Search Results (8,540)

Background/Objectives: Mechanical ventilation (MV) is a crucial intervention in managing severe respiratory failure due to COVID-19. However, its use may be complicated by pulmonary barotrauma, a serious event associated with increased morbidity and mortality. Understanding its incidence and associated risk factors is essential for optimising ventilatory strategies and improving patient outcomes. The aim of this study was to determine the incidence and risk factors associated with the development of pulmonary barotrauma in mechanically ventilated patients with COVID-19. Methods: All mechanically ventilated patients aged 18 years and above who were admitted to the COVID-19 Intensive Care Unit (ICU) from January 2021 to June 2022 were included. Patients who developed pulmonary barotrauma prior to or within 24 h of ICU admission, had iatrogenic pneumothorax, were readmitted to the ICU, or were ventilated for causes other than COVID-19-related respiratory failure were excluded. Data on patient demographics, vaccination status, ventilator parameters, laboratory findings, and the use of steroid or immunomodulatory therapies were collected and analysed. Univariate and multivariate logistic regression analyses were performed to identify the potential risk factors and clinical outcomes associated with pulmonary barotrauma. Results: The medical records of 204 patients were included. The incidence of pulmonary barotrauma was 22.5%. Lower C-reactive protein (CRP) levels at ICU admission, lower FiO₂ requirements during the first week of MV, a higher positive end-expiratory pressure (PEEP) during the second week, and a prolonged mechanical ventilation duration were significantly associated with pulmonary barotrauma (p = 0.039, 0.049, 0.021, and 0.036, respectively). Patients who developed pulmonary barotrauma experienced longer ICU stays (p = 0.006) and higher all-cause ICU mortality (p = 0.009). Conclusions: Lower CRP levels and a lower FiO₂ requirements, a higher PEEP use, and longer ventilator days were the independent risk factors for pulmonary barotrauma in our study population, leading to a longer ICU stay and higher all-cause ICU mortality. Full article

The biliary tract, long considered a sterile environment, is now recognized to harbor a resident microbiota with important implications for health and disease. This review aims to summarize current knowledge on the composition and function of the biliary microbiota in physiological conditions, and its alterations in pathological states such as infection and lithiasis, with a particular focus on antimicrobial resistance. In healthy individuals, the biliary microbiota appears to be shaped by bile acids and gut–bile axis interactions, playing a role in local immune modulation. In disease, microbial dysbiosis contributes to conditions such as acute cholecystitis, cholangitis, and gallstone formation, with distinct microbial signatures linked to specific stone types. Common biliary pathogens, including E. coli, Enterococcus spp., Pseudomonas spp., and K. pneumoniae, often exhibit concerning resistance patterns, impacting therapeutic strategies. Emerging evidence highlights the interplay between intestinal and biliary microbiota, suggesting potential diagnostic and prognostic applications. Understanding these dynamics opens new avenues for microbiota-informed antibiotic stewardship, targeted microbiota modulation, and precision medicine approaches. Further research, particularly culture-independent and longitudinal studies, is crucial to fully elucidate the clinical significance of the biliary microbiota and to integrate microbiota profiling into patient management strategies. Full article

