Search Results (1,356)

Background: Early identification of bacteremia in immunosuppressed cancer patients remains difficult, especially in neutropenia. This study evaluated the diagnostic accuracy of NLR, PLR, and NLPR for identifying bacteremia and sepsis in patients undergoing blood culture episode. Methods: We conducted a retrospective diagnostic accuracy study at a tertiary oncology center between January 2023 and December 2024. All bacteremia identified were included as cases. Culture-negative episodes were subsequently sampled as controls using a frequency-matching strategy. Hematological parameters were obtained within ±24 h of first blood culture episode. Diagnostic performance was assessed using ROC curve analysis and multivariable logistic regression. Results: Of 369 screened episodes, 337 from 323 unique patients were included after excluding 31 records. NLPR showed the highest accuracy for bacteremia (AUC 0.730; 95% CI 0.671–0.788). The optimal cut-off was 0.038 (sensitivity 69.2%, specificity 72.3%) and remained consistent after excluding episodes with antibiotic therapy (AUC 0.768), corticosteroids (AUC 0.708), or growth factor use (AUC 0.718). In severe neutropenia, NLPR showed the highest accuracy (AUC 0.887; 95% CI 0.797–0.978). In multivariable analysis (n = 304), NLPR remained independently associated with bacteremia (p < 0.001), with good model discrimination (AUC 0.815; 95% CI 0.763–0.866). Diagnostic performance for sepsis was lower and not statistically significant. Conclusions: These findings suggest that NLPR may represent a simple, inexpensive, widely accessible adjunctive biomarker to support early bacteremia risk stratification in immunosuppressed cancer patients, particularly in patients with severe neutropenia. Although its overall discrimination was comparable to isolated lymphocyte count, NLPR may provide clinically relevant contextual information by integrating multiple dimensions of immune dysregulation. Further prospective multicenter validation is warranted. Full article

Background: Although less frequently encountered, aortic valve stenosis is associated with complications separate from its hemodynamic burdens, such as infective endocarditis. Case Summary: We report the case of a 77-year-old female patient with regular cardiac follow-up in the setting of an asymptomatic severe aortic stenosis, who presented to the emergency department with signs and symptoms of sepsis and acute decompensated heart failure. Echocardiography revealed two vegetations attached to the tricuspid valve, an abscess of the anterior aortic ring, and a high-velocity ventricular septal defect. The patient was started on adequate antibiotic therapy. Surgical treatment in an urgent manner (within a few days) was decided by the Heart Team, in accordance with the ESC guidelines on the management of infective endocarditis. Whilst awaiting surgery, the patient presented with a sudden hemodynamic deterioration a few days after diagnosis, with cardiopulmonary arrest and subsequent death. Discussion: We hypothesize that the patient developed an infective endocarditis of the degenerated stenotic aortic valve with extension from left to right via a ventricular septal defect, the development of which was facilitated by the high trans-aortic valve gradient. Some reported cases describe a ventricular septal defect as a complication of native aortic valve endocarditis, though not all involve concomitant aortic stenosis. In conclusion, our case illustrates a very rare scenario of infective endocarditis complicating aortic stenosis with fulminant development. This case highlights a rare, albeit severe complication associated with aortic stenosis and therapeutic challenges in managing the dismal evolution of endocarditis in this setting. Full article

