Search Results (162)

Background and Objectives: Early recognition of life-threatening organ dysfunction is central to modern sepsis frameworks. We systematically reviewed the prognostic performance and clinical utility of the Neonatal Sequential Organ Failure Assessment (nSOFA) for mortality and major morbidity in NICU populations. The search identified 939 records across databases; after screening and full-text assessment, 16 studies met the inclusion criteria. Methods: Following PRISMA guidance, we searched major databases (2019–2025) for observational or interventional studies reporting discrimination or risk stratification using nSOFA in neonates. Populations included suspected/proven infection and condition-specific cohorts. Heterogeneity in timing, thresholds, and outcomes precluded meta-analysis. Results: A cumulative sample exceeding 25,000 neonates was identified across late- and early-onset infection, all-NICU admissions, necrotizing enterocolitis, respiratory distress, and very preterm screening cohorts. Across settings and timepoints, nSOFA demonstrated consistent, good-to-excellent mortality discrimination, with reported AUROCs ≥ 0.80 and upper ranges near 0.90–0.92; serial scoring within the first 6–12 h generally improved risk classification. Disease-specific applications (NEC, early-onset infection) showed similar discrimination for death or composite adverse outcomes. Conclusions: Evidence from diverse NICU contexts indicates that nSOFA is a pragmatic, EHR-ready organ dysfunction score with robust discrimination for mortality and serious morbidity, supporting routine, serial use for risk stratification and standardized endpoints in neonatal sepsis pathways, aligned with contemporary organ dysfunction–based pediatric criteria. Full article

Background/Objectives: Emergency Medical Services (EMSs) frequently provide the first medical contact for sepsis patients, but recognition is challenging. This study thus aimed to determine how often EMSs suspect sepsis and to evaluate the diagnostic accuracy of the quick Sequential Organ Failure Assessment (qSOFA), the Prehospital Early Sepsis Detection (PRESEP) score, and the Modified Early Warning Score (MEWS). Methods: A retrospective observational study of all EMS transports to one emergency department during a one-month period in 2023 was conducted. Prehospital vital signs, EMS working diagnoses, and final in-hospital diagnoses were abstracted. Scores were calculated post hoc. The primary outcome was the diagnostic accuracy of the EMSs’ working diagnosis of “suspected sepsis.” Secondary outcomes included the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of qSOFA, PRESEP, and MEWS. Results: Among 786 EMS encounters, 597 met the inclusion criteria. Twelve patients (2.0%) were ultimately diagnosed with sepsis. EMSs explicitly suspected sepsis in three of them (25.0%; sensitivity 16.7%, specificity 99.8%). Retrospective application of scores yielded markedly higher sensitivity: qSOFA 83.3%, PRESEP 91.7%, and MEWS 83.3%. Specificities were 74.2% for qSOFA, 41.2% for PRESEP, and 77.6% for MEWS. The AUCs were 0.838 for qSOFA, 0.695 for PRESEP, and 0.863 for MEWS, with MEWS significantly outperforming PRESEP (p = 0.0215). Conclusions: EMS personnel rarely labeled patients with sepsis, recognizing 3 of 12 cases (25%). Retrospective use of scoring systems based on routine vital signs substantially improved diagnostic accuracy, with MEWS performing best overall. Structured screening tools should be prospectively validated and potentially implemented in EMS. Full article

Background: Sepsis remains a leading cause of morbidity and mortality, particularly when caused by multidrug-resistant organisms (MDROs). Early identification of colonising or infecting pathogens may inform initial antimicrobial selection. Surveillance cultures, providing microbiological data prior to infection onset, could guide timely and targeted therapy. This retrospective study analysed routine surveillance culture results from patients with bloodstream infection (BSI) episodes, assessing pathogen prevalence, resistance phenotypes, and concordance with specimen type in haemato-oncology (HO) and acute care (AC) settings. Methods: Data were retrieved from the institutional Laboratory Information System of the Department of Clinical Microbiology and ATB Centre, General University Hospital in Prague, covering 1 January to 31 December 2024. All positive blood cultures containing ESCAPE pathogens (excluding Clostridioides difficile) were reviewed. Corresponding surveillance culture records were analysed to evaluate concordance with subsequent BSI episodes. Results: In 2024, 6046 AC and 7267 HO surveillance cultures were performed; MDRO prevalence was 5% and 6.56%, respectively. ESBL-producing Enterobacterales predominated (AC 86.9%, HO 81.6%). In HO, BSI-causing Gram-negative and Gram-positive pathogens were frequently detected in rectal swabs, whereas in AC, concordance was higher with upper and lower respiratory tract samples. Rectal screening detected 100% of E. coli and K. pneumoniae BSI episodes in HO. Other specimen types showed limited concordance. Conclusions: Surveillance culture utility varies by specimen type and clinical setting. In both HO and AC units, these cultures provided valuable insights into colonisation and resistance patterns, supporting early risk stratification and guiding initial therapy in high-risk patients. Full article

