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Scientific Reports May 2024In pancreatic ductal adenocarcinoma (PDAC) patients, the importance of peritoneal lavage cytology, which indicates unresectability, remains controversial. This study...
In pancreatic ductal adenocarcinoma (PDAC) patients, the importance of peritoneal lavage cytology, which indicates unresectability, remains controversial. This study sought to determine whether positive peritoneal lavage cytology (CY+) precludes pancreatectomy. Furthermore, we propose a novel liquid biopsy using peritoneal lavage fluid to detect viable peritoneal tumor cells (v-PTCs) with TelomeScan F35, a telomerase-specific replication-selective adenovirus engineered to express green fluorescent protein. Resectable cytologically or histologically proven PDAC patients (n = 53) were enrolled. CY was conducted immediately following laparotomy. The resulting fluid was examined by conventional cytology (conv-CY; Papanicolaou staining and MOC-31 immunostaining) and by the novel technique (Telo-CY; using TelomeScan F35). Of them, 5 and 12 were conv-CY+ and Telo-CY+, respectively. All underwent pancreatectomy. The two double-CY+ (conv-CY+ and Telo-CY+) patients showed early peritoneal recurrence (P-rec) postoperatively, despite adjuvant chemotherapy. None of the three conv-CY+ Telo-CY- patients exhibited P-rec. Six of the 10 Telo-CY+ conv-CY- patients (60%) relapsed with P-rec. Of the remaining 38 double-CY- [conv-CY-, Telo-CY-, conv-CY± (Class III)] patients, 3 (8.3%) exhibited P-rec. Although conv-CY+ status predicted poor prognosis and a higher risk of P-rec, Telo-CY was more sensitive for detecting v-PTC. Staging laparoscopy and performing conv-CY and Telo-CY are needed to confirm the indication for pancreatectomy.
Topics: Humans; Peritoneal Lavage; Pancreatic Neoplasms; Male; Female; Aged; Middle Aged; Pancreatectomy; Carcinoma, Pancreatic Ductal; Cytodiagnosis; Aged, 80 and over; Neoplasm Recurrence, Local; Liquid Biopsy; Peritoneal Neoplasms; Adult; Cytology
PubMed: 38702437
DOI: 10.1038/s41598-024-60936-4 -
Journal of Clinical Microbiology Jun 2024Invasive mold infections (IMIs) are associated with high morbidity, particularly in immunocompromised patients, with mortality rates between 40% and 80%. Early...
UNLABELLED
Invasive mold infections (IMIs) are associated with high morbidity, particularly in immunocompromised patients, with mortality rates between 40% and 80%. Early initiation of appropriate antifungal therapy can substantially improve outcomes, yet early diagnosis remains difficult to establish and often requires multidisciplinary teams evaluating clinical and radiological findings plus supportive mycological findings. Universal digital high-resolution melting (U-dHRM) analysis may enable rapid and robust diagnoses of IMI. A universal fungal assay was developed for U-dHRM and used to generate a database of melt curve signatures for 19 clinically relevant fungal pathogens. A machine learning algorithm (ML) was trained to automatically classify these pathogen curves and detect novel melt curves. Performance was assessed on 73 clinical bronchoalveolar lavage samples from patients suspected of IMI. Novel curves were identified by micropipetting U-dHRM reactions and Sanger sequencing amplicons. U-dHRM achieved 97% overall fungal organism identification accuracy and a turnaround time of ~4 hrs. U-dHRM detected pathogenic molds (, , , and ) in 73% of 30 samples classified as IMI, including mixed infections. Specificity was optimized by requiring the number of pathogenic mold curves detected in a sample to be 8 and a sample volume to be 1 mL, which resulted in 100% specificity in 21 at-risk patients without IMI. U-dHRM showed promise as a separate or combination diagnostic approach to standard mycological tests. U-dHRM's speed, ability to simultaneously identify and quantify clinically relevant mold pathogens in polymicrobial samples, and detect emerging opportunistic pathogens may aid treatment decisions, improving patient outcomes.
IMPORTANCE
Improvements in diagnostics for invasive mold infections are urgently needed. This work presents a new molecular detection approach that addresses technical and workflow challenges to provide fast pathogen detection, identification, and quantification that could inform treatment to improve patient outcomes.
Topics: Humans; Lung Diseases, Fungal; Fungi; Sensitivity and Specificity; Molecular Diagnostic Techniques; Transition Temperature; Bronchoalveolar Lavage Fluid; Machine Learning; Invasive Fungal Infections
PubMed: 38695528
DOI: 10.1128/jcm.01476-23 -
Journal of Nanobiotechnology Apr 2024The main issues faced during the treatment of apical periodontitis are the management of bacterial infection and the facilitation of the repair of alveolar bone defects...
