Search Results (7,356)

Heterotrimeric G_i proteins are crucial modulators of G protein-coupled receptor signaling, with Gα_i2 ubiquitously expressed and implicated in diverse physiological processes. Previous reports described partial lethality in Gnai2-deficient mice, but the timing and mechanism of death remained unclear. Here, we demonstrate that impaired neonatal respiratory adaptation contributes to mortality in Gnai2-deficient neonates. Despite normal Mendelian distribution at birth and no overt malformations, at least 20% of the expected Gnai2-deficient neonates died within minutes after birth, displaying abnormal breathing, cyanosis, and features resembling neonatal respiratory distress syndrome (RDS). Histological and ultrastructural analyses revealed reduced alveolar surface area, thickened septa, increased mesenchymal tissue, and impaired surfactant ultrastructure, despite unaltered alveolar surfactant phospholipid levels. These findings suggest that Gα_i2 modulates the structural deployment and functional organization of surfactant within alveoli, although the incomplete phenotype and survival of some neonates indicate a regulatory rather than indispensable role of Gα_i2. Our data underscore the complexity of neonatal respiratory adaptation and highlight potential systemic and intercellular mechanisms underlying alveolar stabilization. Full article

Transesophageal echocardiography (TEE) has long been established as a cornerstone imaging modality in cardiac surgery and perioperative medicine. In recent years, however, its role has expanded into emergency and intensive care settings, where rapid and accurate hemodynamic assessment is crucial for survival. Point-of-care TEE provides advantages over transthoracic echocardiography when acoustic windows are limited, particularly in mechanically ventilated or critically unstable patients, allowing continuous high-quality visualization of cardiac function, volume status, and great vessel pathology to guide immediate therapeutic interventions. This narrative review examines the evolving role of TEE in acute settings, with emphasis on its application in shock, cardiac arrest, pulmonary embolism, tamponade, and its value in extracorporeal membrane oxygenation (ECMO) cannulation. Advances such as three-dimensional TEE, miniaturized probes, and the integration of artificial intelligence are also discussed, as potential drivers of innovation. While bridging technological progress with clinical practice, TEE emerges as a versatile tool in critical care. However, its broader adoption is still limited by probe availability, operator training, and institutional resources. Overcoming these barriers will be essential to translating technological advances into widespread practice. Full article

Invasive candidiasis (IC) is a life-threatening fungal infection predominantly affecting critically ill patients in intensive care units (ICUs). Despite advances in antifungal therapies, IC remains a diagnostic and therapeutic challenge, with a mortality rate exceeding 40%. The current reliance on blood cultures as the diagnostic gold standard is limited by low sensitivity and prolonged turnaround times, often delaying effective treatment. This often leads to the overuse of empirical antifungal therapies, increasing resistance, healthcare costs, and inconsistent outcomes. To address these issues, this paper introduces a five-step diagnostic strategy developed by an expert panel to optimise IC diagnosis and management. The strategy integrates predictive risk scores, biomarkers, and antifungal susceptibility testing to streamline diagnosis, identify high-risk patients, and promote antifungal stewardship. It also addresses barriers such as resource disparities and variability in clinical practices, offering a practical, standardised strategy for ICUs in the UK and Ireland. The clinical utility of this approach is highlighted through two patient cases. One describes the safe discontinuation of antifungal therapy after a negative (1,3)-β-D-glucan (BDG) assay ruled out IC, reducing unnecessary treatment and adverse effects. The other showcases the use of rapid in-house antifungal susceptibility testing to precisely tailor therapy for a patient with Nakaseomyces glabratus, ensuring effective treatment and preventing resistance. This pragmatic five-step guide simplifies and standardises IC diagnosis, aiming to lower mortality, optimise therapies, and promote judicious antifungal use. Full article

Background: Sepsis remains a major cause of morbidity and mortality in both developed and limited-resource countries. Despite over a century of research, accurate biomarkers for reliable diagnosis and prognosis in critically ill patients have yet to be established. Methods: This multicenter retrospective observational study aims to evaluate serum levels of Calprotectin, Azurocidin, cytokines, chemokines, procalcitonin (PCT) and C-Reactive Protein (CRP) in 15 healthy volunteers (controls), 15 non-infectious SIRS patients, 92 alive septic patients (Sepsis_A) and 29 dead septic patients (Sepsis_D). Results: Most biomarkers showed significantly higher serum concentrations in septic patients compared with controls, with IL-4 being increased only in the Sepsis_D group. In addition, several markers, including Calprotectin, Azurocidin, IL-6, IL-8, IL-10, TNF-α, and IL-35, were progressively elevated from SIRS to Sepsis_A and Sepsis_D cohorts, reflecting disease severity. All biomarkers showed good diagnostic performance for predicting Gram-negative bacteremia, although their accuracy in discriminating survivors from non-survivors was relatively low. Conclusions: In conclusion, calprotectin, azurocidin, IL-8, TNF-α, and IL-35 may assist clinicians in identifying Gram-negative bacteremia in septic patients; however, their prognostic value appears to be limited. Full article

