Evaluation of an automated phenotyping algorithm for rheumatoid arthritis.

To better understand the challenges of generally implementing and adapting computational phenotyping approaches, the performance of a Phenotype KnowledgeBase (PheKB) algorithm for rheumatoid arthritis (RA) was evaluated on a University of California, Los Angeles (UCLA) patient population, focusing on examining its performance on ambiguous cases. The algorithm was evaluated on a cohort of 4,766 patients, along with a chart review of 300 patients by rheumatologists against accepted diagnostic guidelines. The performance revealed low sensitivity towards specific subtypes of positive RA cases, which suggests revisions in features used for phenotyping. A close examination of select cases also indicated a significant portion of patients with missing data, drawing attention to the need to consider data integrity as an integral part of phenotyping pipelines, as well as issues around the usability of various codes for distinguishing cases. We use patterns in the PheKB algorithm's errors to further demonstrate important considerations when designing a phenotyping algorithm.

Exercise rehabilitation for neurogenic thoracic outlet syndrome: a scoping review.

Exercise rehabilitation has been proposed for the management of Neurogenic Thoracic Outlet Syndrome (NTOS). To date there have been no reviews of the literature regarding exercise rehabilitation for NTOS and their proposed clinical rationale. Understanding various exercise protocols and their clinical rationale may help guide rehabilitation clinicians in their exercise selection when managing NTOS. A scoping review was conducted on exercise rehabilitation for NTOS from inception to March 2021 in the PubMed database. Forty-seven articles consisting of literature reviews, non-randomized control trials, prospective and retrospective cohort studies, case series, case studies and clinical commentaries met the inclusion criteria. This scoping review provides a broad overview of the most common exercise protocols that have been published and examines the purported clinical rationale utilized in the management of NTOS.

La rééducation par l'exercice a été proposée pour la prise en charge du syndrome neurologique du syndrome du défilé thoraco-brachial neurologique (SDTB). À ce jour, il n'y a eu aucune publication concernant la rééducation par l'exercice pour le SDTB et leur justification clinique proposée. Comprendre divers protocoles d'exercices et leur justification clinique peut aider à guider les cliniciens en réadaptation dans leur sélection d'exercices lors de la gestion du SDTB. Un examen de la portée a été effectué sur la rééducation par l'exercice pour le SDTB depuis sa création jusqu'en mars 2021 dans la base de données PubMed. Quarante-sept articles composés de revues littéraires, d'essais contrôlés non randomisés, d'études de cohorte prospectives et rétrospectives, de séries de cas, d'études de cas et de commentaires cliniques répondaient aux critères d'inclusion. Cet examen de la portée fournit un large aperçu des protocoles d'exercice les plus courants qui ont été publiés et examine la prétendue justification clinique utilisée dans la gestion du SDTB.

Cardiovascular disease in systemic lupus erythematosus.

There is a well-known increased risk for cardiovascular disease that contributes to morbidity and mortality in systemic lupus erythematosus (SLE). Major adverse cardiovascular events and subclinical atherosclerosis are both increased in this patient population. While traditional cardiac risk factors do contribute to the increased risk that is seen, lupus disease-related factors, medications, and genetic factors also impact the overall risk. SLE-specific inflammation, including oxidized lipids, cytokines, and altered immune cell subtypes all are likely to play a role in the pathogenesis of atherosclerotic plaques. Research is ongoing to identify biomarkers that can help clinicians to predict which SLE patients are at the greatest risk for cardiovascular disease (CVD). While SLE-specific treatment regimens for the prevention of cardiovascular events have not been identified, current strategies include minimization of traditional cardiac risk factors and lowering of overall lupus disease activity.

Challenges of caring for homeless patients with rheumatic and musculoskeletal disorders in Los Angeles.

