Systemic lupus erythematosus (SLE): emerging therapeutic targets.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a heterogeneous clinical presentation whose etiologies are multifactorial. A myriad of genetic, hormonal, immunologic, and environmental factors contribute to its pathogenesis, and its diverse biological basis and phenotypic presentations make development of therapeutics difficult. In the past decade, tens of therapeutic targets with hundreds of individual candidate therapeutics have been investigated. AREAS COVERED: We used a PUBMED database search through April 2020 to review the relevant literature. This review discusses therapeutic targets in the adaptive and innate immune systems, specifically: B cell surface antigens, B cell survival factors, Bruton's tyrosine kinase, costimulators, IL-12/IL-23, the calcineurin pathway, the JAK/STAT pathway, and interferons. EXPERT OPINION: Our ever-improving understanding of SLE pathophysiology in the past decade has allowed us to identify new therapeutic targets. Multiple new drugs are on the horizon that target different elements of the adaptive and innate immune systems. SLE research remains challenging due to the heterogenous clinical presentation of SLE, confounding from background immunosuppressives being taken by SLE patients, animal models that inadequately recapitulate human disease, and imperfect and complicated outcome measures. Despite these limitations, research is promising and ongoing. The search for new therapies that target specific elements of SLE pathophysiology are discussed as well as key findings, pitfalls, and questions surrounding these targets.

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.

Has Rheumatology Become a More Attractive Career Choice? Comparison of Trends in the Rheumatology Fellowship Match From 2008 to 2013 With Those From 2014 to 2017.

OBJECTIVE: Rheumatology has previously been a less attractive career choice than other internal medicine (IM) subspecialties. Recent fellowship data from the National Resident Matching Program (NRMP) has suggested that this may have changed. Therefore, we evaluated the current attractiveness of rheumatology as a career choice and compared it with other medical subspecialties. METHODS: Data from the NRMP from 2008 to 2017, the 2015 American College of Rheumatology workforce study, and Medscape physician salaries from 2010 to 2017 were used to determine annual numbers of fellowship applicants, availability of positions, and post-fellowship salary trends. Data from 2008 to 2013 were compared with those from 2014 to 2017, and rheumatology was compared with other IM subspecialties. RESULTS: The total number of annual fellowship applicants to rheumatology for 2008-2013 decreased by 3% (average annual mean ± SEM percentage change of -1.9 ± 2.6%), from 251 to 244 applicants. However, for 2014-2017, annual rheumatology applications increased by 44% (average annual mean ± SEM percentage change of 20.7 ± 10.5% [P = 0.03]), from 230 to 332 applicants. Other nonprocedural and procedural IM subspecialties did not exhibit a similar increase. For rheumatology, the increases in the ratio of annual applicants to positions (P = 0.02) and in the percentage of US medical graduates applying (P = 0.03) were statistically significant, and mean post-fellowship salary also rose. CONCLUSION: The aforementioned observations suggest that rheumatology has become a more attractive career choice since 2014. We speculate that the increasing popularity of the field is multifactorial, likely reflecting lifestyle, job satisfaction and availability, influence of mentors, and other elements. This salutary and exciting potential opportunity for rheumatology should be exploited.

Long-term Kidney Outcomes in Patients With Acquired Thrombotic Thrombocytopenic Purpura.

INTRODUCTION: Severe acute kidney injury (AKI) and chronic kidney disease (CKD) are considered to be uncommon in patients with acquired thrombotic thrombocytopenic purpura. However, a recent case series from a tertiary care hospital indicated that 54 (59%) of 92 patients with thrombotic thrombocytopenic purpura presented with AKI; 14 (15%) required dialysis; and 12 (22%) of the 54 patients had CKD at follow-up. METHODS: In this prospective analysis of 78 patients diagnosed with their first episode of thrombotic thrombocytopenic purpura and enrolled in the Oklahoma Thrombotic Thrombocytopenic Purpura Registry from 1995 to 2015, we assessed AKI at diagnosis using Kidney Disease: Improving Global Outcomes criteria, and CKD at follow-up as defined by estimated glomerular filtration rate <60 ml/min per 1.73 m2 determined by the Chronic Kidney Disease-Epidemiology Collaboration equation. RESULTS: Forty-five (58%) patients had AKI; 8 (10%) had stage 3 AKI, and 3 (4%) required dialysis. AKI was not associated with the patients' demographic or presenting clinical features. Three of the 8 patients with stage 3 AKI died; among the 5 survivors, estimated glomerular filtration rate was 77 to 107 ml/min per 1.73 m2 (median, 92) with median follow-up of 8.1 years. Among all 62 surviving patients who have had follow-up serum creatinine measurements, 4 (6%) had CKD with median follow-up of 6.4 years. AKI was not associated with the occurrence of CKD (P = 0.74). No patients have required continuing renal replacement therapy. DISCUSSION: In this population-based prospective cohort of consecutive patients with thrombotic thrombocytopenic purpura, without selection or referral bias, severe AKI and CKD are uncommon.

Transthoracic echocardiogram is a useful tool in the hemodynamic assessment of patients with chest trauma.

INTRODUCTION: The utility of transthoracic echocardiogram (TTE) in patients on the trauma service is not well defined. The aim of this study was to evaluate the frequency of abnormal echocardiographic findings that would aid in the assessment and management of cardiovascular hemodynamics in patients with chest trauma. METHODS: A retrospective analysis of all patients who had a TTE on the trauma service at a level 1 trauma center during a 12-month period was performed. RESULTS: There were 94 patients in the study. TTE was performed after cardiac surgery in 5 patients. One of the 5 patients with prior cardiac surgery was excluded from the study because of poor quality images, and each of the remaining 4 patients showed significant TTE abnormalities. Of the 89 patients without prior cardiac surgery, 38 (43%) had significant TTE findings although 32 (84%) of them had no known history of cardiac abnormalities. A decreased left ventricular ejection fraction (<50%) was found in 18% of all patients, and half of them were hemodynamically unstable. Significant valvular regurgitation or stenosis was found in 31 patients, pulmonary hypertension in 25 patients, left ventricular wall motion abnormalities in 12 patients and pericardial effusion in 11 patients. CONCLUSION: Significant echocardiographic abnormalities are detected by TTE in patients with chest trauma. Such findings can be used in the hemodynamic assessment and management of unstable patients during their hospitalization and in planning long-term follow-up and management of these patients after discharge from the hospital.