Understanding immunoregulation in newborns can help to determine the pathophysiology of neonatal sepsis and will contribute to improve the diagnosis, prognosis, and treatment and remains an urgent and unmet medical need to understand hyperinflammation or hypoinflammation associated with sepsis in newborns. This study included infants (up to 4 days old). The “sepsis” criteria was a positive blood culture. C-reactive protein demonstrates a strong dependence on the pathogen etiology. Therefore, its diagnostic odds ratio in Gram-positive bacteremia was 2.7 and the sensitivity was 45%, while Gram-negative was 15.0 and 81.8%, respectively. A neutrophil-lymphocyte ratio above 1 and thrombocytopenia below 10⁹ cells/L generally do not depend on the type of pathogen and have a specificity of 95%; however, the sensitivity of these markers is low. nCD64 demonstrated good analytical performance and was equally discriminated in both Gram (+) and Gram (−) cultures. The sensitivity was 87.5–89%, and the specificity was 65%. The HLA-DR and programmed cell death protein study found that activation-deactivation processes in systemic infection is different at points of application depending on the type of pathogen: Gram-positive infections showed various ways of activation of monocytes (by reducing suppressive signals) and lymphocytes (an increase in activation signals), and Gram-negative pathogens were most commonly involved in suppressing monocytic activation. Thus, the difference in the bacteremia model can partially explain the problems with the high variability of immunologic markers in neonatal sepsis.

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Neonatal sepsis is the main cause of death in newborns, especially preterm infants. The pathogenesis of sepsis is based on a hyper-inflammatory syndrome combined with an immunosuppressive mechanism in sepsis. This study aimed to find critical parameters that are associated with the outcome of newborns with suspected sepsis. Understanding the association might have clinical relevance for immuno-monitoring, outcome prediction, and targeted therapy. Methods: A total of 210 newborn infants no older than 4 days with suspected sepsis at admission in Karaganda (Kazakhstan) were prospectively enrolled. Blood cultures were incubated, and pathogens in positive cultures were determined by MALDI-TOF. An immunological assay for blood cell components was conducted by flow cytometry with antibody cocktails. The diagnostic criteria for neonatal sepsis were identified by qualified neonatologists and included both clinical sepsis and/or positive blood culture. The analyzed infants were grouped into non-septic infants, surviving septic infants, and deceased septic infants. The results showed that deceased septic newborns had a lower level of CD8+ lymphocytes and higher PDL-1 expression in comparison with surviving septic newborns. PDL-1 expression on CD8+ T cells might play an immunosuppressive role during neonatal sepsis and might be used as a laboratory biomarker in the future.

Background/Objectives: This study aims to investigate the potential etiopathogenesis of HFpEF development and identify possible different phenotypes of HFpEF in patients with chronic obstructive pulmonary disease (COPD) and systemic sclerosis-associated interstitial lung diseases (SS-ILDs). It could help clinicians improve early HFpEF personalized detection and management. Methods: This study included 150 patients with chronic lung diseases (CLDs), such as COPD and SS-ILD, who were outside of exacerbation, had no history of chronic heart failure (CHF), and had a left ventricular ejection fraction (LV EF) of ≥50%. The functional status of the lungs, heart, endothelial dysfunction, and acid–base balance was assessed. The results obtained were compared in groups of patients with CLD depending on the presence or absence of HF with preserved ejection fraction (HFpEF). The diagnosis of HFpEF was established based on the HFA-PEFF Score classification. Nonparametric statistical methods were used. Results: In patients with CLD, indicators such as age, longitudinal size of the right atrium, mid-regional pro-atrial natriuretic peptide (MR-proANP), and highly sensitive cardiac troponin T (hsTnT) were higher than in the group of patients without HFpEF. In patients with COPD and HFpEF, statistically significant changes were found in the volume of the left atrium. In patients with SS-ILD and HFpEF, statistically significant differenceswere found in SBP before and after the 6 min walk test (6MWT), the Borg scale before 6MWT, MR-proANP, and the longitudinal dimension of the right atrium. Conclusions: The results of our study allow us to identify two different mechanisms of HFpEF development: In patients with COPD, the predominant factor in the development of HFpEF was hypoxia, while in patients with SS-ILD, myocardial dysfunction with remodeling developed against the background of secondary pulmonary hypertension, highlighting the importance of phenotype-specific evaluation. These findings suggest potential approaches for personalized risk stratification and the development of targeted management strategies for patients with HFpEF.

