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BMC Infectious Diseases Jun 2024The emergence of metagenomic next-generation sequencing (mNGS) may provide a promising tool for early and comprehensive identification of the causative pathogen in...
BACKGROUND
The emergence of metagenomic next-generation sequencing (mNGS) may provide a promising tool for early and comprehensive identification of the causative pathogen in community-acquired pneumonia (CAP). In this study, we aim to further evaluate the etiological diagnostic value of mNGS in suspected CAP.
METHODS
A total of 555 bronchoalveolar lavage fluid (BALF) samples were collected for pathogen detection by mNGS from 541 patients with suspected CAP. The clinical value was assessed based on infection diagnosis and treatment guidance. The diagnostic performance for pathogen identification by mNGS and sputum culture and for tuberculosis (TB) by mNGS and X-pert MTB/RIF were compared. To evaluate the potential for treatment guidance, we analyzed the treatment regimen of patients with suspected CAP, including imaging changes of lung after empirical antibacterial therapy, intensified regimen, antifungal treatment, and a 1-year follow up for patients with unconfirmed diagnosis and non-improvement imaging after anti-infective treatment and patients with high suspicion of TB or NTM infection who were transferred to the Wuhan Pulmonary Hospital for further diagnosis and even anti-mycobacterium therapy.
RESULTS
Of the 516 BALF samples that were analyzed by both mNGS and sputum culture, the positivity rate of mNGS was significantly higher than that of sputum culture (79.1% vs. 11.4%, P = 0.001). A total of 48 samples from patients with confirmed TB were analyzed by both mNGS and X-pert MTB/RIF, and the sensitivity of mNGS for the diagnosis of active TB was significantly lower than that of X-pert MTB/RIF (64.6% vs. 85.4%, P = 0.031). Of the 106 pathogen-negative cases, 48 were ultimately considered non-infectious diseases, with a negative predictive value of 45.3%. Of the 381 pathogen-positive cases, 311 were eventually diagnosed as CAP, with a positive predictive value of 81.6%. A total of 487 patients were included in the evaluation of the therapeutic effect, and 67.1% improved with initial empirical antibiotic treatment. Of the 163 patients in which bacteria were detected, 77.9% improved with antibacterial therapy; of the 85 patients in which fungi were detected, 12.9% achieved remission after antifungal therapy.
CONCLUSIONS
Overall, mNGS had unique advantages in the detection of suspected CAP pathogens. However, mNGS was not superior to X-pert MTB/RIF for the diagnosis of TB. In addition, mNGS was not necessary as a routine test for all patients admitted with suspected CAP. Furthermore, when fungi are detected by mNGS, antifungal therapy should be cautious.
Topics: Humans; Community-Acquired Infections; High-Throughput Nucleotide Sequencing; Male; Female; Middle Aged; Aged; Metagenomics; Bronchoalveolar Lavage Fluid; Adult; Pneumonia; Sputum; Aged, 80 and over; Bacteria; Young Adult
PubMed: 38914949
DOI: 10.1186/s12879-024-09507-6 -
PloS One 2024The efficacy of rosuvastatin in reducing allergic inflammation has been established. However, its potential to reduce airway remodeling has yet to be explored. This...
The efficacy of rosuvastatin in reducing allergic inflammation has been established. However, its potential to reduce airway remodeling has yet to be explored. This study aimed to evaluate the efficacy of rosuvastatin in reducing airway inflammation and remodeling in a mouse model of chronic allergic asthma induced by sensitization and challenge with OVA. Histology of the lung tissue and the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) showed a marked decrease in airway inflammation and remodeling in mice treated with rosuvastatin, as evidenced by a decrease in goblet cell hyperplasia, collagen deposition, and smooth muscle hypertrophy. Furthermore, levels of inflammatory cytokines, angiogenesis-related factors, and OVA-specific IgE in BALF, plasma, and serum were all reduced upon treatment with rosuvastatin. Western blotting was employed to detect AMPK expression, while immunohistochemistry staining was used to observe the expression of remodeling signaling proteins such as α-SMA, TGF-β, MMP-9, and p-AMPKα in the lungs. It was found that the activity of 5'-adenosine monophosphate-activated protein kinase alpha (AMPKα) was significantly lower in the lungs of OVA-induced asthmatic mice compared to Control mice. However, the administration of rosuvastatin increased the ratio of phosphorylated AMPK to total AMPKα, thus inhibiting the formation of new blood vessels, as indicated by CD31-positive staining mainly in the sub-epithelial region. These results indicate that rosuvastatin can effectively reduce airway inflammation and remodeling in mice with chronic allergic asthma caused by OVA, likely due to the reactivation of AMPKα and a decrease in angiogenesis.
