Citations

AbstractBackground and objectiveIdiopathic pulmonary fibrosis (IPF) is increasingly diagnosed by clinical and computed tomography (CT) criteria; however, surgical lung biopsy (SLB) may still be required in patients who lack definite CT features of usual interstitial pneumonia (UIP). We reviewed a cohort of elderly patients who underwent SLB, to evaluate the benefit of SLB in diagnosing idiopathic interstitial pneumonia (IIP).MethodsWe searched the pathology records of Mayo Clinic for ambulatory patients at least 75 years old, who underwent SLB between 2000 and 2012 for indeterminate IIP. Histologic slides were reviewed and clinical data were extracted from the record.ResultsA total of 55 patients (35 male) were enrolled. Median (interquartile range) age was 77 (76–80) years. Forced vital capacity was 70 (61–76)% and diffusing capacity of the lungs for carbon monoxide was 48 (42–54)% of predicted. In total, 37 (67%) patients had IPF, including 61% of those with HRCT findings inconsistent with UIP. Thirty‐day mortality was 10% and 90‐day mortality was 15%.ConclusionThe high mortality rate of SLB complicates the risk–benefit analysis in elderly patients with IIP. The expected value of the SLB is probably highest when the HRCT features are inconsistent with UIP, due to the frequent (39%) retrieval of patterns other than UIP.

Abstract Objective To assess clinical documentation variations across health care institutions using different electronic medical record systems and investigate how they affect natural language processing (NLP) system portability. Materials and Methods Birth cohorts from Mayo Clinic and Sanford Children’s Hospital (SCH) were used in this study (n = 298 for each). Documentation variations regarding asthma between the 2 cohorts were examined in various aspects: (1) overall corpus at the word level (ie, lexical variation), (2) topics and asthma-related concepts (ie, semantic variation), and (3) clinical note types (ie, process variation). We compared those statistics and explored NLP system portability for asthma ascertainment in 2 stages: prototype and refinement. Results There exist notable lexical variations (word-level similarity = 0.669) and process variations (differences in major note types containing asthma-related concepts). However, semantic-level corpora were relatively homogeneous (topic similarity = 0.944, asthma-related concept similarity = 0.971). The NLP system for asthma ascertainment had anF-score of 0.937 at Mayo, and produced 0.813 (prototype) and 0.908 (refinement) when applied at SCH. Discussion The criteria for asthma ascertainment are largely dependent on asthma-related concepts. Therefore, we believe that semantic similarity is important to estimate NLP system portability. As the Mayo Clinic and SCH corpora were relatively homogeneous at a semantic level, the NLP system, developed at Mayo Clinic, was imported to SCH successfully with proper adjustments to deal with the intrinsic corpus heterogeneity.

Abstract Rationale Difficulty of asthma ascertainment and its associated methodologic heterogeneity have created significant barriers to asthma care and research. Objectives We evaluated the validity of an existing natural language processing (NLP) algorithm for asthma criteria to enable an automated chart review using electronic medical records (EMRs). Methods The study was designed as a retrospective birth cohort study using a random sample of 500 subjects from the 1997–2007 Mayo Birth Cohort who were born at Mayo Clinic and enrolled in primary pediatric care at Mayo Clinic Rochester. Performance of NLP-based asthma ascertainment using predetermined asthma criteria was assessed by determining both criterion validity (chart review of EMRs by abstractor as a gold standard) and construct validity (association with known risk factors for asthma, such as allergic rhinitis). Measurements and Main Results After excluding three subjects whose respiratory symptoms could be attributed to other conditions (e.g., tracheomalacia), among the remaining eligible 497 subjects, 51% were male, 77% white persons, and the median age at last follow-up date was 11.5 years. The asthma prevalence was 31% in the study cohort. Sensitivity, specificity, positive predictive value, and negative predictive value for NLP algorithm in predicting asthma status were 97%, 95%, 90%, and 98%, respectively. The risk factors for asthma (e.g., allergic rhinitis) that were identified either by NLP or the abstractor were the same. Conclusions Asthma ascertainment through NLP should be considered in the era of EMRs because it can enable large-scale clinical studies in a more time-efficient manner and improve the recognition and care of childhood asthma in practice.

Significance Antigen recognition by the immune system triggers rapid, specific, and protective responses, which are counterbalanced by inhibitory checkpoints to minimize potentially harmful immunity. The programmed death-1/ programmed death ligand-1 (PD-1/PD-L1) checkpoint is overreactive in cancer patients, curbing antitumor immunity. Whether a failing PD-1/PD-L1 checkpoint contributes to spontaneous autoimmune disease in humans is unknown. Here, we found that in patients with the autoimmune vasculitis giant cell arteritis, antigen-presenting cells provide insufficient negative signaling; unleashing highly activated T cells to infiltrate and damage the walls of large arteries. Thus, immunoinhibitory signals protect large arteries against inflammatory attack and checkpoint activation may be a suitable strategy to treat autoimmune vasculitis.

