Acknowledging and addressing real-world challenges to treating immune-related adverse events.

Immune checkpoint inhibitors (ICIs) have revolutionized oncology treatment. However, their success is mitigated by the recognition that ICI-induced immune-related adverse events (irAEs) pose considerable challenges to patients and clinicians. These autoimmune toxicities are heterogeneous, unpredictable, and reflect a disease state resulting from a change in the immune system of patients. This contrasts with the typical acute nature of toxicities from chemotherapy and molecularly targeted oncology therapies. Management is further complicated by the extended bioavailability of these agents in patients as well as the persistence of autoimmune pathology. Currently, irAE treatment remains suboptimal in many areas, as many expert guidelines remain vague on the optimal selection, dosing, and duration of steroids and the use of other immunosuppressive agents. This coupled with delays in diagnosis and difficulties for patients accessing effective irAE treatment results in barriers to effective irAE care. The latter is complicated by the lack of US Food and Drug Administration-approved irAE treatments that lead to insurance denials, as well as the high cost of biological immunosuppressant therapies. Fortunately, rheumatologists and other subspecialists with expertize in the management of chronic autoimmune conditions have become more involved in irAE diagnosis and management and may help navigate treatment. In this commentary, we discuss these issues and propose potential solutions to advance the field.

Investigating risk factors and treatment options for severe, partially steroid responsive, and steroid-refractory checkpoint inhibitor pneumonitis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized cancer care with incredible reductions in mortality. One of the most devastating complications of treatment is ICI-related pneumonitis (ICI-p). Despite this, little is known regarding risk factors for severe pneumonitis and treatment effectiveness of various therapeutic options for steroid-refractory disease. To address this, we conducted a retrospective study on patients with cancer who developed ICI-p. METHODS: We examined consecutive patients who received ICIs and developed ICI-p. Risk factors of interest for severe disease and steroid-refractory ICI-p, including pre-treatment pulmonary function tests (PFTs) and chest imaging, were compared between patients with severe (grades 3-5) and mild (grades 1-2) pneumonitis. The clinical and treatment courses for patients with steroid-refractory ICI-p were recorded. RESULTS: A total of 132 patients developed ICI-p, with 60 patients having mild and 72 with severe disease. We found that lower forced vital capacity percent predicted (66.24 vs 85.05, P = .05), lower total lung capacity percent predicted (85.23 vs 99.71, P = .13), and specific radiographic patterns on pre-treatment chest imaging were predictors of severe disease. Initial corticosteroid dose of less than 1 milligram per kilogram prednisone equivalent (P = .14) was correlated with partially steroid-responsive or steroid-refractory ICI-p. Ten patients had steroid refractory ICI-p, and those who received IVIG alone as the immune suppressant beyond corticosteroids had improved survival (P = 05). CONCLUSIONS: We are the first to identify pre-treatment PFTs and chest imaging abnormalities as risk factors for severe ICI-p. We also found that lower corticosteroid doses were associated with partially steroid-responsive and steroid-refractory ICI-p. Larger, prospective studies are needed to validate our results.

Immunotherapy Toxicity Management in Clinical Practice: Building the Clinical Infrastructure for Immune-related Adverse Event Evaluation and Care.

Cancer immunotherapy is revolutionary for survival but has complications due to immunogenicity with unpredictable and potentially long-lasting autoimmune side effects known as immune-related adverse events (irAEs). Currently, treatment beyond corticosteroids can be complicated by the diversity of providers who are needed across a variety of clinical settings to manage irAEs. We outline the role of critical players in the management of irAEs, discuss the current limitations that exist, and propose various methodologies that can be adapted across clinical settings to tackle these needs. We aim to better understand who can be affected by irAEs and tailor diagnostics and therapeutics appropriately.

The Need for Classification Criteria of Immune Checkpoint Inhibitor-induced inflammatory Arthritis: A Scoping Review.

Immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA) is an immune-related adverse event that can occur as a result of receiving ICIs for cancer treatment. Thus far, ICI-IA has been described variably in the literature, in part due to varying presentations that evolve over time, as well as a lack of standardized definitions and classification. This scoping review aggregates various descriptions of ICI-IA, highlighting the most prominent attributes of ICI-IA from categories such as symptoms, signs, imaging, and laboratory findings as well as discussing potential mimic conditions.

Graduate medical education success coaching for residents and fellows: a single-institution real-world experience.

While coaching has been employed as a success strategy in many areas such as athletics and business for decades, its use is relatively new in the medical field despite evidence of its benefits. Implementation and engagement regarding coaching in graduate medical education (GME) for residents and fellows is particularly scarce. We report our three-year experience of a GME success coaching program that aims to help trainees reach their full potential by addressing various areas of medical knowledge, clinical skills, efficiency, interpersonal skills and communication, professionalism, and mental health and well-being. The majority of participants (87%) were identified by themselves, their program director, and/or the GME coaches to have more than one area of need. The majority (79%) of referrals were identified by the coaches to have additional needs to the reasons for referral. We provide a framework for implementation of a GME coaching program and propose that coaching in GME may provide an additional safe environment for learners to reveal areas of concerns or difficulty that otherwise would not be disclosed and/or addressed.