Background and Objectives: This study aimed to investigate changes in the descending thoracic aorta (DTA) values in athletes while performing a bench press exercise, and to evaluate their relationship with vitamin levels and nutritional values. Materials and Methods: The study used speckle tracking to assess changes in DTA parameters in athletes before and after bench press exercise, compared to non-athlete controls. Measurements included rotational and radial velocities, circumferential strain and strain rate, and displacement. Results: The study included 60 non-athlete controls and 178 athletes performing bench press exercises. In a 10-year follow-up of 30 weightlifters, aortic speckle tracking values were age-matched with controls. No significant baseline differences were observed between groups. However, following exercise, all measurements demonstrated increases: DTA rotational velocity (55.44 ± 16.15 vs. 88.98 ± 10.31°/s), radial velocity (1.02 ± 0.36 vs. 1.56 ± 0.42 cm/s), circumferential strain (−8.52 ± 0.31 vs. −12.55 ± 1.13), strain rate (−1.55 ± 0.72 vs. −2.28 ± 0.56 s⁻¹), rotational displacement (6.22 ± 0.36 vs. 14.91 ± 0.85°), and radial displacement (0.89 ± 0.31 vs. 1.19 ± 0.65 mm), with all p-values < 0.05. Rotational displacement correlated with maximal repetition (88.56 ± 12.59 Kg) and vitamin levels. Conclusions: This study hypothesizes that bench press exercise is linked to increased DTA velocities, strain, strain rate, and displacement. Full article

Background/Objectives: Epidemiological surveillance of healthcare-associated infections (HAIs) and multidrug-resistant (MDR) bacteria is a key responsibility of hospital infection control committees (HICC). Active surveillance swabs facilitate the early detection of colonized patients; helping to prevent MDR pathogen transmission in intensive care units. This study aimed to describe antimicrobial resistance profiles of bacterial isolates from clinical samples in neonatal and pediatric intensive care units. Methods: A retrospective cross-sectional study was conducted at a maternal and child hospital in Rio de Janeiro, Brazil including patients aged 0–18 years admitted to neonatal (NICU), surgical (SICU), and pediatric (PICU) intensive care units between January and December 2023. A total of 286 positive cultures were analyzed from different sample types including blood, urine, tracheal aspirates, cerebrospinal fluid (CSF), and catheter tips as well as screening swabs (nasal and rectal) for colonization surveillance. Bacterial isolates were identified and tested for antimicrobial susceptibility following BrCAST (Brazilian Committee on Antimicrobial Susceptibility Testing) guidelines. Results: Of the 286 cultures, 146 (51%) originated from the NICU, 70 (24%) from the SICU, and 70 (24%) from the PICU. Coagulase-negative staphylococci (CoNS) predominated in blood cultures, especially among neonates, while MRSA was found in all nasal swabs. Among the Gram-negative bacteria; Klebsiella pneumoniae and Pseudomonas aeruginosa were the most frequent isolates, with 30–50% resistant to third-generation cephalosporins or carbapenems. ESBL-producing organisms were found in 40% of rectal swabs. Conclusions: The predominance of CoNS in neonatal ICUs and high resistance rates among Gram-negative bacteria highlight the urgent need for continuous microbiological surveillance and antimicrobial stewardship in vulnerable pediatric populations. Full article

Background/Objectives: The Parental Stressor Scale: Neonatal Intensive Care Unit (PSS:NICU) is one of the most widely used tools for assessing parental stress in neonatal intensive care settings. This study aimed to translate, culturally adapt and validate the PSS:NICU in a Greek cohort. Methods: A multicenter, cross-sectional study was conducted with 150 parents (89 mothers, 61 fathers; mean age = 34.1 years, SD = 7.2) of hospitalized neonates from three Greek NICUs. The translation followed forward–backward procedures, expert review, and pilot testing. Data were analyzed for internal consistency, factorial validity, and group differences. Results: Confirmatory factor analysis supported the adequacy of the original three-factor structure (Sights and Sounds, Infant Behavior and Appearance, and Parental Role Alteration). Cronbach’s alpha and McDonald’s omega coefficients indicated excellent reliability for the total scale and its subscales. Female participants reported higher stress levels than males in most dimensions. Conclusions: The Greek version of the PSS:NICU demonstrated strong psychometric properties and cultural relevance. This adaptation provides a valid and reliable tool for assessing parental stress in Greek NICUs and facilitates cross-cultural comparisons and the development of targeted psychosocial interventions. Full article

