Search Results (1,146)

Background/Objectives: Low levels of lysophosphatidylcholine (LPC) in the blood can be used as a diagnostic marker for sepsis. SARS-CoV-2 infection, a more recent cause of sepsis, shares similarities with non-SARS-CoV-2 sepsis but also exhibits distinct features. We have recently shown that plasma cholesteryl ester levels are higher in patients with SARS-CoV-2 infection than in patients without, and this study analysed whether this may extend to differences in LPC, a bioactive constituent of lipoproteins. Methods: The plasma levels of 13 LPC species were measured by flow injection analysis tandem mass spectrometry (FIA-MS/MS) in 157 patients with systemic inflammatory response syndrome (SIRS), sepsis or septic shock. Of these patients, 24 had SARS-CoV-2 infection. Results: Patients with SIRS exhibited higher plasma levels of the minor LPC species LPC 15:0 and 22:4 compared to those with sepsis or septic shock. Five LPC species were also reduced in the plasma of 31 patients with liver cirrhosis; therefore, patients with cirrhosis or SIRS were excluded from subsequent analyses. Compared to 76 non-COVID-19 patients with sepsis or septic shock, SARS-CoV-2 infection in 21 patients was associated with significantly higher plasma levels of ten individual LPC species and total LPC concentration. In patients with sepsis/septic shock, LPC species showed negative correlations with procalcitonin and interleukin-6, and positive correlations with gamma-glutamyltransferase and cholesteryl ester levels. In contrast, no significant associations were observed between LPC levels and C-reactive protein, aminotransferases, or free cholesterol. Conclusions: Differential LPC levels, despite comparable disease severity, may serve as metabolic biomarkers to distinguish SARS-CoV-2 sepsis from other causes of sepsis and inform targeted therapeutic approaches. Full article

(1) Background: COVID-19 sepsis, marked by hyperinflammation and cardiac injury, poses significant challenges in high-comorbidity populations. This prospective cohort study evaluates the prognostic value of IL-6, troponin, NT-proBNP, and radiological findings for mortality and unfavorable outcomes in a post-2022 Eastern European cohort. (2) Methods: At “Victor Babes” Hospital, Timisoara, Romania (September 2022–December 2024), 207 adults with COVID-19 sepsis (Sepsis-3 criteria) were enrolled. Baseline IL-6, troponin, NT-proBNP, CRP, PCT, D-dimers, and chest CT lung involvement were measured. Unfavorable outcomes (in-hospital death, ICU transfer, mechanical ventilation, or vasopressor use) were analyzed using logistic and linear regression. (3) Results: Among 207 patients (mean age: 68.7 years, 54.1% male), 52 (25.1%) experienced unfavorable outcomes. Multivariable analysis identified IL-6 (OR 1.016 per pg/mL, p = 0.013), troponin (OR 1.013 per ng/L, p = 0.017), NT-proBNP (OR 1.009 per pg/mL, p = 0.049), >50% lung involvement (OR 1.835, p = 0.011), unvaccinated status (OR 2.312, p = 0.002), and higher BMI (OR 1.112 per kg/m², p = 0.005) as independent predictors of unfavorable outcomes. Tocilizumab use (n = 12) was associated with reduced mortality (p = 0.041). IL-6 (cut-off 39.0 pg/mL, AUC = 0.91) and troponin (cut-off = 111.3 ng/L, AUC = 0.88) showed strong predictive accuracy. (4) Conclusions: Elevated IL-6, troponin, NT-proBNP, severe lung involvement, unvaccinated status, and higher BMI predict adverse outcomes in COVID-19 sepsis. Tocilizumab may offer survival benefits, warranting larger trials. These findings support targeted risk stratification in high-comorbidity populations. Full article