BACKGROUND
The main issues faced during the treatment of apical periodontitis are the management of bacterial infection and the facilitation of the repair of alveolar bone defects to shorten disease duration. Conventional root canal irrigants are limited in their efficacy and are associated with several side effects. This study introduces a synergistic therapy based on nitric oxide (NO) and antimicrobial photodynamic therapy (aPDT) for the treatment of apical periodontitis.
RESULTS
This research developed a multifunctional nanoparticle, CGP, utilizing guanidinylated poly (ethylene glycol)-poly (ε-Caprolactone) polymer as a carrier, internally loaded with the photosensitizer chlorin e6. During root canal irrigation, the guanidino groups on the surface of CGP enabled effective biofilm penetration. These groups undergo oxidation by hydrogen peroxide in the aPDT process, triggering the release of NO without hindering the production of singlet oxygen. The generated NO significantly enhanced the antimicrobial capability and biofilm eradication efficacy of aPDT. Furthermore, CGP not only outperforms conventional aPDT in eradicating biofilms but also effectively promotes the repair of alveolar bone defects post-eradication. Importantly, our findings reveal that CGP exhibits significantly higher biosafety compared to sodium hypochlorite, alongside superior therapeutic efficacy in a rat model of apical periodontitis.
CONCLUSIONS
This study demonstrates that CGP, an effective root irrigation system based on aPDT and NO, has a promising application in root canal therapy.
Topics: Animals; Photochemotherapy; Nitric Oxide; Biofilms; Rats; Nanoparticles; Photosensitizing Agents; Periapical Periodontitis; Male; Root Canal Irrigants; Rats, Sprague-Dawley; Bacterial Infections; Chlorophyllides; Anti-Bacterial Agents; Anti-Infective Agents
PubMed: 38689259
DOI: 10.1186/s12951-024-02483-8 -
In Vivo (Athens, Greece) 2024Patients with pneumonia after prolonged neutropenia are at increased risk for acute respiratory distress syndrome (ARDS). The key molecule of endothelial barrier...
BACKGROUND/AIM
Patients with pneumonia after prolonged neutropenia are at increased risk for acute respiratory distress syndrome (ARDS). The key molecule of endothelial barrier breakdown in sepsis is lipopolysaccharide (LPS), which is a component of the outer membrane of gram-negative bacterial cell walls. Maintaining increased cyclic adenosine monophosphate (cAMP) levels in endothelial cells is effective in preventing endothelial dysfunction and microvascular permeability. The aim of this study was to elucidate whether roflumilast, a phosphodiesterase-4 (PDE-4) inhibitor, is effective in LPS-induced acute lung injury (ALI) during neutropenia recovery in a murine model.
MATERIALS AND METHODS
To induce neutropenia, all mice were administered intraperitoneal cyclophosphamide. On day 2 after neutropenia, mice were administered LPS by intra-tracheal instillation. In the prevention group, roflumilast was given orally on day 0, when neutropenia was induced. In the treatment group, roflumilast was administered orally 1 hour after LPS injection.
RESULTS
Roflumilast attenuated histopathological changes associated with LPS-induced lung injury. The accumulation of neutrophils and the concentrations of inflammatory cytokines IL-1β, TNF-α, and IL-6 in bronchoalveolar lavage fluids were inhibited effectively by roflumilast. Also, MMP-9 and TGF-β expression was attenuated in the roflumilast group.
CONCLUSION
Roflumilast significantly attenuated LPS-induced ALI during neutropenia recovery.
Topics: Animals; Aminopyridines; Cyclopropanes; Acute Lung Injury; Lipopolysaccharides; Mice; Benzamides; Neutropenia; Disease Models, Animal; Phosphodiesterase 4 Inhibitors; Cytokines; Male; Bronchoalveolar Lavage Fluid; Neutrophils
PubMed: 38688656
DOI: 10.21873/invivo.13547 -
In Vivo (Athens, Greece) 2024Odontogenic maxillary sinusitis is a clinically popular disease, but radical surgery and endoscopic surgery are often required. In the present study, we compared for the...
BACKGROUND/AIM
Odontogenic maxillary sinusitis is a clinically popular disease, but radical surgery and endoscopic surgery are often required. In the present study, we compared for the first time the therapeutic efficacy of the extraction of causative teeth with or without irrigation of the extraction fossa.