Topics: Animals; Asthma; Rosuvastatin Calcium; AMP-Activated Protein Kinases; Signal Transduction; Airway Remodeling; Mice; Disease Models, Animal; Ovalbumin; Female; Mice, Inbred BALB C; Bronchoalveolar Lavage Fluid; Chronic Disease; Inflammation; Lung; Immunoglobulin E
PubMed: 38913666
DOI: 10.1371/journal.pone.0305863 -
The Canadian Journal of Urology Jun 2024Holmium enucleation of the prostate (HoLEP) is a gold-standard, size-independent surgical treatment for benign prostatic hyperplasia (BPH) distinguished for its efficacy...
Holmium enucleation of the prostate (HoLEP) is a gold-standard, size-independent surgical treatment for benign prostatic hyperplasia (BPH) distinguished for its efficacy in tissue removal, shorter catheterization durations, lower transfusion rates, and decreased hospital stays when compared to transurethral resection of the prostate (TURP). The objective of this article is to demonstrate the step-by-step procedure of holmium laser cystolitholapaxy and enucleation of the prostate for BPH, emphasizing a top-down modified two-lobe technique with early apical release which enhances visualization and irrigation flow during the enucleation process.
Topics: Humans; Male; Prostatic Hyperplasia; Lasers, Solid-State; Prostatectomy; Laser Therapy
PubMed: 38912945
DOI: No ID Found -
Respiratory Research Jun 2024Lower respiratory tract infections(LRTIs) in adults are complicated by diverse pathogens that challenge traditional detection methods, which are often slow and...
A single-center, retrospective study of hospitalized patients with lower respiratory tract infections: clinical assessment of metagenomic next-generation sequencing and identification of risk factors in patients.
INTRODUCTION
Lower respiratory tract infections(LRTIs) in adults are complicated by diverse pathogens that challenge traditional detection methods, which are often slow and insensitive. Metagenomic next-generation sequencing (mNGS) offers a comprehensive, high-throughput, and unbiased approach to pathogen identification. This retrospective study evaluates the diagnostic efficacy of mNGS compared to conventional microbiological testing (CMT) in LRTIs, aiming to enhance detection accuracy and enable early clinical prediction.
METHODS
In our retrospective single-center analysis, 451 patients with suspected LRTIs underwent mNGS testing from July 2020 to July 2023. We assessed the pathogen spectrum and compared the diagnostic efficacy of mNGS to CMT, with clinical comprehensive diagnosis serving as the reference standard. The study analyzed mNGS performance in lung tissue biopsies and bronchoalveolar lavage fluid (BALF) from cases suspected of lung infection. Patients were stratified into two groups based on clinical outcomes (improvement or mortality), and we compared clinical data and conventional laboratory indices between groups. A predictive model and nomogram for the prognosis of LRTIs were constructed using univariate followed by multivariate logistic regression, with model predictive accuracy evaluated by the area under the ROC curve (AUC).
RESULTS
(1) Comparative Analysis of mNGS versus CMT: In a comprehensive analysis of 510 specimens, where 59 cases were concurrently collected from lung tissue biopsies and BALF, the study highlights the diagnostic superiority of mNGS over CMT. Specifically, mNGS demonstrated significantly higher sensitivity and specificity in BALF samples (82.86% vs. 44.42% and 52.00% vs. 21.05%, respectively, p < 0.001) alongside greater positive and negative predictive values (96.71% vs. 79.55% and 15.12% vs. 5.19%, respectively, p < 0.01). Additionally, when comparing simultaneous testing of lung tissue biopsies and BALF, mNGS showed enhanced sensitivity in BALF (84.21% vs. 57.41%), whereas lung tissues offered higher specificity (80.00% vs. 50.00%). (2) Analysis of Infectious Species in Patients from This Study: The study also notes a concerning incidence of lung abscesses and identifies Epstein-Barr virus (EBV), Fusobacterium nucleatum, Mycoplasma pneumoniae, Chlamydia psittaci, and Haemophilus influenzae as the most common pathogens, with Klebsiella pneumoniae emerging as the predominant bacterial culprit. Among herpes viruses, EBV and herpes virus 7 (HHV-7) were most frequently detected, with HHV-7 more prevalent in immunocompromised individuals. (3) Risk Factors for Adverse Prognosis and a Mortality Risk Prediction Model in Patients with LRTIs: We identified key risk factors for poor prognosis in lower respiratory tract infection patients, with significant findings including delayed time to mNGS testing, low lymphocyte percentage, presence of chronic lung disease, multiple comorbidities, false-negative CMT results, and positive herpesvirus affecting patient outcomes. We also developed a nomogram model with good consistency and high accuracy (AUC of 0.825) for predicting mortality risk in these patients, offering a valuable clinical tool for assessing prognosis.
