Opioid use in patients with polymyalgia rheumatica.

OBJECTIVES: To examine the trends of chronic opioid use in patients with polymyalgia rheumatica (PMR) over an 11-year period in Olmsted County, Minnesota, USA and compare use to subjects without the disease. METHODS: Retrospective data on opioid prescriptions were collected from 2005 to 2015 in a population-based incidence cohort of patients meeting the 2012 American College of Rheumatology classification criteria for PMR alongside comparison subjects. Poisson regression methods were used to compare opioid use between these groups. RESULTS: 244 patients with PMR and 211 non-PMR comparator subjects were included in the study. Rates of chronic opioid use were not significantly different between the two groups. 7.5% of patients with PMR were identified as chronic users by the end of the study period compared with 5.2% of non-PMR subjects. Any opioid use was also not significantly higher in PMR, with relative risk of 1.10 (95% CI 0.97, 1.26, p=0.14). Rates of chronic use among patients over 80 years were higher in both groups. CONCLUSIONS: Patients with PMR do not appear to have higher rates of opioid use compared with the general population.

Clinical Presentations and Outcomes of Patients Receiving Immune Checkpoint Inhibitors Presenting to the Emergency Department.

Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of cancer. Immune checkpoint inhibitors may cause a wide-range of autoimmune toxicities referred to as immune-related adverse events (irAEs). There is a paucity of data regarding the presentations and outcomes of patients receiving ICIs who seek care in an emergency department (ED). We performed a retrospective review of patients receiving an ICI who presented to a tertiary care ED between May 1, 2017, and April 30, 2018. Data including ED chief complaint, diagnosis, treatment, and disposition were collected along with baseline characteristics and diagnosis at the time of outpatient oncology follow-up. We report descriptive statistics summarizing the characteristics of the cohort. There were 98 ED visits identified among 67 unique patients. Immune-related adverse events were diagnosed in 16 (16.3%) cases. The most common chief complaints within the irAE group were gastrointestinal symptoms 10 (62.5%). Among the 16 confirmed irAE cases, the most common irAE diagnosed was colitis 9 (56.3%). Two (12.5%) patients with irAEs received corticosteroids during their stay in the ED, and 10 (62.5%) patients with irAEs required hospital admission. Emergency medicine providers documented consideration of an irAE in the differential diagnosis in 14.3% of all ED visits and in 43.8% of visits in which an irAE was ultimately diagnosed. Emergency providers should be familiar with ICIs given their expanding use and potential adverse effects to improve early recognition and patient outcomes in ED settings.

Immunologic adverse events from immune checkpoint therapy.

The growth of cancer immunotherapy has led to an urgent need for a multispecialty approach to treating patients with advanced malignancies. Checkpoint inhibitor therapies cause a wide range of toxicities termed immune-related adverse events (irAEs) that can affect any organ system. Similar to the anti-tumor responses induced by these medications, irAEs represent an interruption of self-tolerance that results in T cell-driven cytotoxicity, the exact mechanisms of which are likely heterogeneous. This review describes the various immunologic pathways that may lead to irAEs along with the diverse clinical manifestations seen in clinical practice. Treatment based on the severity and specific organ involvement will also be discussed, along with an overview of current guidelines and potential challenges that arise with immunosuppressive medications.

Rituximab Therapy for Systemic Rheumatoid Vasculitis: Indications, Outcomes, and Adverse Events.

OBJECTIVE: To characterize the indication, outcomes, and adverse effects of rituximab (RTX) treatment in a large single-center cohort of patients with systemic rheumatoid vasculitis (RV). METHODS: We retrospectively reviewed the medical charts of 17 patients treated with RTX for systemic RV from 2000 to 2017. Clinical characteristics, outcomes, and adverse effects were analyzed. RESULTS: At RV diagnosis, mean age was 59 years, 59% were female, 94% were white, and 82% had positive rheumatoid factor. At the time of initiating RTX, median Birmingham Vasculitis Activity Score for rheumatoid arthritis was 4.0 (interquartile range 2.0-7.5). RV presented in the skin in 8 patients (47%), as mononeuritis multiplex in 2 (12%), inflammatory ocular disease in 2 (12%), and affected multiple organ systems in 5 (29%). RTX was used for induction therapy in 8 patients (47%), relapsing RV in 4 (24%), second-line therapy in 2 (12%), and salvage therapy or in combination with another agent in 3 (18%). At 3 months, 2 (13%) of 15 patients with available followup information achieved complete remission (CR), and 10 (67%) achieved partial response (PR). At 6 months, 6 patients (40%) achieved CR, 8 (53%) achieved PR, and one had no response. At 12 months, 8 of 13 patients with available records (62%) had CR and 5 patients (38%) had PR. CONCLUSION: Systemic RV is difficult to treat effectively. CR of RV was achieved in 62% and PR in 38% of patients within 12 months of RTX use. Further evidence is needed to inform treatment for patients with RV.

