Search Results (819)

Background/Objectives: Late-onset neonatal sepsis (LOS) remains a leading cause of morbidity and mortality in very low birth weight (VLBW) infants (<1500 g and/or gestational age <32 weeks), with limited preventive strategies. We evaluated whether early enteral bovine lactoferrin (bLf), given its antimicrobial, immunomodulatory, and antioxidant properties, reduces LOS and improves immunologic, antioxidant, and hematologic markers in these infants. Methods: In this randomized, double-blind, placebo-controlled trial, 103 VLBW infants received bLf (150 mg/kg/day; n = 50) or the placebo (n = 53) within 72 h of birth for four weeks or until discharge. Outcomes included culture-confirmed LOS, mortality, and major morbidities. Risk ratios (RRs) were calculated, adjusting for gestational age, human milk intake, and ventilatory support when ≥25 events occurred. Pre/post changes in cytokines, total antioxidant capacity (TAC), and hemoglobin (Hb) were analyzed for interaction effects (time x intervention). Results: bLf reduced LOS (adjusted RR 0.54; 95% CI 0.31–0.93; p = 0.028), without differences in other morbidities or mortality. bLf preserved MCP-1 levels, declining in the placebo group (interaction p = 0.022). Among LOS infants receiving bLf, IL-6 remained stable and MCP-1 increased, while both declined in other groups (interaction p = 0.007 for IL-6; p = 0.052 for MCP-1). Although TAC showed a non-significant interaction, the placebo group declined (p = 0.002), while bLf remained stable (p = 0.400) in the post hoc analysis. In non-transfused infants, bLf increased Hb by 0.9 g/dL vs. controls (p = 0.028). Conclusions: Early bLf supplementation safely reduces LOS in VLBW infants and may support immunologic, antioxidant, and hematologic stability. Full article

Background: Sarcoidosis is a systemic granulomatous disease with a highly variable clinical course, and distinguishing it from other diseases and predicting its prognosis can be challenging. In recent years, hematological and biochemical parameters have been investigated as potential biomarkers for assessing inflammation and predicting disease prognosis. This study aimed to evaluate the prognostic value of the lactate dehydrogenase-to-albumin ratio (LAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR). Methods: This retrospective, single-center study included 369 newly diagnosed patients with sarcoidosis who were admitted between January 2020 and October 2024. Sarcoidosis was diagnosed based on current ERS, ATS, and WASOG guidelines. At the 6-month follow-up, patients’ clinical courses were classified as regression, stable, or progression based on clinical, radiological, and pulmonary function tests. The predictive values of various hematological and biochemical parameters were analyzed using statistical methods, including binary logistic regression analysis and ROC analysis. Results: A total of 369 patients were included in the study. At the 6-month follow-up, 63.4% of patients showed regression, 21.4% had a stable course, and 15.2% showed progression. The progression group had a significantly higher LAR (5.26 [4.21–7.76]) compared to the stable/regression group (4.59 [3.82–5.86]) (p = 0.033). Additionally, baseline FVC% (OR, 0.97; p = 0.036) and the presence of dyspnea (OR, 3.08; p = 0.03) were identified as independent risk factors for disease progression. No significant associations were found between NLR, PLR, LMR, and serum ACE levels and the clinical course. The cutoff value of LAR for predicting disease progression was 4.87 (AUC: 0.605), with a sensitivity of 58.8% and specificity of 59.7%. Conclusions: Our study, which is the first to evaluate the prognostic value of LAR in sarcoidosis, identified this parameter as a significant indicator for the clinical course. The finding of significantly higher LAR levels in patients with disease progression suggests its potential as a prognostic biomarker. These results may help guide treatment and follow-up strategies, although further large-scale prospective studies are needed for validation. Full article

