Search Results (1,489)

Heart failure (HF) remains a major global health challenge defined by the inability of the heart to adequately meet systemic metabolic requirements. While ventricular dysfunction has traditionally been the primary focus in both conceptual and clinical frameworks of HF, emerging evidence highlights atrial myopathy—covering structural, functional, electrical, metabolic, and neurohormonal remodeling—as a central yet often overlooked contributor to disease progression across the HF spectrum. This review offers a comprehensive overview of the molecular and cellular mechanisms underlying atrial remodeling, with a focus on inflammation and innate immune activation as key pathogenic mediators. Among pattern recognition receptors, Toll-like receptors (TLRs) and NOD-like receptors (NLRs) play crucial roles in translating myocardial stress into pro-inflammatory, profibrotic, and pro-arrhythmic signals that exacerbate HF. By combining experimental and clinical evidence, we emphasize atrial myopathy as both a biomarker and an active driver of HF deterioration, advocating for the inclusion of atrial-targeted diagnostics and immunomodulatory therapies in future HF treatment approaches. Such a paradigm shift holds significant potential for improved risk stratification, arrhythmia prevention, attenuation of structural remodeling, and ultimately, better prognosis and clinical outcomes in this increasingly common syndrome. Full article

Potato (Solanum tuberosum L.) is a globally significant staple crop that faces constant threats from Phytophthora infestans, the causative agent of late blight (LB). The battle between Phytophthora infestans and its host is driven by the molecular interplay of RXLR-encoded avirulence (PiAvr) effectors and nucleotide-binding leucine-rich repeat (NLR) immune receptors in potato. This review provides a comprehensive analysis of the structural characteristics, functional diversity, and evolutionary dynamics of RXLR effectors and the mechanisms by which NLR receptors recognize and respond to them. The study elaborates on both direct and indirect modes of effector recognition by NLRs, highlighting the gene-for-gene interactions that underlie resistance. Additionally, we discuss the molecular strategies employed by P. infestans to evade host immunity, including effector polymorphism, truncation, and transcriptional regulation. Advances in structural biology, functional genomics, and computational modeling have provided valuable insights into effector–receptor interactions, paving the way for innovative resistance breeding strategies. We also discuss the latest approaches to engineering durable resistance, including gene stacking, synthetic NLRs, and CRISPR-based modifications. Understanding these molecular mechanisms is critical for developing resistant potato cultivars and mitigating the devastating effects of LB. This review aims to bridge current knowledge gaps and guide future research efforts in plant immunity and disease management. Full article

Background/Objectives: Prognostic biomarkers are essential for guiding the clinical management of pulmonary hypertension (PH). This study aimed to assess both established and novel biomarkers—specifically, the red cell distribution width-to-estimated glomerular filtration rate ratio (RGR) and the NT-proBNP-to-albumin ratio (NTAR)—for their ability to predict length of hospital stay (LOS), prolonged LOS (ELOS), in-hospital mortality, and 3-month all-cause mortality in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Methods: A retrospective analysis was conducted on 275 PH-related hospital regular admissions (148 PAH; 127 CTEPH). Established biomarkers—including serum albumin, neutrophil-to-lymphocyte ratio (NLR), Log NT-proBNP, red cell distribution width (RDW), and estimated glomerular filtration rate (eGFR)—as well as novel indices (RGR, and NTAR) were examined for their relationships with LOS, ELOS, in-hospital mortality, and 3-month all-cause mortality. Spearman correlation, univariate logistic regression, and ROC analyses evaluated biomarker relationships and predictive performance. Results: Serum albumin independently predicted in-hospital and 3-month mortality in PAH, while in CTEPH, it inversely correlated with LOS and strongly predicted prolonged hospitalization and mortality (AUC = 0.833). NLR had limited correlation with LOS but predicted mortality across both groups. RDW correlated weakly with LOS, significantly predicting prolonged hospitalization (threshold > 52.1 fL) in PAH but not in CTEPH. Preserved renal function (eGFR > 60 mL/min/1.73 m²) was inversely associated with LOS in CTEPH patients, suggesting a protective effect. Additionally, reduced eGFR significantly predicted mortality in both PAH (AUC = 0.701; optimal cut-off ≤ 97.4 mL/min/1.73 m²) and CTEPH (AUC = 0.793; optimal cut-off ≤ 59.2 mL/min/1.73 m²) groups. NTAR (AUC = 0.817) outperformed Log NT-proBNP alone in predicting extended hospitalization and mortality, whereas RGR correlated with LOS and predicted in-hospital mortality. Phenotype-specific analysis demonstrated that inflammatory and renal biomarkers had a stronger prognostic impact in CTEPH. Conclusions: Stratification by PH phenotype highlighted the greater prognostic significance of inflammatory and renal indices, particularly in patients with CTEPH. Incorporating NTAR and RGR into clinical workflows may enhance risk stratification and enable more precisely targeted interventions to improve outcomes in pulmonary hypertension. Full article