Background/Objectives: Sepsis is a severe medical condition characterized by a dysregulated host response to infection, with potentially fatal outcomes, requiring early diagnosis and rapid intervention. The limitations of traditional sepsis identification methods, as well as the complexity of clinical data generated in intensive care, have driven increased interest in applying artificial intelligence in this field. The aim of this narrative review article is to analyze how artificial intelligence is being used in the diagnosis and prognosis of sepsis, to present the most relevant current models and algorithms, and to discuss the challenges and opportunities related to integrating these technologies into clinical practice. Methods: We conducted a structured literature search for this narrative review, covering studies published between 2016 and 2024 in databases such as PubMed/Medline, Scopus, Web of Science, IEEE Xplore, and Google Scholar. The review covered models based on machine learning (ML), deep neural networks (DNNs), Recurrent Neural Networks (RNNs), and clinical alert systems implemented in hospitals. The clinical data sources used, algorithms applied, system architectures, and performance outcomes are presented. Results: Numerous artificial intelligence models demonstrated superior performance compared to conventional clinical scores (qSOFA, SIRS), achieving AUC values above 0.90 in predicting sepsis and mortality. Systems such as Targeted Real-Time Early Warning System (TREWS) and InSight have been clinically validated and have significantly reduced the time to treatment initiation. However, challenges remain, such as a lack of model transparency, algorithmic bias, difficulties integrating into clinical workflows, and the absence of external validation in multicenter settings. Conclusions: Artificial intelligence has the potential to transform sepsis management through early diagnosis, risk stratification, and personalized treatment. A responsible, multidisciplinary approach is necessary, including rigorous clinical validation, enhanced interpretability, and training of healthcare personnel to effectively integrate these technologies into everyday practice. Full article

Background: Fibrinolytic impairment is one of the key factors involved in the pathogenesis of hemostasis disturbances in sepsis, significantly contributing to microthrombosis, organ dysfunction, and mortality rates. While hemostatic assessment in sepsis typically focuses on coagulation activation, evaluating fibrinolytic activity remains challenging due to methodological limitations and a lack of standardization of the currently available methods. Objectives: This comprehensive review examines current methods for assessing fibrinolytic activity in bacterial sepsis, their clinical applications, strengths and limitations, and future perspectives for improved diagnostic approaches. Methods: We conducted a systematic literature search and identified 52 studies that investigated fibrinolysis assessment in adult patients with bacterial sepsis using biomarkers or global tests. Studies included mainly observational cohorts examining various fibrinolytic assessment methods. Results: Fibrinolytic shutdown, primarily mediated by the overproduction of plasminogen activator inhibitor-1 (PAI-1), occurs early in sepsis and correlates with disease severity and mortality. Current assessment methods include plasma biomarker measurements (PAI-1, plasmin-antiplasmin complexes, D-dimer), global plasma-based tests (clot lysis time, plasmin generation assays), and whole-blood viscoelastic testing (rotational thromboelastometry, ROTEM; thromboelastography, TEG). Modified viscoelastic tests incorporating tissue plasminogen activators demonstrate enhanced sensitivity for detecting fibrinolytic resistance. Despite efforts, standardization is still limited, and routine clinical implementation has not been achieved yet. Conclusions: Fibrinolytic assessment provides important prognostic information in sepsis, despite methodological challenges. The integration of point-of-care viscoelastic testing with modified protocols shows promise for real-time evaluation. Future research should focus on developing standardized, automated assays suitable for routine clinical practice, enabling personalized therapeutic interventions that target fibrinolytic dysfunction in sepsis. Full article

Objectives: Personalized sepsis care requires understanding how pre-existing health status can influence outcomes. The aim of this study is to evaluate its impact on in-hospital and 12-month mortality in patients with sepsis, taking into account age, comorbidities, the Charlson Comorbidity Index, frailty, anemia, and the Sequential Organ Failure Score Assessment (SOFA) in the first 24 h. Methods: An observational and retrospective study was conducted using data from the Sepsis Code program at the Hospital Universitario de La Princesa. The relationship between risk factors and mortality, as well as Intensive Care Unit (ICU) admission, was analyzed for the period 2016–2018 using bivariate and multivariate logistic regression. Results: A total of 547 patients were included. In the multivariate analysis, the risk factors independently associated with mortality were Rockwood Clinical Frailty Scale ≥ 5 (OR 2.45, p < 0.05); SOFA ≥ 4 (OR 2.13, p < 0.05); age (OR 1.98, p < 0.05); anemia (OR 1.85, p < 0.05); and specific comorbidities such as ischemic heart disease (OR 2.34, p < 0.05), severe liver disease (OR 3.62, p < 0.05), and metastatic cancer (OR 3.14, p < 0.05). Patients who were frail, had dementia, or heart failure were less likely to be admitted to the ICU. Conclusions: Frailty, comorbidities, age, and anemia are associated with outcomes in patients with sepsis and could be incorporated into mortality prediction models to guide tailored treatment strategies. Full article

