Differentiating pulmonary cavities.
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ABSTRACT:
SUBMITTER: O'Connell C
PROVIDER: S-EPMC9487378 | biostudies-literature | 2013 Jun
REPOSITORIES: biostudies-literature
Publications
Differentiating pulmonary cavities.
O'Connell Caroline C Abdul Aziz Mardiana M O'Keane John C JC Healy David D O'Callaghan Dermot S DS
European respiratory review : an official journal of the European Respiratory Society 20130601 128
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Project description:Rationale: There is poor understanding about protective immunity and the pathogenesis of cavitation in patients with tuberculosis.Objectives: To map pathophysiological pathways at anatomically distinct positions within the human tuberculosis cavity.Methods: Biopsies were obtained from eight predetermined locations within lung cavities of patients with multidrug-resistant tuberculosis undergoing therapeutic surgical resection (n = 14) and healthy lung tissue from control subjects without tuberculosis (n = 10). RNA sequencing, immunohistochemistry, and bacterial load determination were performed at each cavity position. Differentially expressed genes were normalized to control subjects without tuberculosis, and ontologically mapped to identify a spatially compartmentalized pathophysiological map of the cavity. In silico perturbation using a novel distance-dependent dynamical sink model was used to investigate interactions between immune networks and bacterial burden, and to integrate these identified pathways.Measurements and Main Results: The median (range) lung cavity volume on positron emission tomography/computed tomography scans was 50 cm3 (15-389 cm3). RNA sequence reads (31% splice variants) mapped to 19,049 annotated human genes. Multiple proinflammatory pathways were upregulated in the cavity wall, whereas a downregulation "sink" in the central caseum-fluid interface characterized 53% of pathways including neuroendocrine signaling, calcium signaling, triggering receptor expressed on myeloid cells-1, reactive oxygen and nitrogen species production, retinoic acid-mediated apoptosis, and RIG-I-like receptor signaling. The mathematical model demonstrated that neuroendocrine, protein kinase C-θ, and triggering receptor expressed on myeloid cells-1 pathways, and macrophage and neutrophil numbers, had the highest correlation with bacterial burden (r > 0.6), whereas T-helper effector systems did not.Conclusions: These data provide novel insights into host immunity to Mycobacterium tuberculosis-related cavitation. The pathways defined may serve as useful targets for the design of host-directed therapies, and transmission prevention interventions.
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Project description:BackgroundIt is increasingly recognized that recipient risk factors play a prominent role in possible transfusion-related acute lung injury (pTRALI) and transfusion-associated circulatory overload (TACO). We hypothesized that both transfusion and recipient factors including natriuretic peptides could be used to distinguish TRALI from TACO and pTRALI.Study design and methodsWe performed a post hoc analysis of a case-control study of pulmonary transfusion reactions conducted at the University of California at San Francisco and Mayo Clinic, Rochester. We evaluated clinical data and brain natriuretic peptides (BNP) levels drawn after transfusion in patients with TRALI (n = 21), pTRALI (n = 26), TACO (n = 22), and controls (n = 24). Logistic regression and receiver operating characteristics curve analyses were used to determine the accuracy of clinical and biomarker predictors in differentiating TRALI from TACO and pTRALI.ResultsWe found that pTRALI and TACO were associated with older age, higher fluid balance, and elevated BNP levels relative to those of controls and TRALI. The following variables were useful in distinguishing cases of pTRALI and TACO from TRALI: age more than 70 years, BNP levels more than 1000 pg/mL, 24-hour fluid balance of more than 3 L, and a lower number of transfused blood components. Using the above variables, our logistic model had a 91% negative predictive value in the differential diagnosis of TRALI.ConclusionsModels incorporating readily available clinical and biomarker data can be used to differentiate transfusion-related respiratory complications. Additional studies examining recipient risk factors and the likelihood of TRALI may be useful in decision making regarding donor white blood cell antibody testing.
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Project description:BACKGROUND:Although cavities are an important finding in Mycobacterium avium complex pulmonary disease (MAC-PD), there is little information regarding the types of cavities that indicate disease progression. This study was performed to identify cavity characteristics that were associated with disease progression in patients with MAC-PD. METHODS:This retrospective cohort study included 97 patients presenting with MAC-PD with cavities between December 2006 and June 2016. We compared initial and final computed tomography (CT) findings, classified 52 and 45 patients in the progressive and non-progressive cavity groups, respectively, and examined the progression-related imaging features in initial CT images. A progressive cavity was defined by more than two-fold increase in internal diameter or emergence of a new cavity around the initial cavity. RESULTS:Patients in the progressive group were older (p < 0.001), had a lower body mass index (p = 0.043), and showed higher diabetes complication rates (p = 0.005). The initial CT in the progressive group showed a longer maximum internal diameter of the cavity (p < 0.001) and higher rates of cavities close to the chest wall (p < 0.001), multiple cavities (p = 0.023), consolidation around the cavity (p < 0.001), atelectasis (p = 0.011), and pleural thickening (p < 0.001). Multivariable logistic regression analysis revealed that the maximum internal diameter of the cavity (odds ratio [OR]: 1.11, 95% confidence interval [CI]: 1.02-1.21; p=0.012) and consolidation around the cavity (OR: 16.15, 95% CI: 4.05-64.46; p < 0.001) were significantly associated with progressive cavities. In cavities with a maximum internal diameter of ≥10 mm and simultaneous consolidation, the probability of progression was as high as 96.2%. The 10-year mortality rates in the progressive and non-progressive cavity groups were 46.7 and 9.8% (p < 0.001), respectively, while the 10-year respiratory failure rates were 28.1 and 0%, respectively (p < 0.001). CONCLUSIONS:Large cavity size and consolidation on CT showed strong relationships with disease progression, which led to respiratory failure and high mortality rate.