Background/Objectives: This study was designed to investigate the relationship between peripheral hematological inflammation markers, namely, neutrophil/lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), systemic immune inflammation index (SII), and systemic inflammatory response index (SIRI) and high-grade cervical lesions (CIN2+). Methods: A retrospective cohort analysis was conducted on 358 patients who underwent cervical excision procedures. Patients were divided into two groups: <CIN2 and CIN2+. Preoperative complete blood count data were used to calculate the inflammation indices. HPV genotypes were also recorded. Logistic regression and ROC analyses were performed to evaluate the predictive performance. Results: CIN2+ lesions were detected in 69.6% of participants. In the univariate analysis, only age and HPV 16 positivity (p < 0.005) showed a significant association with the presence of CIN2+. NLR, PLR, MLR, SII, and SIRI values did not show significant differences between groups (all p > 0.05). In the multivariate analysis, increasing age was independently associated with a decrease in the risk of CIN2+ (OR = 0.96, 95% CI: 0.94–0.99), while HPV 16 positivity was associated with an increase in risk (OR = 2.44, 95% CI: 1.43–4.18). ROC analysis showed that combining age and HPV 16 status improved the specificity (85.1%) of predicting CIN2+ compared to using age alone (42.2%). Conclusions: Peripheral haematological inflammation markers (NLR, PLR, MLR, SII, and SIRI) did not show predictive value in predicting CIN2+ lesions. However, age and HPV 16 infection were found to be independent predictors. These findings suggest that haematological indices may reflect systemic inflammatory responses but are not sufficient on their own for the detection of CIN2+. HPV genotyping is of critical importance for the early detection of high-grade lesions. Full article

Background: The Naples Prognostic Score (NPS) is a composite inflammation–nutrition index whose prognostic value has been scarcely examined in extensive-stage small cell lung cancer (ES-SCLC). This study aimed to evaluate the prognostic significance of the NPS in this setting. Methods: A retrospective analysis was performed on 142 patients diagnosed with ES-SCLC between March 2014 and June 2024. The NPS was calculated using the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), serum albumin, and total cholesterol levels. Patients were classified into three NPS categories (0, 1–2, and 3–4), and subsequently dichotomized into low-risk (0–2) and high-risk (3–4) groups. Survival outcomes were assessed using Kaplan–Meier estimates and multivariate Cox regression models. Results: Median overall survival (OS) was significantly longer in the low-risk group compared to the high-risk group (10.3 vs. 6.3 months; p = 0.012). High NPS remained an independent predictor of reduced OS (HR: 1.45; 95% CI: 1.02–2.06; p = 0.041). The prognostic strength of the NPS was primarily driven by low LMR and hypoalbuminemia, which were individually associated with worse outcomes. Conclusions: The NPS may serve as a simple, accessible, and independent prognostic tool in ES-SCLC, potentially aiding in clinical risk stratification and treatment planning. Full article

