Search Results (596)

(1) Background: Sepsis is characterized by profound heterogeneity of immune responses, complicating biomarker-based prediction of clinical outcomes. Latent human cytomegalovirus (HCMV) infection is one of the strongest modulators of the human immune system and may influence cytokine-mediated signaling during sepsis. (2) Methods: In this post hoc analysis of 331 patients from the prospective multicenter SepsisDataNet.NRW cohort (German Clinical Trial Registry No. DRKS00018871), we quantified 13 serum cytokines on day 1 after sepsis diagnosis and determined HCMV IgG serostatus via ELISA. Using nested cross-validated logistic regression with exhaustive feature selection, we identified cytokine panels predictive of 30-day survival in the total cohort and in subgroups stratified by HCMV serostatus. (3) Results: In the total cohort, a four-cytokine panel (IL-6, IL-10, TNF-α, IL-12p70) predicted 30-day survival with a cross-validated area under the curve (AUC) of 0.66 [95% CI: 0.59–0.72]. Stratification by HCMV serostatus revealed distinct predictive profiles: in HCMV-seropositive patients, a two-cytokine model (IL-10, IL-23) achieved an AUC of 0.69 [95% CI: 0.61–0.77], whereas in seronegative patients, a model based on IL-8 and IL-17A failed to generalize (AUC = 0.47 [95% CI: 0.33–0.61]). Kaplan–Meier analysis confirmed a significant separation of survival curves for the HCMV-seropositive group (p < 0.001) but not for seronegative patients (p = 0.282). (4) Conclusions: HCMV serostatus defines an immunological context in which cytokine-based prediction of sepsis outcome becomes feasible. These data suggest that viral serostatus should be systematically incorporated into biomarker discovery and immunophenotyping approaches to improve the reproducibility and biological interpretability of sepsis endotyping. Full article

Background and Objectives: Acute and obstructive pyelonephritis (AOP) management, despite advancements in diagnostic imaging and antimicrobial therapy, is characterized by delayed recognition and increasing antimicrobial resistance. This review aimed to summarize current evidence regarding the clinical characteristics, microbiological spectrum, biomarkers, and imaging findings associated with AOP. Materials and Methods: A systematic review was conducted according to PRISMA guidelines and registered in PROSPERO (CRD420251162736). Literature searches were performed across the PubMed, Scopus, and Web of Science databases for articles published between January 2014 and 31 March 2025 using the term “acute obstructive pyelonephritis”. Inclusion criteria comprised original full-text English-language studies, published in the last 10 years and conducted in adults, reporting clinical, laboratory, microbiological, and imaging characteristics. Exclusion criteria are letters to the editor, expert opinions, case reports, conference or meeting abstracts, reviews, and redundant publications; having unclear or incomplete data; and being performed on cell cultures or on mammals. The quality of included studies was assessed using the Newcastle–Ottawa Scale. Results: Twenty-three studies met the inclusion criteria. AOP predominantly affected elderly patients with comorbidities, especially diabetes mellitus and urinary tract obstruction. Predictors of septic shock included thrombocytopenia, hypoalbuminemia, elevated procalcitonin (>1.12 µg/L), presepsin, and a neutrophil-to-lymphocyte ratio ≥ 8.7. Escherichia coli remained the leading pathogen (60–95%) with extended-spectrum β-lactamase (ESBL) rates between 20 and 70%, followed by Klebsiella pneumoniae. CT demonstrated 71–100% sensitivity for detecting obstructive complications, confirming its superiority over ultrasound, while MRI provided comparable diagnostic accuracy in selected cases. Source control through double-J stenting or percutaneous drainage significantly improved survival. Conclusions: AOP requires prompt recognition and early decompression to prevent sepsis-related mortality. Biomarkers such as procalcitonin, presepsin, and neutrophil to lymphocyte ratio enhance risk stratification, while CT remains the gold-standard imaging modality. The increasing prevalence of ESBL-producing pathogens underscores the need for antimicrobial stewardship and individualized therapeutic strategies guided by local resistance data. Full article