Background and Objectives: The presence of comorbidities in both the pre- and post-diagnostic periods is a critical consideration in the diagnosis and management of patients with cancer. This study aimed to investigate the prevalence and burden of pulmonary and extrapulmonary comorbidities in patients diagnosed with lung cancer (LC) and malignant pleural mesothelioma (MPM). Materials and Methods: The data were obtained from official patient records of the Turkish Ministry of Health. Patients diagnosed with either lung cancer (LC) or malignant pleural mesothelioma (MPM) between 2015 and 2018 were included in the study. Comorbidities were classified as pulmonary or extrapulmonary. Results: A total of 74,835 patients with LC and 1678 patients with MPM were included. The burden of comorbid conditions increased significantly in the post-diagnostic period in both males and females across both cancer types. When the two cancer groups were compared with respect to diagnostic periods, comorbidities such as hypertension (HT), phlebitis/venous thrombosis/thrombophlebitis, pulmonary embolism, pneumothorax, and pleural effusion were significantly more prevalent in the MPM group (p < 0.05). Compared with the pre-diagnostic period, the comorbidity risk in LC was highest for pulmonary embolism, ARF, and pneumonia in the post-diagnostic period, whereas renal failure was the most frequent comorbidity in the MPM group (p < 0.001 and p = 0.024). When comparing changes in comorbidity burden between sexes in the lung cancer group, male patients had higher frequencies of pulmonary embolism, pneumonia, pneumothorax, and coronary artery disease than females. In contrast, in the female lung cancer group, the prevalence of chronic renal failure was higher than in males (OR = 2.14 vs. 2.00), whereas acute renal failure was more prominent in the male patient group (OR = 2.64 vs. 1.94). In gender-based comparison of comorbid conditions among patients with MPM, the risk of renal failure was higher in females than in males (CRF and ARF respectively: OR = 2.63 vs. 2.16 and OR = 6.80 vs. 5.44). Additionally, increased rates of COPD were observed in male patients within this group (OR = 1.93 vs. 1.81). Conclusions: Patients with LC and MPM are burdened not only by their primary malignancies but also by a wide spectrum of comorbidities, particularly in the post-diagnostic period. Comprehensive knowledge of comorbid conditions is essential for clinicians to guide clinical decision-making, anticipate disease progression, and optimize treatment strategies, thereby informing national healthcare policies. Future studies incorporating matched control groups or longitudinal designs with standardized surveillance protocols may help conduct better research. Full article

Background and Clinical Significance: Alpha-1 antitrypsin deficiency (AATD) is an autosomal codominant disorder caused by pathogenic variants in the SERPINA1 gene, resulting in reduced circulating alpha-1 antitrypsin (AAT) or production of dysfunctional protein. AAT is the principal inhibitor of neutrophil elastase, and its deficiency leads to unchecked proteolytic activity, progressive destruction of lung parenchyma, and increased susceptibility to infections. Severe deficiency, particularly in individuals homozygous for the Z allele (PI*ZZ), predisposes to early-onset panacinar emphysema, chronic airflow obstruction, and liver disease. Despite its clinical relevance, AATD remains markedly underdiagnosed and is frequently misclassified as smoking-related chronic obstructive pulmonary disease (COPD), delaying access to disease-modifying therapy, genetic counselling, and preventive strategies. Early recognition is therefore essential to improve outcomes. Case Presentation: We report the case of a 68-year-old ex-smoker with a long-standing diagnosis of “COPD” who presented with acute-on-chronic type 2 respiratory failure and community-acquired pneumonia. Spirometry revealed severe airflow obstruction, and high-resolution computed tomography demonstrated extensive basilar panlobular emphysema, raising suspicion for AATD. Serum AAT concentration was critically low at 26.8 mg·dL⁻¹, and isoelectric focusing confirmed a PI*ZZ phenotype. Next-generation sequencing identified homozygosity for the SERPINA1 c.1096G>A (Z) variant, with no additional pathogenic alleles. Cascade family screening revealed multiple heterozygous PI*MZ relatives. Before augmentation therapy could be initiated, the patient developed severe Legionella pneumophila pneumonia with secondary bacterial superinfection, progressing to refractory septic shock and death. Conclusions: This case illustrates how AATD can masquerade as smoking-related COPD for years, leading to missed opportunities for timely intervention. It underscores the importance of testing all adults with COPD or refractory asthma at least once, regardless of age or smoking history. Early diagnosis enables initiation of augmentation therapy, targeted vaccination, lifestyle modification, and genetic counselling, ultimately improving prognosis and reducing preventable morbidity and mortality. Full article

