Biomarkers of Disease: Discovery and Clinical Applications

Background: Septic arthritis is an orthopedic emergency. However, optimal biomarkers and diagnostic criteria remain unclear. The study aimed to evaluate the diagnostic performance of routinely used and novel biomarkers, including serum C-reactive protein (CRP), synovial white blood cells (WBC), pentraxin-3 (PTX3), interleukin-6 (IL-6), and presepsin, in distinguishing septic from non-septic arthritis. Methods: Thirty-one patients undergoing arthrocentesis were included. Patients were categorized into septic and non-septic arthritis groups. Synovial fluid and serum samples were analyzed for five biomarkers. Diagnostic performance was assessed by calculating the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: Synovial WBC demonstrated the highest diagnostic performance among single biomarkers (AUC = 0.837, p = 0.012). Among novel biomarkers, PTX3 showed the highest accuracy and sensitivity. The serum CRP and synovial WBC combination yielded an AUC of 0.853, with 100% sensitivity, 68.0% specificity, 42.9% PPV, and 100% NPV. Adding all three novel biomarkers to this combination increased the AUC to 0.887 (p = 0.004), maintaining 100% sensitivity and NPV. When individually added, PTX3 achieved 100% sensitivity and NPV, while presepsin showed the highest specificity (96.0%), PPV (75.0%), and accuracy (87.1%). Conclusions: Serum CRP and synovial WBC remain essential biomarkers for diagnosing septic arthritis; however, combining them with PTX3, IL-6, and presepsin improved diagnostic accuracy. PTX3 is best suited for ruling out septic arthritis due to its high sensitivity and NPV, whereas presepsin is more useful for confirmation, given its specificity and PPV. These results support a tailored biomarker approach aligned with diagnostic intent. Full article

Background/objectives: Polycystic ovary syndrome (PCOS) and metabolic dysfunction-associated steatotic liver disease (MASLD) are common co-morbidities in women of reproductive age. PCOS is highly heterogeneous and is, therefore, divided into four phenotypes. MASLD leads to numerous systemic complications. Studies to date have shown an association between PCOS and MASLD. This study was designed to compare the FIB-4 score (based on age, alanine aminotransferase, aspartate aminotransferase and platelet count) and the results of shear wave elastography in assessing the risk of developing MASLD by patients with PCOS divided by phenotypes. Methods: The study enrolled 242 women age 18–35 years with PCOS diagnosed according to Rotterdam criteria, hospitalized at the Department of Gynaecological Endocrinology of the University Clinical Centre in Katowice. The study subjects were assigned to phenotypes A to D. Clinical and biochemical assessments were performed (including androgens and metabolic parameters), and the FIB-4 index was calculated. Liver fibrosis was evaluated by shear wave elastography. To balance the group sizes of phenotypes, oversampling with replacement was applied (PROC SURVEYSELECT, SAS), increasing the number of observations for phenotypes B, C, and D fivefold. Statistical analyses were performed based on data distribution (Shapiro–Wilk test), using ANOVA or the Kruskal–Wallis test with Dunn’s correction. Statistical significance was set at p < 0.05. Results: The FIB-4 score was the highest in phenotype B patients (0.50 ± 0.15), and the lowest in phenotypes A and C (0.42 ± 0.14). The highest rate of positive elastography findings was recorded in phenotype A patients (34.7%) and the lowest in phenotype C group (13.5%). Significant differences between the phenotypes were also found in terms of androgen levels, insulin, HOMA-IR, and the lipid profile. Among patients with positive elastography, the highest FIB-4 scores were recorded in phenotype C group (0.44 ± 0.06), but the differences between the phenotypes were not statistically significant. Conclusions: The FIB-4 score was the highest in phenotype B patients and differed significantly from phenotypes A, C and D. In the elastography exam, the fibrosis index was statistically significantly higher in phenotype A compared to other phenotypes. No correlation was detected between the FIB-4 index and positive elastography. The findings suggest that the FIB-4 index may be used for MASLD screening, but its usefulness as a predictor of eligibility for elastography requires more research. Full article