Background: Osteoarthritis (OA) is a major global health issue, increasing with aging and obesity. Current therapies mainly address symptoms without modifying disease progression. Platelet-rich growth factor (PRGF) therapy has potential regenerative effects through high cytokines and growth factors, but the outcomes of these therapies remain heterogeneous. This study explores the relationship between patient nutritional status, PRGF characteristics, and clinical outcomes in knee OA treatment. Methods: Baseline anthropometric, metabolic, and nutritional assessments of 41 patients with knee OA who underwent PRGF treatment were conducted. Blood samples were analyzed for metabolic and inflammatory markers. PRGF composition was assessed by protein content and extracellular vesicle (EV) markers. KOOS and VAS pain scores were collected at 2, 6, and 12 months. Responders improved KOOS by ≥10 points. An elastic-net regularized logistic model allowed the identification of the predictors of treatment response. Results: KOOS and VAS scores improved significantly at all follow-ups. At 2 months, the PRGF of responder patients showed higher PRGF G-CSF levels; at 12 months, increased CD49e and HLA-ABC expression. Higher BMI correlated with increased IL-6, IL-1ra, and resistin in PRGF samples. Hypercholesterolemic patients displayed altered EV profiles, with elevated levels of CD8 but reduced CD49e, HLA-ABC, CD42a, and CD31. Multivariate analysis identified BMI, biceps fold, fat percentage, red blood cell, platelet, and neutrophil counts as predictors of early response. Conclusions: Metabolic and immunological factors influence PRGF composition and clinical efficacy in knee OA. Baseline body composition and hematological parameters as key predictors of response, highlighting the potential of personalized PRGF therapy. Full article

Background/Objectives: Modern healthcare faces a growing burden of antimicrobial resistance, prominently driven by ESKAPE pathogens. These organisms—Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.—are the leading causes of healthcare-associated infections, associated with limited therapeutic options and increased morbidity. Continuous surveillance is crucial for informing empirical therapy and guiding stewardship. Methods: We perform a single-center, seven-year retrospective study (2018–2024) at a 1000-bed tertiary hospital in Warsaw, Poland. Bloodstream isolates of ESKAPE pathogens were identified according to the EUCAST guidelines. Data were analyzed by pathogen, ward, and year of isolation. Results: From 2483 positive blood cultures, 3724 ESKAPE pathogens were recovered. S. aureus and K. pneumoniae predominated, particularly in the Intensive Care Unit and Hematology ward. Resistance analysis revealed persistently high vancomycin resistance in E. faecium, variable but notable methicillin resistance in S. aureus, and frequent ESBL production in K. pneumoniae with an alarming rise in carbapenemase-producing strains, including dual NDM + OXA-48 co-producers. A. baumannii exhibited near-universal multidrug resistance. P. aeruginosa demonstrated lower resistance rates with preserved colistin susceptibility, while Enterobacter spp. remained fully carbapenem-susceptible. Linezolid retained activity against E. faecium, while colistin remained effective against A. baumannii and P. aeruginosa. Modern β-lactam/β-lactamase inhibitor combinations were active against K. pneumoniae. Conclusions: Our findings underscore the critical role of ESKAPE pathogens in bloodstream infections and highlight divergent resistance patterns across species. The emergence of carbapenemase-producing K. pneumoniae and the persistence of multidrug-resistant A. baumannii are of particular concern. Sustained surveillance, robust antimicrobial stewardship, and tailored infection control strategies remained essential to curb the evolving resistance threat in tertiary care settings. Full article

Background: The COVID-19 pandemic has disproportionately affected the elderly population, with inflammation and impaired immune response being key drivers of disease progression. Clinicians require predictive models integrating immunological and inflammatory biomarkers to optimize risk stratification in this vulnerable group. Methods: We retrospectively analyzed 1429 elderly patients (aged >60 years) admitted with COVID-19 between March 2020 and August 2022. Demographic, clinical, and laboratory data were collected at admission. Correlation and regression analyses were performed to assess the prognostic significance of hematological and inflammatory markers. Results: Lymphopenia and neutrophilia were predominant findings, frequently associated with elevated C-reactive protein levels. Correlation analyses revealed significant associations between inflammatory markers and discharge status or death, while lymphocytes exerted a protective effect, reducing mortality risk by 14.4%. Notably, a higher platelet-large cell ratio (PLCR) was linked to increased mortality, suggesting an important contribution of thrombosis to severe COVID-19. Conclusions: Our findings indicate that immunological and inflammatory markers may serve as significant predictors of outcomes in elderly COVID-19 patients. While the predictive power of the model remains limited, these biomarkers can contribute to a better understanding of patient trajectories and may inform therapeutic strategies. Full article