Background: Even though there have been improvements in antimicrobial and supportive therapies, sepsis and septic shock are still major causes of death in intensive care units. Early prognostic stratification is very important for helping doctors make decisions. Platelet-derived indices may provide useful, low-cost indicators that signify both inflammatory activation and coagulation irregularities. This study looked at how well different platelet-based ratios could predict death in the hospital from sepsis. Materials and Methods: We performed a prospective observational study spanning one year in a tertiary ICU, enrolling 114 adult patients diagnosed with sepsis or septic shock. Upon admission, four platelet-related biomarkers were measured: the C-reactive protein-to-platelet ratio (CPR), the platelet-to-lymphocyte ratio (PLR), the platelet-to-white blood cell ratio (PWR), and the platelet-to-creatinine ratio (PCR). Logistic regression models and receiver operating characteristic (ROC) analyses were employed to assess predictive accuracy. Results: Compared to survivors, non-survivors (n = 39) had much higher CRP levels and CPR values, alongside lower platelet and lymphocyte counts. The CPR index showed the best ability in differentiating between non-survivors and survivors (AUC 0.757), with a best cutoff of 0.886. In simplified multivariate models, CPR was still an independent predictor of death in the hospital (OR 1.98; 95% CI 1.22–3.21), whereas PLR and PWR were not. PCR showed a non-significant trend toward lower values in not survivors. Conclusions: CPR is a strong and clinically viable predictor of early mortality in sepsis, outperforming other platelet-based indices. Derived from routine laboratory parameters, CPR serves as a valuable adjunct for initial risk stratification in the ICU. To further confirm its prognostic role and incorporation into current scoring systems, large-scale multicenter studies with longitudinal measurements are warranted to validate its prognostic utility and integration into existing scoring systems. Full article

Background and Objectives: Procalcitonin (PCT), presepsin (PSEP), interferon-λ3 (IFN-λ3), and bioactive adrenomedullin (bio-ADM) are promising sepsis biomarkers. We explored the clinical utility of a multi-marker approach using these four biomarkers in patients with suspected sepsis. Materials and Methods: In a total of 248 patients, the biomarkers were evaluated with the sequential organ failure assessment (SOFA) score. Receiver operating characteristic curves with area under the curve (AUC) were analyzed to diagnose sepsis and predict in-hospital mortality. Survival and reclassification analyses were also used to predict in-hospital mortality. Results: The four biomarkers showed comparable diagnostic performance (AUC = 0.61–0.95, p < 0.001–0.003), and sepsis proportion increased significantly as the number of biomarkers used in the multi-marker approach increased (7.7–91.7%, p < 0.001). The proportion of biomarker quartiles (Q1–Q4) differed significantly according to SOFA score (p < 0.001). The four biomarkers predicted in-hospital mortality (AUC = 0.63–0.84, p < 0.001–0.004). The multi-marker approach performed better than the SOFA score (mortality rate, 58.3% vs. 31.3%; adjusted hazard ratio [HR], 14.7 vs. 4.6), and the addition of biomarkers to the SOFA score increased the performance. The multi-marker approach resulted in a higher HR in patients aged ≥75 years than in the overall population (9.2 vs. 4.2). Conclusions: Each biomarker showed clinical utility in patients with suspected sepsis. The multi-marker approach showed complementary clinical utility in addition to the SOFA score and better prognostic performance in patients aged ≥75 years. The use of biomarkers, alone or in combination, would be a valuable tool in combination with the SOFA score. Full article

Oral infections in neutropenic patients are an underestimated but likely fatal cause of infectious complications, with clinical manifestations often diminished or absent due to immune deficiency. The evaluation and management of these infections requires a personalized multidisciplinary strategy, including prevention through pre-therapy dental assessment, individualized oral hygiene protocols, and rapid treatment of dental lesions. Antimicrobial strategies should be adapted not only to the local resistance profile and individual risk, with a priority on antibiotic stewardship and rapid de-escalation when possible, but also to individual patterns of colonization and comorbidities. Dental procedures can be performed without risk in neutropenic patients with a low complication rate, but further studies are key to stratifying risk. Future research directions include the application of artificial intelligence for infectious risk stratification, the use of salivary or microbiome biomarkers for early detection, and the development of innovative technologies for targeted antimicrobial delivery. This narrative review aims to provide an overview of the common clinical manifestations in neutropenic patients and also the potential progression of dental infections into sepsis in this category of patients. Full article

