Search Results (85)

Patients undergoing thoracic surgery or intensive care are frequently exposed to high-voltage electric fields generated by medical devices; however, the duration-dependent effects of such exposure on lung tissue remain unclear. This study aimed to investigate the histopathological and immunoinflammatory effects of exposure to a uniform 10 kV/m electric field for varying durations using a rat model. Thirty-five adult female Wistar rats were randomly assigned to five groups (n = 7): control, and 1, 5, 15, and 30 min exposure groups. Lung tissues were analyzed histologically with hematoxylin and eosin staining, and the immunohistochemical expression of IL-1β, RANKL, and TNF-α was semi-quantitatively assessed. Histopathological examination revealed a duration-dependent increase in lung injury, with the 30 min group showing marked epithelial loss, mononuclear infiltration, edema, and vascular congestion (p < 0.001). The expression of IL-1β, RANKL, and TNF-α remained minimal in the 1–15 min groups but was significantly elevated in the 30 min group (p < 0.001). These findings suggest that prolonged exposure to high-voltage electric fields induces substantial pulmonary inflammation and tissue damage, indicating the presence of a threshold beyond which inflammatory pathways are abruptly activated. These results highlight the importance of establishing safety guidelines for electric field exposure in clinical settings. Full article

Objectives: To determine the frequency of development of hypogammaglobulinemia in rheumatoid arthritis (RA) patients receiving rituximab (RTX) and to examine the relation between the development of hypogammaglobulinemia and RTX treatment response. Methods: The data of 165 RA patients who applied to our outpatient clinic between January 2010 and June 2021, and who received at least 2 courses of RTX with an interval of 6 months, were retrospectively evaluated. The demographic, clinical, and laboratory data, as well as treatment characteristics, were collected. Results: Of 165 patients, 35 (21.2%) developed hypogammaglobulinemia. In the multivariable analysis examining the risk factors for the development of hypogammaglobulinemia in RA patients receiving RTX, it was determined that having pre-treatment IgG value below 10.5 g/l (OR= 4.24 (95% CI 1.69–10.66) and the increase in the number of RTX courses (OR= 1.1 (95% CI 1.01–1.22) were independently associated risk factors. During their follow-up, patients who developed hypogammaglobulinemia and those who did not were compared. No difference was observed between DAS28-ESR levels, but CRP levels were significantly lower in the group that developed hypogammaglobulinemia. Conclusions: In this study, there was no difference in DAS28-ESR levels between patients with and without hypogammaglobulinemia, although a difference was observed in acute phase reactants, which are more objective parameters. This may be due to subjective parameters in DAS28-ESR scoring or other concomitant conditions such as fibromyalgia. Therefore, additional objective findings or methods may guide the evaluation of treatment response. Full article

Background: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment of relapsed/refractory large B-cell lymphoma (LBCL), but its administration is often complicated by cytokine release syndrome (CRS). Interleukin-6 (IL-6) is widely used to monitor CRS, though its clinical value diminishes after tocilizumab administration. We aimed to evaluate serum amyloid A (SAA), a dynamic acute-phase reactant, as a treatment-independent biomarker of inflammation and toxicity in CAR-T recipients. Methods: This retrospective study included 43 adults with LBCL treated with axicabtagene ciloleucel. SAA and other inflammatory markers were assessed from lymphodepletion through day +11 post-infusion. CRS and ICANS were graded per ASTCT criteria. Statistical analyses included Mann–Whitney U tests, Spearman’s correlation, and ROC curve analysis to evaluate predictive performance. Results: SAA levels peaked at day +4 and normalized by day +11, displaying wave-like kinetics. Levels were significantly higher in patients with any-grade CRS at early timepoints but showed no association with ICANS. SAA correlated strongly with CRP, suPAR, sST2, fibrinogen, ferritin, procalcitonin, and IL-6. Compared to IL-6, SAA was more predictive of CRS at day +2 and +4, and unaffected by tocilizumab. Baseline SAA also correlated with the mEASIX score, suggesting linkage to endothelial stress. Non-responders at 3-month PET had higher baseline SAA than responders (196.0 vs. 17.7 mg/L, p = 0.036), with ROC analysis yielding an AUC of 0.74 and an optimal threshold of 79.8 mg/L. Conclusions: SAA is a robust and dynamic marker of systemic inflammation, with potential utility in both toxicity monitoring and response prediction in the CAR-T setting. Its independence from IL-6 modulation positions it as a promising biomarker for future integration into clinical algorithms. Full article