PATIENTS AND METHODS
A total of 60 patients underwent extraction of causative tooth. Among them, 34 patients underwent irrigation, while other 26 patients did not. Based on computed tomography (CT) images, treatment efficacy was quantified by the percentage of the remaining maxillary sinus mucosal lesions. The extent of therapeutic efficacy was evaluated following five grades, based on the percentage of remaining lesions: Grade 1 (0%) (disappearance of lesions), Grade 2 (roughly 10%), Grade 3 (roughly 30%), Grade 4 (approximately 50%) and Grade 5 (100%) (no improvement of the lesions).
RESULTS
Irrigation significantly augmented the therapeutic efficacy of tooth extraction for maxillary sinus mucosal lesions (mean grade: decreasing from 3.27 to 1.35).
CONCLUSION
The combination of tooth extraction and irrigation may contribute to the reduction of the necessity of surgery for the maxillary sinuses.
Topics: Humans; Tooth Extraction; Male; Female; Maxillary Sinusitis; Middle Aged; Adult; Treatment Outcome; Aged; Therapeutic Irrigation; Tomography, X-Ray Computed; Maxillary Sinus
PubMed: 38688640
DOI: 10.21873/invivo.13560 -
Microbiology Spectrum Jun 2024The rapid and effective identification of pathogens in patients with pulmonary infections has posed a persistent challenge in medicine, with conventional microbiological...
The rapid and effective identification of pathogens in patients with pulmonary infections has posed a persistent challenge in medicine, with conventional microbiological tests (CMTs) proving time-consuming and less sensitive, hindering early diagnosis of respiratory infections. While there has been some research on the clinical performance of targeted sequencing technologies, limited focus has been directed toward bronchoalveolar lavage fluid (BALF). This study primarily evaluates the pathogen detection capabilities of nanopore-targeted sequencing (NTS) in BALF, providing a comprehensive analysis. The retrospective study, spanning from January 2022 to November 2023, includes 223 patients exclusively sourced from a single center. We conducted a detailed comparative analysis among NTS, targeted next-generation sequencing (tNGS), and CMTs. Initially, we compared the detection capabilities of NTS and tNGS and found no significant differences in their sensitivity and specificity. Specifically, we observed that the sensitivity of NTS was significantly higher than that of CMTs (74.83% vs 33.11%, < 0.001). Furthermore, NTS exhibited a higher positivity rate in common pulmonary infections (62.88% vs. 23.48%) and in clinically suspected tuberculosis patients compared to CMTs (87.18% vs. 48.72%). Additionally, NTS showed less susceptibility to antibiotic interference, indicating a more sensitive detection capability, especially in detecting fastidious organisms. It complements GeneXpert in tuberculosis diagnosis and offers excellent advantages in identifying pathogens challenging for CMTs, such as non-tuberculous mycobacteria and viruses. Moreover, NTS significantly shortens the reporting time and is only a quarter of the cost of metagenomic next-generation sequencing. Clearly, NTS can facilitate faster and more cost-effective early diagnosis of respiratory infections.IMPORTANCEThis study holds paramount significance in advancing the field of respiratory infection diagnostics. By assessing the pathogen detection capabilities in bronchoalveolar lavage fluid (BALF) of patients with pulmonary infections, we illuminate the promising potential of nanopore-targeted sequencing (NTS). The findings underscore NTS as a comparable yet distinct alternative to traditional methods like comprehensive conventional microbiological tests (CMTs). Notably, NTS demonstrates a pivotal edge, expanding the spectrum of identified pathogens, particularly excelling in the detection of challenging entities like non-tuberculous mycobacteria and viruses. The study also highlights the complementary role of NTS alongside GeneXpert in the identification of tuberculosis, providing a comprehensive overview of the diagnostic landscape for respiratory infections. This insight carries significant implications for clinicians seeking rapid, cost-effective, and accurate diagnostic tools in the realm of pulmonary infections.
Topics: Humans; Bronchoalveolar Lavage Fluid; Male; Female; High-Throughput Nucleotide Sequencing; Middle Aged; Retrospective Studies; Aged; Respiratory Tract Infections; Nanopore Sequencing; Adult; Nanopores; Bacteria; Sensitivity and Specificity; Aged, 80 and over
PubMed: 38687074
DOI: 10.1128/spectrum.00026-24 -
Italian Journal of Pediatrics Apr 2024Persistent airway inflammation is a central feature of bronchiectasis. Arachidonate 15-lipoxygenase (ALOX-15) controls production of endogenous lipid mediators,...
Association between arachidonate lipoxygenase 15,c.-292 C > T gene polymorphism and non-cystic fibrosis bronchiectasis in children: a pilot study on the effects on airway lipoxin A4 and disease phenotype.