Objective: In addition to hyperoxia, inflammation and infection contribute to the pathogenesis of retinopathy of prematurity (ROP). However, the differential effects of specific bacterial pathogens on ROP development remain unclear. This study aimed to evaluate the association between sepsis due to Gram-positive and Gram-negative bacteria and the development and severity of ROP. Materials and Methods: Infants at risk for ROP, defined as those with birth weight ≤1500 g or gestational age ≤32 weeks, or those with birth weight >1500 g or gestational age >32 weeks who required cardiorespiratory support, were included in this retrospective study. Patients were categorised into no-ROP and any-stage ROP groups, as well as treatment-requiring and non-treatment-requiring ROP groups. The clinical characteristics, laboratory findings, and microbiological data were compared between the groups. Results: Among the 319 enrolled infants, 193 (60.6%) did not develop ROP, whereas 126 (39.4%) developed any-stage ROP. Clinical early-onset sepsis, clinical and proven late-onset sepsis, and increased frequency of late-onset sepsis episodes were significantly associated with any-stage and treatment-requiring ROP (p < 0.05). In multivariate analysis, both Gram-positive (OR 2.36, 95% CI 1.2–4.6, p = 0.012) and Gram-negative bacterial sepsis (OR 3.56, 95% CI 1.5–8.3, p = 0.004) were independently associated with any-stage ROP. In addition, Gram-positive bacterial sepsis (OR 4.4, 95% CI 1.1–16.9, p = 0.031) was independently associated with treatment-requiring ROP. Conclusions: Gram-positive bacterial sepsis was associated with both any-stage ROP and treatment-requiring ROP, whereas Gram-negative bacterial sepsis was associated with any-stage ROP only. These findings support the potential role of pathogen-specific inflammatory processes in ROP development and progression. Further prospective studies incorporating detailed inflammatory and oxygenation parameters are required to clarify these relationships. Full article

Klebsiella pneumoniae is an opportunistic pathogen associated with both community-acquired and nosocomial infections. Multidrug-resistant (MDR) strains are increasingly implicated in urinary tract infections (UTIs), traveller’s diarrhoea, bacteraemia, and sepsis. β-lactam antibiotics are commonly used for treatment; however, antimicrobial resistance has emerged largely due to the production of extended-spectrum β-lactamases (ESBLs), which confer resistance mainly to penicillins, oxyimino-cephalosporins, and monobactams, while cephamycins and carbapenems usually remain stable to ESBL-mediated hydrolysis and compromise therapeutic efficacy. ESBL-producing strains represent a major cause of severe Gram-negative infections. This study aimed to determine the prevalence of ESBL-producing K. pneumoniae among UTI patients in Jordanian hospitals (Al Mafraq, Ma’an, and Islamic Hospitals), evaluate their antimicrobial susceptibility patterns, and detect antimicrobial resistance genes at the molecular level. A total of 450 urine isolates of K. pneumoniae were collected from UTI patients between November 2023 and May 2024. Isolates were identified in hospital laboratories using standard microbiological methods. Antimicrobial susceptibility testing was performed, and molecular characterisation of ESBL-associated genes was conducted using polymerase chain reaction (PCR). Out of 450 K. pneumoniae isolates collected from UTI patients across three Jordanian regions, 72 (16%) were confirmed as ESBL producers. Among the 72 ESBL-positive K. pneumoniae isolates, 34 (47.2%) were recovered from the Central region, 20 (27.8%) from the North, and 18 (25.0%) from the South. Molecular analysis revealed that 41.7% of ESBL-producing isolates carried the blaCTX-M gene, while 33.3% harboured the blaOXA gene. All ESBL-producing isolates demonstrated antimicrobial resistance to third-generation cephalosporins. A significantly higher proportion of ESBL-producing isolates was identified in female patients (84.7%) compared with males (15.3%). A significant association was observed between blaOXA gene distribution and geographic region (p = 0.016), whereas blaCTX-M gene distribution showed no significant regional association. ESBL-producing K. pneumoniae accounted for a substantial proportion of UTI isolates in Jordan, with blaCTX-M identified as the predominant resistance gene. The higher burden observed in the Central region and among female patients highlights notable distribution patterns in this cohort. These findings emphasise the necessity for sustained molecular surveillance and strengthened antimicrobial stewardship strategies to limit the dissemination of ESBL-producing strains in Jordanian healthcare settings. Full article

