Search Results (836)

Background: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of immature T cells, driven by dysregulated transcriptional networks and oncogenic signaling pathways. Here, we present the first comprehensive analysis of the expression and regulation of TSPAN32, a tetraspanin implicated in lymphocyte homeostasis, in T-ALL. Methods: Transcriptomic data from the Leukemia MILE study (GSE13159) were analyzed to assess TSPAN32 expression across leukemic subtypes. Gene Set Enrichment Analysis (GSEA) was performed to explore biological pathways associated with TSPAN32-correlated genes. For mechanistic validation, HPB-ALL cells were used as a model, with NOTCH signaling inhibited by γ-secretase inhibitor (GSI) treatment and TAL1–LMO1 overexpression induced through doxycycline-inducible lentiviral vectors. Gene expression changes were quantified by RT-qPCR. Results: TSPAN32 was frequently downregulated in T-ALL compared to healthy bone marrow, although expression was retained in a subset of cases. GSEA revealed that TSPAN32-correlated genes were inversely associated with cell cycle–related programs, consistent with its established role as a negative regulator of T cell proliferation. Mechanistically, TAL1–LMO1 overexpression strongly induced TSPAN32, while GSI-mediated NOTCH inhibition partially reactivated its expression. Interestingly, GSI treatment also increased TAL1 levels despite downregulating LMO1. Conversely, TAL1–LMO1 overexpression suppressed NOTCH1 and NOTCH3, highlighting a reciprocal regulatory interplay between NOTCH and TAL1/LMO1 oncogenic circuits that shapes TSPAN32 expression dynamics in T-ALL. Conclusions: This study identifies TSPAN32 as a novel transcriptional target under the influence of key leukemogenic pathways and suggests its potential role as a modulator of leukemic T cell proliferation, with implications for therapeutic strategies targeting TAL1 and NOTCH signaling. Full article

Background and Objectives: Prognostic stratification in trauma patients admitted to the intensive care unit (ICU) remains a clinical challenge. While conventional scoring systems such as Acute Physiology and Chronic Health Evaluation II (APACHE II), Injury Severity Score (ISS), and Glasgow Coma Scale (GCS) are widely used, the utility of biochemical biomarkers in predicting mortality is still evolving. This study aimed to evaluate the prognostic value of key inflammatory and metabolic biomarkers: platelet-to-lymphocyte ratio (PLR), C-reactive protein-to-albumin ratio (CAR), serum lactate, base deficit, and neutrophil-to-lymphocyte ratio (NLR) in relation to ICU mortality in trauma patients. Materials and Methods: In this retrospective cohort study, data from 240 ICU-admitted trauma patients were analyzed. Group comparisons between survivors and non-survivors were conducted using t-tests or Mann–Whitney-U tests. Pearson correlation and ROC analyses were performed to assess relationships and discriminatory performance of biomarkers alongside clinical scores. Results: Non-survivors (n = 50) exhibited significantly higher CAR, lactate, and base-deficit values, and lower PLR (p < 0.05) compared to survivors (n = 190). CAR strongly correlated with CRP (r = 0.96), while lactate and base deficit were inversely correlated (r = –0.69). ROC analysis revealed that ISS (AUC = 0.86) and APACHE II (AUC = 0.77) had the highest discriminatory power, followed by lactate (AUC = 0.75). NLR did not demonstrate significant prognostic utility (p > 0.05). Conclusion: PLR, CAR, lactate, and base deficit are accessible, cost-effective biomarkers with significant prognostic value in ICU trauma care. Their integration with established scoring systems can enhance early risk stratification. NLR, however, may require time-sensitive and context-specific evaluation. Full article