Background/Objectives: Whilst adoptive cell therapy (ACT) using chimeric antigen receptor-engineered T (CAR-T) cells represents an efficient approach for the treatment of patients suffering from several hematological malignancies, solid tumors have been shown to be far more challenging to tackle, mainly due to the hostile tumor microenvironment that inhibits optimal T cell functionality. As proven by the broad clinical success of immune checkpoint inhibitors, blocking the interaction of programmed cell death ligand 1 (PD-L1) expressed on tumor cells and the checkpoint receptor programmed cell death 1 (PD-1) expressed on activated T cells allows an intrinsic T cell-mediated anti-tumor response to be unleashed. We developed a cellular product (MDG1015) consisting of New York esophageal squamous cell carcinoma-1 (NY-ESO-1)/L antigen family member 1a (LAGE-1a)-specific CD8+ T cell receptor-transduced (TCR-)T cells co-expressing the costimulatory switch protein (CSP) PD1-41BB, which turns an inhibitory signal mediated by the PD-1:PD-L1 axis into positive T cell costimulation. Methods: In vitro co-cultures of MDG1015 and PD-L1-positive or -negative target cells were used to analyze TCR-T cell functionality, such as TCR-T (poly-)cytokine release, the killing of target cells, and TCR-T proliferation. The safety of MDG1015 was evaluated via different panels of antigen-negative cell lines or primary cells expressing or lacking PD-L1. Results: Preclinical analyses demonstrated TCR-gated activation of the CSP, leading to enhanced functionality of MDG1015 against antigen-expressing, PD-L1-positive tumor cells without any impact on antigen-negative target cells. Conclusions: The favorable, preclinical functionality and safety profile qualifies MDG1015 as a promising cellular therapy for explorative clinical testing in hard-to-treat solid tumor indications. Full article

Background: Urothelial carcinoma of the bladder (UCB) demonstrates considerable heterogeneity, with markedly varying outcomes between non–muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). The pan-immune-inflammation value (PIV), derived from routine hematological parameters, has emerged as a novel biomarker reflecting systemic inflammation and immune dysregulation. This pilot, exploratory analysis evaluated the prognostic relevance of the PIV in UCB and contextualized PIV against other inflammation-based indices. Methods: We retrospectively analyzed 119 patients with histologically confirmed UCB who were treated between 2019 and 2024. PIV was calculated as (neutrophils × platelets × monocytes) ÷ lymphocytes. Additional indices included the NLR, SII, SIRI, and PLR. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier analysis, and prognostic factors were assessed using Cox regression. Results: Among 119 patients (median age, 72 years; 88% male), 68 were diagnosed with NMIBC and 51 with MIBC. Elevated PIV levels were significantly associated with NMIBC progression to MIBC (p = 0.028) and strongly correlated with NLR, SII, SIRI, and PLR. Patients with high PIV exhibited shorter OS (24 vs. 45 months) and PFS (20 vs. 35 months) than those with low patients (p < 0.001). Although the prognostic value was evident in the univariate analyses, PIV did not retain significance in multivariate models. Conclusion: Elevated PIV levels predict adverse survival outcomes and progression in UCB, underscoring its potential as a cost-effective and accessible biomarker for risk stratification. Prospective validation in larger cohorts is warranted to confirm its role in personalized patient management. Full article

Objective: This study aimed to analyze the epidemiological, hematological, and oxidative stress profile of truck drivers. Method: It involved 63 drivers from the western border of a state in southern Brazil who completed a questionnaire, had vital signs and anthropometric evaluations, and provided blood samples. Hematological parameters, leukocytes, and oxidative damage to proteins and lipids were analyzed. Results: A high prevalence of overweight and obesity was found among the drivers, with an increased risk of cardiovascular issues and hypertension. Obese drivers had higher monocyte counts, while those with normal weight had increased protein carbonylation levels. Conclusions: It is crucial to implement health interventions to prevent chronic diseases in truck drivers, given their high exposure to risk factors. Full article