Introduction: The aim of this study was to evaluate the potential biomarkers of bacterial translocation: lipopolysaccharide‐binding protein (LBP) and soluble CD14 subtype (sCD14‐ST), and intestinal wall damage: intestinal fatty acid binding protein (I‐FABP), zonulin, and regenerating islet‐derived protein‐3α (REG3α), in the patients with multiple organ dysfunction syndrome (MODS).Methods: The study involved 78 patients over the age of 18 with MODS set according to the Sequential Organ Failure Assessment (SOFA) scale. Venous blood was sampled during diagnostics of MODS, on the 3rd and on the 7th day of its development. The sCD14‐ST, LBP, I‐FABP, REG3α, and zonulin in blood serum were determined by enzyme‐linked immunosorbent assay (ELISA).Results: Out of 78 patients with MODS, 43 patients survived (55.1%) and 35 patients died (44.9%). Levels of sCD14‐ST on Day 1, I‐FABP on Day 3, and REG3α on Days 3 and 7 and SOFA scores on Days 1, 3, and 7, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores on Days 1, 3, and 7, and Modified Nutrition Risk in Critically Ill (mNUTRIC) scores on Days 1, 3, and 7 were statistically significantly higher in deceased patients (p < 0.05).Conclusion: In patients with MODS, an increase in sCD14‐ST, I‐FABP, and REG3α in blood serum can indicate the violation of intestinal barrier function and increased bacterial translocation, which ultimately may aggravate the severity of MODS and increase the risk of death. It is required to further study the factors leading to intestinal wall permeability disorders in order to screen for timely intensive care measures that can help reduce the stay of patients in the intensive care unit (ICU) as well as mortality.Trial Registration: ClinicalTrials.gov identifier: NCT06221293

Due to the fact that there are scientific discussions about the significance of gene polymorphisms in the risk of developing cardiovascular complications after a percutaneous coronary intervention, it is of interest to evaluate the genetic predictors of the development of cardiovascular events. This study is a molecular genetic study. Association with the genes of biomarkers for inflammation and immune response increases the risk of cardiovascular events: rs1234313 (TNFSF4): (A/G, OR-4.57 (2.35–8.87), p ≤ 0.0001), (A/G-A/A, OR-3.14 (1.75–5.63), p ≤ 0.0001), and (A/G, OR = 4.01 (2.19–7.36), p ≤ 0.0001); rs3184504 (SH2D3); ATXN2: (C/T, OR-2.53 (1.28–5.01), T/T, OR-2.99 (1.13–7.92), p = 0.017)), (C/T-T/T, OR-2.61 (1.35–5.07), p = 0.000), and (OR-1.89 (1.15–3.09), p = 0.009)). According to the lipid metabolism biomarker genes, rs2943634: (A/C OR-2.57 (1.18–5.62), p = 0.013); according to the endothelial biomarker genes, rs2713604: (DNAJB8-AS1; GATA2): (C/T, OR-4.27 (2.35–7.76), p ≤ 0.0001), (C/T-C/C, OR-4.13 (2.31–7.40), p ≤ 0.0001), (OR-4.05 (2.24–7.30), p ≤ 0.0001), and (C/T, OR-3.46 (1.99–6.00), p ≤ 0.0001). The regression analysis found that in the presence of the rs2943634 gene polymorphism, the risk of late cardiovascular events increases by 4.007 times with 95% CI (1.502:10.692), p = 0.006. The genes of biomarkers for the risk of cardiovascular events are rs1234313(TNFSF4), rs3184504 (SH2D3; ATXN2), rs2943634, and rs2713604 (DNAJB8-AS1; GATA2). The only predictor of the development of new cardiovascular events was rs2943634, which belongs to the group of lipid metabolism biomarkers.

This study assesses the utility of early biomarkers—5-hydroxyindoleacetic acid (5-HIAA) and insulin-like growth factor 1 (IGF-1)—for diagnosing and monitoring pulmonary hypertension (PH) in children with congenital heart defects (CHD). Due to the risks associated with invasive diagnostics, such as right heart catheterization, non-invasive biomarkers provide a safer alternative for early PH detection. This cohort-based study utilized blood and urine samples to measure 5-HIAA and IGF-1 levels via enzyme immunoassays. Our findings revealed significant changes in 5-HIAA concentrations across various biological matrices, supporting its potential as a diagnostic tool. Specifically, altered levels in urine and plasma reflect its role in serotonin metabolism and vascular remodeling in PH. IGF-1 levels were notably reduced in plasma, suggesting its involvement in PH pathophysiology. ROC analysis confirmed the diagnostic efficacy of these biomarkers, particularly 5-HIAA’s high specificity and sensitivity. In conclusion, 5-HIAA and IGF-1 levels correlate well with PH, underscoring their diagnostic value for early PH detection in children with CHD.