Search Results (6,756)

Since ancient times, essential oils obtained from various aromatic plants have been utilized as bioactive ingredients in medicines, foods and cosmetics. The present study aimed to investigate the chemical composition and biological activities of St John’s Wort (Hypericum perforatum L.) essential oil (SJW EO) from Bulgaria, which is known to possess various biological properties. Gas chromatography and mass spectrometry (GC–MS) analysis, determination of antioxidant activity (by the ABTS method), an antimicrobial activity test and an in vitro anti-inflammatory activity test were performed. The main classes of compounds identified by GC–MS analysis were monoterpenes (43.55%), followed by sesquiterpenes (36.81%) and alkanes (16.92%). The predominant chemical components of SJW EO were α-pinene (27.52%), followed by β-pinene (10.08%), β-caryophyllene (6.77%), germacrene D (6.37%) and caryophyllene oxide (4.48%). The highest antibacterial activity was observed against the Gram-negative bacteria Klebsiella pneumoniae ATCC 13883 (inhibition zone of 12.0 mm) and Pseudomonas aeruginosa ATCC 9027 (inhibition zone of 11.0 mm). SJW EO exhibited significant in vitro anti-inflammatory activity, as the results demonstrated that its anti-inflammatory effect was stronger than those of the conventional anti-inflammatory drugs Prednisolon Cortico and acetylsalicylic acid (Aspirin), which were used as controls (all in concentration of 1 mg/mL). The obtained results demonstrated that Bulgarian SJW EO can be used as an active ingredient in the composition of new products for the pharmaceutical and cosmetic industries. Full article

Rhinoviruses and respiratory enteroviruses remain among the leading causes of acute respiratory infections, particularly in children. Little is known about the genetic diversity of enteroviruses and rhinoviruses in pediatric patients with acute respiratory infections in Russia. We assessed the prevalence of human rhinoviruses/enteroviruses (HRV/EV) in 1992 children aged 0 to 17 years hospitalized with acute respiratory infections during the 2023–2024 epidemic season using PCR. The detection rate of HRV/EV was 11% (220/1992). We performed typing of 58 HRV and 28 EV viruses by partial sequencing of the VP1 gene. Rhinovirus A was the most common among HRV, followed by rhinovirus C; rhinovirus B was detected in only three cases. Enteroviruses were represented by all four species, with the EV-D68 genotype being the most frequently detected. Phylogenetic analysis of the VP1 fragment of EV-D68 showed that all our sequences belonged to the B3 subclade. We identified the first case of EV-C105 infection in Russia in a two-year-old girl hospitalized with pneumonia. Phylogenetically, the Novosibirsk strain EV-C105 was closely related to a strain discovered in France in 2018. This research helped to fill a critical gap in understanding the epidemiological landscape of HRV/EV in pediatric populations within Russia. Full article

Porcine reproductive and respiratory syndrome virus (PRRSV) causes reproductive disorders in sows and severe pneumonia in piglets, alongside immunosuppressive effects on the host. It poses a significant global threat to the swine industry, with no effective control measures currently available due to its complex pathogenesis and high variability. Conventional inactivated and attenuated vaccines provide inadequate protection and carry biosafety risks. In this study, we designed a universal multi-epitope peptide vaccine against PRRSV using bioinformatics and immunoinformatics approaches to address these limitations. By selecting sequences from seven representative PRRSV strains, we predicted highly conserved and immunogenic T cell (Th and CTL) epitopes across all encoded proteins. These were rationally concatenated with reported B cell neutralizing epitopes into a multi-epitope vaccine construct. We performed comprehensive assessments of the construct’s physicochemical and biochemical properties, along with predictions and refinements of its secondary and tertiary structures. Molecular docking simulations with TLR2 and TLR4 revealed strong potential binding interactions. Immune simulations indicated that the multi-epitope vaccine could induce robust humoral and cellular immune responses. This study provides a scientific foundation for the development of safe and effective PRRSV subunit vaccines and offers new perspectives for designing vaccines against other viral diseases. Full article

