Neutrophil extracellular trap formation linked to idiopathic pulmonary fibrosis severity and survival.

RATIONALE: Neutrophil counts in bronchoalveolar lavage fluid in idiopathic pulmonary fibrosis are associated with worse outcomes; however, the underlying mechanisms are unknown. Neutrophil extracellular trap formation is associated with worse outcomes in several chronic lung diseases however, there is an unknown role in idiopathic pulmonary fibrosis. OBJECTIVES: To determine the relationship between neutrophil extracellular trap formation in the lungs of idiopathic pulmonary fibrosis patients and clinical outcomes. METHODS: In a discovery cohort of 156 patients with idiopathic pulmonary fibrosis, we measured neutrophil extracellular trap markers in bronchoalveolar lavage fluid, including extracellular DNA, DNA-myeloperoxidase complexes, calprotectin, and neutrophil elastase. We assessed the correlation of these markers with baseline pulmonary function and survival. In a subset of 50 patients, label-free quantitative proteomics was performed to identify the source of extracellular DNA. A validation cohort of 52 patients was similarly assessed. MEASUREMENTS AND MAIN RESULTS: Neutrophil extracellular trap markers in the discovery cohort were significantly correlated with worse pulmonary function (p<0.03). Higher levels of these markers predicted worse survival after adjusting for gender, age, and baseline physiologic severity (hazard ratio range: 1.79 - 2.19). Proteomics revealed a significant correlation between extracellular DNA levels and proteins related to neutrophil extracellular trap formation. The validation cohort showed that extracellular DNA levels were associated with reduced pulmonary function (p=0.04) and trend towards worse survival (hazard ratio=2.16). CONCLUSIONS: Neutrophil extracellular trap formation markers were associated with disease severity and worse survival in idiopathic pulmonary fibrosis. These findings suggest neutrophil extracellular trap formation contributes to lung injury and decreased survival and may represent a potential therapeutic target.

YouTube and pudendal neuralgia: Is it a good source of information for patients?

OBJECTIVE: This study aims to identify the shortcomings and quality content of YouTube videos and its effectiveness as a source of patient information on pudendal neuralgia treatment. METHODS: A search was conducted on YouTube using the words "pudendal neuralgia physical therapy," "medications for pudendal neuralgia," "pudendal nerve block," "pudendal neuralgia surgery," and "alternative treatments for pudendal neuralgia." The results were analyzed based on the source, general descriptive statistics, the intended audience, and five content areas. The DISCERN scoring system was used to evaluate the quality of videos. RESULTS: After the search, 73 videos met the inclusion criteria for further analysis. The majority of these videos (61.64%) were intended to target the general population, whereas a smaller percentage were identified as professional (41.10%) or targeted for physicians (35.62%). From the videos included, 10 (13.70%) described treatment options in a balanced and evidence-based manner. The higher DISCERN score positively correlated with the presence of this last content criterion. With a total DISCERN mean score of 35.42, a significant proportion of the videos (41.10%) were rated very poor. The remaining videos were classified as poor (23.29%), fair (19.18%), good (8.22%), and excellent (8.22%). CONCLUSION: The quality of the information included in YouTube videos regarding pudendal neuralgia treatment was considered generally poor. Healthcare providers must recognize the potential influence of this platform on patients' understanding of pudendal neuralgia treatment. There is a need for additional research and randomized studies regarding YouTube content about this condition.

Examining the Effects of Music-Based Interventions on Pain and Anxiety in Hospitalized Children: An Integrative Review.

PROBLEM: Children often experience pain and anxiety during a hospital stay. Effective pain and anxiety management plays a crucial role in healing. However, recent literature has highlighted multiple barriers to managing pain and anxiety in children, such as parent and provider fears of the adverse effects of pain and anxiety medications. ELIGIBILITY CRITERIA: A database search was conducted for articles published between 2009 and 2019 to evaluate the impact of nurse-led, music-based interventions as an adjunct method of pain and anxiety management in hospitalized children. Articles were included if study subjects were ages 0-21 years old, the study used live or recorded music as an intervention, and occurred in an inpatient setting. SAMPLE: A total of seven randomized control trials and one quasi-experimental study were included for analysis. RESULTS: There is consistent and significant evidence that music can reduce anxiety in hospitalized children before and during procedures. Results with respect to pain and vital signs, often viewed as the physiologic analogs to pain, were mixed. CONCLUSIONS: Music-based interventions are safe for hospitalized children. Several studies highlighted the importance of patient preference in selecting music for children. A heavy reliance on pre-recorded audio, delivered via headphones illustrates the feasibility and cost-effectiveness of music-based interventions. IMPLICATIONS: Nurse-led, music-based interventions have been shown to be an affordable, safe, effective, and feasible alternative for managing anxiety in hospitalized children. Music should be considered as an adjunct therapy to traditional anxiety treatment. Further research is needed to determine the effects of music on pain.

Gene therapy-mediated reprogramming tumor infiltrating T cells using IL-2 and inhibiting NF-κB signaling improves the efficacy of immunotherapy in a brain cancer model.

Immune-mediated gene therapy using adenovirus expressing Flt3 ligand and thymidine kinase followed by ganciclovir administration (Flt3/TK) effectively elicits tumor regression in preclinical glioma models. Herein, we assessed new strategies to optimize Flt3L/TK therapeutic efficacy in a refractory RG2 orthotopic glioblastoma model. Specifically, we aimed to optimize the therapeutic efficacy of Flt3L/TK treatment in the RG2 model by overexpressing the following genes within the brain tumor microenvironment: 1) a TK mutant with enhanced cytotoxicity (SR39 mutant TK), 2) Flt3L-IgG fusion protein that has a longer half-life, 3) CD40L to stimulate DC maturation, 4) T helper cell type 1 polarizing dendritic cell cytokines interleukin-12 or C-X-C motif ligand 10 chemokine (CXCL)-10, 5) C-C motif ligand 2 chemokine (CCL2) or C-C motif ligand 3 chemokine (CCL3) to enhance dendritic cell recruitment into the tumor microenvironment, 6) T helper cell type 1 cytokines interferon-γ or interleukin-2 to enhance effector T-cell functions, and 7) IκBα or p65RHD (nuclear factor kappa-B [NF-κB] inhibitors) to suppress the function of Foxp3+ Tregs and enhanced effector T-cell functions. Anti-tumor immunity and tumor specific effector T-cell functions were assessed by cytotoxic T lymphocyte assay and intracellular IFN-γ staining. Our data showed that overexpression of interferon-γ or interleukin-2, or inhibition of the nuclear factor kappa-B within the tumor microenvironment, enhanced cytotoxic T lymphocyte-mediated immune responses and successfully extended the median survival of rats bearing intracranial RG2 when combined with Flt3L/TK. These findings indicate that enhancement of T-cell functions constitutes a critical therapeutic target to overcome immune evasion and enhance therapeutic efficacy for brain cancer. In addition, our study provides novel targets to be used in combination with immune-therapeutic strategies for glioblastoma, which are currently being tested in the clinic.