Background: Nutritional indices are increasingly studied as prognostic tools in sepsis, but their comparative value remains uncertain. We conducted a systematic review and meta-analysis to evaluate associations between major nutritional indices and mortality in adult sepsis. Methods: PubMed, Embase, and Web of Science were searched for eligible studies. Pooled odds ratios (ORs), hazard ratios (HRs), and diagnostic accuracy measures were synthesized using random-effects models. Subgroup and sensitivity analyses explored heterogeneity and tested robustness. Results: Twenty-two studies comprising 51,769 patients were included. Higher modified Nutrition Risk in the Critically Ill (mNUTRIC) and Nutrition Risk in the Critically Ill (NUTRIC) scores were associated with increased mortality (OR 3.10, 95% CI 1.39–6.89; OR 4.54, 95% CI 2.13–9.66, respectively). In contrast, a higher Prognostic Nutritional Index (PNI) was consistently associated with lower mortality (OR 0.64, 95% CI 0.50–0.83; HR 0.66, 95% CI 0.54–0.81), and a higher Geriatric Nutritional Risk Index (GNRI) was associated with improved survival (HR 0.66, 95% CI 0.44–0.98). Controlling Nutritional Status (CONUT) showed a non-significant trend toward higher mortality (OR 1.83, 95% CI 0.94–3.54). In diagnostic analyses, mNUTRIC demonstrated better discrimination than PNI (AUC 0.84 vs. 0.74). Heterogeneity in mNUTRIC analyses decreased markedly after stratification by mortality endpoint. Conclusions: Nutritional indices are prognostically informative in sepsis, but performance is context-dependent. mNUTRIC/NUTRIC show stronger short-term signals in ICU cohorts, likely reflecting illness-severity components, and cross-index comparisons remain indirect due to heterogeneous thresholds and endpoints. Full article

Pediatric sepsis is a life-threatening systemic infectious response syndrome. Its core pathophysiological process involves a systemic imbalance between oxygen delivery and demand, coupled with cellular energy metabolism dysfunction, which collectively contribute to high mortality rates. Parameters of oxygen metabolism serve as critical indicators reflecting tissue perfusion and cellular oxygen utilization. Consequently, these parameters hold significant value for the early identification, severity stratification, therapeutic guidance, and prognostic evaluation of pediatric sepsis. This review systematically elucidates the pathophysiological mechanisms underlying oxygen metabolism disorders in pediatric sepsis. Furthermore, it highlights the current clinical applications and significance of key monitoring indices, including blood lactate, central venous oxygen saturation, oxygen delivery, and oxygen consumption. By integrating recent research advancements, this paper also explores therapeutic strategies aimed at optimizing oxygen metabolism, such as blood purification, microcirculation-targeted therapies, and extracorporeal membrane oxygenation. Finally, we provide future perspectives on emerging biomarkers and metabolomic approaches, aiming to establish a theoretical foundation for the optimized clinical management of pediatric sepsis. Full article

Frail older adults face an increased risk and severity of sepsis, which contributes to a notably high mortality rate. The management of sepsis in this population presents significant challenges, such as diagnostic complexity, a higher prevalence of multidrug-resistant pathogens, difficulties in achieving effective source control, and an increased risk of adverse events and toxicity associated with antibiotic therapy. In addition, accurate prognostic evaluation based on a comprehensive geriatric assessment is essential to determine the intensity of care required and to develop a personalized plan of care. Despite these considerations, frail older adults are still often underrepresented in randomized clinical trials and guidelines. In this narrative review, we discuss the main pillars of tailored antimicrobial stewardship in frail older adults. We propose a practical, stepwise approach to individualized care, delivered by a multidisciplinary team and based on a careful balance between treatment intensity and patients’ vulnerabilities, needs, and priorities. Full article

Background: Immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) is a rare, life-threatening complication following CAR T-cell therapy. Diagnosis is challenging due to overlap with severe CRS, sepsis and lack of standardized criteria. Clinical data remain limited. Methods: We retrospectively analyzed 301 patients treated with CD19- or BCMA-directed CAR T-cells for hematologic malignancies at a single center from January 2019 to January 2026. IEC-HS was defined according to American Society for Transplantation and Cellular Therapy criteria. Results: Median follow-up was 31 months. IEC-HS was diagnosed in 14 patients (4.7%), median age 67 years. Underlying diseases included diffuse large B-cell lymphoma (n = 4), multiple myeloma (n = 7), mantle cell lymphoma, Burkitt lymphoma and B-lymphoblastic leukemia (n = 1 each). All patients had hyperferritinemia and cytopenias at baseline; most had high tumor burden (9/14) and elevated LDH (10/14). CRS occurred in all patients and ICANS in 6/14. IEC-HS occurred at median 10 days and was characterized by hyperferritinemia (median 15,321 µg/L), neutropenia, thrombocytopenia, hepatic dysfunction and high CAR-T-cell expansion in peripheral blood. Treatment included corticosteroids and anakinra (12/14). Refractory patients received IVIG (5/14), tocilizumab (3/14), siltuximab, ruxolitinib, emapalumab or etoposide (each n = 1). Infections occurred in 11/14; 4/14 had mixed infections. IEC-HS resolved in 7/14 (median 7 days). Mortality was 79% (11/14), mainly due to IEC-HS (7/14). Three patients were alive at last follow-up. One-year OS was lower vs. the whole cohort (31% vs. 69%, p < 0.0001). Conclusions: IEC-HS was associated with severe cytopenias, hyperferritinemia, hepatic dysfunction and high infection risk. Despite intensive immunosuppressive therapy, outcomes remain poor. Early biomarker-driven identification and multicenter studies are needed. Full article