Homelessness is a public health crisis. Homeless individuals have significantly worse health outcomes than the general population. We have begun examining challenges of caring for homeless patients with rheumatic and musculoskeletal diseases. Difficulties include physical environment, food and financial insecurity, access to healthcare, low health literacy, and comorbid mental illness, and substance abuse. Based on known prevalences of rheumatic and musculoskeletal diseases (RMSDs), we extrapolate that there are thousands of homeless with rheumatoid arthritis (RA), systemic lupus erythematosus, psoriatic arthritis, gout, and osteoarthritis. We present preliminary observations of disparities in the care of homeless patients with RA seen at the Los Angeles County Medical Center of the Keck School of Medicine of the University of Southern California. They tended to be African American males, missed appointments, utilized emergency services frequently, tended not to be on medications, and exhibited severe disease. We reviewed the available literature on homelessness and homeless healthcare to consider what further studies might be helpful and what interventions might improve the care of patients with RMSDs. We identified several aspirational and practical recommendations. These include ensuring access to healthcare for the homeless (indeed for all); reducing disparities through policy, tailored care, and enhanced social services; and recognizing and treating disease early. Developing better approaches for the care of these homeless has obvious and important implications for other underserved populations needing rheumatologic care, patients with early arthritis, or situations where rheumatologists are unavailable. We believe that physicians have a special responsibility to mitigate inequities in this particularly disadvantaged population.

Should a patient with rheumatoid arthritis be a kidney donor?

We cared for a woman with sero-positive rheumatoid arthritis (RA), in clinical remission on oral methotrexate (MTX) and hydroxychloroquine, who wished to donate a kidney to a brother with end-stage renal disease (ESRD). We could find scant literature about this unusual clinical circumstance, and therefore review pertinent aspects of renal disease in RA, perioperative medical management, maintenance of disease remission, outcomes for RA patients who have donated kidneys, and relevant ethical issues. Renal complications in RA are not uncommon, with as many as 50% of patients at risk of reduced eGFR. This reflects anti-rheumatic and analgetic medication use (non-steroidal anti-inflammatory drugs, acetaminophen, DMARDs [cyclosporine and, historically, D-penicillamine and gold compounds], and others), glomerulitis, interstitial nephritis, complicating Sjogren's syndrome, vasculitis, or amyloidosis, and/or emergence of an "overlap" syndrome or other rheumatic disorder. The literature suggests that MTX need not be interrupted for surgery. The risk of perioperative infection to our patient would be low and remission should be sustained. We are aware of one study of six patients with RA who donated kidneys; they experienced no complications, ESRD, or deaths after a median follow-up of 8.2 years. Our ethical responsibilities are to balance patient autonomy of decision-making while assuring clinical beneficence and minimizing potential maleficence. Our perspective was that it would not be unreasonable to support this patient donating a kidney if, when fully informed, that remained her wish.

Differential expression of circulating biomarkers of tumor phenotype and outcomes in previously treated non-small cell lung cancer patients receiving erlotinib vs. cytotoxic chemotherapy.

BACKGROUND: The objective of this study was to identify serum biomarkers capable of predicting clinical outcomes in previously-treated NSCLC patients with wild-type for EGFR activating mutations or insufficient tissue for mutation status determination. METHODS: Sixty-six Luminex immunoassays representative of biological themes that emerged from a re-analysis of transcriptome data from the Cancer Genome Atlas (TCGA) were evaluate against pretreatment serum specimens from previously-treated advanced NSCLC patients received either cytotoxic chemotherapy (n=32) or erlotinib (n=79). Known EGFR mutation positive cases were excluded from analysis. Associations of biomarkers with outcome parameters and their differential interaction with treatment for survival outcomes were assessed using multivariate Cox PH analyses. RESULTS: Our EMT-based transcriptomic analysis revealed a range of biological processes associated with angiogenesis, apoptosis, cachexia, inflammation, and metabolism emerging as those most highly associated with patient outcome. These processes were evaluated via surrogate serum biomarkers. A treatment-biomarker interaction analysis revealed that higher pretreatment levels of c-Met signaling biomarkers (i.e. HGF levels), pro-inflammatory/ pro-cachexia (e.g. IL-8, sIL-2Rα, FGF-2) processes and a pro-angiogenic (e.g. TGF-α, IL-8, VEGF) milieu were associated with inferior survival (HR=0.35, 0.29, 0.58, 0.50, 0.61, 0.45, respectively; all p<0.05) for patients receiving chemotherapy, relative to erlotinib. In contrast, high levels of decoy receptor for IL-1, sIL-1RII, and a high tissue vimentin/E-cadherin ratio were associated with a poor OS (HR=3.78; p=0.00055) in the erlotinib cohort. CONCLUSIONS: Contemporary precision medicine initiatives that pair patient tumor characteristics with the optimal therapy type may maximize the use of agents targeting EGFR in the treatment of NSCLC.