Search Results (760)

Introduction: The combination of ceftazidime−avibactam (CAZ-AVI) with aztreonam (ATM) may be an option for the treatment of infections due to metallo-β-lactamases (MBLs) producing bacteria, as recommended by current guidelines. MBLs protect the pathogen from any available β-lactam/β-lactamase inhibitor (BL/BLI). Moreover, in vitro and clinical data suggest that double carbapenem therapy (DCT) may be an option for such infections. Materials and Methods: This retrospective study was conducted in two mixed intensive care units (ICUs) at the University Hospital of Larissa, Thessaly, Greece, and the General Hospital of Larissa, Thessaly, Greece, during a three-year period (2022−2024). Mechanically ventilated patients with bloodstream infection (BSI) caused by K. pneumoniae resistant to all BL/BLI combinations were studied. Patients were divided into three groups: in the first, patients were treated with CAZ-AVI + ATM; in the second, with DCT; and in the third, with antibiotics other than BL/BLIs that presented in vitro susceptibility. The primary outcome of the study was the change in Sequential Organ Failure Assessment (SOFA) score between the onset of infection and the fourth day of antibiotic treatment. Secondary outcomes were SOFA score evolution during the treatment period, total duration of mechanical ventilation (MV), ICU length of stay (LOS), and ICU mortality. Results: A total of 95 patients were recruited. Among them, 23 patients received CAZ-AVI + AZT, 22 received DCT, and 50 patients received another antibiotic regimen which was in vitro active against the pathogen. The baseline characteristics were similar. The mean (SE) overall age was 63.2 (1.3) years. Mean (SE) Acute Physiology and Chronic Health Evaluation II (APACHE II) and SOFA scores were 16.3 (0.6) and 7.6 (0.3), respectively. The Charlson Index was similar between groups. The control group presented a statistically lower SOFA score on day 4 compared to the other two groups [mean (SE) 8.9 (1) vs. 7.4 (0.9) vs. 6.4 (0.5) for CAZ-AVI + ATM, DCT and control group, respectively (p = 0.045)]. The duration of mechanical ventilation, ICU LOS, and mortality were similar between the groups (p > 0.05). Comparison between survivors and non-survivors revealed that survivors had a lower SOFA score on the day of BSI, higher PaO₂/FiO₂ ratio, higher platelet counts, and lower lactate levels (p < 0.05). Septic shock was more frequent among non-survivors (60.3%) in comparison to survivors (27%) (p = 0.0015). Independent factors for mortality were PaO₂/FiO₂ ratio and lactate levels (p < 0.05). None of the antibiotic regimens received by the patients was independently associated with survival. Conclusions: Treatment with CAZ-AVI + ATM or DCT may offer similar clinical outcomes for patients suffering from BSI caused by K. pneumoniae strains resistant to all available BL/BLIs. However, larger studies are required to confirm the findings. Full article

Lower respiratory tract infections remain a leading cause of morbidity and mortality among Intensive Care Unit patients, with severe cases often progressing to acute respiratory distress syndrome (ARDS). This life-threatening syndrome results from alveolar–capillary membrane injury, causing refractory hypoxemia and respiratory failure. Early detection and management are critical to treat the underlying cause, provide protective lung ventilation, and, eventually, improve patient outcomes. The 2012 Berlin definition standardized ARDS diagnosis but excluded patients on non-invasive ventilation (NIV) or high-flow nasal cannula (HFNC) modalities, which are increasingly used, especially after the COVID-19 pandemic. By excluding these patients, diagnostic delays can occur, risking the progression of lung injury despite ongoing support. Indeed, sustained, vigorous respiratory efforts under non-invasive modalities carry significant potential for patient self-inflicted lung injury (P-SILI), underscoring the need to broaden diagnostic criteria to encompass these increasingly common therapies. Recent proposals expand ARDS criteria to include NIV and HFNCs, lung ultrasound, and the SpO₂/FiO₂ ratio adaptations designed to improve diagnosis in resource-limited settings lacking arterial blood gases or advanced imaging. However, broader criteria risk overdiagnosis and create challenges in distinguishing ARDS from other causes of acute hypoxemic failure. Furthermore, inter-observer variability in imaging interpretation and inconsistencies in oxygenation assessment, particularly when relying on non-invasive measurements, may compromise diagnostic reliability. To overcome these limitations, a more nuanced diagnostic framework is needed—one that incorporates individualized therapeutic strategies, emphasizes lung-protective ventilation, and integrates advanced physiological or biomarker-based indicators like IL-6, IL-8, and IFN-γ, which are associated with worse outcomes. Such an approach has the potential to improve patient stratification, enable more targeted interventions, and ultimately support the design and conduct of more effective interventional studies. Full article