Pseudomonas aeruginosa bloodstream infections (PABSIs) are a major clinical challenge due to their association with significant mortality and antimicrobial resistance mechanisms. The COVID-19 pandemic changed antimicrobial practices, intensive care management, and patient risk profiles, potentially influencing the epidemiology and outcomes of PABSIs. In the post-pandemic period, practices were expected to revert to normal. The objective of this scoping review was to identify and summarize reported mortality rates and risk factors for PABSIs in studies published between 2023 and 2025. Literature searches were conducted across PubMed, Web of Science, Embase, and Scopus. Screening was performed in accordance with PRISMA-ScR guidelines. Twenty-two eligible studies were included. Mortality rates varied across the study setting and populations; however, several consistent predictors were consistently identified, including carbapenem exposure, multidrug-resistant Pseudomonas aeruginosa, hematologic disease or malignancy, corticosteroid therapy, sepsis or septic shock, mechanical ventilation, and higher severity-of-illness scores. Few studies have linked molecular mechanisms to patient outcomes, highlighting important gaps in knowledge. Notably, only a small number of studies included the post-pandemic period but did not analyze the data separately. Despite limited available evidence, critically ill and immunocompromised patients remain at greatest risk of death from PABSIs. This review highlights the need for a broader comparative analysis in future. Full article

Acute kidney injury (AKI) is a critical clinical syndrome characterized by a rapid decline in renal function, frequently resulting from ischemia, nephrotoxicity, or sepsis. It represents a major global health burden due to its high morbidity and mortality and its strong association with progression to chronic kidney disease. In this study, we identified a novel small-molecule TLR4 inhibitor, DB03476, via structure-based virtual screening targeting the intracellular TIR domain of murine Tlr4. Molecular dynamics simulations confirmed that DB03476 stabilizes Tlr4 without altering its global conformation. In a murine ischemia–reperfusion-induced AKI model, DB03476 administration significantly attenuated renal inflammation, macrophage infiltration, and apoptosis and suppressed the TLR4/MyD88/NF-κB pathway. Moreover, DB03476 exhibited cross-species efficacy by binding conserved residues in human TLR4 with high affinity. Functional validation using human kidney organoids confirmed its protective effects against inflammatory challenge. These results demonstrate DB03476 as a promising therapeutic agent for AKI through selective inhibition of TLR4-mediated inflammatory responses. Full article

Group B Streptococcus (GBS) is a component of the natural human microbiota, colonizing the genitourinary tract and the distal gastrointestinal tract. Due to its production of numerous virulence factors, GBS can cause infections in pregnant women, newborns, and immunocompromised individuals. In newborns, GBS infection may present as severe pneumonia, meningitis, or sepsis. Screening for maternal GBS colonization, combined with intrapartum antibiotic prophylaxis for colonized women, is currently regarded as the most effective strategy for preventing neonatal GBS infections. However, growing concerns regarding antibiotic resistance and the negative impact of antibiotics on the neonatal microbiome have intensified the search for alternative approaches. These include the development of a vaccine and methods to reduce vaginal colonization in pregnant women. Full article

