Across all groups, the follow-up eGFR was significantly associated with low baseline serum PRDX 1, 2, 3, and 5 (p = 0.043; p = 0.001; p = 0.036; p = 0.007, respectively). Significant associations were also observed between 24 h follow-up proteinuria and low baseline serum PRDX 2, 3, and 5 (p = 0.025; p = 0.025; p = 0.005, respectively), medium PRDX 4 (p = 0.010), and high PRDX 2 (p = 0.019). No significant associations were found within the study groups; however, these associations were more pronounced in IgAN and MN patients. These findings suggest a potential role for PRDXs in predicting and monitoring CKD progression, especially eGFR decline.

INTRODUCTION:The immune system protects the body against pathogens, and its dysfunction leads to primary and secondary immunodeficiencies, increasing infection susceptibility. Epstein-Barr virus (EBV) reactivation is linked to immune homeostasis disorders, particularly in common variable immunodeficiency (CVID) and chronic lymphocytic leukemia (CLL). Toll‑like receptor (TLR) pathways play a crucial role in innate immunity, and their deregulation may contribute to immune dysfunction. OBJECTIVES:This study aimed to assess the impact of EBV reactivation on immune homeostasis, focusing on TLR2, TLR4, TLR7, and TLR9 expression in T and B lymphocyte subpopulations and their soluble forms in CVID and CLL patients. PATIENTS AND METHODS:The study included 60 CVID patients, 60 CLL patients, and 30 healthy controls. EBV antigens, viral DNA levels, T and B lymphocyte immunophenotypes, and serum soluble TLR (sTLR) concentrations were analyzed using flow cytometry and enzyme‑linked immunosorbent assay. RESULTS:EBV reactivation was detected in 55% of CVID and 60% of CLL patients. These patients showed significant TLR expression disturbances and increased sTLR levels. Notably, TLR7 and TLR9 expression was elevated in CD4+, CD8+ T, and CD19+ B cells, correlating with EBV load and immune dysfunction severity. CONCLUSIONS:EBV reactivation plays a key role in TLR pathway deregulation in CVID and CLL, potentially accelerating disease progression and increasing infection risk. TLR expression and sTLR levels could serve as biomarkers for EBV reactivation, aiding therapeutic strategies to stabilize immune responses.

INTRODUCTION:Paediatric vulval lichen sclerosus (VLS) is a chronic disease with distressing symptoms and severe consequences when left untreated. Majority of existing data on pathophysiology and treatment is based on studies conducted among adult patients. Whereas the course of VLS, its symptomatology and prognosis are distinct to some extent in paediatric and adolescent patients as compared with adults. The purpose of this scoping review is to systematically examine what symptoms of VLS are typical of paediatric and adolescent patients, how often specific signs and symptoms are reported in the literature, if there are differences between paediatric and adolescent patients and what could be the implication of such differences. METHODS AND ANALYSIS:This scoping review will adopt the methodology for Joanna Briggs Institute scoping reviews and will consider studies that include female patients aged 1-18, with VLS symptoms and signs with no exclusion based on ethnicity, comorbidity or previous history of treatment. Studies on any aspect of paediatric VLS, including pathogenesis, diagnosis and treatment, which included patients and reported patients' symptoms and signs, will be considered eligible. There will be no geographical or cultural limitation applied in relation to this scoping review. The search will include Embase, Academic Search Premier, CINAHL, Cochrane Library, Google Scholar, Health Source, Ovid Embase, Ovid Medline, PubMed, Scopus and Web of Science Principal Collection. A critical synthesis and results will be presented in the final review as tables and accompanying narrative summary. ETHICS AND DISSEMINATION:Ethical approval is not required for this review. To date, no systematic approaches were undertaken to classify symptoms of the VLS that would aid in formulating disease severity criteria adequate for the paediatric population. We believe that the results of this review will facilitate the development of disease severity scales that could aid in intraindividual and interindividual comparability, both in real-life settings and clinical trials. TRIAL REGISTRATION NUMBER:https://doi.org/10.17605/OSF.IO/FB9EG.