Pre-oxygenation is the key step prior to endotracheal intubation, particularly in a critically ill patient, to prevent life-threatening peri-procedural hypoxemia. This narrative review explores the emerging interest of Non-Invasive Positive Pressure Ventilation (NIPPV) as a pre-oxygenation modality in the intensive care unit (ICU) context. We reviewed data from randomized controlled trials (RCTs) and observational studies published from 2000 to 2024 that compare NIPPV to conventional oxygen therapy and High Flow Nasal Cannula Oxygen (HFNCO). The pathophysiological mechanisms for the successful use of NIPPV, including alveolar recruitment, the decrease of shunting, and the maintenance of functional residual capacity, were reviewed in depth. Existing studies show that NIPPV significantly prolongs the apnea time, reduces the rate of peri-intubation severe hypoxaemia in selected patients and is especially effective for patients with acute hypoxaemic respiratory failure. Nevertheless, appropriate patient selection is still crucial because some diseases can contraindicate or even be harmful with NIPPV. We further discussed the practical aspects of how to use this ventilatory support (the best ventilator settings, which interface, and when to apply it). We lastly discuss unanswered questions and offer suggestions and opportunities for future exploration in guiding the role of NIPPV use in the pre-oxygenation of the critically ill patient requiring emergent airway management. Full article

Objectives: Patients with acute heart failure (AHF) often receive initial non-invasive ventilation (NIV). This study aimed to evaluate the prognostic role of NIV in patients hospitalized for AHF. Methods: This was a retrospective cohort study. We enrolled patients admitted to our cardiac intensive care unit with a diagnosis of AHF. Anthropometric, clinical, pharmacological, and instrumental assessments were collected. Both in-hospital and 180-day post-discharge mortality were evaluated. Results: Among 200 patients (mean age 81 ± 9 years; 52% male), NIV was applied in 80 cases (40%). These patients had more severe NYHA functional class, a higher prevalence of de novo AHF, required higher diuretic doses, and had longer hospital stays. In multivariate analysis, NIV remained significantly associated with length of stay (LOS) (r = 0.26; p = 0.0004). In-hospital mortality was 5% overall and significantly higher in the NIV group compared to non-NIV patients (10% vs. 1.6%, p < 0.001). At 180 days, mortality was also significantly higher in the NIV group [hazard ratio (HR) 1.84; 95% confidence interval (CI): 1.18–2.85; p = 0.006]. After adjusting for age, BNP, CRP, arterial blood gas parameters, renal function, and LVEF, NIV remained an independent predictor of 180-day mortality (HR 1.61; 95% CI: 1.01–2.54; p = 0.04). Conclusions: Patients with AHF who required NIV exhibited more severe disease and longer hospital stays. NIV use was independently associated with both in-hospital and post-discharge mortality, suggesting its potential role as a prognostic marker in AHF. Full article

Objective: To evaluate the prognostic utility of the Sequential Organ Failure Assessment (SOFA) and Simplified Acute Physiology Score 3 (SAPS 3) in COVID-19 patients and assess whether incorporating C-reactive protein (CRP), procalcitonin, lactate, and lactate dehydrogenase (LDH) enhances their predictive accuracy. Methods: Single-center, observational, cohort study. We analyzed a database of adult ICU patients with severe or critical COVID-19 treated at a large academic center. We used binary logistic regression for all analyses. We assessed the predictive performance of SAPS 3 and SOFA scores within 24 h of admission, individually and in combination with serum lactate, LDH, CRP, and procalcitonin. We examined the independent association of these biomarkers with hospital mortality. We evaluated discrimination using the C-statistic and determined clinical utility with decision curve analysis. Results: We included 1395 patients, 66% of whom required mechanical ventilation, and 59.7% needed vasopressor support. Patients who died (39.7%) were significantly older (61.1 ± 15.9 years vs. 50.1 ± 14.5 years, p < 0.001) and had more comorbidities than survivors. Among the biomarkers, only procalcitonin was independently associated with higher mortality in the multivariable analysis, in a non-linear pattern. The AUROC for predicting hospital mortality was 0.771 (95% CI: 0.746–0.797) for SAPS 3 and 0.781 (95% CI: 0.756–0.805) for the SOFA score. A model incorporating the SOFA score, age, and procalcitonin demonstrated high AUROC of 0.837 (95% CI: 0.816–0.859). These associations with the SOFA score showed greater clinical utility. Conclusions: The SOFA score may aid clinical decision-making, and incorporating procalcitonin and age could further enhance its prognostic utility. Full article