Pelvic inflammatory disease (PID), although traditionally viewed as a sexually transmitted infection (STI), can also result from non-sexually transmitted microorganisms that display distinct epidemiologic and clinical characteristics. Unlike STI-related PID, these infections are less influenced by sexual behavior, often show a bimodal age distribution, and are linked to bacterial vaginosis (BV)-associated dysbiosis, iatrogenic uterine procedures, postpartum states, or inadequate access to timely screening and care. Non-STI-related PID is usually polymicrobial, predominantly involving BV-associated vaginal, enteric, or urinary commensals that ascend into the upper genital tract, while respiratory tract organisms, mycobacteria, and biofilm-associated pathogens may also play a role. Pathophysiological mechanisms include disruption of the endocervical barrier, mucus degradation, biofilm formation, hematogenous or iatrogenic seeding, and chronic cytokine-mediated inflammation and fibrosis. Clinical manifestations range from asymptomatic/subclinical disease to acute pelvic pain and tubo-ovarian abscess (TOA) and can progress to systemic infection and sepsis. Diagnosing non-STI PID is challenging due to nonspecific symptoms, negative STI tests, and inconclusive imaging findings, while management relies on broad-spectrum antimicrobials with surgery as needed. Given these complexities, this review aims to synthesize current knowledge on non-STI-related PID, clarify key considerations for its diagnosis, management, and prevention, and outline future perspectives to improve clinical outcomes. Full article

Background: D-dimers are frequently elevated in older Emergency Department (ED) patients and often lead to diagnostic dilemmas as specific underlying causes remain unclear. We aimed to investigate the association of elevated D-dimer levels with serious diseases with special focus on occult malignancy in the following 6 months. Methods: In this Dutch prospective cohort study in older (≥65 years) medical ED patients, D-dimer levels were routinely measured upon ED arrival but blinded to clinicians. Associations with serious medical conditions were evaluated using Cox regression, in a real-life clinical context. Results: Among 407 patients (median age 79 years), 69.8% had elevated age-adjusted D-dimers (AADD). Sepsis, ischemia, and venous thromboembolism (VTE) were all associated with AADD, although VTE was present in only 4.2% of patients. In 336 patients without active malignancy, occult malignancy was diagnosed in 9.2% within 6 months, with a time to diagnosis of 5 days. D-dimer levels ≥2000 µg/L predicted occult malignancy (HR of 2.61) and interval likelihood ratios (LRs) increased with higher D-dimer levels (highest LR 2.88). Low D-dimers (<500 µg/L) had very low LR 0.21. Conclusions: Older ED patients frequently have elevated D-dimer levels, and these levels are often associated with non-thrombotic conditions including sepsis, ischemia, and occult malignancy. While elevated levels are associated with an increased risk of occult malignancy, the absolute risk increment is modest. Consequently, routine screening for occult malignancy solely based on D-dimers is not recommended, as most malignancies were diagnosed within a short timeframe. Interestingly, occult malignancy is extremely unlikely in patients with low D-dimer levels. Full article

Background: Timely recognition of sepsis remains a critical clinical challenge, particularly in cancer patients, who are at higher risk due to immunosuppression. Monocyte distribution width (MDW) has emerged as a biomarker with potential utility in the early detection of sepsis. Methods: This retrospective study analyzed 1167 patients who presented to the emergency department of a cancer specialty hospital in Republic of Korea. Patients were classified according to Sepsis-2 and Sepsis-3 criteria, and the diagnostic performance of MDW was compared with conventional biomarkers, including C-reactive protein (CRP) and procalcitonin (PCT). Subgroup analyses were conducted based on malignancy status, leukopenia, and initial signs of infection. Additionally, turnaround times (TATs) were compared among the biomarkers. Results: MDW demonstrated diagnostic accuracy comparable to or exceeding that of CRP and PCT for identifying sepsis and infection across both Sepsis-2 and Sepsis-3 criteria. In the context of diagnosing sepsis using the Sepsis-3 criteria, MDW yielded the highest area under the curve (0.869), sensitivity (91.0%), and negative predictive value (98%). Notably, in cancer patients, MDW maintained strong diagnostic reliability. It also demonstrated high diagnostic capability in patients with leukopenia or presenting with initial signs of infection. Moreover, the TAT was significantly shorter for MDW (median 59 min) than for CRP (105 min) or PCT (111 min). Conclusions: MDW is a rapid and accessible biomarker with demonstrated value for early sepsis detection in emergency settings. Its balanced diagnostic profile and consistent performance across diverse patient subgroups support its integration into routine clinical workflows, especially as part of multimodal sepsis screening strategies. Full article