Sepsis is a life-threatening syndrome driven by a dysregulated host response to infection and is frequently complicated by sepsis-associated encephalopathy (SAE), which contributes to long-term cognitive and neuropsychiatric sequelae. Despite advances in critical care, effective targeted therapies for SAE remain limited. Aquaporin-4 (AQP4), the predominant astrocytic water channel, plays a central role in cerebral water homeostasis, neuroinflammatory signaling, and blood–brain barrier integrity, suggesting its potential involvement in sepsis-induced cerebral dysfunction and neurorepair processes. Polymicrobial sepsis was induced in C57BL/6J mice using the cecal ligation and puncture (CLP) model. AQP4 activity was pharmacologically modulated through either inhibition or facilitation following sepsis induction. Disease severity was assessed using physiological parameters and a modified murine sepsis score. Neurological outcomes were evaluated through standardized behavioral tests assessing locomotor activity, motor coordination, cognitive performance, and depressive-like behavior. Neuroinflammatory and neuronal changes were examined by immunohistochemical analyses of microglial activation (Iba1), astroglial reactivity (GFAP), neuronal integrity (NeuN), and AQP4 expression. Compared with AQP4 facilitation, pharmacological inhibition of AQP4 was associated with a more favorable clinical recovery profile, reflected by lower sepsis severity scores and a more favorable body weight trajectory during the recovery phase. Behavioral analyses demonstrated preserved cognitive function, enhanced motor coordination, and reduced depressive-like behavior in AQP4 inhibitor-treated mice compared with animals receiving AQP4 facilitation. At the histological level, the inhibitor-treated group showed lower microglial and astroglial activation and better preservation of neuronal markers than the facilitator-treated group, whereas AQP4 facilitation exacerbated neuroinflammatory responses and neuronal alterations. These findings highlight a dual, context-dependent role of AQP4 in sepsis-associated cerebral dysfunction. These findings suggest that AQP4 modulation influences sepsis-associated cerebral dysfunction in a context-dependent manner. Within our experimental design, AQP4 facilitation was associated with worse outcomes, whereas AQP4 inhibition was associated with a comparatively more favorable neurobehavioral and histological profile. Full article

Background/Objectives: Sepsis is a dynamic clinical syndrome characterized by a rapidly evolving inflammatory response, where early identification of patients at risk for adverse outcomes remains a major challenge. While inflammatory biomarkers are widely used, their prognostic value at baseline is limited. This study aimed to evaluate whether early changes in inflammatory biomarkers, particularly the neutrophil-to-lymphocyte ratio (ΔNLR), provide additional prognostic value in predicting short-term outcomes in patients with sepsis. Methods: A retrospective longitudinal observational study was conducted, including 168 adult patients admitted with sepsis at a tertiary infectious diseases hospital. Inflammatory biomarkers (CRP, procalcitonin, leukocyte subpopulations, and NLR) were assessed at admission and at 48–72 h. Early changes (Δ values) were calculated and analyzed in relation to a composite adverse outcome, including ICU admission, vasopressor requirement, mechanical ventilation, or in-hospital mortality. Logistic regression and ROC curve analyses were used to evaluate predictive performance. Results: Patients with adverse outcomes had significantly higher baseline inflammatory markers and severity scores. Early reductions in CRP and NLR were more pronounced in survivors, whereas non-survivors showed persistently elevated or minimally decreasing values. In multivariate analysis, ΔNLR remained independently associated with in-hospital mortality (OR 0.91, 95% CI 0.84–0.98, p = 0.015), alongside Sequential Organ Failure Assessment (SOFA) score and septic shock. ΔNLR demonstrated better discriminative performance (AUC 0.74) compared to baseline markers and improved predictive accuracy when combined with SOFA score (AUC 0.81). Higher baseline NLR quartiles were associated with a stepwise increase in adverse outcomes. Conclusions: Early changes in inflammatory biomarkers, particularly ΔNLR, provide clinically relevant prognostic information beyond baseline measurements and severity scores in sepsis. Dynamic assessment of immune response may improve early risk stratification and support more individualized clinical decision-making. Full article