Background: ESKAPE constitutes a group of six nosocomial bacteria that can evade available antimicrobials due to their great potential to develop multi-drug resistance and biofilm-forming abilities. These pathogens often cause hospital-acquired infections and pose a serious threat to public health. The search for efficient innovative therapeutic strategies to fight ESKAPE bacteria have been intensively investigated topics. One promising approach to fight resistant pathogens and their biofilms is combination therapy, which allows the effectiveness against microorganisms to be increased while reducing the applied concentrations and risks of potential unwanted side effects. Objectives: The object of the study was to determine if there is an interaction of short lipopeptides ((C₁₀)₂-KKKK-NH₂, C₁₆-KK-NH₂) together with erythromycin and tetracycline against pathogens of the ESKAPE group (Acinetobacter baumannii, Enterobacter aerogenes, Enterococcus faecium Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus). Methods: The checkerboard assay was used to examine the activity of compounds applied in combinations against ESKAPE strains in planktonic cells and toward biofilms formed by Staphylococcus aures and Pseudomonas aeruginosa. Results: The lipopeptides demonstrated a great potential of their application as additives to conventional antimicrobials against Gram-negative bacteria, including microorganisms within biofilms. Full article

Background/Objectives: Inhaled corticosteroids (ICS) increase the risk of pneumonia caused by various pathogens in patients with chronic obstructive pulmonary disease (COPD). Treatment may also increase the risk of infection with non-tuberculous mycobacteria (NTM), although evidence remains limited. The aim of this study was to assess the association between ICS treatment and the risk of NTM isolation among patients with COPD. Methods: This retrospective register-based cohort study included patients with a specialist-verified COPD diagnosis between 2008 and 2021. ICS exposure was based on redeemed prescriptions during the year preceding the index date. Exposure was calculated as the mean daily budesonide-equivalent dose and categorized as none, low, medium, or high. A cause-specific Cox proportional hazards regression model with death as a competing risk was applied, adjusted for potential confounders. Sensitivity analyses included, among others, an inverse probability of treatment weighted model, and a time-dependent Cox regression model. Results: A total of 120,006 patients were included, with a median follow-up time of 4.9 years. During follow-up, 378 (0.32%) patients reached the primary endpoint. Medium- and high-dose ICS were associated with an increased hazard of NTM isolation, with hazard ratios of 1.39 (95% CI 1.06–1.88, p = 0.020) and 1.52 (95% CI 1.14–2.04, p = 0.005), respectively. This association remained significant for high-dose ICS across all sensitivity analyses. Conclusions: In patients with COPD, ICS treatment was associated with an increased and dose-dependent hazard of NTM isolation, particularly at high doses. High-dose ICS should, therefore, be prescribed with caution. Full article

Background and Objectives: Romania reported the highest measles incidence in the European Union during the 2023–2024 epidemic, largely driven by declining vaccination coverage. We aimed to characterize the epidemiological, clinical, and laboratory profile of hospitalized measles patients and to identify age-related differences, with particular emphasis on systemic and hepatic involvement. Materials and Methods: We conducted a retrospective observational study including 360 consecutive patients with laboratory-confirmed measles admitted to a tertiary infectious disease hospital in northeastern Romania between 1 January and 31 December 2024. Demographic, clinical, laboratory, therapeutic, and outcome data were collected. Pediatric (<15 years) and adult patients were compared using appropriate statistical tests. Results: Children accounted for 71.4% of cases, including 16.1% infants under one year. Over 90% of patients were unvaccinated or incompletely vaccinated. Household transmission represented the most frequent identifiable source. Adults presented significantly higher inflammatory markers and more pronounced hepatic involvement than children. ALT elevation occurred in 63.1% of adults versus 34.2% of children (p < 0.001), with moderate-to-severe cytolysis predominantly observed in adults (34.9% vs. 1.9%, p < 0.001). Pulmonary complications were documented in 28% of cases, mainly viral interstitial pneumonia. Thrombocytopenia was significantly more frequent in adults (p < 0.001). Overall mortality was 0.27%, occurring in an unvaccinated infant with secondary bacterial pneumonia. Conclusions: The 2024 measles epidemic in our area was characterized by sustained transmission among unvaccinated individuals and frequent systemic involvement. Hepatic dysfunction emerged as a prominent feature in adults, suggesting a shifting clinical phenotype in contemporary outbreaks. Strengthening vaccination coverage and early recognition of systemic complications remain critical to reducing measles-related morbidity and mortality. Full article