Background and Objectives: Carotid artery stenosis is an inflammatory vascular disease closely linked to atherosclerosis and associated with inflammatory biomarkers. The neutrophil/albumin ratio (NAR) is a novel promising biomarker in assessing cardiovascular disease severity. This study aimed to evaluate the relationship between NAR and lesion severity in patients with carotid artery stenosis. Materials and Methods: This retrospective, single-center, comparative study included 625 asymptomatic patients who underwent digital subtraction angiography (DSA) for suspected high-grade carotid artery stenosis between 2012 and 2022. Patients were classified into two groups based on stenosis severity: critical carotid artery stenosis (≥70% stenosis) and non-critical carotid artery stenosis (<70%). Only asymptomatic patients were included; patients with symptoms were excluded. NAR was calculated preoperatively as neutrophil count divided by serum albumin. Additional inflammatory markers, such as neutrophil–lymphocyte ratio (NLR) and C-reactive protein (CRP) to albumin ratio (CAR), were also analyzed. Results: Severe carotid artery stenosis was detected in 191 of the patients who underwent DSA. Individuals in the critical carotid artery stenosis group were older and had a higher prevalence of diabetes mellitus and hypertension (51 (45–57) vs. 60 (54–68), p < 0.001; 143 vs. 83, p = 0.025; 193 vs. 104, respectively, p = 0.021), as well as higher neutrophil counts (4.3 (3.2–6.2) vs. 8.1 (4.9–12.5), p < 0.001), NLR (2.2 (1.4–3.2) vs. 4.2 (2.3–8.9), p < 0.001), while CRP (3.8 (1.8–8) vs. 5.7 (3.6–7.6), p = 0.005) and CAR (0.9 (0.5–1.9) vs. 1.6 (0.8–2.1), p < 0.001) values were significantly higher. NAR was higher in patients of the critical carotid artery stenosis group than the non-critical (1.1 (0.8–1.6) vs. 2.1 (1.4–3.2), p < 0.001). Multivariate analysis identified NAR as an independent predictor of carotid artery stenosis (Odds Ratio [OR]: 3.432; 95% Confidence Interval [CI]: 2.116–5.566; p < 0.001). The best cut-off value of NAR for predicting critical carotid artery stenosis was 1.47, which provided 73.8% sensitivity and 70.5% specificity. Conclusions: NAR, which can be easily measured through a simple blood test, demonstrated moderate sensitivity and specificity in predicting critical carotid artery stenosis, suggesting its potential role as a supportive marker in clinical risk assessment. Full article

Background/Objectives: Preoperative sarcopenia in liver transplantation (LT) recipients is an important prognostic factor of LT outcomes. Systemic inflammatory status (SIS) has been proposed as a unifying mechanism for skeletal muscle loss; thus, considering SIS and sarcopenia together may enhance prognosis assessment in patients undergoing LT. Herein, we aimed to describe the relationship between the SIS and skeletal muscle index (SMI) with short-term and long-term mortality post-living donor LT (LDLT). Methods: In total, 3387 consecutive adult LDLT recipients were retrospectively evaluated. The neutrophil-to-lymphocyte ratio (NLR, using a cut-off of 3) was utilized as an SIS. SMI was calculated using computed tomography scans, measured at the third lumbar vertebra; sex-specific cut-offs were determined from contemporary donors. Univariate and multivariable Cox proportional hazard analyses were performed. Results: Decreasing SMI was associated with increasing NLR. Increasing NLR and decreasing SMI both showed dose-dependent relationships with a risk of 90-day mortality. Within sarcopenic patients, NLR > 3 (vs. NLR ≤ 3) was associated with higher 90-day (9.3% vs. 3.5%, p = 0.049) and overall mortality (28.4% vs. 19.1%, p = 0.045). Sarcopenia and NLR > 3 (vs. neither) were independent predictors of 90-day mortality (hazard ratio [HR] 2.48 [1.40–4.40], p = 0.002) and overall mortality (HR, 1.81 [1.37–2.38], p < 0.001) after multivariable adjustment. When stratified by age, sex, and MELD score, the association between sarcopenia and overall mortality persisted in all subgroups, with the highest risk observed in women (HR 3.43, 95% CI 1.83–6.43). Conclusions: Sarcopenia, with the systemic inflammatory response, nearly doubled the risk of 90-day and overall mortality post-LT, proposing that these readily available biomarkers are a practical index for predicting survival post-LT. Considering that these are potentially modifiable factors, our result may provide a new therapeutic target to improve survival post-LT. Full article