The emergence of bacterial strains resistant to available antibiotics due to overprescription has prompted a search for alternative treatments. Among the most promising is baicalin, a flavonoid extracted from the roots of Scutellaria baicalensis. Roots, the primary natural source of baicalin, have been extensively explored using emerging extraction technologies such as ultrasonic-assisted extraction and supercritical fluid extraction. These methods offer significant advantages over traditional reflux extraction for baicalin preparation, including shorter extraction times, lower energy consumption, and improved environmental sustainability. Baicalin exhibits remarkable antibacterial activity in vitro and has demonstrated therapeutic efficacy against gastrointestinal infections, meningitis, pulmonary diseases, and sepsis, among other infectious disorders, in animal models. Documented mechanisms of action include disrupting the Escherichia coli membrane, downregulating quorum-sensing gene expression in Pseudomonas aeruginosa, and inhibiting host inflammatory pathways such as PI3K/Akt/NF-κB. However, its clinical translation faces several bottlenecks, including reliance on animal experiment data, low bioavailability, and regulatory compliance issues. This review compares baicalin extraction yields from different natural sources, summarizes the advantages and disadvantages of various extraction technologies, analyzes possible mechanisms of action in treating different bacterial diseases, and discusses outstanding challenges and best strategies for expanded clinical use against bacterial infection. Our aim is to provide a valuable reference for future research and clinical applications. Full article

The progression of inflammation during sepsis represents a multifaceted biological cascade that requires effective therapeutic interventions to improve survival. In septic neonatal foals, oxidative stress (OS) arises due to a compromised antioxidant defense system. Oxidative stress may disrupt the functionality of redox-sensitive organelles, such as the endoplasmic reticulum (ER). Endoplasmic reticulum stress disorder affects multiple cellular signaling pathways, including redox balance, inflammation, and apoptosis, and contributes to the pathogenesis of sepsis. The study aimed to elucidate whether OS conditions in sepsis influenced gene expression associated with ER stress. Blood samples were collected from 7 healthy and 21 hospitalized neonatal foals and processed for RNA extraction. RNA sequencing was employed to identify ER stress-responsive genes. Novel findings reported here indicate activation of the ER stress pathway in foals with sepsis. Several genes associated with ER stress, such as clusterin (CLU), BCL2-like 1 (BCL2L1), ubiquitin specific peptidase 14 (USP14), bifunctional apoptosis regulator (BFAR), and optic atrophy 1 (OPA1), were upregulated and positively correlated with sepsis scores and negatively correlated with the combined activities of antioxidant enzymes. In contrast, X-box binding protein 1 (XBP1), homocysteine inducible ER protein with ubiquitin-like domain 1 (HERPUD1), leucine-rich repeat kinase 2 (LRRK2), and selenoprotein S (SELENOS) were negatively correlated with sepsis scores and were downregulated in sepsis and positively correlated with the combined activities of antioxidant enzymes. Furthermore, a positive correlation was observed between cAMP responsive element binding protein 3 like 2 (CREB3L2) and BCL2L1, as well as between the expressions of USP14 and YOD1 deubiquitinase (YOD1) in sepsis. Similarly, the expression levels of XBP1 and Herpud1 demonstrated a positive correlation with each other in sepsis. Additionally, the downregulation of genes with protective function against OS, such as XBP1, HERPUD1, and SELENOS, in septic foals also highlights their significance in mitigating OS in sepsis treatment. The study reported here highlights the potential of ER stress as a promising therapeutic target and prognostic marker in septic foals. Full article