In Mexico, syphilis and tuberculosis are infectious diseases subject to mandatory and immediate epidemiological surveillance, both with special systems that allow nominal follow-up for either variant. Surveillance uses the operational definitions of probable and confirmed cases established in the manual for epidemiological surveillance issued by the General Directorate of Epidemiology of the Ministry of Health. However, both diseases, mainly in the chronic state, present challenges because of their ability to mimic autoimmune disorders. This review explores the phenomenon of clinical and immunological mimicry in secondary and tertiary syphilis, as well as in extrapulmonary tuberculosis, and analyzes its implications for the accuracy of case reporting at the national level. Evidence shows that both infections can present systemic inflammatory features, such as elevated acute phase reactants, positive autoantibodies, and alterations in cerebrospinal fluid that resemble autoimmune profiles. These overlaps can lead to misdiagnosis, inappropriate immunosuppressive treatment and misclassification of confirmed cases within the Mexican surveillance system. Surveillance of these conditions is robust; however, current operational definitions have weaknesses, particularly when atypical or autoimmune conditions are present, as they only focus on cases with the highest prevalence or public health impact. This manuscript proposes the integration of differential diagnostic algorithms and expanded laboratory criteria, including autoimmune markers and molecular tests, into surveillance protocols. Although individual efforts exist in health institutions, in our country, the absence of autoimmune diseases in the national register of obligatory notification stands out, contrasting with surveillance models in other countries, where autoimmune diseases are tracked systematically. To improve diagnostic accuracy and reporting, surveillance systems should incorporate a syndromic and etiological approach, recognizing infectious autoimmune mimicry as a factor in the final recording of confirmed cases to avoid epidemiological silence. Full article

Background/Objectives: Familial Mediterranean fever (FMF) is the most common hereditary autoinflammatory syndrome, characterized by recurrent fever attacks and serositis. Galectin-3, a β-galactoside-binding lectin involved in inflammation and fibrosis, and presepsin, an established biomarker for bacterial infection and sepsis, have emerged as potential biomarkers for improving diagnostic and prognostic accuracy in autoinflammatory diseases. However, their use in FMF patients is not sufficiently evaluated. This study aims to compare serum galectin-3 and presepsin levels in children with FMF and healthy controls and assess their correlations with conventional acute-phase reactants. Methods: This prospective cross-sectional study included 74 children with confirmed FMF during attack-free periods and 67 age- and gender-matched healthy controls. Clinical and genetic characteristics, complete blood count, C-reactive protein (CRP), serum amyloid-A (SAA), and erythrocyte sedimentation rate (ESR) were recorded. Serum galectin-3 and presepsin levels were measured. Group comparisons and correlation analyses were performed using appropriate statistical tests. Results: Median serum galectin-3 and presepsin was significantly higher in FMF patients than controls (p < 0.001). ESR was significantly higher in FMF patients (p < 0.001), while CRP and SAA showed no significant differences. Correlation analysis revealed a strong positive correlation between galectin-3 and presepsin (r = 0.860, p < 0.001) in FMF patients, with neither correlating with other acute-phase reactants. Conclusions: Galectin-3 and presepsin were found to serve as novel biomarkers reflecting alternative inflammatory pathways in FMF, even during remission. These results, obtained during the attack-free period, indicate the need for further studies to determine the relationship between galectin-3 and presepsin levels and disease activity in FMF. Full article

This story began half a century ago with the discovery of an unusually high presence of tryptophan (Trp, W) in transthyretin (TTR), one of the three carrier proteins of thyroid hormones. With the Trp-rich retinol-binding protein (RBP), TTR forms a plasma complex implicated in the delivery of retinoid compounds to body tissues. W has the lowest concentration among all AAs involved in the sequencing of human body proteins. The present review proposes molecular maps focusing on the ratio of W/AA residues found in the sequence of proteins involved in immune events, allowing us to ascribe the guidance of inflammatory processes as fully under the influence of W. Under the control of cytokine stimulation, plasma biomarkers of protein nutritional status work in concert with major acute-phase reactants (APRs) and with carrier proteins to release, in a free and active form, their W and hormonal ligands, interacting to generate hot spots affecting the course of acute stress disorders. The prognostic inflammatory and nutritional index (PINI) scoring formula contributes to identifying the respective roles played by each of the components prevailing during the progression of the disease. Glucagon demonstrates ambivalent properties, remaining passive under steady-state conditions while displaying stronger effects after cytokine activation. In developing countries, inappropriate weaning periods lead to toddlers eating W-deficient cereals as a staple, causing a dramatic reduction in the levels of W-rich biomarkers in plasma, constituting a novel nutritional deficiency at the global scale. Appropriate counseling should be set up using W implementations to cover the weaning period and extended until school age. In adult and elderly subjects, the helpful immune protections provided by W may be hindered by the surge in harmful catabolites with the occurrence of chronic complications, which can have a significant public health impact but lack the uncontrolled surges in PINI observed in young infants and teenagers. Biomarkers of neurodegenerative and neoplastic disorders measured in elderly patients indicate the slow-moving elevation of APRs due to rampant degradation processes. Full article