Comparison of Biologic Discontinuation in Patients With Elderly-Onset Versus Younger-Onset Rheumatoid Arthritis.

OBJECTIVE: The objective of this study is to compare biologic drug discontinuation rates for older- versus younger-onset rheumatoid arthritis (YORA) because this is a key outcome measure that could impact prescribing practices. METHODS: We performed a retrospective medical record review of all patients who fulfilled the 1987 American College of Rheumatology (ACR) criteria for adult-onset rheumatoid arthritis (RA) in 1999-2013 among residents of a geographically defined area, with follow-up until death, migration, or July 1, 2017. Discontinuation rates were estimated using cumulative incidence adjusted for the competing risk of death. RESULTS: A total of 240 cases of elderly-onset rheumatoid arthritis (EORA) and 366 cases of YORA were identified (65% and 73% female, respectively; P = 0.025). Cumulative incidence of biologic initiation was lower among the EORA cohort compared with the YORA cohort (18% vs 33%, respectively, at 10 years after RA incidence; P < 0.001). Among those treated with a biologic, years from RA diagnosis to first biologic treatment was not significantly different between the two groups (P = 0.62). Drug survival of first biologic was 64% at 1 year (95% confidence interval [CI]: 45%-77%) and 53% at 2 years (95% CI: 33%-66%) for EORA, compared with 61% at 1 year (95% CI: 50%-69%) and 45% at 2 years (95% CI: 34%-53%) for YORA (P = 0.75). Concurrent glucocorticoid use at initiation of first biologic was statistically and significantly associated with a lower risk of discontinuation in EORA (hazard ratio 0.21; 95% CI: 0.08-0.53) but not in YORA (interaction P = 0.04). CONCLUSION: Drug survival rates of biologic medications did not differ significantly between patients with EORA and YORA.

Rheumatic Syndromes Associated With Immune Checkpoint Inhibitors: A Single-Center Cohort of Sixty-One Patients.

OBJECTIVE: To describe the prevalence, clinical presentation, and management of rheumatic immune-related adverse effects (Rh-irAEs) from immune checkpoint inhibitor (ICI) therapy. METHODS: From a database of all patients who received any ICI at the Mayo Clinic Rochester, Minnesota campus between January 1, 2011 and March 1, 2018, we retrospectively identified those with Rh-irAEs, using diagnostic codes, search terms, and manual chart review. RESULTS: Of the 1,293 patients who received any ICI, Rh-irAEs were clinically diagnosed in 43. Eighteen patients with Rh-irAEs who received ICI therapy elsewhere were also analyzed. Clinical syndromes included inflammatory arthritis (n = 34 [prevalence 2%]), myopathy (n = 10), and other rheumatic syndromes (n = 17). Inflammatory arthritis was most commonly polyarticular, and glucocorticoid treatment was required in 26 patients (76%). The mean ± SD duration of treatment was 18 ± 18 weeks. Five patients (15%) also received disease-modifying antirheumatic drugs, and ICI therapy had to be discontinued in 3 patients (9%). Myopathy was treated with glucocorticoids in all cases (mean ± SD treatment duration 15 ± 17 weeks) and led to 2 deaths and permanent ICI discontinuation in 9 patients (90%). Other syndromes included connective tissue diseases, vasculitis, polymyalgia rheumatica-like syndrome, and flare of preexisting rheumatic disease. Most (71%) were treated with immunosuppression, with 12% requiring ICI discontinuation. CONCLUSION: This study represents the largest cohort of patients with Rh-irAEs reported to date. Most patients received long courses of immunosuppressive treatment, although discontinuation of ICI therapy was required in only a minority.

Orthopedic Surgery Among Patients With Rheumatoid Arthritis: A Population-Based Study to Identify Risk Factors, Sex Differences, and Time Trends.