Background: Fusobacterium species are anaerobic Gram-negative bacilli that are part of the normal oropharyngeal and gastrointestinal flora. Although rare, they can cause infective endocarditis (IE), a severe condition with high morbidity. The clinical characteristics, treatment strategies, and outcomes of IE caused by Fusobacterium spp. remain incompletely defined. This systematic review aimed to synthesize available data on Fusobacterium IE and compare its features with IE caused by other pathogens. Methods: We conducted a systematic literature search in PubMed, Scopus, and the Cochrane Library up to 27 February 2025, using the terms “Fusobacterium” and “endocarditis.” Eligible studies included case reports or series describing adult or pediatric patients with Fusobacterium-associated IE. Data were extracted on demographics, risk factors, clinical features, microbiology, treatment, and outcomes. Results: A total of 21 studies (all case reports) involving 21 patients were included. The median age was 48 years, and 85.7% were male. Poor dental hygiene or recent dental work was the most common predisposing factor (47.6%). The mitral valve was most frequently affected (44.4%). Fever and sepsis were reported in nearly all cases, and embolic phenomena occurred in 81%. The most commonly isolated species were F. necrophorum (47.6%) and F. nucleatum (42.9%). Treatment commonly included metronidazole (61.9%), while surgical management was required in 23.8%. All-cause and infection-attributable mortality were both 9.5%. Conclusions: Fusobacterium IE predominantly affects younger males and is often linked to oral sources. This disease is associated with a high risk of systemic complications but seems to have a lower mortality compared to IE from other pathogens, including other anaerobic bacteria. Early diagnosis and appropriate antimicrobial treatment are of utmost importance for optimal outcomes. Further research is required to guide evidence-based management of this rare but serious infection. Full article

Chronic skin wounds are difficult to heal or nonhealing. These wounds may become infected and progress to tissue necrosis, potentially leading to limb amputation, sepsis, reduced quality of life, depression, economic burden on the healthcare system, and social isolation. Several clinical strategies, including negative pressure wound therapy, antibiotic-based infection control, and wound debridement, have been developed to treat skin wounds. However, these approaches primarily target local wound conditions and offer only short-term relief, not achieving sustained functional regeneration. Stem cell-based therapy has emerged as an alternative therapeutic method for skin wound treatment owing to its ability to suppress inflammation, stimulate angiogenesis, and promote cellular proliferation. However, the low post-transplantation survival rate of stem cells remains a major limitation. Exosomes, nanosized extracellular vesicles, transport proteins, lipids, mRNAs, and miRNAs and mediate regenerative functions, including anti-inflammatory effects, angiogenesis promotion, and extracellular matrix remodeling. Stem cell-derived exosomes (SC-Exos) offer several advantages over their parent cells, including greater stability, lower immunogenicity, absence of tumorigenic risks, and ease of storage and distribution. These attributes render SC-Exos particularly attractive for cell-free regenerative therapies. In this review, we introduce exosomes derived from various types of stem cells and explore their therapeutic applications in skin wound regeneration. Full article

Background: Severe sepsis and septic shock remain major contributors to ICU mortality. Polymyxin B hemoperfusion (PMX-HP) has been widely adopted as adjunctive therapy in Asian ICUs for endotoxemia, but its real-world effectiveness and prognostic factors remain uncertain, especially in high Gram-negative settings. Methods: This retrospective cohort study included 64 adult patients with severe sepsis or septic shock who received at least one session of PMX-HP in a 25-bed tertiary medical ICU in Taiwan between July 2013 and December 2019. Demographic, clinical, microbiological, and treatment data were extracted. The primary outcome was 28-day mortality. Prognostic factors were analyzed using logistic regression. Results: The mean age was 66.1 ± 12.3 years; 67.2% were male. Pneumonia (29.7%) and intra-abdominal infection (18.8%) were the most common sources of sepsis, with E. coli and K. pneumoniae as leading pathogens. Median APACHE II score at ICU admission was 26 (IQR 21–32), and 79.7% received two PMX-HP sessions. The 28-day mortality rate was 46.9%, with ICU and hospital mortality both 53.1%. Non-survivors were older, had higher APACHE II scores, and more frequent use of continuous renal replacement therapy (CRRT). Positive changes in vasoactive-inotropic score (VIS) after PMX-HP were also more common among non-survivors. Multivariate analysis identified advanced age, higher APACHE II score, and CRRT requirement as independent predictors of mortality. Conclusions: In this real-world Asian ICU cohort, PMX-HP was used mainly for severe cases with a high disease burden and Gram-negative predominance. Despite its frequent use, overall mortality remained high. Prognosis was primarily determined by underlying disease severity, organ dysfunction (especially renal failure), and persistent hemodynamic instability. In this high-severity cohort, mortality appeared to be primarily driven by baseline organ dysfunction and persistent hemodynamic instability; PMX-HP session number or sequencing showed no association with survival. Given the absence of a contemporaneous non-PMX-HP control group, mortality observations in this cohort cannot be causally attributed to PMX-HP and should be interpreted with caution as hypothesis-generating rather than definitive evidence of efficacy. Further multicenter studies are needed to clarify the optimal role of PMX-HP in modern sepsis management. Full article