CONCLUSION
The study underscores mNGS as a superior tool for lower respiratory tract infection diagnosis, exhibiting higher sensitivity and specificity than traditional methods.
Topics: Humans; Retrospective Studies; Male; Female; Middle Aged; High-Throughput Nucleotide Sequencing; Metagenomics; Respiratory Tract Infections; Risk Factors; Aged; Adult; Bronchoalveolar Lavage Fluid; Hospitalization; Predictive Value of Tests
PubMed: 38902783
DOI: 10.1186/s12931-024-02887-y -
International Journal of Molecular... Jun 2024The nanosized vesicles secreted from various cell types into the surrounding extracellular space are called extracellular vesicles (EVs). Although mesenchymal stem...
The nanosized vesicles secreted from various cell types into the surrounding extracellular space are called extracellular vesicles (EVs). Although mesenchymal stem cell-derived EVs are known to have immunomodulatory effects in asthmatic mice, the role of identified pulmonary genes in the suppression of allergic airway inflammation remains to be elucidated. Moreover, the major genes responsible for immune regulation in allergic airway diseases have not been well documented. This study aims to evaluate the immunomodulatory effects of secretoglobin family 1C member 1 (SCGB1C1) on asthmatic mouse models. C57BL/6 mice were sensitized to ovalbumin (OVA) using intraperitoneal injection and were intranasally challenged with OVA. To evaluate the effect of SCGB1C1 on allergic airway inflammation, 5 μg/50 μL of SCGB1C1 was administrated intranasally before an OVA challenge. We evaluated airway hyperresponsiveness (AHR), total inflammatory cells, eosinophils in the bronchoalveolar lavage fluid (BALF), lung histology, serum immunoglobulin (Ig), the cytokine profiles of BALF and lung-draining lymph nodes (LLN), and the T cell populations in LLNs. The intranasal administration of SCGB1C1 significantly inhibited AHR, the presence of eosinophils in BALF, eosinophilic inflammation, goblet cell hyperplasia in the lung, and serum total and allergen-specific IgE. SCGB1C1 treatment significantly decreased the expression of interleukin (IL)-5 in the BALF and IL-4 in the LLN, but significantly increased the expression of IL-10 and transforming growth factor (TGF)-β in the BALF. Furthermore, SCGB1C1 treatment notably increased the populations of CD4CD25Foxp3 regulatory T cells (Tregs) in asthmatic mice. The intranasal administration of SCGB1C1 provides a significant reduction in allergic airway inflammation and improvement of lung function through the induction of Treg expansion. Therefore, SCGB1C1 may be the major regulator responsible for suppressing allergic airway inflammation.
Topics: Animals; T-Lymphocytes, Regulatory; Mice; Asthma; Mice, Inbred C57BL; Ovalbumin; Lung; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Immunoglobulin E; Female; Inflammation; Eosinophils
PubMed: 38892470
DOI: 10.3390/ijms25116282 -
Cells May 2024Chronic obstructive pulmonary disease (COPD) is a progressive lung disease for which there is no cure. Accumulating research results suggest a role for extracellular...