Background/Objectives: Escherichia coli bacteremia is a major cause of morbidity, mortality, and healthcare expenditure. The increasing prevalence of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli) complicates management and resource utilization. This study aimed to identify clinical predictors of higher hospital costs in E. coli bacteremia. Methods: We conducted a cross-sectional study of hospitalized patients with E. coli bacteremia in Surabaya, Indonesia (2022–2024). Hospital costs were categorized into bed costs, diagnostic costs, pharmacy costs, antibiotic costs, total costs, and daily costs. Costs were compared between ESBL and non-ESBL cases. Predictors of higher hospital costs were analyzed using generalized linear models with a Gamma distribution and log-link. Results: Among 209 patients, 131 (62.7%) had ESBL-producing E. coli. ESBL E. coli bacteremia was associated with significantly higher bed, diagnostic, pharmacy, total, and daily hospital costs than non-ESBL cases, while antibiotic costs were similar. ESBL E. coli bacteremia was associated with higher diagnostic and daily costs. High-care/ICU stay was the strongest predictor of increased costs. Pneumonia and infection source influenced cost components. Longer hospitalization increased total cost but reduced daily cost. Conclusions: Hospital costs in Escherichia coli bacteremia are driven by antimicrobial resistance, disease severity, and healthcare utilization. Targeted strategies such as antimicrobial stewardship and optimized critical care use are essential to reduce the economic burden. Full article

The secondary immunomodulatory effects of conventional therapeutics, such as antibiotics and cytostatics, are frequently overlooked despite their significant clinical implications. Building on our previous findings that drugs like paclitaxel and doxorubicin heavily influence macrophage polarization—potentially driving metastasis or inflammation—this study systematically evaluates the secondary immune-modulating actions of standard drugs and natural adjuvants. Using patient-derived bronchoalveolar lavage (BAL) fluid (ex vivo alveolar macrophages), we developed an analytical platform using synthetic carbohydrate-functionalized fluorescent ligands targeting key receptors (CD206, CD209, CD280, CD301). Integrating ligand-binding profiles with Linear Discriminant Analysis (LDA) yielded quantitative immune-state vectors capable of differentiating favorable and unfavorable prognostic signatures and imbalanced immune states. Pro-filing samples across heterogeneous respiratory conditions revealed highly con-text-dependent responses. While some treatments synergistically corrected unfavorable imbalanced profiles, others provoked dysregulation. Notably, in pneumonia or bronchitis with an asthma-prone M2-dominant profile, specific antibiotic regimens are critical; doxycycline, for instance, may exacerbate patient deterioration by further driving M2a polarization. Crucially, we identified that natural adjuvants (e.g., curcumin, coumarins, polyphenols) exhibit potent properties capable of correcting these adverse secondary drug effects. Ultimately, this profiling platform highlights the necessity of evaluating patient-specific secondary drug effects, offering a functional blueprint for precision immunotherapy and the rational design of adjuvant-enhanced treatments. Full article

Klebsiella pneumoniae, a member of the ESKAPEE group of priority pathogens, has become one of the most challenging bacterial pathogens in modern clinical practice, largely due to its multidrug resistance and the immune-evasive effect of its capsular polysaccharide (CPS). Phage-encoded depolymerases, which selectively degrade the capsular polysaccharide, have emerged as promising antimicrobial agents capable of restoring bacterial susceptibility to both immune clearance and phage infection. The fragment corresponding to the C-terminal region of a putative depolymerase of bacteriophage KlebP_144, namely DepKP144ΔC, was cloned, expressed in E. coli, and purified using immobilized metal affinity chromatography. DepKP144ΔC displays an enzymatic activity against capsular polysaccharides of 100% K1 capsular-type strains and 85% K2 capsular-type strains, including classical and hypervirulent isolates. It was demonstrated that this protein is capable of inhibiting K. pneumoniae biofilm formation, but it is unable to disrupt mature biofilms. In vivo experiments using a murine K. pneumoniae infection model further confirmed its therapeutic potential: treatment with DepKP144ΔC improved survival rate in mice infected with K2-type K. pneumoniae, indicating significant attenuation of bacterial virulence. Therefore, these results demonstrate the potential role of the C-terminal domain of the bacteriophage KP144 tail-fiber protein in phage entry and show that its carbohydrate-recognition motifs possess enzymatic activity against the Klebsiella capsular polysaccharides. Full article