Diclofenac is an effective medication for pain and inflammation. However, its use has been linked to hepatitis. To gain insight into diclofenac’s ability to cause hepatitis, we investigated the regulation of major effectors of the immune system following daily treatment of minipigs at 3 and 15 mg/kg for 28 days. Histopathology evidenced lobular inflammation, and through a combination of immunogenomics and immunopathology, we detected marked innate and adaptive immune responses. We identified 109 significantly regulated genes linked to neutrophil, monocyte, Kupffer cell, and lymphocyte responses and 32 code for cytokine- and interferon-γ-signaling. In support of wound repair, immunopathology evidenced manifest upregulation of macrophage migration inhibitory factor and CD74. Furthermore, the strong expression of IgG and IgM underscored humoral immune responses. Diclofenac caused an activation of the complement system, especially the C1 inhibitor of the classical pathway and C3 with critical functions in liver regeneration. The marked expression of complement factor B and H of the alternate pathway modulated B-cell responses. Likely, the upregulation of factor H protected hepatocytes from injury by limiting complement-mediated damage of inflamed cells. Additionally, diclofenac treatment elicited marked hepatic expression of lysozyme and KLF6. The latter earmarks M1-polarized Kupffer cells. We observed an extraordinary induction of calprotectin/S100A9 and of the monocyte/macrophage CD163 scavenger receptor, and therefore, we detected innate immune sensing of damaged cells. Lastly, we noted an unprecedented induction of the acute phase reactant SAA1 and DEC-205, which recognize apoptotic and necrotic cells. Together, our results offer mechanistic insights into immune-mediated liver injury patterns following diclofenac treatment. Full article

Background and Objectives: Vitamin D deficiency is linked to adverse outcomes in chronic obstructive pulmonary disease (COPD). Limited data exist on how vitamin D levels vary by disease severity during acute exacerbations of COPD (AECOPDs). This study aimed to determine whether the vitamin D status during AECOPDs—alongside inflammatory and hematological biomarkers—is associated with COPD severity. Materials and Methods: This observational study included 105 AECOPD hospitalized patients, stratified according to GOLD stages 1–2, 3, and 4. Blood samples were collected to measure serum vitamin D—as 25-hydroxyvitamin D [25(OH)D], acute phase reactants, serum calcium, and selected hematological parameters. Inter-group differences were evaluated using Kruskal–Wallis tests, with Spearman correlations applied for intra-strata associations. ROC analysis and logistic regression assessed the discriminatory power of significant biomarkers. Results: C-reactive protein (CRP) and fibrinogen concentrations were elevated across all COPD stages, whereas calcium and vitamin D remained consistently below normal. Interleukin (IL)-6 and 25(OH)D levels varied significantly with COPD stage (p = 0.033 and p = 0.047, respectively), with a marked drop from GOLD stage 3 to stage 4. High-IL-6 patients revealed significantly elevated CRP (p = 0.045), erythrocyte sedimentation rate (ESR) (p = 0.032), fibrinogen (p = 0.011), and procalcitonin (p = 0.044). The strongest correlations were seen between CRP, ESR, and fibrinogen (r_s ≥ 0.58, p ≤ 0.05), indicating a coordinated acute-phase response that weakened with advancing disease. Serum 25(OH)D was a significant independent predictor of COPD severity (AUC = 0.631, p = 0.048), while IL-6 had a weaker predictive value, losing significance in the combined regression model. Conclusions: Vitamin D deficiency is more pronounced in very severe COPD, serving as a potential clinical indicator of disease severity during exacerbation episodes. Full article