Background: Serum markers are commonly used to diagnose bone and joint infections; however, their accuracy for diagnosing pyogenic spondylitis remains unproven. This study aimed to validate the diagnostic accuracy of inflammatory, nutritional, and immunological serum markers for spinal infections and identify the most effective combinations. Methods: The retrospective cohort study analyzed 656 patients who visited the hospital for spinal diseases between 1 January 2004 and 31 March 2021; a total of 76 were diagnosed with pyogenic spondylitis. Blood samples were analyzed for serum albumin (Alb), total protein (TP), globulin (Glb), C-reactive protein (CRP), platelet count, white blood cell count, neutrophil count, lymphocyte count, and monocyte count. Combination markers, including albumin–globulin ratio (AGR), CRP–albumin ratio (CAR), CRP–AGR (CAGR), neutrophil–lymphocyte ratio (NLR), and platelet–lymphocyte ratio (PLR), were also evaluated. Receiver operating characteristic curves were used to determine each marker’s diagnostic performance. Furthermore, multivariate analysis was performed to examine the odds ratios. Results: Patients with pyogenic spondylitis showed significantly different levels in Alb (p < 0.0001), Glb (p < 0.0001), CRP (p < 0.0001), platelet count (p < 0.0001), WBC count (p < 0.0006), neutrophil count (p = 0.0019), lymphocyte count (p = 0.0085), AGR (p < 0.0001), CAR (p < 0.0001), CAGR (p < 0.0001), NLR (p < 0.0001), and PLR (p < 0.0001). CRP (AUC = 0.80) showed good diagnostic accuracy, while combination markers CAR (AUC = 0.82) and CAGR (AUC = 0.83) had the highest areas under the curve (AUC). Multivariate analysis indicated that decreased age and the presence of comorbidities (including chronic kidney disease, chronic liver disease, malignancy, or diabetes), were independent predictors of early pyogenic spondylitis (OR_age = 0.93, OR_comorbidities = 16.98, p_age = 0.0005, and p_comorbidities = 0.0001). In patients with low-inflammatory pyogenic spondylitis, significant differences were observed in TP (p = 0.0293), Glb (p = 0.0012), CRP (p = 0.0023), platelet count (p = 0.0108), AGR (p = 0.0044), CAR (p = 0.0006), CAGR (p = 0.0004), PLR (p = 0.0192), and NLR (p = 0.0027), with CAGR showing the highest AUC (AUC = 0.70) among them. Conclusions: Serum combination markers (AGR, CAGR, CAR, PLR, and NLR) showed diagnostic value for pyogenic spondylitis, with CAGR achieving the highest accuracy. In low-inflammatory pyogenic spondylitis patients (CRP ≤ 1.0 mg/dL), these markers may aid diagnosis. Full article

Chimeric antigen receptor (CAR) T-cell therapy directed to CD19 and B-cell maturation antigen has revolutionized treatment of B-cell leukemia and lymphoma, and multiple myeloma. However, identifying suitable targets for acute myeloid leukemia (AML) remains challenging due to concurrent expression of potential target antigens on normal hematopoietic stem cells or tissues. As the stress-induced B7H6 molecule is rarely found on normal tissues but expressed on many cancers including AML and melanoma, the NKp30-ligand B7H6 emerges as a promising target for NKp30-based CAR T therapy for these tumors. In this study, we report a comprehensive B7H6 expression analysis on primary AML and melanoma as well as on different tumor cell-lines examined by RT-qPCR and flow cytometry, and efficient anti-tumor reactivity of NKp30-CAR T cells to AML and melanoma. To overcome limitations of autologous CAR T-cell fitness-dependent efficacy and patient-tailored production, we generated CRISPR/Cas9-mediated TCR-knockout (TCR^KO) NKp30-CAR T cells as an off-the-shelf approach for CAR T therapy. Functional studies comparing NKp30-CD28 CAR or NKp30-CD137 CAR TCR⁺ and TCR^KO T lymphocytes revealed superior anti-tumoral immunity of NKp30-CD28 CAR TCR^KO T cells to AML and melanoma cell lines in vitro, and effective control of tumor burden in an NSG melanoma-xenograft mouse model. In conclusion, these findings highlight the therapeutic potential of NKp30 CAR TCR^KO T cells for adoptive T-cell therapy to B7H6-expressing cancers, including melanoma and AML. Full article

Background: Gut microbiota dysregulation is increasingly recognized as a key contributor to the progression of liver cirrhosis and its complications, particularly hepatic encephalopathy. Fecal microbiota transplantation (FMT) has emerged as a novel therapeutic strategy aimed at restoring intestinal microbial homeostasis and modulating systemic inflammation. Methods: This prospective, single-center clinical trial evaluated the short-term safety and efficacy of FMT in patients with alcohol-related liver cirrhosis. Clinical assessment, liver stiffness (via elastography), steatosis (controlled attenuation parameter), inflammatory biomarkers, and extended biochemical panels were analyzed at baseline, one week and one month post-FMT. A control group receiving standard medical therapy was used for comparison. Results: FMT was associated with a significant reduction in hepatic encephalopathy severity (p = 0.014), sustained improvements in liver stiffness (p = 0.027) and decreased steatosis (p = 0.025). At one month, C-reactive protein and neutrophil-to-lymphocyte ratio both declined significantly (p = 0.043), indicating a measurable anti-inflammatory effect. No serious adverse events were recorded. In comparison with controls, FMT recipients showed lower systemic inflammation and improved neuropsychiatric status. Conclusions: FMT demonstrated a favorable safety profile and yielded early clinical and biochemical benefits in patients with cirrhosis. These preliminary findings support the potential utility of microbiota-based interventions in chronic liver disease and warrant validation in larger, multicenter trials. Full article