Sarcoid-like reactions to immune checkpoint inhibitors: Incidence, treatment course, and impact on cancer progression and survival.

INTRODUCTION: Sarcoid-like reactions (SLRs) to immune checkpoint inhibitors (ICIs) are a rare but increasingly recognized immune-related adverse event of which the clinical significance is unclear. METHODS: We conducted a retrospective cohort study at a tertiary academic center of consecutive patients who received at least one dose of ICI from 2013 to 2020. Patient characteristics, risk factors, and outcomes were compared between patients with and without SLR following ICI treatment. RESULTS: A total of 2963 cancer patients received at least 1 dose of ICI between 2013 and 2020, and 7 patients (0.24 %) developed SLR. There were no significant demographic differences between patients with and without SLR following ICI. SLRs occurred in 5 of 451 (1.07 %) melanoma patients and 2 of 840 (0.24 %) non-small cell lung cancer patients. Two of the 7 patients had multi-organ SLR, and both were symptomatic requiring systemic corticosteroids and permanent ICI discontinuation, while single organ SLR patients did not require immune suppression. Development of SLR did not appear to have negative impact on cancer progression or overall survival; in fact, a trend towards improved progression-free and overall survival was observed (median time: 1363 days vs 127 days, p = 0.091; 1387 days vs 428.5 days, p = 0.19, respectively). CONCLUSIONS: SLRs are a known but understudied complication associated with ICI therapy. Multisystem SLR patients were more symptomatic and required ICI discontinuation and immune suppression. Larger studies are needed to fully evaluate the impact of SLR on cancer outcomes.

Defining domains: developing consensus-based definitions for foundational domains in OMERACT core outcome sets.

OBJECTIVE: To develop a set of detailed definitions for foundational domains commonly used in OMERACT (Outcome Measures in Rheumatology) core domain sets. METHODS: We identified candidate domain definitions from prior OMERACT publications and websites and publications of major organizations involved in outcomes research for six domains commonly used in OMERACT Core Domain Sets: pain intensity, pain interference, physical function, fatigue, patient global assessment, and health-related quality of life. We conducted a two-round survey of OMERACT working groups, patient research partners, and then the OMERACT Technical Advisory Group to establish their preferred domain definitions. Results were presented at the OMERACT 2023 Methodology Workshop, where participants discussed their relevant lived experience and identified potential sources of variability giving the needed detail in our domain definitions. RESULTS: One-hundred four people responded to both rounds of the survey, and a preferred definition was established for each of the domains except for patient global assessment for which no agreement was reached. Seventy-five participants at the OMERACT 2023 Methodology Workshop provided lived experience examples, which were used to contextualise domain definition reports for each of the five domains. CONCLUSION: Using a consensus-based approach, we have created a detailed definition for five of the foundational domains in OMERACT core domain sets; patient global assessment requires further research. These definitions, although not mandatory for working groups to use, may facilitate the initial domain-match assessment step of instrument selection, and reduce the time and resources required by future OMERACT groups when developing core outcome sets.

Cardiovascular toxicities associated with bispecific T-cell engager therapy.

BACKGROUND: Bispecific T-cell engagers (BTEs) are novel agents used to treat hematological malignancies. Early trials were underpowered to define cardiovascular adverse events (CVAE) and no large-scale studies systematically examined the CVAEs associated with BTEs. METHODS: Leveraging the US Food and Drug Administration's Adverse Event Reporting System-(FAERS), we identified the relative frequency of CVAEs after initiation of five BTE products approved by the Food and Drug Administration between 2014 and 2023 for the treatment of hematological malignancies. Adjusted reporting ORs (aROR) were used to identify disproportionate reporting of CVAEs with BTEs compared with background rates in the database. Fatality rates and risk ratios (RRs) for each adverse event (AE) were calculated. RESULTS: From 3668 BTE-related cases reported to FAERS, 747 (20.4%) involved CVAEs. BTEs as a class were associated with fatal CVAEs (aROR 1.29 (95% CI 1.12 to 1.50)), an association mainly driven by teclistamab (aROR 2.44 (95% CI 1.65 to 3.60)). Teclistamab was also associated with a disproportionate risk of myocarditis (aROR 25.70 (95% CI 9.54 to 69.23)) and shock (aROR 3.63 (95% CI 2.30 to 5.74)), whereas blinatumomab was associated with a disproportionate risk of disseminated intravascular coagulation (aROR 3.02 (95% CI 1.98 to 4.60)) and hypotension (aROR 1.59 (95% CI 1.25 to 2.03)). CVAEs were more fatal compared with non-CVAEs (31.1% vs 17.4%; RR 1.76 (95% CI 1.54 to 2.03)). Most CVAEs (83.3%) did not overlap with cytokine release syndrome. CONCLUSION: In the first postmarketing surveillance study of BTEs, CVAEs were involved in approximately one in five AE reports and carried a significant mortality risk.