OBJECTIVE: To identify risk factors for large-joint surgery (LJS) versus small-joint surgery (SJS) in rheumatoid arthritis (RA) and evaluate trends in surgery rates over time. METHODS: A retrospective medical record review of all orthopedic surgeries following first fulfillment of the 1987 American College of Rheumatology criteria for adult-onset RA among residents of Olmsted County, Minnesota between 1980 and 2013 was performed. Risk factors were examined using Cox models adjusted for age, sex, and calendar year of RA incidence. Trends in incidence of joint surgeries were examined using Poisson regression models. RESULTS: A total of 1,077 patients with RA (mean age 56 years, 69% female, 66% seropositive for rheumatoid factor [RF] and anti-cyclic citrullinated peptide [anti-CCP] antibodies) were followed for a median of 10.7 years, during which 112 patients (90 women) underwent at least 1 SJS and 204 (141 women) underwent at least 1 LJS. Risk factors included advanced age, and RF and anti-CCP antibody positivity for both SJS and LJS, and body mass index ≥30 kg/m2 for LJS. Risk factors for SJS and LJS at any time during followup included the presence of radiographic erosions, large-joint swelling, and methotrexate use. SJS rates decreased by calendar year of incidence (hazard ratio 0.53, P = 0.001), with significant decline in the rates of SJS after 1995. The cumulative incidence of SJS was higher in women than men (P = 0.008). CONCLUSION: In recent years, there has been a significant decline in the rates of SJS but not LJS in patients with RA. The incidence of SJS is higher among women. Traditional RA risk factors are strong predictors for SJS and LJS. Increasing age and obesity are predictive of LJS.

Brief Report: Cancer Immunotherapy in Patients With Preexisting Rheumatic Disease: The Mayo Clinic Experience.

OBJECTIVE: To determine the risk of rheumatic disease flare and adverse effects in patients with preexisting rheumatic disease who were receiving immune checkpoint inhibitor (ICI) therapy. METHODS: A retrospective medical record review was performed to identify all patients who received ICI therapy at Mayo Clinic in Rochester, Minnesota between 2011 and 2016 (~700 patients). Those with a preexisting rheumatic disease were identified using specific diagnostic codes. RESULTS: Sixteen patients were identified (81% female, median age 68.5 years). The most common rheumatic diseases were rheumatoid arthritis (n = 5), polymyalgia rheumatica (n = 5), Sjögren's syndrome (n = 2), and systemic lupus erythematosus (n = 2). Seven patients were receiving immunosuppressive therapy or glucocorticoids for their rheumatic disease at the time of initiation of the ICI. The primary malignancies were melanoma (n = 10), pulmonary (n = 4), or hematologic (n = 2). In most cases, ICIs were offered only after failure of several other therapies. Immune-related adverse effects (IRAEs) occurred in 6 patients, and all were treated successfully with glucocorticoids and discontinuation of the ICI therapy. There were no significant differences in time from cancer diagnosis to immunotherapy, duration of immunotherapy, age, or sex between the patients with and those without IRAEs. CONCLUSION: To our knowledge, this represents the largest single-center cohort of patients with rheumatic diseases who were exposed to modern cancer immunotherapy. Only a minority of these patients experienced a flare of their preexisting rheumatic disease or any other IRAE.

Radiology resident preliminary reporting in an independent call environment: multiyear assessment of volume, timeliness, and accuracy.

PURPOSE: The objective of this paper is to assess the volume, accuracy, and timeliness of radiology resident preliminary reports as part of an independent call system. This study seeks to understand the relationship between resident year in training, study modality, and discrepancy rate. METHODS: Resident preliminary interpretations on radiographs, ultrasound, CT, and MRI from October 2009 through December 2013 were prospectively scored by faculty on a modified RADPEER scoring system. Discrepancy rates were evaluated based on postgraduate year of the resident and the study modality. Turnaround times for reports were also reviewed. Differences between groups were compared with a chi-square test with a significance level of 0.05. Institutional review board approval was waived as only deidentified data were used in the study. RESULTS: A total of 416,413 studies were reported by 93 residents, yielding 135,902 resident scores. The rate of major resident-faculty assessment discrepancies was 1.7%. Discrepancy rates improved with increasing experience, both overall (PGY-3: 1.8%, PGY-4: 1.7%, PGY-5: 1.5%) and for each individual modality. Discrepancy rates were highest for MR (3.7%), followed by CT (2.4%), radiographs (1.4%), and ultrasound (0.6%). Emergency department report turnaround time averaged 31.7 min. The average graduating resident has been scored on 2,746 ± 267 reports during residency. CONCLUSIONS: Resident preliminary reports have a low rate of major discrepancies, which improves over 3 years of call-taking experience. Although more complex cross-sectional studies have slightly higher discrepancy rates, discrepancies were still within the range of faculty report variation.

