Enhancing the Identification of Rheumatoid Arthritis-Associated Lung Disease

Rheumatoid arthritis (RA) is a systemic autoimmune disease that predisposes afflicted individuals to reduced quality of life, physical disability, and premature mortality. While joint involvement is the primary manifestation of RA, extra-articular features including lung disease are responsible for a significant portion of the excess mortality. In this dissertation I demonstrate the contribution of chronic lung diseases to premature mortality in RA, contrasting with the more widely recognized comorbidity in RA of cardiovascular disease. Then, I establish that a novel serum biomarker, anti-malondialdehyde-acetaldehyde adduct (MAA) antibody, is associated with the presence of interstitial lung disease (ILD) in RA subjects. Further implicating its role in the pathogenesis of RA-ILD, I will demonstrate the presence of MAA as well as the co-localization of MAA with RA autoantigens and immune effectors cells in the lungs of RA-ILD subjects. Finally, I describe how biomedical informatics algorithms that incorporate multiple ILD diagnosis codes, provider specialty, and diagnostic testing can accurately classify ILD status in RA subjects. Together, these studies advance our ability to identify RA-associated lung diseases across the spectrum of clinical and translational research. These results will pave the way for future clinical and translational research studies to compose biomarker panels that aid in the screening of RA subjects for lung disease, identify pathways that could be targeted for novel therapeutics in RA-ILD, and facilitate the completion of comparative effectiveness and outcomes research studies using real-world data

Cancer Immunotherapy Comes of Age

Modern cancer immunotherapy is the reemergence of an old field striving to use the body’s immune system to target cancer. Though cancer subverts the innate and adaptive immune systems, various non-cellular and cellu-lar based therapies have been developed to overcome these mechanisms. The variety of these techniques and their potential in the treatment of cancer has been a truly exciting development in medicine

Updating and Validating the Rheumatic Disease Comorbidity Index to ICD-10-CM

Background/Objective: Comorbidities can contribute to increased risk for mortality and disability in individuals with rheumatoid arthritis (RA)1,2. The Rheumatic Disease Comorbidity Index (RDCI) assesses 11 comorbidities and produces a weighted score (0-9) that accurately predicts several health outcomes3. The RDCI was developed with self-report data and later validated with ICD-9-CM codes collected from administrative data3,4. On October 1, 2015, the U.S. transitioned to ICD-10-CM, resulting in a nearly five-fold increase in the number of codes available to classify conditions5. Our objective was to update the RDCI by translating it into ICD-10-CM. Methods: We defined an ICD-9-CM cohort and an ICD-10-CM cohort using patient data from the Veterans Affairs Rheumatoid Arthritis Registry (VARA). ICD-10-CM codes were generated by converting ICD-9-CM codes using tools that provide suggested crosswalks, and the codes were reviewed by a physician to assess clinical relevance. Comorbidities were collected from national VA administrative data over a two-year period in both cohorts (ICD-9-CM: October 1, 2013 to September 30, 2015; ICD-10-CM: January 1, 2016 to December 31, 2017). Comorbidity frequencies were compared using Cohen’s Kappa, and RDCI scores were compared using Intraclass Correlation Coefficients (ICC). Results: Both the ICD-9-CM cohort (n=1,082) and ICD-10-CM cohort (n=1,446) were predominantly male (ICD-9-CM: 89%; ICD-10-CM: 87%), Caucasian (ICD-9-CM: 76%; ICD-10-CM: 73%), and middle to old-aged (ICD-9-CM: 67.3 ± 10.2 years; ICD-10-CM: 68.2 ± 10.0 years). Prevalence of comorbidities were similar between coding systems, with absolute differences less than 4% (range: 0.28 to 3.91). Myocardial infarction, hypertension, diabetes mellitus, depression, stroke, other cardiovascular, lung disease, and cancer had moderate agreement or higher (range κ: 0.47 to 0.84), while fracture and ulcer/stomach problem had slight and fair agreement, respectively (κ = 0.13; κ = 0.27)6,7. The RDCI scores were 2.95 ± 1.73 (mean ± SD) for the ICD-9-CM cohort and 2.93 ± 1.75 for the ICD-10-CM cohort. RDCI scores had moderate agreement (ICC: 0.71; 95% CI: 0.68-0.74)8 among individuals who were observed during both the ICD-9-CM and ICD-10-CM eras. Conclusion: We have mapped the RDCI from ICD-9-CM to ICD-10-CM codes, generating comparable RDCI scores in a large RA registry. Individual comorbidity agreement varied, with more chronic conditions such as diabetes and hypertension having higher agreement and more acute conditions such as fractures and ulcer/stomach problems having lower agreement. The updated RDCI can be used in clinical outcomes research with ICD-10-CM era patient data.https://digitalcommons.unmc.edu/surp2021/1043/thumbnail.jp

The PiSpec: A Low-Cost, 3D-Printed Spectrometer for Measuring Volcanic SO2 Emission Rates

Spectroscopy has been used to quantify volcanic gas emission rates, most commonly SO2, for a number of decades. Typically, commercial spectrometers costing 1000s USD are employed for this purpose. The PiSpec is a new, custom-designed, 3D-printed spectrometer based on smartphone sensor technology. This unit has ≈1 nm spectral resolution and a spectral range in the ultraviolet of ≈280–340 nm, and is specifically configured for the remote sensing of SO2 using Differential Optical Absorption Spectroscopy (DOAS). Here we report on the first field deployment of the PiSpec on a volcano, to demonstrate the proof of concept of the device’s functionality in this application area. The study was performed on Masaya Volcano, Nicaragua, which is one of the largest emitters of SO2 on the planet, during a period of elevated activity where a lava lake was present in the crater. Both scans and traverses were performed, with resulting emission rates ranging from 3.2 to 45.6 kg s−1 across two measurement days; these values are commensurate with those reported elsewhere in the literature during this activity phase (Aiuppa et al., 2018; Stix et al., 2018). Furthermore, we tested the PiSpec’s thermal stability, finding a wavelength shift of 0.046 nm/∘C between 2.5 and 45∘C, which is very similar to that of some commercial spectrometers. Given the low build cost of these units (≈500 USD for a one-off build, with prospects for further price reduction with volume manufacture), we suggest these units hold considerable potential for volcano monitoring operations in resource limited environments