Background: Enterotoxigenic Bacteroides fragilis (ETBF) carries the bft toxin gene, which influences the host immune response and inflammatory pathways and promotes colorectal cancer (CRC). This study investigated the potential role of ETBF in CRC liver metastasis. Methods: We reviewed the records of 226 consecutive patients who underwent curative-intent (R0) resection of CRC liver metastases. ETBF DNA in fresh-frozen metastasis specimens was quantified using droplet digital PCR (ddPCR). Patients were grouped into very-low (≤80%; N = 178), low (80–90%; N = 24), and high (>90%; N = 24) ETBF-DNA groups. Three tissue cores per specimen were stained for CD8, CD4, CD20, FOXP3, CD68, and CD163, and immune-cell densities were measured digitally (cells/mm²). Results: ETBF DNA was detected in 219 of 226 lesions (96.9%). The densities of cytotoxic CD8⁺ T-cells, effector CD4⁺ T-cells, CD20⁺ B-cells, and CD163⁺ macrophages did not differ significantly by ETBF-DNA group (P_trend all > 0.12). FOXP3⁺ regulatory T-cells (Tregs) decreased (P_trend = 0.010), and CD68⁺ macrophages increased (P_trend = 0.020) as ETBF-DNA levels increased. ETBF-DNA levels in CRC liver metastases were not associated with disease-free survival or overall survival or serum C-reactive protein levels. Conclusions: ETBF was present in almost all CRC liver metastases. Higher ETBF levels were associated with a tumor-immune microenvironment enriched in CD68⁺ macrophages and deficient in FOXP3⁺ Tregs, suggesting that ETBF facilitates immune evasion without loss of effector lymphocytes. Although ETBF-DNA levels did not predict survival in this single-center cohort, the potential role of ETBF in immune remodeling and as a candidate biomarker and therapeutic target in metastatic CRC warrants further study. 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: 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

Background: Chronic hepatitis B (CHB) remains being a major public health threat, and currently existing CHB therapies have limited efficacy and side effects. We have recently developed a vaccine termed VVX001 based on a recombinant fusion protein consisting of the preS domain of the large surface protein of hepatitis B virus (HBV) fused to grass pollen allergen peptides. VVX001 has been shown to induce preS-specific antibodies in grass pollen allergic patients, and sera of immunized subjects inhibited HBV infection in vitro. Methods: In this study we investigated if immunization with VVX001 can induce preS-specific antibodies in CHB using the adeno-associated virus (AAV)-HBV murine model of CHB. Six groups of C57BL/6 female mice (n = 6) were transduced with AAV-HBV or AAV-Empty, and after six weeks, they were immunized five times with 20 µg of aluminum hydroxide-adsorbed VVX001 or preS or vehicle (Alum alone). Serum samples were taken continuously. Two weeks after the last immunization, spleen and liver mononuclear cells were collected. Serum reactivity to preS and preS-derived peptides was assessed by ELISA. B-cell responses were measured by ELISPOT assay, and intrahepatic lymphocyte (ILH) counts were determined by FACS. HBV DNA, HBsAg, HBeAg, ALT, and AST were assessed using commercial kits. Results: Our results show that VVX001 induces preS-specific IgG antibodies that cross-react with different HBV genotypes A-H and are directed against the sodium taurocholate co-transporting polypeptide (NTCP) receptor binding site of preS both in mice with and without HBV. Actively immunized AAV-HBV-treated mice had a higher number of intrahepatic lymphocytes than vehicle-vaccinated and mock-transduced animals. Conclusions: These findings encourage performing further trials to study the potential of VVX001 for therapeutic vaccination against CHB. Full article