Background: Down syndrome (DS) is associated with unique anatomical and physiological characteristics that complicate the perioperative management of infants undergoing cardiac surgery. While ventricular septal defect (VSD) repair is commonly performed in this population, detailed data comparing perioperative outcomes in DS versus non-syndromic infants remain limited. Methods: This retrospective matched study analysed 100 infants (50 with DS and 50 without DS) who underwent isolated VSD closure between January 2021 and January 2025. Patients were matched by age and surgical date. Intraoperative anesthetic management, complications, postoperative outcomes, and mortality were compared between groups. Results: DS patients had lower age, weight, and height at surgery. They required significantly smaller endotracheal tube sizes, more intubation and vascular access attempts. The DS group had significantly lower rates of extubation in the operating room and experienced longer durations of mechanical ventilation and ICU stay. However, no significant differences were observed in total hospital stay or mortality between groups. Conclusions: Although DS infants present with increased anesthetic complexity and respiratory challenges, they do not exhibit higher surgical mortality following isolated VSD closure. Tailored perioperative strategies may improve respiratory outcomes in this high-risk group. Full article

Traumatic liver injury remains a significant contributor to trauma-related morbidity and mortality worldwide. In Saudi Arabia, motor vehicle accidents (MVAs) are the predominant mechanism of injury, particularly among young adults. This study aimed to evaluate the clinical characteristics, management strategies, and outcomes of patients with liver trauma over a ten-year period at a tertiary academic level-one trauma center. A retrospective cohort study was conducted from January 2015 to December 2024. All adult patients (aged 18–65 years) who sustained blunt or penetrating liver injuries and underwent a pan-CT trauma survey were included. Demographic data, Injury Severity Scores (ISSs), imaging timelines, management approach, and clinical outcomes were analyzed. Statistical analysis was performed using JASP software with a significance threshold set at p < 0.05. A total of 111 patients were included, with a mean age of 33 ± 12.4 years; 78.1% were male. MVAs were the leading cause of injury (75.7%). Most patients (80.2%) had low-grade liver injuries and received non-operative management (NOM), with a high NOM success rate of 94.5%. The median time to CT was 55 ± 64 min, and the mean time to operative or IR intervention was 159.9 ± 78.8 min. Complications occurred in 32.4% of patients, with ventilator-associated pneumonia (19.8%) being most common. The overall mortality was 6.3%. Multivariate analysis revealed that shorter time to CT significantly reduced mortality risk (OR = 0.5, p < 0.05), while a positive e-FAST result was strongly associated with increased mortality (OR = 3.3, p < 0.05). Higher ISSs correlated with longer monitored unit stays (ρ = 0.3, p = 0.0014). Traumatic liver injuries in this cohort were predominantly low-grade and effectively managed conservatively, with favorable outcomes. However, delays in imaging and operative intervention were observed, underscoring the requirement for streamlined trauma workflows. These findings highlight the requirement for continuous trauma system improvement, including protocol optimization and timely access to imaging and surgical intervention. Full article