Continuous extradural infusions (CEIs) provide sustained analgesia, avoiding fluctuations seen with bolus administrations. An extradural catheter was placed in a cat with severe abdominal trauma following a vehicular accident. To provide sustained pain relief, a CEI of 0.5% ropivacaine at 0.18 mg/kg/h or 0.036 mL/kg/h was initiated, resulting in improved analgesia, as shown by lower scores on both the Feline Grimace Scale (FGS) and the Glasgow Composite Measure Pain Scale-Feline (CMPS-Feline). During treatment, the cat developed hypersalivation, which persisted after catheter removal at 72 h. Eventually, the cat’s condition deteriorated, with signs of sepsis leading to euthanasia due to a poor prognosis. Potential contributors to the cat’s decline included systemic infection, local anaesthetic systemic toxicity, or opioid-related effects. This report describes the placement of an extradural catheter in a cat, highlighting the potential of CEI in feline pain management while emphasising the need for further research on its pharmacokinetics and safety. Full article

Background/Objectives: Despite overlapping inflammatory responses and frequent culture-negative results in severe burn patients, early and accurate sepsis diagnosis remains challenging. We aimed to evaluate the diagnostic performance of seven candidate biomarkers and their clinical utility, particularly in culture-negative cases. Methods: We conducted a prospective diagnostic accuracy study (January 2021–December 2022; N = 221) in the burn intensive care unit, applying a two-step feature selection to 41 candidate variables. Seven top biomarkers—presepsin, procalcitonin (PCT), albumin, C-reactive protein (CRP), prothrombin time (PT), hematocrit (Hct), and D-dimer—were measured at the moment of clinical sepsis suspicion, concurrently with blood cultures and prior to empirical antibiotic administration, within ±2 h of Sequential Organ Failure Assessment (SOFA). Diagnostic performance was evaluated using a Receiver Operating Characteristic (ROC) curve analysis to determine the area under the curve (AUC), Youden index-derived cut-offs, decision curve analysis, and Net Reclassification Improvement (NRI). Results: Presepsin achieved the highest overall AUC (0.810; 95% CI, 0.742–0.878) and outperformed other markers in culture-negative cases (AUC, 0.846 vs. 0.604; p = 0.015). In the decision curve analysis, presepsin and PCT maintained the largest net benefits at high thresholds, although PT, D-dimer, and Hct also retained smaller positive benefits. Patients were stratified into high- vs. low-risk groups for survival analysis using Youden index cut-offs; Cox regression confirmed PCT (Hazard Ratio 3.78; p < 0.001) and PT (HR 2.12; p = 0.018) as a significant mortality predictor, with presepsin showing borderline significance (HR 3.14; p = 0.055). Conclusions: The high rate of culture-negative sepsis reflects early antibiotic use suppressing culture yield rather than resistance patterns alone. Presepsin’s rapid rise and preserved accuracy under pre-sampling antibiotics suggest its value for early sepsis detection and antimicrobial stewardship. Future work will incorporate polymicrobial and multidrug-resistant bloodstream infection profiles to refine biomarker utility. Full article