Healthcare-associated infections (HAIs) are clinically relevant complications in critically ill stroke patients, particularly in neurological intensive care settings, where severe neurological injury, dysphagia, immobilization, invasive device exposure, and prolonged hospitalization increase infection susceptibility. Romanian data focused on deceased stroke patients admitted to neurological intensive care units remain limited. This retrospective descriptive single-center hospital-based study, supported by focused literature contextualization, was conducted in the Neurological Intensive Care Unit of the Brașov County Emergency Clinical Hospital, Romania. Adult stroke patients who died during hospitalization over a six-year observation period were included. Clinical data were extracted from a working hospital database and analyzed descriptively after data cleaning and harmonization. The final cohort comprised 190 deceased stroke patients; ischemic stroke was documented in 69.5% and hemorrhagic stroke in 28.9%. Hypertension (73.7%) and ischemic heart disease and/or previous myocardial infarction (60.0%) were the most frequently recorded comorbidities. Pneumonia was the dominant documented infectious complication, recorded in 52.6% of patients, followed by urinary tract infection (11.6%), pressure sore-related infection (4.7%), and sepsis-related coding (6.8%). The median in-hospital survival interval was 6 days (IQR 3.0–10.75). Because year-by-year stratification was not sufficiently robust, the temporal component was interpreted only in aggregate form. These findings provide a descriptive hospital-based profile of documented infectious complications in a fatal stroke ICU cohort and support the need for more standardized infection documentation and better linkage between clinical and microbiological data in neurocritical care settings. Full article

Background: Acute kidney injury (AKI) is a common and serious complication in patients with liver cirrhosis and is associated with poor outcomes. However, whether the association between nephrotic-range proteinuria (NRP) and severe AKI varies by liver disease severity remains unclear. Methods: This retrospective cohort study included 408 adult patients with cirrhosis stratified by Child–Pugh class (A, B, and C). Severe AKI was defined as Kidney Disease: Improving Global Outcomes stage 2–3. Multivariable logistic regression analyses were performed in the overall cohort and within each class, with the additional evaluation of interaction effects. Results: The incidence of severe AKI increased from 18.4% in class A to 38.8% in class C. In the extended multivariable model incorporating hemodynamic and inflammatory variables, nephrotic-range proteinuria was not significantly associated with severe AKI. In stratified analyses, a significant association was observed only in Child–Pugh class A. Additional analyses suggested that this relationship was attenuated after accounting for sepsis and systemic severity. Conclusions: Although NRP prevalence was similar across Child–Pugh classes, the association between NRP and severe AKI appeared to vary by disease stage, particularly before adjustment for systemic severity. Full article