Staphylococcus aureus is a human pathogen responsible for a wide range of diseases, such as skin and soft tissue infections, pneumonia, toxic shock syndrome, and urinary tract infections. Methicillin-resistant S. aureus (MRSA) is a well-known pathogen with consistently high mortality rates. Detecting the mecA resistance gene and phenotypical profile to β-lactams allows for the differentiation of MRSA from methicillin-susceptible S. aureus (MSSA) isolates. In this study, we characterized 57 S. aureus clinical isolates for β-lactam susceptibility and mecA presence. We classified 52.63% as MRSA and 45.61% as MSSA. However, some isolates evidenced different oxacillin resistance profiles, such as borderline oxacillin-resistant or modified S. aureus (BORSA/MODSA). The cefazolin inoculum effect (CzIE) was established for these samples, emphasizing the relevance of these isolates as a source of therapeutic failure. We also performed the detection of the Panton-Valentine Leucocidin virulence genes as well as the S. aureus spa-type clonality. As expected, spa-types t002 and t008 were the most prevalent clones, demonstrating the success of well-established clones. These findings emphasize the importance of establishing sensitivity profiles, especially in isolates with poor resistance mechanisms, to determine their prevalence and their impact on public health. Full article

After first appearing in December 2019, coronavirus disease 2019 (COVID-19) spread rapidly, leading to global effects and significant risks to health systems. The virus’s high replication competence in the human lung accelerated the severity of lung pneumonia cases, resulting in a catastrophic death rate. Variable observations in the clinical testing of virus-related and patient-related cases across different populations led to ambiguous results. Medical and epidemiological studies on the virus effectively use imaging and scanning devices to help explain the virus’s behavior and its impact on the lungs. Varying equipment resources and a lack of uniformity in medical imaging acquisition led to disorganized and widely dispersed data collection worldwide, while high heterogeneity in datasets caused a poor understanding of the virus and related strains, consequently leading to unstable results that could not be generalized. Hospitals and medical institutions, therefore, urgently need to collaborate to share and extract useful knowledge from these COVID-19 datasets while preserving the privacy of medical records. Researchers are turning to an emerging technology that enhances the reliability and accessibility of information without sharing actual patient data. Federated learning (FL) is a technique that learns distributed data locally, sharing only the weights of each local model to compute a global model, and has the potential to improve the generalization of diagnosis and treatment decisions. This study investigates the applicability of FL for COVID-19 under the impact of data heterogeneity, defining the lung imaging characteristics and identifying the practical constraints of FL in medical fields. It describes the challenges of implementation from a technical perspective, with reference to valuable research directions, and highlights the research challenges that present opportunities for further efforts to overcome the pitfalls of distributed learning performance. The primary objective of this literature review is to provide valuable insights that will aid in the formulation of effective technical strategies to mitigate the impact of data heterogeneity on the generalization of FL results, particularly in light of the ongoing and evolving COVID-19 pandemic. Full article

Background: The COVID-19 pandemic has intensified concerns over bacterial infections and antimicrobial resistance, particularly in Romania. This systematic review explores bacterial infection patterns and resistance during the pandemic to address critical gaps in knowledge. Methods: A systematic review, following PRISMA guidelines, was conducted using databases such as PubMed and Scopus, focusing on studies of bacterial infections from 2020 to 2022. Articles on bacterial infections in Romanian patients during the pandemic were analyzed for demographic data, bacterial trends, and resistance profiles. Results: A total of 87 studies were included, detailing over 20,000 cases of bacterial infections. The review found that Gram-negative bacteria, particularly Escherichia coli and Klebsiella pneumoniae, were the most frequently identified pathogens, alongside Gram-positive Staphylococcus aureus and Enterococcus spp. Multidrug resistance (MDR) was noted in 24% of the reported strains, with common resistance to carbapenems and cephalosporins. Conclusions: The pandemic has amplified the complexity of managing bacterial infections, particularly in critically ill patients. The rise in MDR bacteria underscores the need for stringent antimicrobial stewardship and infection control measures. Continuous monitoring of bacterial trends and resistance profiles will be essential to improve treatment strategies in post-pandemic healthcare settings. Full article