Background and Objectives: Sepsis is a life-threatening condition caused by a dysregulated host response to infection. Early recognition is crucial to improve outcomes, but conventional biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) show limited diagnostic accuracy. Materials and Methods: We performed a narrative review of the literature on sepsis biomarkers, with a focus on their biological role, diagnostic performance, clinical applicability, and limitations. Particular attention was given to presepsin (P-SEP) and monocyte distribution width (MDW), which have recently gained relevance. Results: Several novel biomarkers—including lipopolysaccharide-binding protein (LBP), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), mid-regional pro-adrenomedullin (MR-proADM), neutrophil gelatinase-associated lipocalin (NGAL), Proenkephalin (PENK), and circulating microRNAs—have been studied, though most remain investigational. Among them, P-SEP shows rapid kinetics and correlation with disease severity, while MDW, derived from routine complete blood count, offers encouraging sensitivity and cost-effectiveness in emergency settings. Both biomarkers appear practical and potentially valuable for early sepsis detection. Conclusions: P-SEP and MDW emerge as the most promising biomarkers for timely sepsis recognition and risk stratification. Further validation and standardization are required to include them into routine clinical practice. Full article

Vascular endothelial cadherin (VE-Cadherin) is a major endothelial adhesion molecule and can be cleaved explicitly by metalloproteinase domain-containing protein 10 (ADAM10). Vascular hyperpermeability may contribute to a greater susceptibility to sepsis in left ventricular assist device (LVAD) support patients. We aim to evaluate the efficacy of VE-Cadherin and ADAM10 for predicting sepsis in LVAD patients. We prospectively recruited 50 patients with advanced heart failure receiving LVAD therapy. Baseline and weekly postoperative blood samples (weeks 1–4) were collected, and plasma VE-cadherin and ADAM10 levels were measured. Sepsis occurred in 9 of 50 patients (18.0%). Across all sampling points, plasma VE-cadherin and ADAM10 levels were significantly higher in the sepsis group relative to the non-sepsis group. From pre-implantation to 1-week and 1-month post-operation, VE-Cadherin alone showed good performance for sepsis prediction, with areas under the receiver operating characteristic (AUC) of 0.75, 0.81, 0.69, 0.72, and 0.77, respectively. A significant positive correlation between VE-cadherin and ADAM10 was detected only among sepsis patients. Incorporating ADAM10 into the prediction models significantly enhances their predictive performance. Plasma VE-Cadherin levels can be a valuable biomarker for predicting sepsis in LVAD patients, with predictive performance further enhanced when combined with circulating ADAM10 levels. Full article

Background: Severe sepsis and septic shock remain major causes of ICU mortality despite advances in critical care. Polymyxin B hemoperfusion (PMX-HP) is widely used in Asia for refractory endotoxemia, yet the optimal session strategy remains unclear. Methods: We retrospectively analyzed adult ICU patients with severe sepsis or septic shock treated with PMX-HP between 2013 and 2019 in a tertiary center in Taiwan. Patients were divided into sequential (≥2 sessions within 24 h) and non-sequential groups. The primary outcome was 28-day mortality; secondary outcomes included ICU and hospital mortality, length of stay, organ support, and vasoactive-inotropic score (VIS) changes. Results: Among 64 patients, 33 (51.6%) received sequential therapy. The 28-day mortality was 46.9%, with no difference between groups after adjustment for baseline severity. Patients receiving sequential PMX-HP had longer hospital stays and more frequent CRRT use, likely reflecting greater underlying disease severity rather than a causal effect of treatment sequencing. Conclusions: Multivariate analysis identified higher APACHE II score, positive VIS change, and CRRT requirement as independent predictors of mortality. Sequential therapy itself was not associated with improved outcomes. Prognosis in PMX-HP-treated patients is determined mainly by underlying severity and hemodynamic instability, underscoring the need for patient selection and biomarker-guided strategies rather than routine sequential use. Full article

