Project description:Multidrug-resistant tuberculosis (MDR-TB), resistance to at least isoniazid and rifampin, is a worldwide problem.To develop a clinical prediction rule to stratify risk for MDR-TB among patients with pulmonary tuberculosis.Derivation and internal validation of the rule among adult patients prospectively recruited from 37 health centers (Perú), either a) presenting with a positive acid-fast bacillus smear, or b) had failed therapy or had a relapse within the first 12 months.Among 964 patients, 82 had MDR-TB (prevalence, 8.5%). Variables included were MDR-TB contact within the family, previous tuberculosis, cavitary radiologic pattern, and abnormal lung exam. The area under the receiver-operating curve (AUROC) was 0.76. Selecting a cut-off score of one or greater resulted in a sensitivity of 72.6%, specificity of 62.8%, likelihood ratio (LR) positive of 1.95, and LR negative of 0.44. Similarly, selecting a cut-off score of two or greater resulted in a sensitivity of 60.8%, specificity of 87.5%, LR positive of 4.85, and LR negative of 0.45. Finally, selecting a cut-off score of three or greater resulted in a sensitivity of 45.1%, specificity of 95.3%, LR positive of 9.56, and LR negative of 0.58.A simple clinical prediction rule at presentation can stratify risk for MDR-TB. If further validated, the rule could be used for management decisions in resource-limited areas.
Project description:It is estimated that over 1.5 million lung nodules are detected annually in the United States. Most of these are benign but frequently undergo invasive and costly procedures to rule out malignancy. A risk predictor that can accurately differentiate benign and malignant lung nodules could be used to more efficiently route benign lung nodules to non-invasive observation by CT surveillance and route malignant lung nodules to invasive procedures. The majority of risk predictors developed to date are based exclusively on clinical risk factors, imaging technology or molecular markers. Assessed here are the relative performances of previously reported clinical risk factors and proteomic molecular markers for assessing cancer risk in lung nodules. From this analysis an integrated model incorporating clinical risk factors and proteomic molecular markers is developed and its performance assessed on a subset of 222 lung nodules, between 8mm and 20mm in diameter, collected in a previously reported prospective study. In this analysis it is found that the molecular marker is most predictive. However, the integration of clinical and molecular markers is superior to both clinical and molecular markers separately.Clinical trial registrationRegistered at ClinicalTrials.gov (NCT01752101).
Project description:A serum miRNA combination could be a favourable classifier to differentiate malignant pulmonary nodules from benign pulmonary nodules.
Project description:There are no large samples or exact prediction models for assessing the cancer risk factors of solitary pulmonary nodules (SPNs) in the Chinese population. We retrospectively analyzed the clinical and imaging data of patients with SPNs who underwent computer tomography guided needle biopsy in our hospital from Jan 1st of 2011 to March 30th of 2016. These patients were divided into a development data set and a validation data set. These groups included 1078 and 344 patients, respectively. A prediction model was developed from the development data set and was validated with the validation data set using logistic regression. The predictors of cancer in our model included female gender, age, pack-years of smoking, a previous history of malignancy, nodule size, lobulated and spiculated edges, lobulation alone and spiculation alone. The Area Under the Curves, sensitivity and specificity of our model in the development and validation data sets were significantly higher than those of the Mayo model and VA model (p < 0.001). We established the largest sampling risk prediction model of SPNs in a Chinese cohort. This model is particularly applicable to SPNs > 8 mm in size. SPNs in female patients, as well as SPNs featuring a combination of lobulated and spiculated edges or lobulated edges alone, should be evaluated carefully due to the probability that they are malignant.
Project description:The proteomics aspect of this project was simply to catalog the protein content in microlith nodule isolated from a Pulmonary alveolar microlithiasis patient or from a mouse model of the disease
Project description:BackgroundNon-invasive biomarkers are needed to improve management of indeterminate pulmonary nodules (IPNs) suspicious for lung cancer.MethodsProtein biomarkers were quantified in serum samples from patients with 6-30 mm IPNs (n = 338). A previously derived and validated radiomic score based upon nodule shape, size, and texture was calculated from features derived from CT scans. Lung cancer prediction models incorporating biomarkers, radiomics, and clinical factors were developed. Diagnostic performance was compared to the current standard of risk estimation (Mayo). IPN risk reclassification was determined using bias-corrected clinical net reclassification index.ResultsAge, radiomic score, CYFRA 21-1, and CEA were identified as the strongest predictors of cancer. These models provided greater diagnostic accuracy compared to Mayo with AUCs of 0.76 (95 % CI 0.70-0.81) using logistic regression and 0.73 (0.67-0.79) using random forest methods. Random forest and logistic regression models demonstrated improved risk reclassification with median cNRI of 0.21 (Q1 0.20, Q3 0.23) and 0.21 (0.19, 0.23) compared to Mayo for malignancy.ConclusionsA combined biomarker, radiomic, and clinical risk factor model provided greater diagnostic accuracy of IPNs than Mayo. This model demonstrated a strong ability to reclassify malignant IPNs. Integrating a combined approach into the current diagnostic algorithm for IPNs could improve nodule management.
Project description:Rationale: The management of indeterminate pulmonary nodules (IPNs) remains challenging, resulting in invasive procedures and delays in diagnosis and treatment. Strategies to decrease the rate of unnecessary invasive procedures and optimize surveillance regimens are needed.Objectives: To develop and validate a deep learning method to improve the management of IPNs.Methods: A Lung Cancer Prediction Convolutional Neural Network model was trained using computed tomography images of IPNs from the National Lung Screening Trial, internally validated, and externally tested on cohorts from two academic institutions.Measurements and Main Results: The areas under the receiver operating characteristic curve in the external validation cohorts were 83.5% (95% confidence interval [CI], 75.4-90.7%) and 91.9% (95% CI, 88.7-94.7%), compared with 78.1% (95% CI, 68.7-86.4%) and 81.9 (95% CI, 76.1-87.1%), respectively, for a commonly used clinical risk model for incidental nodules. Using 5% and 65% malignancy thresholds defining low- and high-risk categories, the overall net reclassifications in the validation cohorts for cancers and benign nodules compared with the Mayo model were 0.34 (Vanderbilt) and 0.30 (Oxford) as a rule-in test, and 0.33 (Vanderbilt) and 0.58 (Oxford) as a rule-out test. Compared with traditional risk prediction models, the Lung Cancer Prediction Convolutional Neural Network was associated with improved accuracy in predicting the likelihood of disease at each threshold of management and in our external validation cohorts.Conclusions: This study demonstrates that this deep learning algorithm can correctly reclassify IPNs into low- or high-risk categories in more than a third of cancers and benign nodules when compared with conventional risk models, potentially reducing the number of unnecessary invasive procedures and delays in diagnosis.