Hypercoagulation is central to the pathogenesis of acute and post-acute COVID-19. This prospective observational study explored whether rotational thromboelastometry (ROTEM), a method that unveils coagulation status, predicts outcomes of hospitalized patients with COVID-19 pneumonia. We investigated 62 patients using ROTEM that was conducted at enrollment, clinical deterioration, discharge and follow-up visits 1 and 3 months post-discharge. A hypercoagulable ROTEM was more common at clinical deterioration than at enrollment and the levels of hypercoagulable ROTEM indices correlated with the clinical severity score. Hypercoagulable ROTEM at enrollment was not associated with in-hospital death. Patients with hypercoagulable ROTEM at enrollment, discharge and 1 month post-discharge had an increased risk of persistent symptoms 1 and 3 months after discharge. Patients with hypercoagulable ROTEM at enrollment, discharge, and 1 month after discharge were more likely to have lung diffusion capacity (DLco) impairment 3 months after discharge. High levels of hypercoagulable ROTEM indices were associated with the increased risk of persistent symptoms at later stages of the disease. In a multivariate analysis, (i) hypercoagulable ROTEM at discharge and female gender were linked to the presence of symptoms at one month post-discharge, (ii) hypercoagulable ROTEM at one month after discharge was linked to the presence of symptoms at three months post-discharge, (iii) hypercoagulable ROTEM at enrollment and at discharge and female gender were linked to the presence of impaired DLco at three months post-discharge. Excessive coagulation may contribute to long-COVID pathogenesis and ROTEM findings during hospitalization may predict post-acute-COVID-19 sequelae in patients with COVID-19-related pneumonia. Full article

Orally administered immunomodulatory lactobacilli can stimulate respiratory immunity and enhance the resistance to primary infections with bacterial and viral pathogens. However, the potential beneficial effects of immunomodulatory lactobacilli against respiratory superinfection have not been evaluated. In this work, we showed that the feeding of infant mice with Lacticaseibacillus rhamnosus CRL1505 or Lactiplantibacillus plantarum MPL16 strains can reduce susceptibility to the secondary pneumococcal infection produced after the activation of TLR3 in the respiratory tract or after infection with RVS. The treatment of mice with CRL1505 or MPL16 strains by the oral route improved the production of interferons in the respiratory tract, differentially modulated the balance of pro- and anti-inflammatory cytokines, reduced bacterial replication, and diminished lung damage. Additionally, we demonstrated that orally administered lactobacilli confer longstanding protection against secondary Streptococcus pneumoniae infection and that this effect would be mediated by the stimulation of trained alveolar macrophages. This work contributes to revealing the mechanisms involved in the modulation of the gut–lung axis by beneficial microbes by demonstrating that specific lactobacilli strains, through the stimulation of the common mucosal immune system, would be able to support the development of trained alveolar macrophages that would confer longstanding protection against secondary bacterial challenges produced after a primary inflammatory event in the respiratory mucosa. Full article

Background: In hospital- and community-acquired central nervous system infections, resistant Gram-positive bacteria are an increasing therapeutic challenge. The present approach does not attempt to identify rapidly bactericidal therapies for susceptible pathogens but aims to improve methods to find antibiotic regimens for multi-resistant pathogens that are effective in vivo in spite of reduced in vitro susceptibility in culture media. Methods: Antibiotic susceptibility was tested in cerebrospinal fluid (CSF) and Mueller–Hinton broth (Enterococcus faecalis, methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis) or brain–heart infusion (Streptococcus pneumoniae). Results: Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) were either lower in CSF than in broth or equal in CSF and broth. The difference between MICs in CSF and broth was prominent with gentamicin, levofloxacin, linezolid (staphylococci), and vancomycin (staphylococci and pneumococcus), whereas it was absent with ampicillin (E. faecalis), penicillin G (S. pneumoniae), linezolid (enterococcus and pneumococcus), and vancomycin (enterococcus). In no case was the MIC or MBC higher in CSF than in broth. Conclusions: Several antibiotics possess an antibacterial effect in CSF at lower concentrations than the MICs determined in broth, i.e., MICs in broth underestimate in situ susceptibility in CSF. Full article