The development of sensitive and specific diagnostic methods for secondary bacterial meningitis remains an urgent challenge in neurosurgical and intensive care units. A combination of various clinical and biochemical parameters, as well as biomarkers and metabolites in cerebrospinal fluid (CSF), can be considered for constructing multivariate diagnostic models. In this study, 96 CSF samples from 53 patients with suspected secondary meningitis were analyzed. The first cohort, consisting of patients with sequelae of severe brain damage, included 7 patients (21 CSF samples) with and 29 patients (56 CSF samples) without secondary bacterial meningitis. The second cohort comprised patients after neurosurgical interventions, including 10 patients (12 CSF samples) with and 7 patients (7 CSF samples) without secondary bacterial meningitis. Combined group 1 with 33 CSF samples from patients with secondary bacterial meningitis and combined group 2 with 63 CSF samples from patients without secondary bacterial meningitis had statistically different cell and biochemical compositions and higher CSF concentrations of biomarkers (interleukin-6 and S100 protein) and lactate-containing aromatic metabolites in group 1. Univariate prognostic models constructed on 4-hydroxyphenyllactic, phenyllactic, and indole-3-lactic acids demonstrated outstanding AUC-ROC of more than 0.91. A multivariate model built on all biomarkers and metabolites resulted in AUC-ROC = 0.94 with a sensitivity of 0.94 and specificity of 0.86, and was found to be the most accurate method for the diagnosis of secondary bacterial meningitis. Full article

Background/Objectives: Sepsis is characterized by a dysregulated host response to infection, where immune-inflammatory and thrombo-inflammation drive organ dysfunction. Early recognition of high-risk patients is essential. In addition, the increasing prevalence of multidrug-resistant (MDR) pathogens complicates therapeutic strategies, as delays in appropriate antimicrobial therapy are strongly associated with poor outcomes. Methods: We conducted a retrospective, single-center cohort study including 120 critically ill patients fulfilling Sepsis-3 criteria. Demographic, clinical, and laboratory data were collected at intensive care unit (ICU) admission, 48 h, and 72 h. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated from complete blood counts. At the same time, the Carmeli score was used as a surrogate for MDR infection risk. Prognostic accuracy was assessed using ROC curve analysis and multivariable logistic regression. Results: Persistently elevated NLR at 72 h and a delayed decline in platelet counts were associated with higher mortality. NLR at 72 h showed good predictive accuracy (AUC = 0.765; 95% CI 0.668–0.863), and the combination of APACHE II and NLR improved prognostic performance (AUC = 0.827). Importantly, the Carmeli score, reflecting MDR infection risk, was an independent predictor of outcome, linking antimicrobial resistance risk with sepsis prognosis. Conclusions: Dynamic immune-inflammatory biomarkers (NLR, platelets), when integrated with MDR risk assessment through the Carmeli score, provide a simple and cost-effective strategy for early prognostic stratification in sepsis. This combined approach may help facilitate early therapeutic decisions and patient care triage. Full article

Background: Neuraxial anesthesia, delivered as a combined spinal–epidural without intubation or neuromuscular blockade, is a promising alternative for patients undergoing minimally invasive colorectal surgery. Evidence is limited to case series, with no cohort studies available. Methods: This is a retrospective analysis of consecutive patients undergoing minimally invasive colorectal surgery for both benign and malignant disease at a single institution, between October 2022 and October 2024. Patients were divided by the type of anesthesia. Propensity score matching was performed to reduce confounding bias. Outcomes assessed included anesthesiologic preparation time, duration of surgery, intraoperative features, intensive care unit admission, length of hospital stay, and 90-day postoperative complications, including anastomotic leak and readmission rates. Results: Thirty-two patients (40.5%) received neuraxial anesthesia and forty-seven (59.5%) received general anesthesia. No conversions from neuraxial to general anesthesia occurred. After matching, anesthesia preparation time was longer in the neuraxial group (42.5 vs. 30 min, p = 0.011), while operative time was significantly shorter (181 vs. 231 min, p = 0.002). Length of stay, postoperative complications, including leak, and readmission rates were comparable between groups. Conclusions: Neuraxial anesthesia may be a valid alternative to general anesthesia for minimally invasive colorectal surgery. In this single-center experience, it required longer anesthetic preparation but was associated with shorter operative times, without affecting surgical outcomes or increasing complication rates. These results support further investigation into its application in colorectal procedures. Full article