Chronic obstructive pulmonary disease (COPD) is a progressive lung disease for which there is no cure. Accumulating research results suggest a role for extracellular vesicles (EVs) in the pathogenesis of COPD. This study aimed to uncover the involvement of EVs and their molecular cargo in the progression of COPD by identification of EV-associated protein and microRNA (miRNA) profiles. We isolated EVs from the bronchial alveolar lavage fluid (BALF) of 18 patients with COPD and 11 healthy controls using size-exclusion chromatography. EV isolates were characterized using nanoparticle tracking analysis and protein content. Proteomic analysis revealed a higher abundance of 284 proteins (log2FC > 1) and a lower abundance of 3 proteins (log2FC < -1) in EVs derived from patients with COPD. Ingenuity pathway analysis showed that proteins enriched in COPD-associated EVs trigger inflammatory responses, including neutrophil degranulation. Variances in surface receptors and ligands associated with COPD EVs suggest a preferential interaction with alveolar cells. Small RNAseq analysis identified a higher abundance of ten miRNAs and a lower abundance of one miRNA in EVs from COPD versus controls (Basemean > 100, FDR < 0.05). Our data indicate that the molecular composition of EVs in the BALF of patients with COPD is altered compared to healthy control EVs. Several components in COPD EVs were identified that may perpetuate inflammation and alveolar tissue destruction.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Extracellular Vesicles; MicroRNAs; Bronchoalveolar Lavage Fluid; Male; Female; Middle Aged; Aged; Case-Control Studies; Proteomics
PubMed: 38891077
DOI: 10.3390/cells13110945 -
BMC Pulmonary Medicine Jun 2024Cystic fibrosis (CF) is a genetic multisystem disorder. Inflammatory processes, which presumably begin early in infancy, play a crucial role in the progression of the... (Comparative Study)
Comparative Study
BACKGROUND
Cystic fibrosis (CF) is a genetic multisystem disorder. Inflammatory processes, which presumably begin early in infancy, play a crucial role in the progression of the disease. The detection of inflammatory biomarkers, especially in the airways, has therefore gained increasing attention. Due to improved treatment options, patients with CF produce less sputum. Nasal lavage samples therefore represent a promising alternative to induced sputum or bronchoalveolar lavage specimens. However, methodology of cytokine measurements is not standardised and comparisons of results are therefore often difficult. The aim of this study was to identify suitable detection methods of cytokines in nasal lavage samples by comparison of two different assays.
METHODS
Nasal lavage samples were obtained from the same patient at the same time by trained respiratory physiotherapists using a disposable syringe and 10 ml of 0.9% sodium chloride per nostril during outpatient visits. The cytokines IL-17 A, IL-2, IL-6 and IL-10 were measured using two different assays (BD™ and Milliplex®), which have already been applied in sputum and nasal lavage samples, despite different lower detection limits.
RESULTS
22 participants were included in the study. In 95.5% of measurements, values were below the limit of detection with respect to the BD™ assay. Only IL-6 could be detected in approximately half of the patients. Individual cytokine levels were considerably higher when measured with Milliplex®, which is also reflected in a statistically significant manner (p = < 0.01).
CONCLUSION
The right choice of analysis method is crucial for measuring inflammatory markers in nasal lavage samples. Compared to the literature, Milliplex® showed higher detection rates and similar concentrations to other studies.
TRIAL REGISTRATION
Ethics approval was obtained from the ethics committee at Medical University of Innsbruck (EK Nr: 1055/2022).
Topics: Humans; Cystic Fibrosis; Male; Female; Cytokines; Adult; Adolescent; Nasal Lavage Fluid; Young Adult; Biomarkers; Child; Interleukin-6; Interleukin-10; Interleukin-2; Interleukin-17
PubMed: 38890643
DOI: 10.1186/s12890-024-03103-9 -
Annals of Clinical Microbiology and... Jun 2024Necrotizing tracheobronchitis is a rare clinical entity presented as a necrotic inflammation involving the mainstem trachea and distal bronchi. We reported a case of...
PURPOSE AND METHOD
Necrotizing tracheobronchitis is a rare clinical entity presented as a necrotic inflammation involving the mainstem trachea and distal bronchi. We reported a case of severe necrotizing tracheobronchitis caused by influenza B and methicillin-resistant Staphylococcus aureus (MRSA) co-infection in an immunocompetent patient.
CASE PRESENTATION
We described a 36-year-old man with initial symptoms of cough, rigors, muscle soreness and fever. His status rapidly deteriorated two days later and he was intubated. Bronchoscopy demonstrated severe necrotizing tracheobronchitis, and CT imaging demonstrated multiple patchy and cavitation formation in both lungs. Next-generation sequencing (NGS) and bronchoalveolar lavage fluid (BALF) culture supported the co-infection of influenza B and MRSA. We also found T lymphocyte and NK lymphocyte functions were extremely suppressed during illness exacerbation. The patient was treated with antivirals and antibiotics including vancomycin. Subsequent bronchoscopy and CT scans revealed significant improvement of the airway and pulmonary lesions, and the lymphocyte functions were restored. Finally, this patient was discharged successfully.