Common Position of Scientific Societies: Polish Society of Dermatology (PTD), Polish Society for Fundamental and Clinical Immunology (PTiDiK), Polish Society of Paediatric Oncology and Haematology (PTOHD) Background and Objectives This paper aims to analyse, assess and appraise appropriate use of Normal Polyvalent Immunoglobulins (IgGs) across multiple indications, wherever these therapies are known to be used and have been proven to be an effective therapeutic modality. This assessment is based on a framework proposed by a group of international experts in the recent Green Paper „Appropriate Use of Immunoglobulins in Europe”.1 Based on a systematic application of the framework’s criteria to all IgG conditions and diseases, this paper presents a short-list of indications, where IgG use is appropriate, together with a guidance on optimal therapeutic paradigms. As such, this paper is aimed to assist the clinical community and policy makers in navigating the extremely complex clinical landscape of rare and ultra-rare diseases and conditions, which are either immune-mediated or stem from deficient, dysregulated or dysfunctional immune system. Some of the indications considered in this study are currently not registered for IgG use in Poland or, if registered, not fully covered with reimbursement. In cases where IgG use in such conditions or diseases is found to be appropriate, this study may be also considered by the relevant regulatory and/or HTA bodies as a contribution towards reassessment or reappraisal.

Coronary artery atherosclerosis is a common condition characterized by different symptomatology and incidences of risk factors. The disease manifestation may differ; therefore, proper diagnosis is essential. The preventive, diagnostic, and therapeutic arms are still developing to improve patient outcomes. Among diagnostic steps, the non-invasive tools for evaluating non-classical factors related to metabolomic profiles are gaining attention. The aim of this study was to investigate possible metabolic profiling differences between patients with chronic coronary artery disease (CAD) and a control group based on plasma sphingomyelin levels. The study group consisted of 23 patients (72% male, median age of 69 (63-72) years) presenting with chronic coronary syndrome and confirmed epicardial disease in coronary angiography and 15 patients (33% male, median age of 70 (64-72) years) with normal angiographic results. Clinical data were recorded, and blood samples were collected for standard biochemical laboratory assessment and metabolomic profiling. The plasma sphingomyelin levels were evaluated in patients with different degrees of coronary artery atherosclerosis involvement. In addition, the severity of the epicardial disease was estimated by the Gensini Score. The study subgroups did not differ in terms of age (p = 0.765) and co-morbidities, though the male sex was more common in the CAD group (p = 0.007). The analysis revealed significant differences regarding neutrophil count (p = 0.014), neutrophil-to-lymphocyte ratio (NLR) (p = 0.016), and high-density lipoprotein (HDL) (p = 0.003). Among different plasma sphingomyelin species, there was a significant difference in plasma SM42:1 level (16.2 (14.2-19.1) vs. 20.8 (18.9-21.7) (p = 0.044) between the CAD and control groups, respectively. The SM 42:1 plasma level was independent of the number of involved epicardial arteries (p = 0.109). However, Spearman correlations tests were performed between the SM 42:1 plasma level and the number of coronary arteries diagnosed with atherosclerosis disease (rho = -0.356, p = 0.014) and the severity of the disease measured by the Gensini Score (rho = -0.403, p = 0.006). There was no correlation between plasma sphingomyelin levels and NLR (Spearman's rho = -0.135, p = 0.420), suggesting a lack of inflammatory associations. Further, sphingomyelins showed no relationship with coronary artery disease risk factors such as dyslipidemia and diabetes. Lower plasma SM 42:1 levels were revealed in the CAD group compared with the control group, indicating a possible significance of sphingomyelin 42:1 in coronary artery disease progression.

Hair mineral analysis (HMA) has emerged as a promising non-invasive method for assessing long-term exposure to trace elements and metals, potentially complementing traditional biochemical and clinical markers of cardiovascular risk. This review synthesizes current evidence on the relationships between hair elemental profiles and cardiovascular disease (CVD), with an emphasis on toxic metals (As, Hg, Pb, Cd, Ni, Al) and essential micronutrients (Mg, Mn, Zn, Cu, Fe, Cr, Li). The reviewed studies consistently show that patients with CVD exhibit elevated levels of toxic elements and reduced concentrations of protective ones, reflecting oxidative stress, inflammation, and endothelial dysfunction as mechanistic links. Methodologically, the review highlights inductively coupled plasma mass spectrometry (ICP-MS) with collision/reaction cell technology and microwave digestion as gold-standard analytical approaches, while underscoring the urgent need for harmonized protocols, validated washing procedures, and certified reference materials. The interpretation of HMA requires consideration of temporal dynamics, external contamination, and regional variability. Although current evidence supports the research utility of HMA, its clinical integration remains limited by the absence of reference ranges and prospective validation. HMA may hold future value in environmental risk stratification and primary prevention in exposed populations, but further standardization and large-scale longitudinal studies are necessary to define its diagnostic and prognostic relevance in cardiovascular medicine.