Determining the optimal duration of antibiotic therapy for infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) is a critical challenge in clinical medicine, balancing therapeutic efficacy against the risks of adverse effects and antimicrobial resistance. This narrative review synthesises current evidence and guidelines regarding antibiotic duration for MDR-GNB infections, emphasising bloodstream infections (BSI), hospital-acquired and ventilator-associated pneumonia (HAP/VAP), complicated urinary tract infections (cUTIs), and intra-abdominal infections (IAIs). Despite robust evidence supporting shorter courses (3–7 days) in uncomplicated infections caused by more susceptible pathogens, data guiding optimal therapy duration for MDR-GNB remain limited, particularly concerning carbapenem-resistant Enterobacterales (CRE), difficult-to-treat Pseudomonas aeruginosa (DTR-Pa), and carbapenem-resistant Acinetobacter baumannii (CRAB). Current guidelines from major societies, including IDSA and ESCMID, provide explicit antimicrobial selection advice but notably lack detailed recommendations on the duration of therapy. Existing studies demonstrate non-inferiority of shorter versus longer antibiotic courses in specific clinical contexts but frequently exclude critically ill patients or those infected with non-fermenting MDR pathogens. Individualised duration decisions must integrate clinical response, patient immunologic status, infection severity, source control adequacy, and pharmacologic considerations. Significant knowledge gaps persist, underscoring the urgent need for targeted research, particularly randomised controlled trials assessing optimal antibiotic duration for the most challenging MDR-GNB infections. Clinicians must navigate considerable uncertainty, relying on nuanced judgement and close monitoring to achieve successful outcomes while advancing antimicrobial stewardship goals. Full article

Background and Objectives: Acute respiratory failure (ARF) represents an increasingly relevant clinical challenge in older subjects due to population aging and the high prevalence of cardiopulmonary comorbidities. Non-invasive ventilation (NIV), developed as continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP), has become a first-line treatment in various forms of ARF, including acute cardiogenic pulmonary oedema (ACPE) and acute exacerbations of COPD (AECOPD), offering several clinical advantages. In this context, the limited evidence on the efficacy of NIV in older patients leaves considerable uncertainty as to whether it constitutes a valid therapeutic option or represents medical futility in these patients. Materials and Methods: This narrative review explores the use of NIV and its outcomes in four key clinical scenarios in the elderly: ARF due to ACPE, AECOPD, community-acquired pneumonia (CAP), and palliative/end-of-life care. Results: Strong evidence supports NIV use with improved outcomes in ACPE and AECOPD, even in older populations. Conversely, data on its use in pneumonia are inconclusive, with potential harm if applied inappropriately. In palliative care, NIV can help relieve symptoms, but if not used appropriately, it may extend suffering. Conclusions: Age alone does not appear to be a sufficient factor to determine whether or not to use NIV; it becomes relevant only when considered in conjunction with the purpose of its use and the patient’s clinical history and condition. Data remain limited and often conflicting, particularly when investigating the elderly population and patients with a “do not intubate” (DNI) order. There is a need for additional research on these patients, focusing on long-term outcomes and quality of life. Full article

Objective: This study aimed to assess the effect of antibiotic de-escalation on 30-day mortality, duration of intravenous (IV) antibiotic therapy and length of hospital stay (LOS) in severe community-acquired pneumonia (sCAP). Methods: We performed a retrospective analysis of prospectively collected data from a cohort of adults diagnosed with sCAP and microbiologically confirmed etiology between 1995 to 2022. Two distinct time points of the de-escalation were analyzed: 3 and 6 days post-admission, corresponding, respectively, to the availability of microbiological results and the median time to clinical stability. Inverse propensity score-weighted binary logistic regression was used to adjust for potential confounders. Results: A total of 398 consecutive cases of sCAP were analyzed. No significant differences were observed between the de-escalation and non-de-escalation groups in terms of age, sex, comorbidities, or severity-related variables (such as impaired consciousness, shock, respiratory failure, or multilobar pneumonia). Patients in the de-escalation group had lower rates of leukopenia, bacteremia and empyema, and less need for mechanical ventilation, with variations depending on the timing of de-escalation. After adjusting for confounding factors in an inverse propensity score-weighted analysis, de-escalation within 3 or 6 days after admission was not associated with increased mortality risk (adjusted odds ratio [aOR] 1.48, 95% confidence interval [CI] 0.29–7.4; p = 0.63, and aOR 0.57, 95% CI 0.14–2.31, p = 0.43, respectively). Similar findings were observed for prolonged LOS. However, antibiotic de-escalation was related to a lower risk of prolonged IV antibiotic. Conclusions: Antibiotic de-escalation in microbiologically confirmed sCAP did not negatively impact clinical outcomes, supporting the safety of this strategy for optimizing antibiotic use in this serious infection. Full article