Background/Objectives: Acute Pancreatitis (AP) is an unpredictable inflammatory disease associated with high morbidity and significant mortality, particularly in severe forms. Early death is primarily linked to Systemic Inflammatory Response Syndrome (SIRS) and Multi-Organ Failure (MOF). The objective of this study was to identify objective clinical and laboratory predictors of early and one-year mortality in AP patients and to evaluate the prognostic accuracy of commonly used severity scoring systems. Methods: This prospective, observational study enrolled 50 adult patients admitted to the Intensive Care Unit (ICU) at the University Hospital Center Bežaniska Kosa. Patients with chronic pancreatitis, trauma-induced AP, or late presentation were excluded. Severity scores (APACHE II, BISAP, Ranson, Pancreas) and biomarkers (C-reactive protein, Procalcitonin) were collected at admission (0 h) and dynamically at 48 h, 72 h and day 7. Endpoints were early (in-hospital) and one-year mortality. Results: Overall mortality was 16% (n = 8). Mortality was significantly associated with sepsis/septic shock (p < 0.001), severe AP (p = 0.001), prolonged mechanical ventilation, and ICU stay. At admission, APACHE II (AUROC 0.813) and BISAP (AUROC 0.807) showed good accuracy. Reassessment at 48 h markedly improved prediction: APACHE II achieved excellent value (AUROC 0.917), and the Ranson score became a strong predictor (p < 0.001). Procalcitonin (PCT) was identified as a significant and superior predictor of mortality from 48 h onwards (p < 0.001), outperforming CRP. One-year survival was significantly shorter among patients with sepsis, septic shock, severe AP, and prolonged ICU stay. Conclusions: Dynamic assessment using clinical scoring systems, particularly APACHE II and BISAP within the first 48 h, provides reliable mortality prediction in acute pancreatitis. The presence of sepsis, severe disease, and the need for prolonged organ support are key mortality determinants. Serial PCT monitoring offers sensitive, incremental value for risk stratification and guiding intensive care decisions in both short- and long-term outcomes. Full article

ROS derived from NADPH oxidase, particularly NOX2, are central to antimicrobial defense, coupling direct pathogen killing with redox signaling that shapes inflammation. This narrative review integrates recent advances on NOX2 structure, assembly, and spatiotemporal control in phagocytes, and outlines how ROS interact with NF-κB, MAPK, and Nrf2 networks to coordinate microbicidal activity and immune modulation. We summarize evidence that both ROS deficiency, as in chronic granulomatous disease, and uncontrolled excess, as in sepsis and severe COVID-19, drive clinically significant pathology, emphasizing the need for precise redox balance. Emerging therapeutic strategies include selective NOX2 inhibitors that limit pathological oxidative bursts, redox-modulating peptides that disrupt upstream activation cues, and Nrf2 activators that enhance endogenous antioxidant capacity, with attention to dosing challenges that preserve host defense while mitigating tissue injury. Key gaps remain in biomarker standardization, real-time in vivo ROS monitoring, and translation from animal models to patients, motivating personalized, combination approaches to redox medicine in infectious diseases. Full article

Background: Serum lactate is a key biomarker of tissue hypoperfusion and metabolic stress in sepsis. Although lactate clearance is widely recognized, many intensive care units record only a peak lactate within 24 h (pLac-24h). The prognostic value of pLac-24h among patients receiving blood purification therapy remains unclear in Asian intensive care settings. Methods: We retrospectively analyzed the 2018–2020 ICU dataset from MacKay Memorial Hospital, Taiwan. Among 16,693 adult ICU admissions, 2506 patients received continuous renal replacement therapy (CRRT) as blood purification for severe sepsis or septic shock. Of these, 1264 (50.4%) had available pLac-24h data, and 27 (1.1%) also required extracorporeal membrane oxygenation (ECMO). The primary outcome was 28-day all-cause mortality. Multivariate logistic regression adjusted for age, sex, APACHE II score, infection source, and CRRT/ECMO use. Discrimination was evaluated by receiver operating characteristic (ROC) curves and decision-curve analysis. This analysis was conducted as a predefined sub-analysis of an institutional ICU database. Results: The mean age of the cohort was 65.7 ± 13.4 years, and 64.8% were male. Median pLac-24h was 5.1 mmol/L (IQR 3.2–8.6). The overall 28-day mortality among CRRT patients was 47.3%. Mortality rose progressively across pLac-24h quartiles (Q1–Q4: 28.9%, 39.4%, 54.7%, and 68.1%; p < 0.001). Each 1 mmol/L increase in pLac-24h independently predicted higher mortality (adjusted OR 1.18, 95% CI 1.10–1.26, p < 0.001). The area under the ROC curve for pLac-24h predicting 28-day mortality was 0.78 (95% CI 0.74–0.82), outperforming the APACHE II score (AUC 0.69, p = 0.02). Conclusions: In critically ill patients with septic shock undergoing CRRT, peak lactate within 24 h was a strong, independent predictor of 28-day mortality. pLac-24h offers a pragmatic, readily available prognostic indicator when serial lactate measurements are unavailable, supporting its integration into bedside risk assessment in real-world Asian ICU practice. Full article

