Search Results (1,228)

Introduction: The appropriate use of antibiotic prophylaxis (AP) in surgical procedures is an ongoing debate. There is a lack of evidence, and urological guidelines provide limited, procedure-specific recommendations. Our aim was to develop a generic model of an audit to define the need for AP in urological procedures, as well as in other surgical specialties. Material and Methods: Based on our experience with the Global Prevalence of Infections in Urology (GPIU) study and a literature review, we defined benchmark standards for 30-day infection rates, including sepsis, and estimated the number of patients needed to be included in a comparative study of AP versus no AP for a surgical procedure within one year. The generic study model was developed during a modified consensus process within the UTISOLVE research group. Urology departments giving and not giving AP were invited to join our development project as an extension of GPIU. Results: Radical prostatectomy was used as a model procedure. Ca. 60 urology centers performing more than 50 radical prostatectomies per year signed up. There was variation in AP practice among sites. Our own review showed that infection rates were ca. 5%, with severe infections, including sepsis, occurring in <0.5% of cases. A sample of 1825 patients would be required to achieve a 95% confidence interval half-width of ±1.0% for general infections. For sepsis, assuming an incidence of 0.5%, a sample of 2124 patients would be needed to reach a 95% confidence interval precision of ±0.30%. Enrollment of 2070 consecutive procedures would be needed to yield precisions of ±0.94% for infection and ±0.30% for sepsis. Based on the number of procedures performed and the number of interested study sites, we agreed on a prospective, multi-center, non-interventional service evaluation, expected to collect standardized data over a 3-month period. The primary outcome was defined as the 30-day incidence of infectious complications. All patients will undergo 30-day post-procedure follow-up through routine clinical care pathways. Conclusions: Our audit model is based on benchmarking of relevant outcomes. It defines how to assess AP in surgical procedures and clarifies a series of issues necessary to defend the status of a generic study model. We regard DEEP-URO to be a comprehensive, multi-center-based initiative that will help balance infection prevention with antimicrobial stewardship and improve the quality of clinical practice and personalized medicine. 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

Background and Clinical Significance: Cutaneous aspergillosis caused by Aspergillus flavus is rare and coinfection with Klebsiella pneumoniae was reported only in pulmonary disease. Case Presentation: We describe a 57-year-old woman with no prior comorbidities who developed septic shock requiring intensive care, broad-spectrum antibiotics, corticosteroids, and renal replacement therapy. Six days after discharge, she was readmitted with fever, leukopenia, thrombocytopenia, cavitary lung lesions, and multiple erythematous nodules on the limbs and mammary regions. Bronchial aspirate cultures detected K. pneumoniae, while progressive cutaneous lesions required surgical debridement. Histopathology revealed angioinvasive septate hyphae, and MALDI-TOF identified A. flavus. The K. pneumoniae strain was extensively drug resistant; A. flavus was susceptible only to azoles. Despite targeted therapy, lesions progressed requiring bilateral mastectomy. Conclusions: This case illustrates a previously unreported scenario in which secondary immunosuppression after severe sepsis led to concurrent cutaneous A. flavus infection and extensively drug-resistant (XDR) K. pneumoniae. Early recognition of mixed fungal–bacterial infections is essential for appropriate management. 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

Drug use–associated infective endocarditis (DUA-IE) is an increasingly important clinical problem that affects younger patients and poses substantial diagnostic, therapeutic, and surgical challenges. We conducted a retrospective cohort study of adults with definite infective endocarditis treated at a tertiary referral center between 2017 and 2022, comparing patients with DUA-IE to those with non–drug use–associated infective endocarditis. Of the 189 patients, 43 (22.8%) had DUA-IE. These patients were significantly younger and had higher rates of HIV and hepatitis C coinfections. Staphylococcus aureus was the predominant pathogen, and right-sided valve involvement was more frequent; however, left-sided disease predominated among patients requiring valve surgery. Compared with non-DUA-IE patients, those with DUA-IE had larger vegetations, higher inflammatory markers, more frequent complications(including sepsis, embolic events, and heart failure), higher rates of emergency surgical intervention, longer hospitalizations, and increased in-hospital mortality rates. In conclusion, DUA-IE represents a distinct and more aggressive form of infective endocarditis, characterized by severe infection, increased complication rates, and a substantial surgical burden despite the younger patient age, underscoring the need for integrated infectious disease, surgical, and addiction-focused care models for these patients. Full article