Background/Objectives: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SN), pathological accumulation of alpha-synuclein, and chronic neuroinflammation. The aim of this study is to evaluate the serum levels of systemic inflammatory markers such as neutrophil–lymphocyte ratio (NLR), neutrophil-HDL ratio (NHR), monocyte-HDL ratio (MHR), platelet–lymphocyte ratio (PLR), IL-6, IGF-1, systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) in patients with PD, and to analyze the relationship between these markers and the clinical stage of the disease as well as its motor and non-motor symptoms. Methods: Fifty-one patients diagnosed with PD and forty-nine HC matched for age and sex were evaluated prospectively. Results: NLR, NHR, and IGF-1 levels were found to be significantly higher in the PD group compared to the HC group (p < 0.05). There was no significant difference between the two groups in terms of PLR, MHR, SII, and SIRI. No significant relationship was found between the inflammatory markers and disease duration, clinical scales, or symptoms. Conclusions: These findings support the role of systemic inflammation in the pathophysiology of PD. Further multi-center, long-term follow-up studies—including simultaneous measurements of central nervous system inflammation markers—are needed for translation into clinical practice. Full article

Myopia is one of the major public health conditions with significant complications. This study investigates the role of transforming growth factor (TGF)-β2, complement activation, and inflammasome pathways in myopia progression using a Brown Norway rat model. Myopia was induced, and complement regulation was manipulated using gene therapy via adeno-associated virus (AAV) vectors delivering CD55 or CD55 siRNA. Results showed that TGF-β2 exacerbated myopia by upregulating complement components C3 and C5, suppressing CD55, and activating inflammasome pathways through nuclear factor (NF)-κB signaling, leading to axial elongation and increased refractive errors. Overexpression of CD55 via AAV gene therapy effectively counteracted these effects, reducing axial length elongation and inflammation by suppressing inflammasome markers interleukin (IL)-1β and NLR family pyrin domain containing 3 (NLRP3), as confirmed by real-time quantitative PCR and immunofluorescence analyses. Conversely, silencing CD55 intensified TGF-β2-induced effects, further promoting axial elongation and inflammation. These findings highlight the critical role of CD55 in modulating TGF-β2-driven complement and inflammasome activation during myopia progression. The study suggests that gene therapy targeting CD55 could serve as a novel therapeutic strategy to mitigate myopia and related inflammatory processes, offering a promising avenue for managing this significant public health challenge. Full article

Background/Objectives: Obstructive sleep apnea (OSA) is a common disorder characterized by intermittent hypoxia and sleep fragmentation, assessed using the Apnea–Hypopnea Index (AHI). Systemic inflammation is central to OSA progression, and the systemic inflammatory response index (SIRI) has emerged as a potential biomarker for inflammatory diseases. This study investigates the relationship between SIRI and OSA severity while comparing other inflammatory markers. Methods: A retrospective study was conducted among 150 OSA patients at a tertiary care hospital. Based on AHI, patients were categorized into mild, moderate, and severe OSA groups. Blood parameters, including neutrophil, monocyte, and lymphocyte counts, were analyzed, and inflammatory indices (SIRI, NLR, PLR) were calculated. Correlation, ROCs, and regression analyses assessed associations between inflammatory markers and OSA severity. Results: SIRI demonstrated an excellent predictive ability for severe OSA with an AUC of 0.960 (cut-off: 1.105; sensitivity: 92.2%; specificity: 91.4%). The STOP-BANG score alone had lower discriminatory power (AUC: 0.737), but combining it with SIRI improved accuracy (AUC: 0.983). The best performance was observed when SIRI, STOP-BANG, PLR, and CRP were combined, yielding an AUC of 1.00, indicating perfect discrimination. Conclusions: SIRI shows strong predictive value for identifying severe OSA, underscoring its utility as a simple, cost-effective biomarker to aid early recognition and referral, particularly in primary care and resource-limited settings. Full article