Background: Polymyalgia rheumatica (PMR) has a multifaceted onset and course, and making a distinction between true PMR and so-called “polymyalgic syndrome” (that is, similar manifestations caused by different conditions) is far from easy in clinical practice. The existence of subsets within true PMR may further complicate the diagnostic question. Distinguishing PMR subsets from PMR-mimicking conditions does not just carry nomenclature value and speculative significance. Indeed, the correct diagnosis influences treatment, prognosis, epidemiological assessments, and health policies. Objectives: We aimed to (1) ascertain the presence of a definite and peculiar subset/subgroup/cluster of PMR in the scientific literature; (2) describe any possible subset/cluster/subgroup of PMR identified in at least two different studies. Methods: We performed a non-systematic (PRISMA protocol not followed) literature search on Embase and Medline (OVID interface). The following search terms were used: polymyalgia rheumatica, subset, cluster, subgroup, subclinical giant cell arteritis, mimicking conditions, polymyalgia rheumatica-like conditions, immunotherapy, checkpoint inhibitor, acute-phase reactants or acute-phase proteins, vaccination, infection, and calcium pyrophosphate deposition disease or chondrocalcinosis. Each paper’s reference list was scanned for additional publications meeting this study’s aim. Abstracts submitted at conferences or from non-peer-reviewed sources were not included. Results: The initial search yielded 2492 papers, of which 2389 articles were excluded based on title and abstract screening. A total of 103 articles underwent a full-length review, and 84 of them were finally assessed for eligibility. A total of seven large subsets of PMR could be identified: (1) PMR with normal acute-phase reactants; (2) PMR with an infection trigger; (3) PMR with a vaccination trigger; (4) PMR with subclinical giant cell arteritis (GCA); (5) PMR and calcium pyrophosphate deposition disease (CPPD); (6) PMR following immune checkpoint inhibitor (ICI) therapy; (7) PMR with peculiar clinical clusters (based on clinical or statistic clustering methods). Conclusions: PMR with normal baseline acute-phase reactants and PMR with an infection or a vaccination trigger could be categorized as subsets of disease. PMR with subclinical GCA and most cases of PMR/CPPD should be categorized as mimickers. Finally, further studies are required to better categorize some peculiar clinical subsets emerging from cluster analyses, and ICI-induced PMR. Full article

Spondylodiscitis is a devastating invasive infection that can lead to debilitating pain, motor weakness, or paralysis, even with appropriate medical and surgical treatment. Over the past two decades, there has been a worldwide increase in the incidence of spondylodiscitis, which can be attributed to a higher prevalence of various risk factors including intravenous drug use, hemodialysis, and spinal surgeries. The lumbar spine is the most likely region to be affected, with Staphylococcus aureus being the predominant pathogen. Management of spondylodiscitis requires a multi-disciplinary approach, with close coordination between the spinal surgeon and the infectious diseases specialist. Clinicians should become familiar with the epidemiology and presentation of patients with suspected spondylodiscitis because timely diagnosis and treatment may lead to improved outcomes. This unique review incorporates the perspectives from infectious disease and spine surgery specialists. Full article

The acute phase response is a hallmark of all inflammatory reactions and acute phase reactants, such as C-reactive protein (CRP) and serum amyloid A (SAA) proteins, are among the most useful plasma and serum markers of inflammation in clinical medicine. Although it is well established that inflammatory cytokines, mainly interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) induce SAA in the liver, the biological functions of elicited SAA remain an enigma. By the classical multi-step protein purification studies of chemotactic factors present in plasma or serum, we discovered novel chemokines and SAA1 fragments, which are induced during inflammatory reactions. In contrast to earlier literature, pure SAA1 fails to induce chemokines, an ascribed function that most probably originates from contaminating lipopolysaccharide (LPS). However, intact SAA1 and fragments thereof synergize with CXC and CC chemokines to enhance chemotaxis. Natural SAA1 fragments are generated by inflammatory proteinases such as matrix metalloproteinase-9 (MMP-9). They mediate synergy with chemokines by the interaction with cognate G protein-coupled receptors (GPCRs), formyl peptide receptor 2 (FPR2) and (CC and CXC) chemokine receptors. In conclusion, SAA1 enforces the action of many chemokines and assists in local leukocyte recruitment, in particular, when the concentrations of specifically-induced chemokines are still low. Full article