Background: Difficult-to-treat resistant Pseudomonas aeruginosa (DTR-PA) infections are associated with high morbidity and mortality, but data on prognostic factors remain limited. Given the limited real-world data on outcomes of DTR-PA infections, we aimed to identify clinical predictors of mortality and response to therapy in this setting. Methods: We conducted a single-center retrospective cohort study of 51 patients with DTR-PA infections. The primary endpoint was 30-day all-cause mortality; secondary endpoints were clinical and microbiological cure at end of therapy. An exploratory analysis evaluated 30-day infection-related mortality. Logistic regression models (univariable, multivariable and Firth bias-reduced) were used to identify independent predictors. Results: Median age was 64 years (IQR 22); 63% were male and 71% were in the ICU at infection onset. Sepsis occurred in 80% and septic shock in 45%. Thirty-day all-cause mortality was 49% (25/51). According to multivariable analysis, septic shock was an independent predictor of mortality (aOR 5.52, 95% CI 1.04–29.27; p = 0.045) as younger age (aOR 1.06, 95% CI 1.00–1.12; p = 0.052), whereas targeted therapy with ceftazidime/avibactam or ceftolozane/tazobactam is a protective factor (aOR 0.15, 95% CI 0.02–1.17; p = 0.070) did not reach significance in the final model. Clinical cure occurred in 33% (17/51) and was negatively associated with device burden and bloodstream infection, whereas microbiological cure (45%, 23/51) was more likely with targeted therapy and absence of sepsis. The exploratory analysis of infection-related mortality (35%) showed similar predictors. Conclusions: DTR-PA infections are associated with high mortality. Septic shock and older age predict death, while the use of novel β-lactam/β-lactamase inhibitors is associated with improved outcomes. Early recognition of severe illness and timely administration of active therapy may improve survival in these infections. 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

Background: Postnatal cytomegalovirus (pCMV) infection is a frequent viral condition in early infancy and is primarily acquired through maternal breastfeeding. Although usually asymptomatic in term infants, it can lead to significant morbidity in preterm neonates (gestational age < 32 weeks) and in those with very low birthweight (<1500 g), presenting with sepsis-like syndrome, pneumonia, cytopenia, hepatitis, or colitis. Severe cases may result in long-term sequelae or death. Objectives: To describe a series of cases of pCMV infection and review the current evidence on its epidemiology, clinical manifestations, outcomes, and therapeutic management, aiming to identify gaps in knowledge and propose opportunities for improving the care of preterm infants. Methods: We analyzed clinical presentations of pCMV disease in a case series of preterm infants and reported cases and reviewed the recent literature regarding diagnostic approaches, antiviral therapy, and strategies for breastmilk management. Results: Current data highlight substantial variability in clinical management and outcomes. The lack of consensus on antiviral indications and treatment duration reflects a limited understanding of the disease’s natural history. Approaches to breastmilk handling differ widely among centers and countries, further complicating the standardization of care. Conclusions: pCMV infection remains a relevant yet under-recognized condition in neonatal medicine. Improved diagnostic strategies, clearer therapeutic guidelines, and harmonized recommendations for breastmilk management are needed to optimize the care of preterm infants at risk of or affected by pCMV disease. Full article

Background: Accurate prediction of survival in septic patients remains a major challenge in intensive care medicine. Established severity scores such as the Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) are widely used to estimate prognosis, while biochemical markers such as serum lactate may provide complementary information. However, the prognostic interplay between these scores, lactate dynamics, vasopressor requirement, and infection focus has not been fully elucidated in septic populations. Methods: We conducted a retrospective observational study of 146 adult patients with sepsis admitted to the intensive care unit (ICU) of the Hospital Clínico Universitario de Valladolid (HCUV), Spain, between 2022 and 2024. Demographic data, APACHE II and SOFA scores at admission, lactate levels at admission and 24 h, albumin, and procalcitonin were recorded. Vasopressor use (categorized by intensity) and infection focus (urinary vs. non-urinary) were documented. The primary outcome was ICU mortality. Correlation analyses (Pearson or Spearman as appropriate) were performed separately for urinary and non-urinary subgroups. Multivariable logistic regression models were constructed using APACHE II, SOFA, log-transformed lactate at 24 h, vasopressor use, and urinary focus as predictors. Model performance was assessed using Nagelkerke R², area under the ROC curve (AUC), and classification accuracy. Results: ICU mortality was 23.3%. APACHE II (OR 1.092; p = 0.004) and SOFA (OR 1.185; p = 0.023) were independent predictors of ICU mortality, while log-transformed lactate at 24 h showed a positive trend (OR 1.920; p = 0.066). The addition of urinary focus (protective effect, OR 0.19; p = 0.035) and vasopressor requirement (OR 2.20; p = 0.04) modestly improved model discrimination (Nagelkerke R² = 0.395). ROC analyses showed AUCs of 0.800 for APACHE + SOFA + log-lactate, 0.824 for the vasopressor model, and 0.833 for the urinary focus model. The best-performing models achieved >85% overall accuracy, with specificity consistently above 95%. Conclusions: In septic ICU patients, APACHE II and SOFA scores remain independent predictors of ICU mortality, and lactate at 24 h adds prognostic value—particularly in non-urinary infections. Vasopressor requirement and infection focus modestly improved model discrimination, underscoring their clinical relevance. These findings suggest that integrating severity scores with selected metabolic and clinical variables may modestly refine survival prediction in septic patients. Full article