Background/Objectives: Inflammation plays a key role in acute coronary syndromes (ACS). The systemic immune-inflammation index (SII), which integrates immune and inflammatory markers, may serve as a valuable prognostic tool. This study aimed to evaluate the utility of SII as a short-term predictor of mortality and major adverse cardiovascular and cerebral events (MACCE) in ACS patients. Methods: A retrospective analysis was conducted on 964 ACS patients admitted in 2023. SII was calculated from admission hematological parameters. Primary and secondary outcomes were 30-day mortality and MACCE, respectively. Results: SII levels differed significantly across ACS subtypes (p < 0.001), highest in ST-segment elevation myocardial infarction (STEMI) and lowest in unstable angina. SII was markedly higher in deceased patients (2003.79 ± 1601.17) vs. survivors (722.04 ± 837.25; p < 0.001) and remained an independent predictor of mortality (OR = 1.038, p < 0.001). Similarly, SII was elevated in MACCE cases (1717 ± 1611.32) vs. non-MACCE (664.68 ± 713.11; p < 0.001) and remained predictive in multivariate analysis (OR = 1.080, p < 0.001). Predictive accuracy for MACCE was moderate (AUC = 0.762), improved when combined with GRACE 2, especially in specificity (p = 0.07). In STEMI, SII had excellent accuracy (AUC = 0.874), outperforming neutrophil–lymphocyte ratio and C-reactive protein. SII rose at 24 h and declined at 48 h in STEMI, with a slower decline in MACCE patients. Conclusions: SII proved to be a cost-effective biomarker reflecting inflammation, immunity, and thrombosis. Elevated SII predicted short-term MACCE and mortality in ACS, with improved prognostic power when combined with GRACE 2. Persistent elevation may signal ongoing inflammation and increased MACCE risk. Full article

Background and Objectives: Clostridioides difficile infection (CDI) poses a major public health problem worldwide. Materials and Methods: In this retrospective study, we included 274 patients with CDI, who were hospitalized in Internal Medicine Departments in Evangelismos General Hospital in Athens, Greece, during the past decade. Demographic, clinical and laboratory parameters of the patients were recorded. Statistical analysis revealed an association between older age and mortality as well as heart failure and mortality among patients with CDI. Results: Notably, WBC (white blood count), neutrophils, NLR (neutrophil-to-lymphocyte ratio), dNLR (derived NLR), SII (systemic immune–inflammation index) and hs-CRP (high-sensitivity C-reactive protein) demonstrated a positive association with mortality, whereas serum albumin levels and PNR (platelet-to-neutrophil ratio) exhibited an inverse relationship with mortality. We propose that the aforementioned biomarkers may be used as prognostic parameters regarding mortality from CDI. Conclusions: Large scale studies among patients with CDI with the advent of AI (artificial intelligence) may incorporate demographic, clinical and laboratory features into prognostic scores to further characterize the global CDI threat. Full article

Streptococcus iniae (S. iniae) is a globally significant aquatic pathogen responsible for severe economic losses in aquaculture. While the S. iniae infection often exhibits distinct seasonal patterns strongly correlated with water temperature, there is limited knowledge regarding the temperature-dependent immune evasion strategies of S. iniae. Our results demonstrated a striking temperature-dependent virulence phenotype, with significantly higher A. latus mortality rates observed at high temperature (HT, 33 °C) compared to low temperature (LT, 23 °C). Proteomic analysis revealed temperature-dependent upregulation of key virulence factors, including streptolysin S-related proteins (SagG, SagH), antioxidant-related proteins (SodA), and multiple capsular polysaccharide (cps) synthesis proteins (cpsD, cpsH, cpsL, cpsY). Flow cytometry analysis showed that HT infection significantly reduced the percentage of lymphocyte and myeloid cell populations in the head kidney leukocytes of A. latus, which was associated with elevated caspase-3/7 expression and increased apoptosis. In addition, HT infection significantly inhibited the release of reactive oxygen species (ROS) but not nitric oxide (NO) production. Using S. iniae cps-deficient mutant, Δcps, we demonstrated that the cps is essential for temperature-dependent phagocytosis resistance in S. iniae, as phagocytic activity against Δcps remained unchanged across temperatures, while NS-1 showed significantly reduced uptake at HT. These findings provide new insights into the immune evasion of S. iniae under thermal regulation, deepening our understanding of the thermal adaptation of aquatic bacterial pathogens. Full article