Background and Objectives: Infective endocarditis (IE) remains associated with high mortality, and real-world (RW) patients often differ from trial populations. We evaluated predictors of complications and mortality, the trial-eligibility gap, and temporal trends in guideline adherence across two periods (Period 1 [P1]: 2011–2016 vs. Period 2 [P2]: 2017–2025) in a Romanian county hospital. Materials and Methods: We conducted a retrospective analysis of consecutive adult patients with definite IE. Patients were categorized as trial-eligible (TE) or RW according to predefined criteria. The composite endpoint included acute heart failure, cardiogenic or septic shock, embolic events, infectious complications, need for renal replacement therapy, and in-hospital mortality. We evaluated guideline adherence using a predefined quality indicator (QI) score ≥ 3. We identified independent predictors of outcome using multivariable logistic regression. Results: Among 206 patients (mean age 63.0 ± 14.8 years; 70.4% male), blood cultures were positive in 64.1%, with Staphylococcus aureus accounting for 14.1%. Vegetations were documented in 72.8%, and cardiac surgery was performed in 26.2%. Overall, at least one event from the composite endpoint occurred in 61.6%, and mortality was 32.5%. TE patients represented 63.1% of the cohort. Guideline adherence improved over time (QI ≥ 3: from 18.3% in P1 to 25.4% in P2, p = 0.32). In P2, the composite endpoint (66.8% vs. 42.9%, p = 0.002) and embolic events (31.8% vs. 8.2%, p < 0.001) were more frequent, whereas mortality remained unchanged (31.8% vs. 34.7%, p = 0.844). Sepsis at admission and left ventricular ejection fraction (LVEF) < 50% independently predicted adverse outcomes; model discrimination was acceptable, with an area under the curve (AUC) of 0.77. Conclusions: RW IE showed high complication rates and a persistent trial gap; improved guideline adherence was offset by greater clinical severity. Full article

Background: COPD remains a leading cause of hospitalization and mortality worldwide. This study aimed to analyze trends in COPD patients in Spain from 2016 to 2023, compare outcomes between patients with COPD as a primary versus secondary diagnosis, and identify factors associated with in-hospital mortality. Methods: Retrospective observational study using the Spanish database CMBD. 711.799 patients were analyzed. Demographic characteristics, Charlson Comorbidity Index (CCI), complications, mortality, and hospitalization costs were also evaluated. Multivariate logistic regression was used to identify mortality risk factors. Results: The overall hospitalization rate was 20.02 per 1000 admissions. It decreased by 30% during 2020–2021 before rebounding to peak levels in 2023. The proportion of female patients increased from 19.9% (2016) to 26.4% (2023). Patients with COPD as a secondary diagnosis had higher mortality (13% vs. 5.4%, p < 0.001), greater comorbidity burden (mean CCI 3.5 vs. 2.8), and higher costs. While overall admissions dropped in 2020, mortality peaked at 11.7%, and the number of patients with extremely severe disease nearly doubled. Independent risk factors for mortality included sepsis, age ≥ 66 years, CCI ≥ 3, and COVID-19. Conclusions: Hospitalization involving COPD in Spain showed pandemic-related fluctuations with increasing clinical complexity and increasing female sex. The higher mortality and cost associated with secondary COPD diagnosis highlight the need for comprehensive risk stratification of comorbid conditions and multidisciplinary management of these patients. Early identification of sepsis and CCI scores is essential to improve clinical outcomes in the aging population. Full article

Background and Objectives: Healthcare-associated infections (HAIs) remain a relevant complication in coronary care units (CCUs), particularly among patients with cardiac dysfunction requiring invasive monitoring and prolonged hospitalization. In this setting, infection occurrence may reflect the cumulative interaction between baseline biological vulnerability and care-related exposure. This study aimed to explore whether a simple cumulative framework integrating these components can describe patterns of HAI occurrence and support early identification of patients at risk for severe infectious complications and sepsis. Materials and Methods: The retrospective cohort study included 870 consecutive adult patients admitted to a tertiary-care CCU. A four-component cumulative framework was constructed using reduced left ventricular ejection fraction (LVEF < 40%), diabetes mellitus, urinary catheterization, and CCU length of stay > 5 days. Each component contributed one point (range 0–4). HAIs were defined according to CDC/NHSN criteria and required microbiological confirmation. Associations between cumulative burden and infection occurrence were assessed using trend analysis and exploratory modeling. Results: HAI occurrence increased progressively across cumulative framework levels, demonstrating a stepwise pattern from low to higher vulnerability strata (p for trend < 0.001). A substantial proportion of infections clustered in patients with higher cumulative values, despite representing a minority of the cohort. Increasing cumulative burden was accompanied by higher observed infection occurrence, supporting a graded association between cumulative vulnerability and infection occurrence. Conclusions: In CCU patients, HAI occurrence appears to reflect the accumulation of biological vulnerability and care-related exposure during hospitalization. A simple cumulative framework may support early identification of patients requiring closer preventive attention and contribute to improved awareness of severe infectious complications in cardiac critical care. Prospective validation is warranted. Full article