Sepsis induces severe immune and metabolic dysfunction driven by mitochondrial failure. Mitochondrial transplantation (MT) has emerged as a promising strategy to restore mitochondrial bioenergetics, but its metabolic impact on immune cells remains unclear. Here, we used gas chromatography–time-of-flight mass spectrometry (GC-TOF-MS)-based metabolomics to evaluate metabolic alterations in peripheral blood mononuclear cells (PBMCs) and splenocytes from a rat polymicrobial sepsis model treated with MT. Principal component and partial least-squares discriminant analyses revealed distinct clustering between sham, sepsis, and MT groups. Sepsis markedly suppressed metabolites related to amino acid, carbohydrate, and lipid metabolism, including aspartic acid, glutamic acid, AMP, and myo-inositol, reflecting mitochondrial metabolic paralysis. MT partially restored these metabolites toward sham levels, reactivating tricarboxylic acid (TCA) cycle, nucleotide, and lipid pathways. Pathway analysis confirmed that exogenous mitochondria reversed sepsis-induced metabolic suppression and promoted bioenergetic recovery in immune cells. These findings provide direct metabolomic evidence that MT reprograms immune metabolism and restores oxidative and biosynthetic function during sepsis, supporting its potential as a mitochondrial-based metabolic therapy. Full article

Background: Frail patients undergoing AF ablation face elevated periprocedural risks. However, prior studies often examined composite or long-term outcomes and did not stratify acute complication risks by frailty severity. Objective: The objective of this study was to assess the impact of frailty, measured by the Hospital Frailty Risk Score (HFRS) on in-hospital outcomes after AF ablation, and to delineate the risk of specific acute complications across frailty levels. Methods: We analyzed a national inpatient cohort of AF ablation hospitalizations (2016–2021). Patients were stratified into low-, intermediate-, and high-frailty groups by HFRS. In-hospital mortality and major complications (stroke, respiratory failure, sepsis, acute dialysis, cardiac arrest, cardiogenic shock) were compared across frailty groups, and multivariable logistic regression identified independent predictors of these outcomes. Results: Among an estimated 42,830 AF ablation admissions, 80.0% were low-frailty, 15.0% intermediate, and 5.0% high-frailty. High-frailty patients had markedly higher complication rates than low-frailty patients. In-hospital mortality was 6.1% in high frailty vs. 1.0% in low frailty, and stroke occurred in 4.0% vs. 0.3%, respectively. Rates of respiratory failure (18.0% vs. 3.5%), sepsis (8.0% vs. 1.2%), and acute dialysis (4.0% vs. 0.5%) were also significantly higher in the high-frailty group (all p < 0.001). In multivariate analyses, frailty remained a strong independent predictor of complications; high frailty conferred over four-fold higher odds of in-hospital mortality and five-fold higher odds of stroke compared to low frailty. Conclusions: Frailty is a powerful predictor of periprocedural complications and mortality in AF ablation patients. Even after accounting for age and comorbidities, patients with higher frailty scores experienced substantially worse in-hospital outcomes. These findings highlight the importance of frailty assessment to identify high-risk patients and inform clinical decision-making for AF ablation. Full article

Acute Respiratory Distress Syndrome (ARDS) represents a critical pathology often necessitating prolonged mechanical ventilation, a clinical course associated with significant complications and elevated mortality. This case report details the successful implementation of early Percutaneous Dilatational Tracheostomy (PDT) in a 61-year-old male presenting with severe ARDS secondary to sepsis-induced Community-Acquired Pneumonia (CAP) and Type I respiratory failure. This case suggests that early PDT serves as a safe and effective strategy to mitigate the risks associated with prolonged mechanical ventilation in patients with severe ARDS, potentially facilitating enhanced recovery and reduced ICU length of stay. Full article

KSRP (KH-type splicing regulatory protein) has emerged as a pivotal regulator of gene expression at multiple levels, acting as a transcription and splicing factor in the nucleus, and mediating AU-rich element (ARE)-dependent mRNA decay, translational silencing, and microRNA (miRNA) maturation in the cytoplasm. We and others have shown that KSRP acts as a regulator of immune responses, e.g., by dampening the expression of proinflammatory cytokines such as TNF-α, IL-6, IL-8, but also of NOS2, and facilitating the maturation of regulatory miRNAs, including let-7a, miR-129, and miR-155. This review aims to present current knowledge on the regulation of KSRP activity as conferred by miRNAs, phosphorylation, ubiquitination, SUMOylation, and interactions with long non-coding RNAs to enable dynamic responses towards inflammatory stimuli, and the effects of KSRP on innate immune reactions. Here, KSRP acts as an inhibitor by attenuating RIG-I-mediated antiviral signaling, cytokine production, and phagocytosis. In vivo, KSRP deficiency reduced arthritis severity but heightened inflammatory responses in sepsis and enhanced pathogen clearance in invasive pulmonary aspergillosis. These findings position KSRP as a dual regulator that limits tissue damage while constraining antimicrobial immunity. As a perspective, modulation of KSRP activity by applying pharmacological inhibitors may provide strategies to either suppress hyperinflammation in autoimmunity and sepsis or enhance host defense in immunocompromised states. Full article