In this review, we explore the complexities of objectively assessing the response to immunotherapy in mycosis fungoides (MF), a prevalent form of cutaneous T-cell lymphoma. The core challenge lies in distinguishing between reactive and malignant lymphocytes amidst treatment, particularly given the absence of uniform pathological biomarkers for MF. We highlight the vital role of emerging histological technologies, such as multispectral imaging and spatial transcriptomics, in offering a more profound insight into the tumor microenvironment (TME) and its dynamic response to immunomodulatory therapies. Drawing on parallels with melanoma—another immunogenic skin cancer—our review suggests that methodologies and insights from melanoma could be instrumental in refining the approach to MF. We specifically focus on the prognostic implications of various TME cell types, including CD8+ tumor-infiltrating lymphocytes, natural killer (NK) cells, and histiocytes, in predicting therapy responses. The review culminates in a discussion about adapting and evolving treatment response quantification strategies from melanoma research to the distinct context of MF, advocating for the implementation of novel techniques like high-throughput T-cell receptor gene rearrangement analysis. This exploration underscores the urgent need for continued innovation and standardization in evaluating responses to immunotherapies in MF, a field rapidly evolving with new therapeutic strategies. Full article

Lifileucel, a tumor-infiltrating lymphocyte (TIL) cell therapy approved for advanced melanoma, demonstrates promise for treating other solid tumors, including endometrial cancer (EC). The current study evaluates the feasibility of manufacturing TILs from EC tumors using Iovance’s proprietary 22-day Gen2 manufacturing process. Key parameters, including TIL yield, viability, immune phenotype, T-cell receptor clonality, and cytotoxic activity, were assessed. Of the 11 EC tumor samples processed at research scale, 10 (91%) successfully generated >1 × 10⁹ viable TIL cells, with a median yield of 1.1 × 10¹⁰ cells and a median viability of 82.8%. Of the four EC tumor samples processed at full scale, all achieved the pre-specified TVC and viability targets. Putative tumor-reactive T-cell clones were maintained throughout the manufacturing process. Functional reactivity was evidenced by the upregulation of 4-1BB in CD8+ T cells, OX40 in CD4+ T cells, and increased production of IFN-γ and TNF-α upon autologous tumor stimulation. Furthermore, antitumor activity was confirmed using an in vitro autologous tumor organoid killing assay. These findings demonstrate the feasibility of ex vivo TIL expansion from EC tumors. This study provides a rationale for the initiation of the phase II clinical trial IOV-END-201 (NCT06481592) to evaluate lifileucel in patients with advanced EC. Full article

Background: Sternal wound infections (SWIs) remain a significant complication following cardiac surgery. Inflammatory and nutritional status are increasingly recognized as key contributors to their development. This study aimed to investigate the predictive utility of immunonutritional biomarkers and to evaluate the protective effect of combining sternal irrigation with an antibiotic-impregnated membrane. Methods: This retrospective cohort study included 480 patients undergoing off-pump coronary artery bypass grafting. Patients were categorized based on sternal management strategy (standard closure or local prophylaxis using gentamicin-enriched irrigation combined with an antibiotic-impregnated fascia lata membrane) and according to the severity of SWIs, classified as superficial or deep. Inflammatory and nutritional markers—including C-reactive protein (CRP), neutrophils, lymphocytes, albumin, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein-to-albumin ratio (CAR), and prognostic nutritional index (PNI)—were assessed at three time points: preoperatively, on postoperative day 3, and after week 1. Results: SWIs were observed in 93 patients, including 75 superficial and 18 deep infections. The combined prophylactic approach was associated with a nearly 1.8-fold reduction in deep SWIs (OR: 0.55; 95% CI: 0.15–0.87) and a modest reduction in superficial infections (OR: 0.89; 95% CI: 0.5–1.3; p = 0.061). Threshold values of 3.75 for preoperative NLR, 9.8 for ΔNLR, and 16.7 for ΔCAR demonstrated strong predictive capacity for identifying patients at increased risk of developing deep SWIs. Patients receiving local prophylaxis exhibited significantly lower CRP, NLR, and CAR values and higher PNI levels at all time points. Conclusions: The combination of sternal irrigation and local antibiotic prophylaxis appears to confer protection against SWIs, potentially by mitigating postoperative inflammation. Immunonutritional biomarkers offer a promising means for early risk stratification. To confirm their clinical utility and broader applicability, these results should be validated in prospective, multicenter studies encompassing a wider range of cardiac surgical procedures. Full article