This study aims to investigate the risk factors for infection and mortality associated with carbapenem-resistant Klebsiella pneumoniae (CRKP) in hospitalized children, with the goal of providing valuable insights for the prevention and treatment of these bacterial infections. A retrospective case-control study was conducted, including 153 cases of carbapenem-sensitive K. pneumoniae infection in children and 49 cases of CRKP infection. Among the CRKP cases, 40 children survived and nine died. Logistic regression analysis was used to screen the risk factors for CRKP infection in children, establish a predictive model, and analyze the factors associated with mortality in CRKP-infected children. The results of the multivariate regression analysis showed that hematopoietic malignancies (OR = 28.272, 95% CI: 2.430–328.889), respiratory tract infections (OR = 0.173, 95% CI: 0.047–0.641), mechanical ventilation (OR = 3.002, 95% CI: 1.117–8.071), number of antibiotic agents (OR = 1.491, 95% CI: 1.177–1.889), WBC (OR = 0.849, 95% CI: 0.779–0.926), and neutrophil count (OR = 0.779, 95% CI: 0.677–0.896) were identified as significant factors associated with CRKP infection in children. Specifically, CRKP-infected children with a history of multiple hospitalizations within the past three months, blood stream infections, and decreased WBC and lymphocyte counts should be monitored closely due to poor prognosis. Underlying hematopoietic malignancies in children, non-respiratory tract infections, mechanical ventilation after admission, and use of multiple antibiotics without significant increase in white blood cell and neutrophil counts are major factors influencing CRKP infection. Particularly, CRKP-infected children with blood stream infections and no significant increase in neutrophil count should be closely monitored for potential severity of illness. Full article

Background/Objectives: Patients with chronic lymphocytic leukemia (CLL) are susceptible to infections that can affect their clinical outcomes. Aims: The aims of this study were to assess the following: (1) the incidence of pneumonia in CLL patients treated with venetoclax-based regimens in a real-world setting, (2) the risk factors for event-free survival (EFS), and (3) overall survival (OS). Methods: This multicenter study included 322 patients from eight centers. Univariable and multivariable analyses (MVA) were performed, with the development of pneumonia during venetoclax-based treatment and OS as outcomes. Results: The most common complication was neutropenia (59%). During treatment with venetoclax-based regimens, 66 (20%) patients developed pneumonia—50 (23%) patients in the rituximab-plus-venetoclax (R-VEN) group and 13 (16%) patients in the obinutuzumab-plus-venetoclax (O-VEN) group (p = 0.15). Chronic obstructive pulmonary disease (COPD)/asthma, splenomegaly, elevated creatinine, and anemia < 8 g/dL were the risk factors for EFS in MVA (HR = 2.08, 95%CI 1.16–3.74, p = 0.014; HR 1.73, 95%CI 1.08–2.78, p = 0.02; HR 2.13, 95%CI 1.10–4.11, p = 0.03, HR 3.58, 95%CI 2.18–5.89, p < 0.001, respectively). Relapsed/refractory (R/R) CLL patients treated with R-VEN with pneumonia had worse OS than those without (p < 0.001). In patients treated with O-VEN, median OS did not differ between patients with and without pneumonia (p = 0.45). Conclusions: Our real-world study showed that pneumonia during venetoclax treatment occurs more frequently than reported in registration trials and has a negative impact on OS, especially in patients with R/R CLL who are treated with R-VEN. Neutropenia is not a risk factor for pneumonia. Full article

Background/Objectives: We aimed to characterize the fibrosis following COVID-19 pneumonia, using quantitative analysis, after three months and subsequently, after two years of patients’ release from the hospital, and to identify the risk factors for pulmonary fibrosis. Methods: We performed a retrospective, observational cohort study on 420 patients with severe forms of COVID-19. For all patients, we registered demographic, inflammatory and biochemical parameters, complete blood count and D-dimers; all patients underwent three computed tomography scans (at admittance, at 3 months and at 2 years). Results: We found fibrosis in 67.9% of patients at the 3-month evaluation and in 42.4% of patients at the 2-year evaluation, registering a significant decrease in the severe and moderate fibrosis cases, with a slight increase in the mild fibrosis cases. The risk of fibrosis was found to be proportional to the values of age, duration of hospital stay, inflammatory markers (ESR, fibrinogen), cytolytic markers (LDH, AST) and D-dimers. The highest correlations with lung fibrosis were registered for interstitial pulmonary involvement (for the 3-month evaluation) and total pulmonary involvement (for the 2-year evaluation). Conclusions: Lung fibrosis represents a significant post-COVID-19 complication found in 42% of patients with severe forms of pneumonia at the 2-year evaluation. A significant overall decrease in the severity of lung fibrosis was registered at the 2-year evaluation compared to the 3-month evaluation. We consider that the amount of interstitial pulmonary involvement represents the optimal parameter to estimate the risk of lung fibrosis following SARS-CoV-2 pneumonia. Full article