Behçet’s syndrome (BS) is a chronic, relapsing inflammatory disease with multisystem involvement and prominent neutrophil activation. The neutrophil-to-lymphocyte ratio (NLR) has gained increasing attention as a potential surrogate marker for systemic inflammation. In this review we aimed to summarize and critically review the current evidence regarding the utility of NLR in BS, including its association with overall disease activity and specific organ involvement, as well as to explore its strengths and limitations as a clinical biomarker. NLR seems to be a simple, accessible, and cost-effective biomarker that can be elevated in Behçet’s syndrome and tends to be higher during active disease. Studies have demonstrated its consistent correlation with overall disease activity, as well as with specific manifestations such as mucocutaneous, ocular, vascular, and articular involvement. Moreover, NLR levels have been shown to decrease in response to anti-inflammatory treatments, supporting its potential utility in monitoring treatment effectiveness. Despite its seemingly cost-effective features, its routine integration into daily practice remains largely limited, mainly due to low specificity and the lack of standardized cut-off level. Further prospective studies are needed to assess its use in daily practice before it can be integrated into any disease activity score. Full article

Ischemic stroke triggers a dynamic immune response that influences both acute damage and long-term recovery. This review synthesizes a decade of evidence on immunological and inflammatory biomarkers in ischemic stroke, emphasizing their prognostic and therapeutic significance. Following ischemic insult, levels of pro-inflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and chemokines like interleukin-8 (IL-8) rapidly rise, promoting blood–brain barrier disruption, leukocyte infiltration, and neuronal death. Conversely, anti-inflammatory mediators such as interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) facilitate repair, neurogenesis, and immune regulation in later phases. The balance between these pathways determines outcomes and is reflected in circulating biomarkers. Composite hematological indices including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) offer accessible and cost-effective prognostic tools. Several biomarkers correlate with infarct size, neurological deterioration, and mortality, and may predict complications like hemorrhagic transformation or infection. Therapeutic strategies targeting cytokines, especially IL-1 and IL-6, have shown promise in modulating inflammation and improving outcomes. Future directions include personalized immune profiling, real-time cytokine monitoring, and combining immunotherapy with neurorestorative approaches. By integrating immune biomarkers into stroke care, clinicians may enhance risk stratification, optimize treatment timing, and identify candidates for novel interventions. This review underscores inflammation’s dual role and evolving therapeutic and prognostic relevance in ischemic stroke. Full article

(1) Background: Acute variceal bleeding (AVB) represents an important cause of upper gastrointestinal bleeding (UGIB). Several prognostic scores may be useful for assessing mortality and rebleeding risk, with the Glasgow-Blatchford score (GBS) and Rockall score being the most commonly used for non-variceal bleeding. Scores assessing liver failure (MELD and Child) do not reflect bleeding severity. The neutrophil-to-lymphocyte ratio (NLR) increases in UGIB and can predict survival and rebleeding. (2) Methods: We analyzed the predictive role of NLR, GBS, Rockall, AIMS65, Child, and MELD for mortality (48 h, 5-day, in-hospital, and 6-week) and rebleeding in AVB patients admitted to our hospital from 2017 to 2021. ROC analysis was performed, and a multivariate analysis with logistic regression was used to construct a simplified model. (3) Results: A total of 415 patients were admitted. NLR exhibited fair accuracy for 48-h mortality (AUC 0.718, 95% CI 0.597–0.839, p < 0.0001), with limited predictive value for medium-term mortality. The NLR accuracy was better than that of the GBS and Rockall score, similar to that of the AIMS65 and Child scores, but inferior to that of MELD. The value for all scores in predicting rebleeding was poor, with the highest AUC for the NLR. (4) Conclusions: The NLR exhibited reasonable accuracy in predicting short-term mortality in AVB. Our model (including NLR, age, creatinine, bilirubin, albumin, INR, platelet count, HCC, and etiology) demonstrated 80.72% accuracy in predicting 6-week mortality. Full article