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Project description:Background: Multidrug-resistant pulmonary tuberculosis (MDR-PTB) has become a major cause of high morbidity and mortality related to TB. Conventional drug regimens are ineffective for the treatment of MDR-PTB patients with cavities. This study aimed to evaluate the clinical efficacy and safety of one-way endobronchial valves (EBVs) for the treatment of cavities in MDR-PTB patients. Methods: MDR-PTB patients with positive sputum cultures, sputum smears, and cavities were treated with EBVs in the drainage bronchus of the pulmonary cavity between November 2013 and March 2018. The participants comprised those who had failed previous anti-tuberculosis therapy, as determined by drug susceptibility testing. Results: Thirty-five MDR-PTB patients were included, three of whom were lost during follow-up. The size of the lung cavity was reduced in all of the patients after EBV implantation, including the three lost to follow-up. In the remaining 32 patients, the sputum culture conversion (SCC) rate reached 100%, and the cavity closure rate was 68.8%. There were no significant differences in the cavity closure rate between patients aged ≤40 and >40 years, between the upper and lower lobes, or between the use and non-use of linezolid groups (p > 0.05). Interestingly, the cavity closure rate was higher in women than in men (p = 0.005). Moreover, the cavity closure rate correlated with the time to SCC (correlation coefficient, 0.8933; p < 0.0001). There were no severe adverse events in the patients treated with EBV implantation. Conclusion: EBV installation is effective and safe for the treatment of cavities in MDR-PTB patients. The efficacy of EBV treatment may not be affected by age, disease course, or the location of the lung lobe in the cavity.
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Project description:ObjectiveTo differentiate nontuberculous mycobacteria (NTM) pulmonary diseases from pulmonary tuberculosis (PTB) by analyzing the CT radiomics features of their cavity.Methods73 patients of NTM pulmonary diseases and 69 patients of PTB with the cavity in Shandong Province Chest Hospital and Qilu Hospital of Shandong University were retrospectively analyzed. 20 patients of NTM pulmonary diseases and 20 patients of PTB with the cavity in Jinan Infectious Disease Hospitall were collected for external validation of the model. 379 cavities as the region of interesting (ROI) from chest CT images were performed by 2 experienced radiologists. 80% of cavities were allocated to the training set and 20% to the validation set using a random number generated by a computer. 1409 radiomics features extracted from the Huiying Radcloud platform were used to analyze the two kinds of diseases' CT cavity characteristics. Feature selection was performed using analysis of variance (ANOVA) and least absolute shrinkage and selection operator (LASSO) methods, and six supervised learning classifiers (KNN, SVM, XGBoost, RF, LR, and DT models) were used to analyze the features.Results29 optimal features were selected by the variance threshold method, K best method, and Lasso algorithm.and the ROC curve values are obtained. In the training set, the AUC values of the six models were all greater than 0.97, 95% CI were 0.95-1.00, the sensitivity was greater than 0.92, and the specificity was greater than 0.92. In the validation set, the AUC values of the six models were all greater than 0.84, 95% CI were 0.76-1.00, the sensitivity was greater than 0.79, and the specificity was greater than 0.79. In the external validation set, The AUC values of the six models were all greater than 0.84, LR classifier has the highest precision, recall and F1-score, which were 0.92, 0.94, 0.93.ConclusionThe radiomics features extracted from cavity on CT images can provide effective proof in distinguishing the NTM pulmonary disease from PTB, and the radiomics analysis shows a more accurate diagnosis than the radiologists. Among the six classifiers, LR classifier has the best performance in identifying two diseases.
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Project description:BackgroundThe presence of cavities is associated with unfavorable prognosis in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD). However, little is known about the characteristics of such cavities and their impact on clinical outcomes. The aim of this study was to investigate the size of cavities and their implications on treatment outcomes and mortality in patients with NTM-PD.MethodsWe included patients diagnosed with NTM-PD at Seoul National University Hospital between January 1, 2007, and December 31, 2018. We measured the size of cavities on chest computed tomography scans performed at the time of diagnosis and used multivariable logistic regression and Cox proportional hazards regression analysis to investigate the impact of these measurements on treatment outcomes and mortality.ResultsThe study cohort comprised 421 patients (noncavitary, n = 329; cavitary, n = 92) with NTM-PD. During a median follow-up period of 49 months, 118 (35.9%) of the 329 patients with noncavitary and 64 (69.6%) of the 92 patients with cavitary NTM-PD received antibiotic treatment. Cavities >2 cm were associated with worse treatment outcomes (adjusted odds ratio, 0.41; 95% CI, 0.17-0.96) and higher mortality (adjusted hazard ratio, 2.52; 95% CI, 1.09-5.84), while there was no difference in treatment outcomes or mortality between patients with cavities ≤2 cm and patients with noncavitary NTM-PD.ConclusionsClinical outcomes are different according to the size of cavities in patients with cavitary NTM-PD; thus, the measurement of the size of cavities could help in making clinical decisions.
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Project description:In a previous analysis of the solvation of protein active sites, a drying transition was observed in the narrow hydrophobic binding cavity of Cox-2. With the use of a crude metric that often seems able to discriminate those protein cavities that dry from those that do not, we made an extensive search of the PDB, and identified five other proteins that, in molecular dynamics simulations, undergo drying transitions in their active sites. Because such cavities need not desolvate before binding hydrophobic ligands they often exhibit very large binding affinities. This article gives evidence that drying in protein cavities is not unique to Cox-2.
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