Objective: To implement a neonatal iron deficiency (ID) guideline as part of a neuroprotective strategy using reticulocyte hemoglobin content (RET-He) for neonates born <33 weeks postmenstrual age (PMA) and small for gestational age (SGA) neonates ≥33 weeks PMA, to achieve ≥80% screening rate by June 2024. Methods: An interdisciplinary team conducted a quality improvement initiative in a level III neonatal intensive care unit (NICU) from April 2022 to August 2024. RET-He is a validated, sensitive marker of early iron deficiency reflecting recent iron supply for erythropoiesis and providing a more reliable measure than ferritin. The primary outcome was RET-He screening at 30 ± 7 days for neonates <33 weeks PMA or pre-discharge for SGA neonates ≥33 weeks PMA. Exclusion criteria were death or transfer before eligibility. Process measures included ID screening failure rate (RET-He level < 29 pg). Results: Of 345 eligible neonates, P-chart analysis showed screening rates for premature neonates <33 weeks PMA declined during PDSA 1–2, before improving to 85.9% in PDSA 3. ID screening failure was 12.6% at one month, increasing to 32.1% at two months. For SGA neonates ≥33 weeks PMA, screening rates remained low, peaking at 36% in PDSA 3, with a 2.2% failure rate. Conclusions: Implementation of a RET-He based ID guideline improved screening rates for premature neonates but was less effective for SGA neonates. Despite improved guideline adherence, ID prevalence remained high at NICU discharge, indicating a further need to improve nutritional prevention and treatment strategies. Full article

Background: Severe traumatic brain injury (sTBI) is a leading cause of death and disability worldwide. Cerebral perfusion pressure (CPP), the difference between mean arterial and intracranial pressure, is crucial for maintaining cerebral blood flow. However, the optimal CPP threshold for improving outcomes remains uncertain. Objective: To identify CPP levels associated with favorable outcomes following sTBI through a systematic review and meta-analysis. Methods: Following PRISMA guidelines, we systematically searched PubMed, Scopus, and Web of Science up to February 2024 for studies involving adult sTBI patients admitted to intensive care units. Studies reporting CPP in relation to outcomes measured by the Glasgow Outcome Scale (GOS) were included. Pooled mean CPP differences between outcome groups were calculated using a random-effects model. Study quality was assessed using the Newcastle–Ottawa Scale, and evidence certainty was evaluated with GRADE. Results: Twenty-two studies with 2986 patients met inclusion criteria. Patients with good outcomes (GOS > 3) had higher CPP (77.5 mmHg; 95% CI: 73.8–81.2) than those with poor outcomes (67.2 mmHg; 95% CI: 60.4–74.1), with a mean difference of 10.01 mmHg (95% CI: 4.23–15.80; p < 0.05). Survivors also demonstrated higher CPP than non-survivors (mean difference 8.15 mmHg; 95% CI: 3.28–13.02). Evidence quality ranged from low to very low due to study heterogeneity. Conclusions: Higher CPP levels (~75–80 mmHg) are associated with better survival and functional outcomes after sTBI, supporting individualized, multimodal CPP management rather than a fixed 60 mmHg threshold. Full article