Accurate post-mortem diagnosis of sepsis remains a critical challenge in forensic pathology, as conventional morphological findings often lack specificity. Circulating microRNAs (miRNAs) have been proposed as stable molecular biomarkers, yet their diagnostic value in cadaveric samples is still unclear. This exploratory study investigated the expression of three candidate miRNAs (miR-122-5p, miR-125b-5p, and miR-27a-3p) in post-mortem peripheral whole blood to assess their association with sepsis-related death versus non-infective controls. Out of 58 cases, 45 met quality-control criteria (26 sepsis-related deaths and 19 controls). miRNA expression was quantified by qRT-PCR, normalized to miR-320, and analyzed using ΔCt values. Group differences were evaluated using linear regression models with adjustment for age, sex, and post-mortem interval, with Benjamini–Hochberg correction for multiple testing. In adjusted models, miR-125b-5p and miR-27a-3p showed evidence of association with sepsis status, whereas miR-122-5p did not. These results support the feasibility of miRNA quantification in post-mortem samples and motivate validation in larger, independent cohorts and within multimodal post-mortem diagnostic frameworks. Full article

Background: Adrenomedullin (ADM) is a multifunctional peptide with vasoregulatory, antimicrobial, and anti-inflammatory properties. Its stable fragment, mid-regional pro-adrenomedullin (MR-proADM), is a validated biomarker in sepsis and systemic infections, but its role in viral neuroinfections remains unexplored. Tick-borne encephalitis (TBE), caused by the tick-borne encephalitis virus (TBEV), is a major viral infection of the central nervous system (CNS) associated with long-term neurological sequelae. This study aimed to assess MR-proADM levels in cerebrospinal fluid (CSF) and serum of patients with TBE and to evaluate their diagnostic utility and pathophysiological significance. Methods: This retrospective observational study included 20 patients with confirmed TBE and 14 non-infectious neurological controls. MR-proADM concentrations were measured in paired CSF and serum samples using an ELISA assay. Statistical analyses included group comparisons (Mann–Whitney U test), correlation analyses (Spearman’s r), and receiver operating characteristic (ROC) curve evaluation. Results: Serum MR-proADM levels at baseline (SER1) were significantly lower in TBE patients compared with controls (p = 0.0197). The CSF/serum MR-proADM ratio differed significantly between groups (p = 0.0063) and showed the best diagnostic performance (AUC = 0.816, 95% CI 0.63–0.93; sensitivity 79%, specificity 80%). MR-proADM concentrations in CSF correlated with total CSF protein (r = 0.53), suggesting an association with blood–CSF barrier dysfunction. Strong reproducibility was observed for serum MR-proADM between sampling points (r = 0.83). Conclusions: MR-proADM levels in CSF and serum are altered in patients with TBE, indicating its potential as a biomarker of CNS infection and inflammation. The CSF/serum MR-proADM ratio may serve as a sensitive indicator of blood–CSF barrier involvement, while decreased serum levels may reflect impaired systemic neuroprotective response. These findings highlight a possible role of ADM in neuroimmune regulation during viral encephalitis and warrant validation in larger prospective studies. Full article