Background: Retinopathy of prematurity (ROP) is a serious disease causing blindness in childhood. Gestational age (GA) and birth weight are major factors associated with the development and progression of ROP, but postnatal systemic inflammation is also an important well-known risk factor. Methods: This study retrospectively analyzed the relationship between systemic inflammation and ROP severity using the corrected GA (CGA), which reflects the intrinsic immaturity of the infant, rather than days of life. Three acute phase reactants (APRs) were analyzed using discriminant probability and compared with conventional ROP prediction models: C-reactive protein, α1AG, and haptoglobin. Results: Alpha 1AG was the best predictor of ROP onset and progression, and could be predicted with blood samples up to 30 weeks (30 W) CGA (p = 0.006). Incorporation of APR into the conventional GA + body weight (BW), ROP score, and Children’s Hospital of Philadelphia (CHOP) predictive models improved the decision to treat (4–5% increase in discrimination probability) and helped determine whether treatment of ROP was necessary by CGA 30 W. Conclusions: Therefore, simply adding α1AG protein to the assessment is useful for predicting the need to treat ROP. Full article

Background/Objectives: Familial Mediterranean fever (FMF) is a chronic autoinflammatory disease. Throughout the disease, subclinical inflammation persists into the remission period. It is known that chronic inflammation causes endothelial dysfunction and, as a consequence, arterial stiffness occurs. In this study, carotid and aortic intima–media thicknesses (IMT) and arterial stiffness were measured in FMF patients to evaluate the risk of possible vascular damage due to chronic inflammation. Methods: The study included pediatric patients with FMF who had been in remission for a minimum of 3 months. Carotid and aortic IMT and arterial stiffness measurements were conducted using sonoelastography. The acute-phase reactants were also evaluated in all participants. Results: Carotid artery stiffness measurements by strain elastography were significantly higher in the patient group than in the control group. However, the aortic and carotid IMT were similar between the two groups. The acute-phase reactants were significantly higher in the patient group than in the control group. Conclusions: This study demonstrated that arterial stiffness increased in pediatric FMF patients. According to the results of the present study, the effects of chronic inflammation on arterial tissues may lead to atherosclerotic changes in the later stages of the disease and may pose a risk for coronary diseases. Arterial ultrasonographic and elastographic measurements to be performed periodically in children with FMF are noninvasive methods that can be used to evaluate the course of endothelial damage. We aimed to show that arterial stiffness may be a marker of early cardiovascular disease. Full article

Background and Objectives: Familial Mediterranean fever (FMF) is a lifelong autoinflammatory disease characterized by episodes of fever and aseptic polyserositis. Commonly associated with vasculitis, FMF’s impact on microcirculation was investigated by examining nailfold capillaries using capillaroscopy. Materials and Methods: This study included 32 female and 28 male FMF patients diagnosed according to the Tel Hashomer and Yalçınkaya criteria and a control group of 20 female and 10 male age-matched cases. Demographic characteristics, medical history (abdominal pain, fever, chest pain, and joint pain), and physical examination findings of the cases were assessed. FMF gene mutations, acute-phase reactants, urine analysis, and spot urine protein/creatinine ratios were evaluated. Nailfold capillaries were examined via capillaroscopy by the same dermatology specialist. Results: There was no significant age or gender difference between groups. The most common symptoms in the case group were abdominal pain (81.7%) and joint pain (65%). Pathological findings in capillaroscopy, such as microhemorrhages and avascular areas, were significantly more frequent in the FMF case group (p < 0.001; p < 0.001). Physiological findings, including hairpin-shaped capillaries and shortened loops, were significantly more common in the control group (p = 0.001; p = 0.034). No significant relationships were found between kidney involvement, subclinical inflammation, presence of microhemorrhages and avascular areas in capillaroscopy, and disease duration. Additionally, no significant differences were observed in capillaroscopic findings between those with exon-10 mutations in the MEFV gene and those with non-exon-10 mutations. Conclusions: In conclusion, our study demonstrated secondary microvascular findings due to inflammation in FMF patients using capillaroscopy, a cost-effective and safe tool. Full article

Research on serum amyloid A (SAA) has seen major advancement in recent years with combined approaches of structural analysis and genetically altered mice. Initially identified as an acute-phase reactant, SAA is now recognized as a major player in host defense, inflammation, lipid metabolism and tumor metastasis. SAA binding and the neutralization of LPS attenuate sepsis in mouse models. SAA also displays immunomodulatory functions in Th17 differentiation and macrophage polarization, contributing to a pro-metastatic tumor microenvironment. In spite of the progress, the regulatory mechanisms for these diverse functions of SAA remain unclear. This review provides a brief summary of recent advances in SAA research on immunity, inflammation, tumor microenvironment and in vivo models. Full article