Background/Objectives: Frailty is a key determinant of outcomes in older adults with heart failure (HF). The free triiodothyronine/free thyroxine (FT₃/FT₄) ratio has emerged as a promising frailty biomarker that reflects metabolic and systemic resilience. This study investigates its association with frailty, nutrition, muscle strength, inflammation, and one-year mortality in very old patients with HF. Methods: In this longitudinal, single-center study, we enrolled 193 older outpatients (mean age, 86.5 ± 6.1 years; 56% women) recently discharged after acute HF. All patients underwent physical examination, blood testing, and comprehensive geriatric assessment, including handgrip strength (HGS). Participants were stratified by FT₃/FT₄ ratio (<1.7 vs. ≥1.7). Associations with the Clinical Frailty Scale (CFS) were examined using multivariable linear regression. Spearman’s correlations assessed relationships with inflammatory and nutritional biomarkers. Cox regression evaluated the association with all-cause mortality. Results: Patients with a low FT₃/FT₄ ratio (31.1%) exhibited greater frailty (CFS: median [IQR], 6 [2] vs. 4 [3]; p = 0.020), poorer nutritional status (Mini Nutritional Assessment: 10 [4] vs. 12 [3]; p = 0.008), and lower HGS (mean ± SD, 16.8 ± 3.7 kg vs. 20.3 ± 4.8 kg; p = 0.002). An inverse association was identified between the FT₃/FT₄ ratio and frailty (adjusted β = −0.09; p = 0.019). Individuals with low FT₃/FT₄ also showed elevated inflammatory markers and had more than double the one-year mortality rate compared to those with higher ratios [HR 2.32 (95% CI, 1.24–4.34; p = 0.007)]. Conclusions: In very old adults recently hospitalized for HF, a lower FT₃/FT₄ ratio was associated with frailty, malnutrition, inflammation, and increased mortality, supporting its potential role as a marker of biological vulnerability. Full article

Background/Objective: Neurofilament light chain (Nf-L), neurofilament heavy chain (Nf-H), and chitinase 3-like 1 (CHI3L1) are cerebrospinal fluid (CSF) biomarkers of neuroaxonal damage and inflammation in multiple sclerosis (MS). Their longitudinal response to disease-modifying therapies and association with clinical and radiological outcomes remain incompletely understood. The aim of this study is to evaluate the impact of interferon beta (IFN-β) therapy on CSF levels of Nf-L, Nf-H, and CHI3L1 in early relapsing–remitting MS (RRMS) and assess their association with long-term clinical outcomes and MRI activity. Methods: We conducted a prospective two-year observational study involving 14 treatment-naive RRMS patients who initiated IFN-β therapy. CSF levels of Nf-L, Nf-H, and CHI3L1 were measured at baseline and after two years. Clinical disability was assessed via the Expanded Disability Status Scale (EDSS) and by studying brain MRI activity. A 15-year clinical follow-up was performed for 12 patients. Results: Nf-L levels significantly decreased after two years of IFN-β treatment (p = 0.039), while CHI3L1 levels significantly increased (p = 0.001). Nf-H levels remained stable. Nf-L and CHI3L1 levels at baseline and follow-up correlated with relapse rate and long-term EDSS. Nf-H levels correlated with EDSS scores but not with relapse or MRI activity. A trend toward a positive correlation between increasing Nf-L levels and MRI activity was observed (p = 0.07). Conclusions: CSF biomarkers demonstrate differential responses to IFN-β therapy in early RRMS. Nf-L emerges as a sensitive biomarker of treatment response and disease activity, while CHI3L1 may reflect ongoing tissue remodeling and inflammation. These findings support the utility of CSF biomarker monitoring for personalized treatment strategies in MS. Full article