Background/Objectives: Pregnancy-induced hypertension (PIH), including preeclampsia (PE), remains a significant cause of maternal and fetal morbidity. Immune imbalance involving T helper (Th17) and regulatory T (Treg) cells is increasingly recognized as contributing to the pathogenesis of PIH. This study aimed to assess the proportions of Th17 and Treg cells and intracellular cytokine expression (IL-17A, IL-17F, IL-21, and IL-22) in the peripheral blood of hypertensive versus normotensive pregnant women. Methods: A total of 108 pregnant women were included: 60 with hypertensive disorders and 48 normotensive controls. Peripheral blood mononuclear cells were analyzed using multiparametric flow cytometry to quantify CD4+CD25+FoxP3+ Treg and CD4+IL-17A+ Th17 cells, along with intracellular IL-17F, IL-21, and IL-22 co-expression. Correlations with clinical and obstetric parameters were evaluated. Results: Hypertensive patients showed significantly increased proportions of activated Th17 cells (CD4+IL-17A+) and Th17 subpopulations co-expressing IL-17F and IL-22, as well as IL-21 and IL-22 (p < 0.0001). Although Treg cell percentages were lower in the hypertensive group, the difference was not statistically significant. A pronounced Th17/Treg imbalance was observed. Positive correlations were found between Th17 subpopulations and gestational age, birth weight, and length, as well as maternal age. Conclusions: The immune profile in hypertensive pregnancies was characterized by a shift toward Th17-mediated proinflammatory responses, supporting the role of immune dysregulation in PIH. The increased frequency of Th17 cells co-expressing IL-21 and IL-22 may serve as a potential biomarker of disease severity and warrants further exploration.

Objectives: This study aimed to assess the systemic and local inflammatory responses in patients with periimplantitis, focusing on key immune markers and clinical parameters. The study further explores the relationship between inflammatory markers, clinical indices, and immune dysregulation, particularly regarding T-cell exhaustion and systemic inflammation. Methods: A cohort of patients with periimplantitis, classified into moderate and advanced stages, was compared to a control group of healthy individuals with dental implants. Clinical parameters, including plaque index (API), bleeding on probing (BoP), probing pocket depth (PPD), and peri-implant sulcus depth (PSI), were recorded. Hematological, immunological, and biochemical analyses were performed, with a focus on immune cell populations (NK cells, T-cells, and their exhaustion markers PD-1 and PD-L1). Results: Patients with periimplantitis exhibited significantly higher clinical indices (API, BoP, PSI, and PPD) than the control group, with the most pronounced differences in the advanced periimplantitis group. Hematological analysis revealed increased leukocyte and neutrophil counts, whereas NK cell levels were significantly reduced. Immunological profiling indicated elevated PD-1 and PD-L1 expression on T-cells, suggesting T-cell exhaustion and immune dysregulation. Furthermore, strong correlations were found between increased PPD values and elevated inflammatory marker levels, highlighting the relationship between peri-implant pocket depth and systemic inflammation. Conclusions: The findings confirm that immune dysregulation plays a central role in periimplantitis progression. The association between increased inflammatory markers, immune alterations, and clinical indices emphasizes the need for a multifactorial diagnostic and treatment approach. Integrating immune modulation strategies, clinical assessments, and lifestyle modifications, such as improved oral hygiene and smoking cessation, could improve disease management and reduce recurrence.

The pro-coagulative characteristics of HF patients are postulated, though no specific therapeutic targets have been proposed. A total of 88 patients (17 female, 19%) with a median age of 68 years (range, 63 - 74) and a de novo congestive HF diagnosis were enrolled in the prospective study. Co-morbidities, laboratory tests, and imaging results (echocardiography, coronary angiography) were compared to the concentration of peripheral blood citrullinated histone 3 (CitH_3), a marker of neutrophil extracellular trap (NET) formation, on admission. The analyzed population was divided into two groups based on LVEF performance: HFmrEF (42 patients, 47%) and HFrEF (46 patients, 53%), with a median (Q1-Q3) age of 68 (62-74) vs. 69 (63-74) years (p = 0.789), respectively. The significant difference in CitH_3 serum concentration between the heart failure with preserved ejection fraction (HFrmEF) group (395 pg/ml [201-482]) and the heart failure with reduced ejection fraction (HFrEF) group (1941 pg/ml [405-3376]) was noted (p = 0.019). A negative correlation was noted between LVEF and citH_3 in the analyzed group (r = -0.444, p = 0.005), and with serum NT-pro-BNP (r =  -0.435, p < 0.001). No correlation between citH_3 and NT-pro-BNP was found (r = 0.305, p = 0.939). Patients with heart failure and a decreased left ventricular ejection fraction can be characterized by increased neutrophil extracellular trap formation. The negative correlation between left ventricular characteristics and CitH_3 concentration suggested an increased pro-thrombotic state in HF patients. NETs could be considered a potential therapeutic target in HF patients to improve clinical outcomes. Further studies are required to confirm these findings.