Background/Objectives: Sudden sensorineural hearing loss (SSNHL) represents a challenging clinical entity with variable prognosis. Audiometric curve configuration has been proposed as a predictor of recovery. This study aimed to evaluate the association between audiogram morphology at onset and hearing outcome in patients with idiopathic unilateral SSNHL treated with standardized therapy. Methods: We retrospectively analyzed 156 patients with idiopathic SSNHL. Hearing thresholds at key frequencies were measured at baseline and 4 weeks post-treatment. Patients were categorized into upsloping, flat, downsloping, or U-shaped audiogram subgroups. Recovery was classified into four levels. Comparisons were made across subgroups for audiometric and laboratory data using ANOVA and chi-square tests. Results: Baseline PTA values were comparable across audiogram subgroups (p = 0.12). Hearing recovery differed significantly according to audiogram configuration (chi-square, p < 0.001), with upsloping and U-shaped patterns showing the best outcomes. Flat and downsloping curves were associated with poorer recovery, lower HDL, and elevated NLR values. Conclusions: Audiogram configuration is a relevant prognostic marker in SSNHL. Patterns linked to adverse metabolic and inflammatory profiles may benefit from tailored treatment strategies in a personalized medicine framework. Full article

Background/Objectives: Increased blood pressure variability (BPV) was found in adults with primary (essential) hypertension (PH) and is associated with increased cardiovascular risk. Our study aimed to analyze the relation between BPV and low-grade inflammation in children with primary hypertension. Methods: In 56 treatment-naive pediatric patients with PH (15.1 ± 2.1 years) and 30 healthy children (14.9 ± 1.4 years), we evaluated BPV: BP dipping, standard deviation (SD) of ambulatory blood pressure measurements (ABPMs), pulse pressure (PP)/systolic blood pressure ratio (24 h PP/SBP), rate–pressure index (24 h RPI), 24-h weighted BPV (24 h WSBPV, 24 h WDBV, 24 h WMAPV), coefficient of variation (24 h CoVSBP, 24 h CoVDBP, 24 h CoVMAP), ambulatory arterial stiffness index (AASI), and morning BP surge. We also analyzed indices of subclinical inflammation (markers derived from complete blood count, high-sensitivity C-reactive protein (CRP), interleukin 18), and office and ambulatory BP. Results: Patients with PH had significantly higher hsCRP, neutrophils, monocytes, and platelets, neutrophil-to-lymphocyte (NLR), platelet-to-mean platelet volume (PMPVR), and lower monocyte-to-neutrophil (MNR) ratios, and higher BPV: 24 h ABPM SBP SD, 24 h ABPM MAP SD, 24 h RPI, 24 h WSBPV, 24 h WDBV, 24 h WMAPV, and 24 h CoVSBP. Low-grade inflammation markers correlated with BPV indices in both groups. In multivariate analysis, MNR predicted 24 h ABPM MAP SD (beta = 0.290, 95CI: 0.029–0.551), 24 h RPI (beta = −0.348, 95CI: −0.587–−0.108), and 24 h WDBPV (beta = 0.286, 95CI: 0.032–0.540); monocyte count—24 h RPI (beta = 0.281, 95CI: 0.041–0.521), and hsCRP—24 h WDBV (beta = 0.310, 95CI: 0.055–0.564). ROC analysis revealed a good diagnostic profile for lymphocyte count as a positive determinant of non-dipping status in PH children (cut-off point 2.59 [×10³/µL]). Conclusions: BPV is higher in children with PH compared to healthy peers and is associated with low-grade inflammation. MNR may be the most helpful indicator of BPV, whereas high lymphocyte count predicts the best non-dipping status in these patients. Full article