Background and Objectives: This study aimed to evaluate the factors influencing early postoperative mortality in patients undergoing cementless hemiarthroplasty for proximal femoral fractures. Materials and Methods: The medical records of 227 patients treated between January 2019 and December 2020 were retrospectively reviewed. Patients were divided into two groups: survivors (Group 1, n = 160) and non-survivors (Group 2, n = 67). The variables assessed included demographic data, neutrophil-to-lymphocyte ratio, surgical duration, hospital stay, American Society of Anesthesiologists (ASA) score, cardiac ejection fraction (EF), Charlson Comorbidity Index (CCI), osteoporosis status, and hemoglobin and albumin levels. Clinical evaluation was performed using the Harris Hip Score. Binary logistic regression was used to analyze risk factors; receiver operating characteristic (ROC) analysis was applied to determine cutoff values. Results: The mean follow-up duration was 14.03 ± 10 months. The mean ages were 80 ± 7.68 yr in Group 1 and 83.99 ± 7.42 yr in Group 2. Statistically significant differences were found between groups regarding ASA scores, intensive care unit (ICU) admission rates, and osteoporosis status (p < 0.001). Preoperative and postoperative albumin levels were also significantly different (p < 0.001). The 1-year and 6-month mortality rates were 39.6% and 29.5%, respectively. Univariate analysis identified age, EF, ASA score, preoperative and postoperative albumin levels, CCI, ICU admission, and ICU stay duration as mortality-related factors. Multivariate binary logistic regression analysis revealed that low postoperative albumin levels may have a significant effect on mortality at 1, 3, and 6 months. ROC analysis showed a significant albumin cutoff value of 2.95 g/dL. Conclusions: Higher postoperative albumin levels were inversely associated with early mortality following hemiarthroplasty in elderly patients. Perioperative monitoring of albumin levels may help improve outcomes, particularly in individuals with severe comorbidities. Full article

Lung ischemia–reperfusion injury (LIRI) remains a major contributor to perioperative morbidity and mortality in thoracic surgery, especially for lung transplantations, where it is one of the principal drivers of primary graft dysfunction (PGD). Although substantial advances have been made in surgical technique, donor management, and perioperative care, LIRI continues to pose a significant clinical challenge. Mechanistically, LIRI reflects a combined pathology of oxidative stress, endothelial and glycocalyx disruption, innate immune activation, mitochondrial dysfunction, and regulated cell death, resulting in loss of alveolar–capillary barrier integrity and gas exchange failure. Current management is phase-specific and multimodal, spanning donor care and preservation, controlled reperfusion and lung-protective ventilation, and pharmacological treatments. Treatment candidates that target oxidative stress and inflammatory cascades (e.g., antioxidants, complement and adenosine pathways, mesenchymal stromal cell products, and dipeptidyl-peptidase-4 inhibition) show promise, yet translation into a clinical scenario remains difficult. Increasing evidence supports endothelial-preserving and mitochondria-sparing strategies, rigorous perioperative bundles, and biomarker-guided trials to move from pathophysiology to practice. Ultimately, addressing LIRI requires an integrated, multidisciplinary approach that spans surgical, anesthetic, and pharmacologic domains, with the goal of improving both early outcomes and long-term graft survival in lung transplant patients. Full article

Background/Objectives: Periprosthetic joint infection (PJI) remains one of the most devastating complications of arthroplasty, with early diagnosis crucial for successful management. The serum neutrophil–lymphocyte ratio (NLR) and monocyte–lymphocyte ratio (MLR) have been proposed as simple, inexpensive inflammatory biomarkers, but their diagnostic performance in PJI remains unclear. This meta-analysis aimed to compare the diagnostic accuracy of serum NLR and MLR in detecting PJI. Materials and Methods: A systematic literature search was conducted in PubMed, Web of Science, and Scopus up to April 2025. Twenty-nine eligible studies (n = 14,040 patients; 3418 with PJI, 10,622 without PJI) reporting diagnostic metrics for serum NLR or MLR were included. Extracted data comprised mean biomarker values, cut-off thresholds, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Non-parametric statistical tests and subgroup analyses were applied to examine performance across infection types and PJI definitions. Results: Both serum NLR and MLR were significantly elevated in PJI patients compared with aseptic cases (p < 0.001 and p = 0.003, respectively). Pooled diagnostic accuracy was moderate: mean AUC 0.719 for NLR and 0.700 for MLR. For NLR, mean sensitivity was 69.9% and specificity 69.8%, with an average cut-off of 2.88. For MLR, mean sensitivity was 68.2% and specificity 70.4%, with an average cut-off of 0.34. Subgroup analyses indicated superior diagnostic performance of NLR in acute infections and variability depending on the PJI definition employed (p = 0.037). Strong correlations were observed between standardized mean differences in biomarker levels and corresponding diagnostic accuracy, particularly for NLR (ρ = 0.802, p = 0.002). Conclusions: Serum NLR demonstrates slightly superior diagnostic accuracy over serum MLR in identifying PJI, especially in acute settings. Both markers are inexpensive and widely accessible but show only moderate discriminative capacity, supporting their role as adjunctive rather than standalone diagnostic tools. Further large-scale prospective studies with harmonized methodologies are needed to refine biomarker thresholds and integrate them into multimodal diagnostic algorithms. Full article