Background/Objectives: Continuous ventilation monitoring during pediatric sedation is essential, as respiratory depression may occur silently and may not be detected promptly by conventional methods such as pulse oximetry. Non-invasive capnography has been proposed to improve early detection of respiratory compromise. This prospective observational study evaluated the diagnostic accuracy of non-invasive capnography, compared to pulse oximetry, for detecting respiratory depression in pediatric patients undergoing sedation. Methods: We conducted a single-center, prospective observational study at a tertiary pediatric hospital, enrolling 101 patients (ages 1–17 years) undergoing sedation for diagnostic or therapeutic procedures. Patients were monitored using both pulse oximetry and non-invasive capnography. Episodes of respiratory depression—defined as apnea, hypopneic hypoventilation, bradypneic hypoventilation, and desaturation—were recorded. We compared the diagnostic performance and time to detection between capnography and pulse oximetry. Results: We identified 93 episodes of respiratory depression in 52 patients (51.1%). Capnography detected all apnea episodes and 76.9% of hypopneic hypoventilation episodes that were not identified by pulse oximetry. The median time advantage of capnography over pulse oximetry was 35 s (p = 0.0055). Combining capnography and pulse oximetry identified more events than pulse oximetry alone (93 vs. 53 episodes). Conclusions: Non-invasive capnography improves the early detection of respiratory depression compared to conventional monitoring with pulse oximetry in pediatric procedural sedation. While these findings support its routine use to enhance patient safety, larger multicenter studies are needed to demonstrate its diagnostic accuracy and impact on clinical outcomes. Full article

Non-invasive ventilation (NIV) is a cornerstone in the management of acute and chronic respiratory failure, offering critical support without the risks of intubation. However, successful weaning from NIV remains a complex, high-stakes process. Poorly timed or improperly executed weaning significantly increases morbidity and mortality, yet current clinical practice often relies on subjective judgment rather than evidence-based protocols. This manuscript reviews the current landscape of NIV weaning, emphasizing structured approaches, objective monitoring, and predictors of weaning success or failure. It examines guideline-based indications, monitoring strategies, and various weaning techniques—gradual and abrupt—with evidence of their efficacy across different patient populations. Predictive tools such as the Rapid Shallow Breathing Index, Lung Ultrasound Score, Diaphragm Thickening Fraction, ROX index, and HACOR score are analyzed for their diagnostic value. Additionally, this review underscores the importance of care setting—ICU, step-down unit, or general ward—and how it influences outcomes. Finally, it highlights critical gaps in research, especially around weaning in non-ICU environments. By consolidating current evidence and identifying predictors and pitfalls, this article aims to support clinicians in making safe, timely, and patient-specific NIV weaning decisions. In the current literature, there are gaps regarding patient selection and lack of universal protocolization for initiation and de-escalation of NIV as the data has been scattered. This review aims to consolidate the relevant information to be utilized by clinicians throughout multiple levels of care in all hospital systems. Full article

Background/Objectives: Dyspnea is one of the main causes of visits to the Emergency Department (ED) and hospitalization, with its differential diagnosis representing a challenge for the clinician. Lung ultrasound (LUS) is a widely used tool in ED. The objective of this study was to evaluate the impact of LUS, performed by a non-expert operator, in determining diagnosis and prognosis of patients with dyspnea. Methods: A total of 60 patients presenting with dyspnea at the ED were prospectively enrolled and underwent LUS examination by a medical student, after brief training, within 3 h of triage. LUS findings were classified into four patterns: N.1, absence of notable ultrasound findings, attributable to COPD/ASMA exacerbation; N.2, bilateral interstitial syndrome, suggestive of acute heart failure; N.3, subpleural changes/parenchymal consolidations, suggestive of pneumoniae; and N.4, isolate polygonal triangular consolidation, attributable to infarction in the context of pulmonary thromboembolism. Results: The diagnostic hypothesis formulated after LUS was compared with the final diagnosis after further investigations in the ED, showing agreement in 90% of cases. The mean LUS score value was higher in patterns N.2 (18.4 ± 8.5) and N.3 (17 ± 6.6), compared to patterns N.1 and N.4 (9.8± 6.7 and 11.5 ± 2.1). Given the high prevalence of pattern N.2, the diagnostic accuracy of LUS in this context was further evaluated, showing a sensitivity of 82% and specificity of 100%. In terms of the prognostic value of LUS, hospitalized patients had a higher LUS score compared to those discharged (17.3 ± 8.1 vs. 8.5 ± 6.8, p value 0.004). A similar trend was obtained in the subgroup of patients requiring non-invasive ventilation (NIV), who present a higher LUS score (21.1 ± 6.6 vs. 13.1 ± 8.1, p value 0.002). When considering a combined outcome (death and NIV), patients with worse outcomes more often had a LUS score > 15 (p value < 0.001). Conclusions: In conclusion, this study confirms that LUS is a very useful tool in the ED, assisting the clinical evaluation for diagnosis, treatment decision, and determination of the appropriate care setting for patients with acute dyspnea. Its short learning curve allows even non-expert staff to use it effectively. Full article