Background/Objectives: Sepsis remains one of the leading causes of mortality, yet its etiopathogenesis is still not fully understood. This study aimed to investigate the effects of cetirizine and dexamethasone (alone and in combination) on serum levels of Maresin-1 (MaR-1), TNF-α, IFN-γ, IL-1, IL-2, IL-6, IL-8, and IL-10 in a rat model of sepsis induced by the cecal ligation and puncture (CLP) method. Methods: Male Sprague Dawley rats aged 8–10 weeks were used and randomly divided into 7 groups, each containing 7 rats: Group 1 (Control), Group 2 (Sham), Group 3 (Sepsis), Group 4 (Sepsis + Saline), Group 5 (Sepsis + Cetirizine), Group 6 (Sepsis + Dexamethasone), and Group 7 (Sepsis + Cetirizine + Dexamethasone). Sepsis was induced via CLP in all groups except Control and Sham. Results: In the sepsis groups (G3–G7), neutrophil and white blood cell counts increased while lymphocyte counts decreased (p < 0.05). In groups treated with cetirizine and/or dexamethasone (G5–G7), a significant decrease in neutrophils and an increase in lymphocytes were observed. MaR-1 levels significantly decreased (p < 0.05) in all sepsis-induced groups compared to controls, while interleukin levels significantly increased. Cetirizine and dexamethasone supplementation significantly increased MaR-1 levels and decreased interleukin levels (p < 0.05). The combined treatment was more effective. Conclusions: This study is the first to highlight the potential of MaR-1 as a critical biomarker in sepsis diagnosis and monitoring, and cetirizine and dexamethasone, especially in combination, may represent a promising therapeutic option in sepsis management. Full article

Background and Objectives: In severe COVID-19-associated sepsis, therapeutic plasma exchange (TPE) is used as a rescue strategy to modulate cytokine and coagulation derangements, but its biomarker and organ-failure effects remain incompletely characterised. We evaluated peri-procedural changes in interleukin-6 (IL-6), other inflammatory markers, and Sequential Organ Failure Assessment (SOFA) scores according to TPE intensity, timing, and inflammatory phenotypes. Methods: We conducted a single-centre retrospective cohort study including 102 mechanically ventilated adults with COVID-19-associated sepsis who received ≥1 TPE session. Patients were grouped by number of sessions (1, 2, ≥3), timing (≤14 vs. >14 days from symptom onset), IL-6 responder status (≥50% reduction), and two unsupervised inflammatory–thrombotic clusters. Peri-procedural changes (Δ) in biomarkers and SOFA were compared using non-parametric tests, with multivariable logistic and linear regression exploring predictors of IL-6 response and ΔSOFA. Results: Baseline severity was similar across TPE-intensity groups, with median APACHE II scores of 11–12 and SOFA scores around 7 in all strata. Median IL-6 concentrations declined after TPE in each group (e.g., Δ −59.4 pg/mL after 1 session and Δ −65.1 pg/mL after ≥3 sessions), but between-group differences in ΔIL-6 were not statistically significant (p = 0.276). By contrast, D-dimer exhibited a marked decline only in the 1-session group (median Δ −1.7 mg/L vs. ~0.0 mg/L in the 2- and ≥3-session groups; p < 0.001). Timing (early vs. late TPE) did not materially affect ΔIL-6, ΔCRP, ΔSOFA (median 0.0 in both), or ΔD-dimer. Overall, 50% of patients were IL-6 responders; baseline IL-6 was the only independent predictor (adjusted OR 1.9 per doubling, 95% CI 1.3–2.8). A hyperinflammatory–thrombotic cluster (n = 44) exhibited higher baseline IL-6 (612.3 vs. 92.4 pg/mL), more ≥3-session TPE (65.9% vs. 29.3%), and higher IL-6 responder rates (75.0% vs. 31.0%), but similar 28-day mortality (40.9% vs. 29.3%). Conclusions: In this real-world TPE programme, biochemical improvements—particularly IL-6 and D-dimer reductions in hyperinflammatory–thrombotic patients—were not consistently accompanied by short-term SOFA or survival benefits, underscoring the need for phenotype-guided and trial-based use. Full article