Background: The intersection between oncology and intensive care has shifted from predominantly end-of-life care to a therapeutic bridge that can preserve anticancer trajectories in carefully selected patients. Yet, criteria separating benefit from futility remain fragmented. Objective: This paper seeks to map contemporary evidence (2015–2025) on outcomes after Intensive Care Unit (ICU) admission in adults with cancer and to identify clinical constellations in which ICU-level care still changes prognosis. Methods: PRISMA-ScR scoping review (PCC framework). PubMed search (2015–2025), dual screening, standardized extraction; narrative/thematic synthesis across six clusters (hematologic, solid tumors, sepsis/non-COVID-19 infection, COVID-19/viral pneumonia, novel/targeted-therapy toxicities, end-of-life/aggressive ICU) were used. No meta-analysis given heterogeneity. Results: Seventy-three studies (>170,000 ICU admissions) were included, mostly cohort designs across 27 countries. ICU mortality ranged 8–72% (weighted mean ≈ 41%); hospital ≈ 38%; 90-day ≈ 46%; 1-year ≈ 62%. About one third of ICU survivors resumed systemic therapy. Benefit concentrated in early admissions, single-organ failure, controlled/remission disease, postoperative/elective monitoring, and reversible treatment-related toxicities (e.g., ICI pneumonitis, CAR-T CRS/ICANS). Futility clustered around ≥3 organ supports, RRT > 7 days, refractory/progressive disease, and ECOG ≥ 3. Sepsis outcomes averaged 45–55% ICU mortality but improved with rapid recognition and source control; COVID-19 mortality was particularly high in hematologic malignancies early in the pandemic, with subsequent declines post-vaccination. Conclusions: In modern oncologic practice, ICU care changes prognosis when the acute physiological insult is reversible and cancer control remains plausible; conversely, high organ-support burden and refractory disease define practical futility thresholds. These signals support time-limited ICU trials, earlier ICU involvement for sepsis/irAEs, and embedded palliative care to align intensity with goals. Full article

Background: Neonatal sepsis (NS) is a life-threatening condition in newborns, which is an infectious process with a systemic inflammatory reaction to bacterial, viral, or fungal infection acquired in the first 28 days of life. Methods: This study examines the major pathogens causing neonatal sepsis in the Gulf Cooperation Council (GCC) and their resistance patterns to antimicrobial agents. We utilized the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to develop this systematic review to follow a systematic and transparent process. The comprehensive literature review was done in several national and global databases, which include PubMed, Scopus, Google Scholar, Embase, and Cochrane Library. The key words inserted in the search strategy were “neonatal sepsis,” “late-onset sepsis,” “early-onset sepsis,” and “Gulf Cooperation Council (GCC),” and the keywords of antimicrobial resistance and pathogens were used: “antimicrobial drug resistance” and “pathogens.” Only articles published from January 1983 to January 2025 were included for screening. Results: The final count of the articles that fit the inclusion criteria is 54, and 5177 neonatal sepsis cases’ data have been identified. The most common pathogens were coagulase-negative staphylococci (CoNS) and Klebsiella spp., which caused 17.4 percent (901 cases) and 15.9 percent (825 cases) of neonatal sepsis, respectively. Coagulase-negative staphylococci (CoNS) were the most resistant, especially to oxacillin and erythromycin. The most isolated pathogens among Gram-negative spp. were Klebsiella spp., which showed a resistance to ampicillin, amoxicillin, and ceftriaxone. Conclusions: The bacterial isolates had a diversity of antimicrobial resistance, stressing the necessity of continuous hospital surveillance. Sophisticated diagnostic methods and well-designed research are necessary, especially in areas characterized by high rates of neonatal mortality, to determine the prevalence of neonatal sepsis, risk factors, and clinical outcomes. Full article