Insights into the state of individual cells within a living organism are essential for identifying diseases and abnormalities. The internal state of a cell is reflected in its morphological features and changes in the localization of intracellular molecules. Using this information, it is possible to infer the state of the cells with high precision. In recent years, technological advancements and improvements in instrument specifications have made large-scale analyses, such as single-cell analysis, more widely accessible. Among these technologies, imaging flow cytometry (IFC) is a high-throughput imaging platform that can simultaneously acquire information from flow cytometry (FCM) and cellular images. While conventional FCM can only obtain fluorescence intensity information corresponding to each detector, IFC can acquire multidimensional information, including cellular morphology and the spatial arrangement of proteins, nucleic acids, and organelles for each imaging channel. This enables the discrimination of cell types and states based on the localization of proteins and organelles, which is difficult to assess accurately using conventional FCM. Because IFC can acquire a large number of single-cell morphological images in a short time, it is well suited for automated classification using machine learning. Furthermore, commercial instruments that combine integrated imaging and cell sorting capabilities have recently become available, enabling the sorting of cells based on their image information. In this review, we specifically highlight practical applications of IFC in four representative areas: cell cycle analysis, protein localization analysis, immunological synapse formation, and the detection of leukemic cells. In addition, particular emphasis is placed on applications that directly contribute to elucidating molecular mechanisms, thereby distinguishing this review from previous general overviews of IFC. IFC enables the estimation of cell cycle phases from large numbers of acquired cellular images using machine learning, thereby allowing more precise cell cycle analysis. Moreover, IFC has been applied to investigate intracellular survival and differentiation signals triggered by external stimuli, to monitor DNA damage responses such as γH2AX foci formation, and more recently, to detect immune synapse formation among interacting cells within large populations and to analyze these interactions at the molecular level. In hematological malignancies, IFC combined with fluorescence in situ hybridization (FISH) enables high-throughput detection of chromosomal abnormalities, such as BCR-ABL1 translocations. These advances demonstrate that IFC provides not only morphological and functional insights but also clinically relevant genomic information at the single-cell level. By summarizing these unique applications, this review aims to complement existing publications and provide researchers with practical insights into how IFC can be implemented in both basic and translational research. Full article

Chimeric Antigen Receptor (CAR)-T cell therapy has transformed the treatment landscape of cancer, yet major challenges remain in enhancing efficacy, reducing adverse effects, and expanding accessibility. Autologous CAR-T cells, derived from individual patients, have achieved remarkable clinical success in hematologic malignancies; however, their highly personalized nature limits scalability, increases costs, and delays timely treatment. Allogeneic CAR-T cells generated from healthy donors provide an “off-the-shelf” alternative but face two critical immune barriers: graft-versus-host disease (GvHD), caused by donor T-cell receptor (TCR) recognition of host tissues, and host-versus-graft rejection, mediated by recipient immune responses against donor HLA molecules. Recent advances in genome engineering, particularly Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9, allow precise modification of donor T cells to overcome these limitations. For example, TRAC gene knockout eliminates TCR expression, preventing GvHD, while disruption of HLA molecules reduces immunogenicity without impairing cytotoxicity. Beyond hematologic cancers, CRISPR-edited allogeneic CAR-T cells targeting the NKG2D receptor have shown promise in preclinical studies and early-phase trials. NKG2D CAR-T cells recognize stress ligands (MICA/B, ULBP1–6) expressed on over 80% of diverse solid tumors, including pancreatic and ovarian cancers, thereby broadening therapeutic applicability. Nevertheless, the genomic editing process carries risks of off-target effects, including potential disruption of tumor suppressor genes and oncogenes, underscoring the need for stringent safety and quality control. This review examines the distinguishing features of allogeneic versus autologous CAR-T therapy, with a particular focus on NKG2D-based allogeneic CAR-T approaches for solid tumors. We summarize current strategies to mitigate immune barriers, discuss practical manufacturing challenges, and analyze available clinical data on NKG2D CAR-T trials. Collectively, these insights underscore both the promise and the hurdles of developing safe, universal, and scalable allogeneic CAR-T therapies for solid malignancies. Full article