Summary Background: Pulmonary artery sarcoma (PAS) is a rare malignant neoplasm with an aggressive behavior and often difficult to distinguish from pulmonary thromboembolic disease. Aim: To assess the demographic, clinical, and radiological characteristics of PAS and clinical course. Design and Methods: We retrospectively identified and analyzed all patients with PAS seen at Mayo Clinic in Rochester, Minnesota, between January 1, 1996 and July 31, 2015. Results: Of nine patients (5 women and 4 men; median age 55 years [range, 24–74 years]), eight were diagnosed while alive with surgical (n = 6) or catheter-based endovascular biopsy (n = 2); the remaining patient was diagnosed at postmortem examination. All tumors manifested on CT as filling defect in the main, right or left pulmonary artery and were not associated with peripheral filling defects in seven patients. Seven patients were initially treated with anticoagulant therapy for presumed PE; two patients were suspected to have tumor based on constrictive or expanding effect seen on CT. Five patients died after a mean duration of 2.1 years (10 months–4.25 years) after diagnosis. Two patients are alive with recurrence and metastases of the disease 23 and 27 months after diagnosis, respectively; one remaining patient is alive and disease-free 116 months after diagnosis. Conclusions: Although PAS is associated with a poor prognosis, long-term survival is possible and can be improved by early diagnosis and prompt surgical resection. Atypical appearance on CT including central mass-like lesion without peripheral emboli and constrictive or expanding effect should raise suspicion of PAS.

Abstract Motivation Chromatin accessibility plays a key role in epigenetic regulation of gene activation and silencing. Open chromatin regions allow regulatory elements such as transcription factors and polymerases to bind for gene expression while closed chromatin regions prevent the activity of transcriptional machinery. Recently, Methyltransferase Accessibility Protocol for individual templates-Bisulfite Genome Sequencing (MAPit-BGS) and nucleosome occupancy and methylome sequencing (NOMe-seq) have been developed for simultaneously profiling chromatin accessibility and DNA methylation on single molecules. Therefore, there is a great demand in developing computational methods to identify chromatin accessibility from MAPit-BGS and NOMe-seq. Results In this article, we present CAME (Chromatin Accessibility and Methylation), a seed-extension based approach that identifies chromatin accessibility from NOMe-seq. The efficiency and effectiveness of CAME were demonstrated through comparisons with other existing techniques on both simulated and real data, and the results show that our method not only can precisely identify chromatin accessibility but also outperforms other methods. Availability and Implementation CAME is implemented in java and the program is freely available online at http://sourceforge.net/projects/came/ Supplementary information Supplementary data are available at Bioinformatics online.

ObjectiveInterstitial lung disease (ILD) is associated with substantial morbidity in rheumatoid arthritis (RA), but very little is known about its long‐term progression. This study was undertaken to investigate the progression of pulmonary disease using a large single‐center cohort of patients with RA‐associated ILD.MethodsRecords of all patients with RA‐associated ILD seen at Mayo Clinic between 1998 and 2014, with at least 4 weeks follow‐up and at least 1 pulmonary function test, were identified and manually screened for study inclusion. Progression was defined as a diffusing capacity for carbon monoxide (DLco) <40% predicted (or patients whose illness was too advanced to undergo screening) or a forced vital capacity (FVC) <50% predicted. Time to progression was analyzed using the Kaplan‐Meier method.ResultsOf the 167 patients included in the study, 81 (49%) were female, with a mean ± SD age of 67 ± 10 years at diagnosis of ILD. Median follow‐up time from diagnosis of ILD was 3.3 years (range 0.01–14.8). One‐third of the patients required supplemental oxygen, 40% developed DLco <40% predicted, and 22% developed FVC <50% predicted within 5 years after ILD diagnosis. Usual interstitial pneumonia (UIP) versus nonspecific interstitial pneumonia (NSIP) was a risk factor for DLco progression (hazard ratio 3.29 [95% confidence interval 1.28–8.41]). Lower DLco and FVC at baseline increased the risk for progression to DLco <40% predicted and FVC <50% predicted, and higher rates of change in the first 6 months also increased the risk of progression.ConclusionProgressive loss of pulmonary function is common in RA‐associated ILD and is worse in patients with UIP than in those with NSIP. Predictors of progression in patients with RA‐associated ILD may aid clinicians in identifying patients at highest risk for progression of ILD.