Objectives: Early identification of sepsis is critical, as delayed diagnosis significantly increases morbidity and mortality. We aimed to develop and validate AI/ML models for early sepsis prediction using structured electronic health record (EHR) data, waveform data, and a combination of both. Methods: We conducted a retrospective observational study using the AIM-AHEAD60 subset of the CHoRUS dataset. Adult patients (≥18 years) with a final diagnosis of sepsis were included. Structured EHR data (demographics, initial vital signs, laboratory results) and waveform data (continuous vital signs) from the first hour of hospital arrival were extracted. Three algorithms (i.e., XGBoost, LightGBM, and HistGB) were developed with a focus on maximizing the performance metric of recall. Other performance metrics were also assessed, including accuracy, precision, F1 score, and the area under the receiver operating characteristic curve (AUROC). Results: A total of 11,312 unique patients met the inclusion criteria, among whom 2245 individuals (19.85%) were diagnosed with sepsis at least once. Using structured EHR data alone, laboratory variables such as lactate and leukocyte count were most predictive. Waveform models identified respiratory rate, systolic blood pressure, and temperature trends in the first hour as key predictors. Combined models highlighted mean temperature and mean systolic blood pressure as top features. XGBoost achieved the highest AUROC (0.922) across all data configurations, with a recall above 80%, demonstrating robust performance despite substantial missing data. Conclusions: High-performing AI/ML models for early sepsis prediction can be developed from publicly available datasets using only first-hour clinical information. XGBoost models demonstrate strong potential for real-time clinical screening. Full article

Burn injury triggers a complex inflammatory cascade in which the interplay between pro- and anti-inflammatory mediators determines recovery or progression to sepsis, ventilator-associated pneumonia (VAP) or multi-organ dysfunction, and mortality. We systematically searched PubMed, Embase, Cochrane Library, Web of Science, and Scopus for studies published between 2006 and 2024, identifying 1883 records. We conducted a comprehensive systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After screening and eligibility assessment, 24 studies covering both pediatric and adult populations met the inclusion criteria. Data on cytokines, acute-phase proteins, complement fragments, and systemic inflammatory indices were synthesized narratively. The evidence indicates that the inflammatory response to burn injury is not a linear sequence of events but a dynamic and unstable equilibrium, where outcomes are determined less by the initial magnitude of cytokine release and more by the persistence of dysregulated inflammation or failure of compensatory mechanisms. Full article

Background and Objectives: Although nutritional status is critical to the clinical outcomes of septic patients, studies on this topic are limited. We aim to assess the prognostic value of five nutritional screening tools (NSTs) for septic patients both at the time of admission to the intensive care unit (ICU) and five days later. Materials and Methods: This prospective observational study included adult septic patients in the ICU. Patients were divided into two groups: survivors and non-survivors. Clinical, laboratory characteristics, and NST values [The Controlling Nutritional Status (CONUT), Prognostic Nutritional Index (PNI), Nutritional Risk Screening (NRS-2002), Geriatric Nutritional Risk Index (GNRI), and Nutrition Risk in the Critically Ill (NUTRIC)] were recorded at admission and on Day-5, and intergroup and intragroup comparisons were performed. Results: A total of 126 patients were included in this study: 97 in the survival group and 29 in the non-survival group. The non-survivors had higher CONUT and NUTRIC scores and lower PNI scores. Multivariate analysis found higher Day-5 NUTRIC scores independently associated with mortality. ROC analysis identified NUTRIC > 6 as a mortality predictor. Conclusions: Although several markers differed significantly between survivors and non-survivors, our findings show that a high Day-5 NUTRIC score was the only factor independently associated with mortality among NSTs. Full article

Epidermolysis bullosa (EB) is a group of debilitating, genetic skin disorders characterized by excessive skin fragility, blistering, and ulcerations that cause a cyclical wound healing process. EB presents itself in various subtypes, such as EB simplex (EBS), junctional EB (JEB), dystrophic (DEB), and Kindler Syndrome (KS), which all differ in their genetic cause, severity, and harbor different causes of mortality. Of these variants, JEB and DEB are the most severe, with EBS being the mildest form of the disease and KS presenting in extremely rare cases. The JEB variant tends to cause mortality early on in children less than two years of age due to failure to thrive, sepsis from wound infections, and airway obstruction. In the recessive form of DEB (RDEB), cutaneous squamous cell carcinoma (cSCC) is the major cause of death in patients, with one study reporting a mere 4-year survival after the first EB-cSCC diagnosis. Cutaneous SCCs in the setting of RDEB are particularly concerning because they are often more aggressive and show greater metastatic potential, as compared to ultraviolet-induced SCCs. This review aims to explore the pathophysiology of these EB variants as well as their implications for developing cSCCs. It will also discuss elements of the clinical presentation of such lesions in EB patients and the challenges associated with making a definitive diagnosis. Additionally, we will illuminate various diagnostic techniques, current and future management and treatment strategies for both cSCC and EB, and the importance of early screening and education for patients with EB to maximize patient lifespan and quality of life. Full article