Project description:Cryptococcal osteomyelitis is an infrequent infection which is usually associated with disseminated cryptococcosis or underlying immunocompromised conditions. Here we described a rare case with isolated iliac cryptococcosis in an immunocompetent patient. Through histological, microbial, and molecular biological examinations, the pathogen was finally identified as C. neoformans VNI genotype, which likely originated from environmental bird droppings. The clinical isolate was hypomelanized but fully virulent in mouse infection model. The patient displayed lower CD4+-T lymphocyte ratio, reduced serum IFN-γ and IL-12, and dysregulated transcriptional profile of blood leukocytes compare with healthy host. After surgical excision and 34 weeks’ antifungal treatment, the patient got clinical cured. Our study suggested that cryptococcosis development was closely associated with the interaction of fungal agent and host immunity. Accurate diagnosis of bone cryptococcosis depends mainly on histological and fungal examinations. A combination of antifungal agent treatment regimen and surgery were quite effective for resolving bone cryptococcosis.
Project description:Pleural infection is a severe and complicated disease with increasing incidence worldwide and is characterised by substantial associated morbidity and mortality.1,2 Although it is accepted that the disease is heterogeneous, and there is a validated clinical prediction score (RAPID)3,4, the biological endotypes of pleural infection remain elusive and pleural fluid specific criteria to assess the intrapleural response are not available. A better understanding of pleural infection subtypes could lead to improved treatment strategies and clinical outcomes. All patients with pleural infection follow the same clinical journey which focusses on hospital admission, pleural fluid drainage and administration of antibiotics however, their recovery progress and clinical outcomes differ significantly.1,2 A subgroup of patients exhibits ineffective or failed intrapleural fibrinolysis leading to the development of fibrous septations which further complicates treatment. Consequently, approximately 30% of patients do not respond to treatment and require invasive treatments including surgical drainage. Tandem mass spectrometry is a high-throughput proteomics assay which is a reliable, unbiased, and hypothesis-free analytical method for investigating the underlying biology of disease using clinical specimens.5 The pleural fluid proteome faithfully reflects the intrapleural environment and could be utilised to identify disease key mediators, biomarkers, and treatment targets. For instance, pleural fluid pH, glucose and lactate dehydrogenase are used as clinical biochemistry markers for diagnosing patients with pleural infection.1 Our study (The Oxford Pleural Infection Endotyping Study, TORPIDS 2) applied mass spectrometry to pleural fluid specimens (n=80) from the PILOT trial.4 Our primary aims were to discover endotypes in pleural infection, characterise the intrapleural immune response and investigate the association between patient endotypes and high-precision bacterial patterns. We assessed the association between pleural infection endotypes and important clinical outcomes (1-year survival and need for surgery)
Project description:Pleural fibrosis is defined as an excessive deposition of extracellular matrix (ECM) that results in destruction of the normal pleural tissue architecture and compromised function. However there is currently no effective medication for pleural fibrosis. Understanding the detailed mechanisms of pleural fibrosis is an important unmet need which could lead to the identification of new targets for treatment of this condition. microRNAs (miRNAs) play an important role in the posttranscriptional control of gene expression. In our study, cellular fractions from TBPE contained activities capable of promoting fibrosis-like behavior in pleural mesothelial cells (PMCs), the goal of this study is to compare the exosomal miRNA composition of TBPE and TPE. We isolated exosomes from transudative pleural effusion and tuberculous pleural effusions and performed miRNA sequencing. Our study represents the first detailed analysis of exosomal miRNA composition of TBPE and TPE with biologic replicates, generated by miRNA-Seq technology.
Project description:Pleural effusion (PE) occurs as a consequence of various pathologies. Malignant effusion due to lung cancer is one of the most frequent causes. Methods for accurate differentiation of malignant from benign PE cases are an unmet clinical need. Proteomics profiling of PE has shown promising results. However, mass spectrometry (MS) analysis typically involves the tedious elimination of abundant proteins before analysis, and clinical annotation of proteomics profiled cohorts is limited. In this study, PE from 97 patients was investigated by applying label-free state-of-the-art liquid chromatography-mass spectrometry (LC-MS) to find potential novel biomarkers that correlate with immunohistochemistry assessment of tumor biopsy or survival data. The data set consists of 214 LC-MS runs.
Project description:RATIONALE: Using BG00001 to insert the gene for interferon-beta into a person’s pleural cavity may improve the body’s ability to fight cancer.
PURPOSE: Phase I trial to study the effectiveness of intrapleural BG00001 in treating patients who have malignant pleural mesothelioma or malignant pleural effusions.