BACKGROUND
Persistent airway inflammation is a central feature of bronchiectasis. Arachidonate 15-lipoxygenase (ALOX-15) controls production of endogenous lipid mediators, including lipoxins that regulate airway inflammation. Mutations at various positions in ALOX-15 gene can influence airway disease development. We investigated association between ALOX-15,c.-292 C > T gene polymorphism and bronchiectasis unrelated to cystic fibrosis in Egyptian children. Also, lipoxin A4 (LXA4) level in bronchoalveolar lavage (BAL) was studied in relation to polymorphism genotypes and disease phenotypes determined by clinical, pulmonary functions, and radiological severity parameters.
METHODS
This was an exploratory study that included 60 participants. Thirty children with non-cystic fibrosis bronchiectasis (NCFB) were compared with 30 age and sex-matched controls. ALOX-15,c.-292 C > T polymorphism was genotyped using TaqMan-based Real-time PCR. LXA4 was measured in BAL using ELISA method.
RESULTS
There was no significant difference between patients and controls regarding ALOX-15,c.-292 C > T polymorphism genotypes and alleles (OR = 1.75; 95% CI (0.53-5.7), P = 0.35) (OR = 1; 95% CI (0.48-2), p = 1). BAL LXA4 level was significantly lower in patients, median (IQR) of 576.9 (147.6-1510) ng/ml compared to controls, median (IQR) of 1675 (536.8-2542) (p = 0.002). Patients with severe bronchiectasis had a significantly lower LXA4 level (p < 0.001). There were significant correlations with exacerbations frequency (r=-0.54, p = 0.002) and FEV1% predicted (r = 0.64, p = 0.001). Heterozygous CT genotype carriers showed higher LXA4 levels compared to other genotypes(p = 0.005).
CONCLUSIONS
Low airway LXA4 in children with NCFB is associated with severe disease phenotype and lung function deterioration. CT genotype of ALOX-15,c.-292 C > T polymorphism might be a protective genetic factor against bronchiectasis development and/or progression due to enhanced LXA4 production.
Topics: Adolescent; Child; Child, Preschool; Female; Humans; Male; Arachidonate 15-Lipoxygenase; Bronchiectasis; Bronchoalveolar Lavage Fluid; Case-Control Studies; Egypt; Genetic Predisposition to Disease; Genotype; Lipoxins; Phenotype; Pilot Projects; Polymorphism, Genetic
PubMed: 38685084
DOI: 10.1186/s13052-024-01654-5 -
Lung Jun 2024Acute respiratory distress syndrome (ARDS) is a major cause of hypoxemic respiratory failure in adults. In ARDS extensive inflammation and leakage of fluid into the...
PURPOSE
Acute respiratory distress syndrome (ARDS) is a major cause of hypoxemic respiratory failure in adults. In ARDS extensive inflammation and leakage of fluid into the alveoli lead to dysregulation of pulmonary surfactant metabolism and function. Altered surfactant synthesis, secretion, and breakdown contribute to the clinical features of decreased lung compliance and alveolar collapse. Lung function in ARDS could potentially be restored with surfactant replacement therapy, and synthetic surfactants with modified peptide analogues may better withstand inactivation in ARDS alveoli than natural surfactants.
METHODS
This study aimed to investigate the activity in vitro and the bolus effect (200 mg phospholipids/kg) of synthetic surfactant CHF5633 with analogues of SP-B and SP-C, or natural surfactant Poractant alfa (Curosurf, both preparations Chiesi Farmaceutici S.p.A.) in a severe ARDS model (the ratio of partial pressure arterial oxygen and fraction of inspired oxygen, P/F ratio ≤ 13.3 kPa) induced by hydrochloric acid instillation followed by injurious ventilation in adult New Zealand rabbits. The animals were ventilated for 4 h after surfactant treatment and the respiratory parameters, histological appearance of lung parenchyma and levels of inflammation, oxidative stress, surfactant dysfunction, and endothelial damage were evaluated.
RESULTS
Both surfactant preparations yielded comparable improvements in lung function parameters, reductions in lung injury score, pro-inflammatory cytokines levels, and lung edema formation compared to untreated controls.
CONCLUSIONS
This study indicates that surfactant replacement therapy with CHF5633 improves lung function and lung architecture, and attenuates inflammation in severe ARDS in adult rabbits similarly to Poractant alfa. Clinical trials have so far not yielded conclusive results, but exogenous surfactant may be a valid supportive treatment for patients with ARDS given its anti-inflammatory and lung-protective effects.