Understanding physiological variability in wild ungulates is essential for ecological monitoring and sustainable wildlife management. This study aimed to examine whether sex and season (autumn vs. early winter) significantly influence hematological and biochemical parameters in free-ranging red deer (Cervus elaphus) from the Eastern Carpathians, Romania. A total of 40 legally harvested adult individuals (20 males, 20 females) were included, and blood samples were collected post-mortem under standardized conditions to minimize pre-analytical variability. Hematological parameters (WBC, RBC, HGB, HCT, PLTs) and serum biochemical markers (glucose, urea, total cholesterol, triglycerides, total protein) were analyzed using automated veterinary analyzers. Statistically significant sex-related differences were found in hematocrit during autumn and hemoglobin concentration during winter, with higher values in males. Seasonal variation within sex groups was not significant but indicated a physiological trend toward hemoconcentration in winter. Biochemical values remained within reference ranges and showed no significant differences across groups. Pearson’s correlation analysis revealed a strong association between hematocrit and urea, and moderate correlations were observed between WBC and glucose, suggesting links between oxygen transport, protein metabolism, and energy balance. Environmental factors such as reduced food availability and temperature shifts during winter likely contribute to these physiological adjustments. These results provide baseline data for the physiological assessment of red deer populations and support the development of ecological health indicators in wildlife monitoring programs. Future studies incorporating hormonal and immunological biomarkers across multiple seasons are encouraged to further understand adaptive responses in cervids. Full article

Dioxins are persistent organic pollutants with long biological half-lives and a high tendency for bioaccumulation, posing serious toxicological risks to humans and wildlife. This study investigates the modulatory role of rutin, a naturally occurring flavonoid, in promoting the excretion and reducing the systemic retention of polychlorinated dibenzo-p-dioxins and dibenzofurans in vivo. Wistar rats were exposed to a controlled dioxin mixture (10 µg/kg body weight) and administered rutin orally (0.02 g/kg) for 30 consecutive days. Biological samples including feces, urine, and serum were collected and analyzed via high-resolution gas chromatography coupled with high-resolution mass spectrometry (HRGC/HRMS). Rutin significantly enhanced the excretion of octachlorodibenzo-p-dioxin (OCDD) by 30% in urine and 25% in feces, while reducing lipid-adjusted serum dioxin levels. Additionally, biochemical and hematological markers showed improved hepatic and renal function in the rutin-treated group. These findings suggest that rutin may facilitate dioxin detoxification through enhanced metabolic clearance and reduced tissue retention. The study contributes to understanding natural detoxification mechanisms and supports future research into bioactive compounds for mitigating environmental toxicant exposure. Full article

Background: Various studies have shown that viral pneumonia pathogens display distinct inflammatory profiles, and hematological indices, such as the Neutrophil/Lymphocyte Ratio (NLR), Lymphocyte/Monocyte Ratio (LMR), and Platelet/Lymphocyte Ratio (PLR), can serve as accessible markers of disease severity. Moreover, the seasonal distribution of respiratory viruses appears to have shifted during the COVID-19 pandemic. Methods: This retrospective case–control study was conducted on patients diagnosed with PCR-confirmed viral pneumonia in the emergency department of a tertiary care center between 1 January and 31 December 2024. The control group comprised age- and sex-matched individuals without viral pneumonia. Subjects with comorbidities or ongoing treatments potentially affecting hematological indices were excluded. Seasonal distribution of viral pathogens was recorded. Hematological and inflammatory parameters at admission—including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR)—were evaluated. The associations between these biomarkers, Pneumonia Severity Index (PSI) scores, and hospitalization status were statistically analyzed. Results: In this study, it was determined that Influenza A/B was more common in winter (67.3%) and SARS-CoV-2 in summer (70.7%). The relationship between the Pneumonia Severity Index and hemogram parameters was examined in determining the severity of pneumonia. In SARS-CoV-2, leukocyte and neutrophil counts were positively correlated (R: 0.392, p: 0.003; R: 0.466, p: <0.001), while in Influenza A/B, lymphocyte, platelet, and monocyte counts showed a negative correlation (R: −0.402, p: 0.005; R: −0.331, p: 0.021; R: −0.327, p: 0.023). Correlations were found between inflammation parameters and the Pneumonia Severity Index, except for the Lymphocyte/Monocyte Ratio, between SARS-CoV-2 and Influenza A/B (p < 0.05). Conclusions: The seasonal distribution of viral pneumonia pathogens has been revealed following the COVID-19 pandemic. Due to differences in inflammation patterns in viral infections, different leukocyte subgroups have been suggested as biomarkers. Full article