Background: Multidrug-resistant (MDR) Gram-negative infections, particularly those caused by carbapenem-resistant Enterobacterales (CRE) and difficult-to-treat Pseudomonas aeruginosa (DTR-Pa), present a growing global healthcare challenge, especially in critically ill populations. Imipenem–relebactam (I/R), a novel β-lactam/β-lactamase inhibitor combination, has shown efficacy in clinical trials, but real-world data remain limited. Methods: We conducted a multicenter, retrospective–prospective observational study across tertiary-care hospitals in Italy between January 2020 and May 2025. Adult patients (≥18 years) treated with I/R for ≥48 h for suspected or confirmed MDR Gram-negative infections were included. Primary endpoints were clinical success at the end of therapy and 30-day all-cause mortality. Secondary endpoints included microbiological eradication, recurrence, safety, and predictors of treatment failure. Statistical analysis involved descriptive methods and correlation analysis for mortality predictors. Results: Twenty-nine patients were included (median age 66 years; 58.6% ICU admission; 71.4% mechanical ventilation). Clinical success was achieved in 22/29 patients (75.9%), while 30-day mortality was 24.1% (7/29). The most common pathogen was Klebsiella pneumoniae (62.1%), with 41.4% of infections being polymicrobial. Microbiological eradication was confirmed in all the BSIs. Parenteral nutrition (p = 0.016), sepsis at presentation (p = 0.04), candidemia (p = 0.036), and arterial catheter use (p = 0.029) were significantly more frequent in non-survivors. Survivors showed significant reductions in CRP, PCT, and bilirubin at 48 h, while non-survivors did not. Parenteral nutrition (rho = 0.427, p = 0.023), sepsis (rho = 0.378, p = 0.043), and arterial catheter use (rho = 0.384, p = 0.04) were significantly correlated with mortality. Conclusions: In this Italian multicenter cohort of critically ill patients, imipenem–relebactam demonstrated high clinical success and acceptable mortality rates in the treatment of severe MDR Gram-negative infections, particularly those caused by KPC-producing K. pneumoniae. Early biomarker dynamics may aid in monitoring treatment response. Larger prospective studies are needed to confirm these findings and define optimal treatment strategies. Full article

Dengue mortality has traditionally been associated with severe thrombocytopenia and hemorrhagic complications. However, during 2024, dengue virus serotype 3 (DENV-3) increased significantly in western Mexico, leading to the emergence of a distinct clinical pattern. We conducted a retrospective cohort study of hospitalized dengue patients at the General Hospital of Colima (January–August 2024). Clinical features, laboratory parameters, and outcomes were compared between survivors and non-survivors. Among 201 hospitalized patients, 6 (3.0%) died. All deceased patients presented with generalized seizures, polyserositis (pleural effusion and/or ascites), and required mechanical ventilation. Contrary to classical patterns, they did not have severe thrombocytopenia. Instead, they showed significantly higher white blood cell counts and notably increased levels of serum urea and BUN, suggesting early renal impairment. ROC analysis indicated that BUN (AUC 0.904) and urea (AUC 0.906) were good to excellent discriminators of mortality. During 2024, with an increase in DENV-3 circulation, mortality was associated with neurological and systemic complications, including seizures and polyserositis, as well as biochemical evidence of renal dysfunction—but not with severe thrombocytopenia. These findings challenge current paradigms and highlight the need for early recognition of atypical clinical patterns. Full article