Prevention and management of infectious complications of percutaneous interventions.

Infectious complications following interventional radiology (IR) procedures can cause significant patient morbidity and, potentially, mortality. As the number and breadth of IR procedures grow, it becomes increasingly evident that interventional radiologists must possess a thorough understanding of these potential infectious complications. Furthermore, given the increasing incidence of antibiotic-resistant bacteria, emphasis on cost containment, and attention to quality of care, it is critical to have infection control strategies to maximize patient safety. This article reviews infectious complications associated with percutaneous ablation of liver tumors, transarterial embolization of liver tumors, uterine fibroid embolization, percutaneous nephrostomy, percutaneous biliary interventions, central venous catheters, and intravascular stents. Emphasis is placed on incidence, risk factors, prevention, and management. With the use of these strategies, IR procedures can be performed with reduced risk of infectious complications.

The performance of a modified RENAL nephrometry score in predicting renal mass radiofrequency ablation success.

OBJECTIVE: To assess the predictive performance of a modified RENAL nephrometry score for renal tumors undergoing radiofrequency ablation (RFA). METHODS: Patients who underwent RFA were identified from 2002 to 2011, and RENAL nephrometry scoring was performed for each. A modified RENAL (m-RENAL) nephrometry score was created to account for the small sizes of tumors ablated for which the size variable, R, was adjusted. A size of 3 cm was calculated as the optimal cutoff for the R component of the m-RENAL nephrometry score, and tumors were given an R score of 1 if <3 cm, 2 if 3-4 cm, or 3 if >4 cm. Other RENAL variables were unchanged. Oncologic outcomes were stratified by complexity tertiles defined as low (4-6), medium (7-9), and high (10-12). Outcomes were reported as initial ablation success (IAS), recurrence-free survival (RFS), and metastatic-free survival (MFS). The Kaplan-Meir method was used to estimate survival based on complexity tertile. RESULTS: Two hundred forty patients were identified who underwent RFA, of which 192 patients were eligible for analysis. Median follow-up was 32.2 months, and median tumor size was 2.4 cm. IAS was achieved in 185 of 192 patients (96.4%). Overall, the estimated 3-year RFS was 95.1% and MFS was 97.3%. There was no statistical difference between complexity tertiles using the standard RENAL nephrometry score; however, the m-RENAL nephrometry score was significantly associated with IAS and RFS (P = .027 and P = .003, respectively). There were too few events (n = 3) to perform statistical analysis for MFS. CONCLUSION: A modification to the size variable increases the performance of the RENAL nephrometry score when used to stratify RFA ablation success.

Removal of luminal content protects the small intestine during hemorrhagic shock but is not sufficient to prevent lung injury.

The small intestine plays a key role in the pathogenesis of multiple organ failure following circulatory shock. Current results show that reduced perfusion of the small intestine compromises the mucosal epithelial barrier, and the intestinal contents (including pancreatic digestive enzymes and partially digested food) can enter the intestinal wall and transport through the circulation or mesenteric lymph to other organs such as the lung. The extent to which the luminal contents of the small intestine mediate tissue damage in the intestine and lung is poorly understood in shock. Therefore, rats were assigned to three groups: No-hemorrhagic shock (HS) control and HS with or without a flushed intestine. HS was induced by reducing the mean arterial pressure (30 mmHg; 90 min) followed by return of shed blood and observation (3 h). The small intestine and lung were analyzed for hemorrhage, neutrophil accumulation, and cellular membrane protein degradation. After HS, animals with luminal contents had increased neutrophil accumulation, bleeding, and destruction of E-cadherin in the intestine. Serine protease activity was elevated in mesenteric lymph fluid collected from a separate group of animals subjected to intestinal ischemia/reperfusion. Serine protease activity was elevated in the plasma after HS but was detected in lungs only in animals with nonflushed lumens. Despite removal of the luminal contents, lung injury occurred in both groups as determined by elevated neutrophil accumulation, permeability, and lung protein destruction. In conclusion, luminal contents significantly increase intestinal damage during experimental HS, suggesting transport of luminal contents across the intestinal wall should be minimized.