Background: Parapneumonic pleural effusion (PPE) remains a relevant complication of pediatric pneumonia, with a substantial burden of morbidity, particularly in complicated forms. Optimal management strategies remain debated, with a recent shift toward more conservative approaches. Contemporary data on epidemiology, management practices, and outcomes are therefore needed. Methods: We conducted a retrospective cohort study of children admitted to our center with radiologically confirmed PPE between 2015 and 2025. Two study phases were defined to reflect the progressive shift in clinical practice: an interventional-prone period, in which complicated PPE (cPPE) was systematically drained, and a conservative period, in which drainage was reserved for patients with clinical deterioration. Data were compared between periods, and risk factors associated with pleural drainage during the conservative period were analyzed. Results: A total of 122 children with PPE were included (median age 4.1 years, 50% female), of whom 62.3% had cPPE. Pleural drainage was performed more frequently during the interventional period (55% vs. 24%). Patients managed during the conservative period had shorter duration of intravenous antibiotic therapy, shorter hospital stays, and faster radiological resolution, adjusting for disease severity. Within the conservative period, patients requiring pleural drainage (24.4%) had greater clinical and radiological severity, including higher rates of respiratory support and need for intensive care. Conclusions: In this cohort, the shift from a predominantly invasive to a more conservative strategy was not associated with worse clinical outcomes after adjusting for baseline severity. Pleural drainage was mainly reserved for patients with greater clinical compromise. These findings support a severity-guided approach to pleural drainage in pediatric PPE, in which conservative management with medical therapy alone may be safely considered in appropriately selected cases. Full article

Background: Shikonins are natural naphthoquinones that exhibit a range of biological activities. They are typically extracted using nonpolar solvents; however, green extraction approaches remain underexplored. Methods: Phytochemical profiling of E. vulgare root extracts was performed using HPLC-ESI-QTOF-MS/MS and quantitative analysis using HPLC-PDA. Shikonin extraction was performed using VNADESs based on thymol, camphor, menthol and benzyl alcohol. The feasibility of removing the VNADES from the extracts via freeze-drying was assessed. The cytotoxic, antioxidant, anti-inflammatory and antimicrobial activities of the hexane extract and the selected VNADES-based extract (TBa 2:8) were compared. Results: Eight shikonin derivatives were identified in the extracts. VNADES extracts contained comparable amounts of shikonin to hexane extracts; however, freeze-drying resulted in significant shikonin content loss. TBa 2:8 extract exhibited noticeably lower cytotoxicity than the hexane extract while its antioxidant potential depended on the assay applied. In contrast to the hexane extract, TBa 2:8 demonstrated the ability to reduce intracellular ROS and NO levels. However, the hexane extract exhibited stronger antimicrobial activity. Conclusions: VNADES systems enable efficient extraction of shikonin derivatives with performance comparable to hexane. Although the resulting extracts exhibit multidirectional biological activity, it remains challenging to remove the VNADESs effectively without losing the shikonins. Full article

Neonatal infections remain a leading cause of morbidity and mortality worldwide, particularly among preterm and low-birth-weight infants and in low- and middle-income countries. This burden has intensified with the global increase in multidrug-resistant (MDR) bacteria, especially in neonatal intensive care units, where prolonged hospitalization, invasive interventions, and exposure to broad-spectrum antibiotics promote colonization, transmission, and invasive infection. In this narrative review, we explore the epidemiology and microbiological characteristics of MDR bacterial infections in newborns, alongside their associated risk factors, diagnostic challenges, treatment outcomes, and prevention strategies. Across different settings, Gram-negative pathogens, particularly Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii, account for a substantial proportion of severe neonatal infections, whereas methicillin-resistant Staphylococcus aureus remains important in selected units. The risk of MDR infection is driven by a complex interplay of factors, ranging from maternal and perinatal exposures to the inherent immunological vulnerability of newborns, hospital-based transmission, antibiotic selection pressure, and structural deficiencies in healthcare infrastructure. Diagnosis remains challenging because clinical presentations are nonspecific and culture-based methods are constrained by low blood volumes, prior antimicrobial exposure, and delayed turnaround times. Treatment is increasingly complicated due to resistance to standard empirical regimens, substantial regional variation in susceptibility profiles, and limited neonatal pharmacokinetic and safety data for reserve agents. Current evidence mainly supports surveillance-informed empirical therapy, susceptibility-guided treatment adjustment, antimicrobial stewardship, and strict infection prevention measures. Future progress will require neonatal-specific clinical trials, harmonized surveillance systems, stronger molecular epidemiology, and more equitable access to microbiological diagnostics and effective treatment. Full article