Background/Objectives: Cholesterolosis is a relatively common, yet often incidental, histopathological finding in cholecystectomy specimens, frequently associated with chronic cholecystitis. Although its clinical significance remains unclear, possible associations with glycemic regulation have been proposed. This study aimed to examine the relationship between cholesterolosis, glycemic parameters, and inflammatory markers in patients with chronic cholecystitis. Methods: We retrospectively analyzed gallbladder specimens from patients who underwent cholecystectomy for chronic cholecystitis between 2014 and 2023. Histopathology assessed cholesterolosis presence, distribution, and inflammatory features. Patients were grouped according to diabetes status (diabetic vs. non-diabetic) as well as the presence or absence of cholesterolosis. Demographic data, gallstone status, one-year mean fasting glucose, HbA1c levels, and hematological/inflammatory indices were compared between groups. Results: Among diabetic patients, those with cholesterolosis had significantly lower fasting glucose than those without cholesterolosis (129.04 ± 28.02 vs. 158.41 ± 54.23 mg/dL, p < 0.05). The presence of cholesterolosis was not significantly associated with diabetes status (p > 0.05). Inflammatory indices, including neutrophil count, did not differ significantly between groups (p > 0.05), although fasting glucose correlated positively with neutrophil count (r = 0.167, p < 0.05). Gallstones were less frequent in cholesterolosis cases compared with non-cholesterolosis cases (59.4% vs. 75%, p < 0.05), suggesting a distinct pathophysiology. Conclusions: This is the first study to assess one-year glycemic profiles in diabetic and non-diabetic patients with and without cholesterolosis. The findings suggest that cholesterolosis may occur independently of poor glycemic control and systemic inflammation, supporting the concept of a distinct underlying mechanism. Full article

Background and Objectives: Pregnancy induces numerous physiological changes, including hematologic adaptations, which affect complete blood count (CBC) parameters. Existing reference intervals for CBC are often based on non-pregnant populations, potentially limiting their clinical utility during pregnancy. This study aimed to evaluate longitudinal changes in CBC parameters throughout pregnancy in Korean women and to establish gestational age-specific reference intervals. Materials and Methods: This retrospective study, conducted between March and May 2025, included CBC tests consecutively performed on the same individuals at five time points: the first trimester (≤12 weeks), second trimester (13–28 weeks), third trimester (29–40 weeks), delivery day, and the second postpartum day. Additionally, to prevent duplication with the primary cohort, CBC data from pregnant outpatients and non-pregnant controls were also analyzed to establish reference intervals. CBC parameters were measured using an automated hematology analyzer. Reference intervals were established using the 2.5th and 97.5th percentile of the distribution. Results: During pregnancy, white blood cell (WBC) counts increased most significantly during the second trimester, while hemoglobin (Hgb) levels declined most markedly at this stage. Platelet (PLT) counts showed a consistent and progressive decline. The reference intervals for CBC parameters—WBC (×10⁹/L), Hgb (g/dL), and PLT (×10⁹/L)—were 5.11–12.14, 11.3–14.3, and 184–374 in the first trimester; 6.11–13.45, 10.1–13.3, and 164–356 in the second trimester; and 5.62–12.42, 10.1–14.1, and 145–349 in the third trimester, respectively. Conclusions: This study examined longitudinal changes in CBC parameters in Korean pregnant women and provided gestational age-specific reference intervals for CBC. This is expected to help clinicians interpret CBC results in pregnant women. Full article