Recurrent laryngeal nerve palsy remains a significant complication following minimally invasive esophagectomy for esophageal cancer. Despite advancements in surgical techniques and lymphadenectomy precision, the incidence of recurrent laryngeal nerve palsy has not been improved. Recurrent laryngeal nerve palsy predominantly affects the left side and may lead to unilateral or bilateral vocal cord paralysis, resulting in hoarseness, dysphagia, and an increased risk of aspiration pneumonia. While most cases of recurrent laryngeal nerve palsy are temporary and resolve within 6 to 12 months, some patients may experience permanent nerve dysfunction, severely impacting their quality of life. Prevention strategies, such as nerve integrity monitoring, robotic-assisted minimally invasive esophagectomy, and advanced dissection techniques, aim to minimize nerve injury, though their effectiveness varies. The management of recurrent laryngeal nerve palsy includes voice and swallowing rehabilitation, reinnervation techniques, and, in severe cases, surgical interventions such as thyroplasty and intracordal injection. As recurrent laryngeal nerve palsy can lead to significant postoperative respiratory complications, a multidisciplinary approach involving surgical precision, early detection, and comprehensive rehabilitation is crucial to improving patient outcomes and minimizing long-term morbidity in minimally invasive esophagectomy. This review article aims to inform esophageal surgeons and other clinicians about strategies for the prevention and management of recurrent laryngeal nerve palsy in esophagectomy. Full article

Background: A potential strategy to maintain the efficacy of carbapenems against carbapenemase-producing Klebsiella pneumoniae (CPKP) is their combination with carbapenemase inhibitors. To address these issues, the effectiveness of a novel combination of meropenem with avibactam against CPKP was studied. Additionally, the applicability of a pharmacokinetically-based approach to antibiotic/inhibitor minimum inhibitory concentration (MIC) determinations to better predict efficacy was examined. Methods: CPKP strains were exposed to meropenem alone or in combination with avibactam in an in vitro hollow-fiber infection model. Treatment effects were correlated with simulated antibiotic and antibiotic/inhibitor combination ratios of the area under the concentration–time curve (AUC) to the MIC (AUC/MIC). All MICs were determined at standard and at high inocula; combination MICs were determined using the conventional approach with fixed avibactam concentration or using the pharmacokinetic (PK)-based approach with a fixed meropenem-to-avibactam concentration ratio, equal to the respective drug therapeutic AUC ratios. Results: Meropenem alone was not effective even against a “susceptible” CPKP strain. The addition of avibactam significantly improved both meropenem MICs and its effectiveness. The effects of meropenem alone and in combination with avibactam (merged data) correlated well with AUC/MIC ratios only when MICs were determined at high inocula and using the PK-based approach (r² 0.97); the correlation was worse with the conventional approach (r² 0.73). Conclusions: The effectiveness of meropenem/avibactam against CPKP is promising. A single “effect–AUC/MIC” relationship useful for predicting meropenem efficacy (alone or in combination with avibactam) was obtained using MICs at high inocula and combination MICs determined using a PK-based approach. Full article

The emergence of SARS-CoV-2 variants of concern (VOCs) during the COVID-19 pandemic necessitates investigation into their clinical differentiation and outcomes. This study aimed to examine these differences among VOCs, considering multiple related factors. An observational cohort study was conducted on patients diagnosed with SARS-CoV-2 infection via nasopharyngeal/oropharyngeal swab who visited the emergency department of a public Greek hospital between October 2020 and July 2022 during different VOC circulation in the region. Data on clinical manifestations, outcomes, and medical history (comorbidities, prior SARS-CoV-2 infection, vaccination status against COVID-19) were collected through a questionnaire and medical records for those hospitalized. A total of 913 patients were included in this study (813 adults ≥18 years old, 100 children <18 years old). Significant differences were observed across VOCs for both adults and children. A lower proportion of children developed symptoms during the non-Omicron variants, 73.5%, compared to Omicron variants, 86.4%. Fever, dyspnea, and taste and smell disorders were observed more frequently among non-Omicron adult cases, in contrast to upper respiratory symptoms, which were more common symptoms among Omicron infections. The non-Omicron variants were associated with higher rates of hospitalization at 30.6%, pneumonia at 23.0%, and death at 6.1% compared to Omicron variants at 8.0%, 5.0%, and 1.8%, respectively. Vaccination against COVID-19 was shown to be a protective factor for severe outcomes. Our findings suggest distinct clinical presentations and outcomes associated with different VOCs. Despite the fact that current VOCs circulating are less severe, the COVID-19 vaccine continues to play a protective role for severe cases. Full article