Background: Low-dose CT scanning is a key tool in lung cancer screening, enabling the detection of clinically significant abnormalities in asymptomatic individuals and often prompting further diagnostic evaluation. Case Presentation: We describe the case of an 80-year-old man with a heavy smoking history who was found to have a new right middle lobe collapse on screening CT. Subsequent positron emission tomography-computed tomography (PET/CT) imaging demonstrated mild fluorodeoxyglucose (FDG) uptake (SUVmax 2.7), raising concern for a low-grade endobronchial malignancy versus mucoid impaction. Flexible fiberoptic bronchoscopy revealed a large exophytic endobronchial mass occluding the airway. Histopathologic examination of the biopsy sample unexpectedly revealed vegetable material, consistent with chronic foreign-body aspiration. Discussion: Unrecognized aspiration events are relatively common in elderly adults and can mimic malignancy on imaging. This case highlights an important diagnostic pitfall: inflammatory endobronchial processes, including foreign-body granulomas, can demonstrate FDG uptake and mimic malignancy. Conclusion: Clinicians should maintain a broad differential diagnosis when evaluating PET-avid endobronchial lesions, especially in elderly patients. Full article

Background: Cemented and cementless fixation techniques in total hip arthroplasty (THA) each present distinct biomechanical properties and perioperative risk profiles. While cementless fixation has gained increasing popularity, large-scale nationally representative comparisons of perioperative outcomes between cemented and cementless elective THA remain limited. This study aimed to compare complication rates, healthcare utilization, and temporal trends between cemented and cementless elective THA using the National Inpatient Sample. Methods: A retrospective cohort study was conducted using the National Inpatient Sample database from 2016 to 2021. Adult patients undergoing elective primary total hip arthroplasty were identified using ICD-10-PCS codes and categorized into cemented and cementless fixation groups. Patient demographics, comorbidities, indications, postoperative complications, length of stay, hospital charges, and in-hospital mortality were compared. Multivariate logistic regression analysis was performed to evaluate the independent association between fixation type and postoperative complications while adjusting for demographic, clinical, and hospital-level variables. Results: A total of 81,668 elective THAs were identified, including 40,290 cemented (49.33%) and 41,378 cementless (50.67%) procedures. Cemented THA was associated with a shorter length of stay (2.09 ± 1.88 vs. 2.26 ± 2.47 days, p < 0.001) and lower total hospital charges ($65,584.53 ± 48,797.21 vs. $72,186.84 ± 49,860.20, p < 0.001). Unadjusted analyses demonstrated higher rates of acute kidney injury and sepsis in the cementless group. After multivariate adjustment, cemented fixation was associated with lower odds of acute kidney injury (OR 0.87, 95% CI 0.79–0.96, p = 0.004). However, cemented THA was associated with higher odds of postoperative delirium (OR 1.20, 95% CI 1.02–1.42, p = 0.030), blood transfusion (OR 1.27, 95% CI 1.17–1.37, p < 0.001), and periprosthetic fracture (OR 1.32, 95% CI 1.02–1.71, p = 0.035). Rates of myocardial infarction, pneumonia, venous thromboembolism, urinary tract infection, and in-hospital mortality were similar between groups. Temporal analysis demonstrated comparable utilization trends, with a decline in elective procedures during 2020–2021. Conclusions: In this nationwide analysis, cemented total hip arthroplasty was associated with lower risk of acute kidney injury, shorter length of stay, and lower hospital charges, but higher odds of postoperative delirium, blood transfusion, and periprosthetic fracture compared with cementless fixation. These findings highlight distinct perioperative risk profiles between fixation strategies and may assist surgeons in individualized decision-making for elective total hip arthroplasty. Full article