Background and Clinical Significance: Anaerococcus tetradius (A. tetradius) and Gardnerella vaginalis (G. vaginalis) are rare etiological factors for postpartum endometritis and are typically associated with bacterial vaginosis. However, in some cases, G. vaginalis and A. tetradius can cause serious postpartum endometritis with complications such as sepsis. Case Presentation: 26-year-old pregnant woman expecting monochorionic diamniotic twins presented to the hospital at 35 weeks and 3 days of gestation and two male infants were delivered via the Cesarean section. On the fifth day after delivery, the patient began to complain of intense abdominal pain, a fever of 37.9 °C, and overall weakness. Blood tests revealed neutrophilic leukocytosis, increased C-reactive protein (CRP) of 225.4 mg/L. Upon examination, abdominal distension, tenderness on palpation, and positive symptoms of peritoneal irritation were present and the site of the abdominal incision was inflamed with flowing foul-smelling greenish pus. Ultrasound examination revealed free fluid collection in the peritoneal cavity, under the liver, and around the uterus. Later, the condition of the patient worsened with progressing hypotension and respiratory distress. As a result, suppurative peritonitis and sepsis was suspected and the patient underwent urgent total hysterectomy without oophorectomy. Acute endometritis, focal myometritis, and chronic cervicitis were concluded from histopathological examination of the removed uterus. Microbiological tests showed the most abundant growth of A. tetradius in the wound cultures and great abundance of G. vaginalis in the abdominal cavity cultures. After trying three different treatment schemes and difficulties with determining the antibiotic sensitivity tests for pathogens, the antibacterial therapy was escalated to Meropenem, which was found to be effective, and the patient was discharged home. Conclusions: This case report highlights the severity of complications of postpartum endometritis that can be caused by rare pathogens (such as G. vaginalis and A. tetradius), and strategies for how to manage it. The clinical presentation of a patient should be monitored closely for several days after Cesarean section and if endometritis is suspected, microbiological cultures are necessary to determine the cause of infection and implement an appropriate treatment. Full article

Background: Larval debridement therapy is used to cleanse necrotic tissue wounds and/or decontaminate wounds that are not amenable to standard therapies. Methods: A patient was diagnosed with septic shock and multiple organ failure caused by Streptococcus pyogenes after thyroidectomy (the patient had experienced contact with a child with scarlet fever six days before admission to the hospital). As a result of systemic infection, numerous necrotic skin lesions appeared, which involved the surgical site, chest and scalp. A tracheocutaneous fistula was confirmed. Due to the ineffectiveness of typical therapy and the patient’s severe clinical condition, she qualified for unconventional therapy (larval debridement therapy). Results: Larval wound debridement therapy and negative-pressure wound therapy were used for the tracheocutaneous fistula; this is the first case of this alternative therapy being described in the English-language literature. In this case, based on an analysis of the health benefits for the patient and the uncertain prognosis, larval therapy was used for a postoperative wound after strumectomy with the presence of a tracheocutaneous fistula, and negative-pressure wound therapy ultimately led to complete wound healing. Conclusions: Sepsis caused by Streptococcus pyogenes can be fulminant and often leads to complications or death, especially if it develops in the perioperative period. Larval therapy can be effectively used in cases of fistulas, such as tracheocutaneous fistulas, to prepare the wound bed for the next stage of healing using negative-pressure therapy, which ultimately leads to complete wound healing. Full article

Sepsis is a complex and heterogeneous condition, arising from a disrupted immune response to infection that can progress to organ failure and carries a high risk of death. In recent years, growing attention has been paid to the role of epigenetic mechanisms—including DNA methylation, histone modifications, non-coding RNAs, and RNA methylation—in shaping immune activity during sepsis. These processes affect immune functions such as macrophage polarization, cytokine release, and the exhaustion of immune cells, and they help explain the shift from an initial phase of overwhelming inflammation to a later state of immune suppression. Epigenetic alterations also contribute to tissue-specific damage, notably in the lungs, kidneys, and heart, and have been linked to disease severity and clinical prognosis. Advances in transcriptomic and epigenetic profiling have made it possible to distinguish molecular subtypes of septic patients, each with distinct immune features and varied responses to treatments such as corticosteroids and metabolic therapies. Emerging biomarkers—like AQP5 methylation, histone lactylation (H3K18la), and m⁶A RNA methylation—are opening new options for patient classification and more tailored therapeutic strategies. This review examines the current understanding of how epigenetic regulation contributes to the pathophysiology of sepsis and considers its implications for developing more individualized approaches to care. Full article