CONCLUSION
Necrotizing tracheobronchitis should be suspected in patients with rapid deterioration after influenza B infection. The timely diagnosis of co-infection and accurate antibiotics are important to effective treatment.
Topics: Humans; Male; Methicillin-Resistant Staphylococcus aureus; Coinfection; Influenza, Human; Adult; Staphylococcal Infections; Bronchitis; Anti-Bacterial Agents; Tracheitis; Influenza B virus; Bronchoscopy; Necrosis; Tomography, X-Ray Computed; Bronchoalveolar Lavage Fluid; Antiviral Agents
PubMed: 38886754
DOI: 10.1186/s12941-024-00715-1 -
Clinical and Experimental Dental... Jun 2024Self-performed oral hygiene is essential for preventing dental caries, periodontal, and peri-implant diseases. Oral irrigators are adjunctive oral home care aids that... (Review)
Review
OBJECTIVES
Self-performed oral hygiene is essential for preventing dental caries, periodontal, and peri-implant diseases. Oral irrigators are adjunctive oral home care aids that may benefit oral health. However, the effects of oral irrigation on oral health, its role in oral home care, and its mechanism of action are not fully understood. A comprehensive search of the literature revealed no existing broad scoping reviews on oral irrigators. Therefore, this study aimed to provide a comprehensive systematic review of the literature on oral irrigation devices and identify evidence gaps.
METHODS
The Joanna Briggs Institute and Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines were utilized to prepare the review. Four databases and eight gray literature sources were searched for English publications across any geographical location or setting.
RESULTS
Two hundred and seventy-five sources were included, predominantly from scientific journals and academic settings. Most studies originated from North America. Research primarily involved adults, with limited studies in children and adolescents. Oral irrigation was safe and well-accepted when used appropriately. It reduced periodontal inflammation, potentially by modulating the oral microbiota, but further research needs to clarify its mechanism of action. Promising results were reported in populations with dental implants and special needs. Patient acceptance appeared high, but standardized patient-reported outcome measures were rarely used. Anti-inflammatory benefits occurred consistently across populations and irrigant solutions. Plaque reduction findings were mixed, potentially reflecting differences in study designs and devices.
CONCLUSIONS
Oral irrigators reduce periodontal inflammation, but their impact on plaque removal remains unclear. Well-designed, sufficiently powered trials of appropriate duration need to assess the clinical, microbiological, and inflammatory responses of the periodontium to oral irrigation, particularly those with periodontitis, dental implants, and special needs. Patient-reported outcome measures, costs, caries prevention, and environmental impact of oral irrigation need to be compared to other oral hygiene aids.
Topics: Humans; Therapeutic Irrigation; Oral Hygiene; Oral Health; Dental Caries; Periodontal Diseases
PubMed: 38881230
DOI: 10.1002/cre2.912 -
Scientific Reports Jun 2024For successful root canal treatment, adequate chemomechanical instrumentation to eliminate microorganisms and pulp tissue is crucial. This study aims to assess the...
For successful root canal treatment, adequate chemomechanical instrumentation to eliminate microorganisms and pulp tissue is crucial. This study aims to assess the organic tissue dissolving activity of various irrigation solutions on bovine tooth pulp tissue. 40 extracted bovine mandibular anterior teeth (n = 10) were used for the study. Bovine pulp pieces (25 ± 5 mg) were placed in 1.5 ml Eppendorf tubes. Each tooth pulp sample was then covered with 1.5 ml of different irrigation solutions, dividing them into four groups: Group 1 with freshly prepared 5% Boric acid, Group 2 with 5% NaOCl, Group 3 with Irritrol, and Group 4 with Saline. Samples were left at room temperature for 30 min, then dried and reweighed. The efficacy of tissue dissolution ranked from highest to lowest was found to be NaOCl, Boric Acid, Irritrol, and saline (p < 0.05). It was observed that the decrease in the NaOCl group was greater than the decrease in the Irritrol and saline groups, and the decrease in the Boric acid group was significantly greater than the decrease in the saline group (p < 0.05). It also emphasizes the need for future studies to further investigate the effects of Irritrol and Boric Acid on tissue dissolution.
Topics: Animals; Cattle; Boric Acids; Root Canal Irrigants; Dental Pulp; Sodium Hypochlorite; Therapeutic Irrigation
PubMed: 38879635
DOI: 10.1038/s41598-024-64904-w