Topics: Animals; Rabbits; Respiratory Distress Syndrome; Pulmonary Surfactants; Lung; Phospholipids; Disease Models, Animal; Biological Products; Pulmonary Surfactant-Associated Protein B; Oxidative Stress; Pulmonary Surfactant-Associated Protein C; Male; Bronchoalveolar Lavage Fluid; Peptide Fragments; Phosphatidylcholines
PubMed: 38684519
DOI: 10.1007/s00408-024-00689-z -
Experimental Lung Research 2024Treatment options for viral lung infections are currently limited. We aimed to explore the safety and efficacy of inhaled ethanol in an influenza-infection mouse model.
AIM
Treatment options for viral lung infections are currently limited. We aimed to explore the safety and efficacy of inhaled ethanol in an influenza-infection mouse model.
MATERIALS AND METHODS
In a safety and tolerability experiment, 80 healthy female BALB/c mice (20 per group) were exposed to nebulized saline (control) or three concentrations of ethanol (40/60/80% ethanol v/v in water) for 3x30-minute periods, with a two-hour break between exposures. In a separate subsequent experiment, 40 Female BALB/c mice were nasally inoculated with 10 plaque-forming units of immediate virulence "Mem71" influenza. Infection was established for 48-h before commencing treatment in 4 groups of 10 mice with either nebulized saline (control) or one of 3 different concentrations of ethanol (40/60/80% ethanol v/v in water) for 3x30-minute periods daily over three consecutive days. In both experiments, mouse behavior, clinical scores, weight change, bronchoalveolar lavage cell viability, cellular composition, and cytokine levels, were assessed 24-h following the final exposure, with viral load also assessed after the second experiment.
RESULTS
In uninfected BALB/c mice, 3x30-minute exposures to nebulized 40%, 60%, and 80% ethanol resulted in no significant differences in mouse weights, cell counts/viability, cytokines, or morphometry measures. In Mem71-influenza infected mice, we observed a dose-dependent reduction in viral load in the 80%-treated group and potentiation of macrophage numbers in the 60%- and 80%-treated groups, with no safety concerns.
CONCLUSIONS
Our data provides support for inhaled ethanol as a candidate treatment for respiratory infections.
Topics: Animals; Ethanol; Female; Mice, Inbred BALB C; Administration, Inhalation; Mice; Viral Load; Orthomyxoviridae Infections; Disease Models, Animal; Macrophages; Cytokines; Bronchoalveolar Lavage Fluid; Aerosols; Lung
PubMed: 38683138
DOI: 10.1080/01902148.2024.2346320 -
Open Veterinary Journal Mar 2024Bronchoalveolar lavage (BAL) is a method for collecting the cellular and fluid components of the airway surface in the lungs. The assessment of differential cell...
BACKGROUND
Bronchoalveolar lavage (BAL) is a method for collecting the cellular and fluid components of the airway surface in the lungs. The assessment of differential cell profiles is potentially valuable in the diagnosis of pulmonary diseases, but there is no information about the normal BAL profiles in the Gezel breed.
AIM
This study aimed to characterize the normal cryptologic findings of BAL with Gezel sheep.
METHODS
Twenty healthy sheep (15 females: 5 males, bodyweight: 55-65 kg) were sedated with xylazine (0.02-0.04 mg/kg IV). Two methods; the transtracheal bronchoalveolar lavage technique and the bronchoscopic bronchoalveolar lavage using a scope were evaluated. Sampling was performed in the summer and winter seasons.
RESULTS
Normal value (Mean ± SEM) for total cell, macrophage, lymphocyte, neutrophil, epithelial, and bronchial cells in BAL sampled in summer were (343.75 ± 30.23), ) 24.50 ± 2.62), (2.81 ± 0.51), (1.43 ± 0.88), and (3.12 ± 0.32), respectively. The normal values for the total cell, macrophage, lymphocyte, neutrophil, epithelial, and bronchial cells in BAL sampled in winter were (355.55 ± 37.67), (59.11 ± 4.30), (21.33 ± 3.10), (3.88 ± 1.07), (8.88 ± 3.78), and (6.33 ± 1.44), respectively.
CONCLUSION
No significant change in the percentage of neutrophils was detected between seasons, although the percentages of bronchial and epithelial cells in winter were significantly high ( < 0.05). Except for the mentioned cases, neither the total cell number nor the percentage differential cell populations of BAL changed significantly ( < 0.05) in different sampling methods and seasons. Normal BAL profiles in the Gezel breed were determined and could be used in result interpretations. Also, both sampling methods can be used without significantly affecting the results.
Topics: Animals; Bronchoalveolar Lavage Fluid; Seasons; Sheep; Female; Male; Bronchoalveolar Lavage; Neutrophils
PubMed: 38682135
DOI: 10.5455/OVJ.2024.v14.i3.5