Consensus on the definitions and descriptions of the domains of the OMERACT Core Outcome Set for shared decision making interventions in rheumatology trials.

OBJECTIVE: To gain consensus on the definitions and descriptions of the domains of the Outcome Measures in Rheumatology (OMERACT) core domain set for rheumatology trials evaluating shared decision making (SDM) interventions. METHODS: Following the OMERACT Handbook methods, our Working Group (WG), comprised of 90 members, including 17 patient research partners (PRPs) and 73 clinicians and researchers, had six virtual meetings in addition to email exchanges to develop draft definitions and descriptions. The WG then conducted an international survey of its members to gain consensus on the definitions and descriptions. Finally, the WG members had virtual meetings and e-mail exchanges to review survey results and finalize names, definitions and descriptions of the domains. RESULTS: WG members contributed to developing the definitions. Fifty-two members representing four continents and 13 countries completed the survey, including 15 PRPs, 33 clinicians and 37 researchers. PRPs and clinicians/researchers agreed with all definitions and descriptions with agreements ranging from 87% to 100%. Respondents suggested wording changes to the names, definitions and descriptions to better reflect the domains. Discussions led to further simplification and clarification to address common questions/concerns about the domains. CONCLUSION: Our WG reached consensus on the definitions and descriptions of the domains of the core domain set for rheumatology trials of SDM interventions. This step is crucial to understand each domain and provides the foundation to identify instruments to measure each domain for inclusion in the Core Outcome Measurement Set. CLINICAL SIGNIFICANCE: The current study provides consensus-based definitions and descriptions for the domains of the OMERACT core domain set for shared decision making interventions from patients/caregivers, clinicians and researchers. This is a crucial step to understand each domain and provides the foundation to identify instruments to measure each domain for inclusion in the Core Outcome Measurement Set for trials of SDM interventions.

Immune checkpoint inhibitor-induced subacute cutaneous lupus erythematosus: a case report and review of the literature.

Immune checkpoint inhibitor (ICI) use has been associated with numerous autoimmune side effects, known as immune related adverse events (irAEs). Cutaneous irAEs are common and affect up to 50% of patients treated with ICIs. There have been an increasing number of cases reported in the literature regarding ICI-induced subacute cutaneous lupus erythematosus (SCLE). ICI-induced SCLE is important to recognize as it can result in a delayed and/or prolonged skin reaction despite treatment discontinuation. We describe a patient with gastro-esophageal adenocarcinoma who developed SCLE following one cycle of nivolumab treatment. A 75-year-old man presented to our clinic with a new photo-distributed rash composed of oval scaly pink papules and plaques involving his chest and arms. Despite treatment with topical corticosteroids, he presented to the emergency department 1 week later with worsening rash. Skin biopsy showed vacuolar interface pattern, along with superficial perivascular lymphocytic infiltrate, consistent with a drug eruption. The clinicopathological presentation was consistent with ICI-induced SCLE. Nivolumab treatment was discontinued due to the severity of the rash. The rash remitted with systemic corticosteroids, high potency topical steroids, and hydroxychloroquine. Unfortunately, the patient developed intraperitoneal metastatic disease, and was enrolled in hospice care. In this paper, we highlight the importance of early identification and treatment of this irAE. A review of the literature, including a discussion on the management of ICI-induced SCLE is also provided.

OMERACT Core outcome measurement set for shared decision making in rheumatic and musculoskeletal conditions: a scoping review to identify candidate instruments.

OBJECTIVES: Shared decision making (SDM) is a central tenet in rheumatic and musculoskeletal care. The lack of standardization regarding SDM instruments and outcomes in clinical trials threatens the comparative effectiveness of interventions. The Outcome Measures in Rheumatology (OMERACT) SDM Working Group is developing a Core Outcome Set for trials of SDM interventions in rheumatology and musculoskeletal health. The working group reached consensus on a Core Outcome Domain Set in 2020. The next step is to develop a Core Outcome Measurement Set through the OMERACT Filter 2.2. METHODS: We conducted a scoping review (PRISMA-ScR) to identify candidate instruments for the OMERACT Filter 2.2 We systematically reviewed five databases (Ovid MEDLINE®, Embase, Cochrane Library, CINAHL and Web of Science). An information specialist designed search strategies to identify all measurement instruments used in SDM studies in adults or children living with rheumatic or musculoskeletal diseases or their important others. Paired reviewers independently screened titles, abstracts, and full text articles. We extracted characteristics of all candidate instruments (e.g., measured construct, measurement properties). We classified candidate instruments and summarized evidence gaps with an adapted version of the Summary of Measurement Properties (SOMP) table. RESULTS: We found 14,464 citations, read 239 full text articles, and included 99 eligible studies. We identified 220 potential candidate instruments. The five most used measurement instruments were the Decisional Conflict Scale (traditional and low literacy versions) (n=38), the Hip/Knee-Decision Quality Instrument (n=20), the Decision Regret Scale (n=9), the Preparation for Decision Making Scale (n=8), and the CollaboRATE (n=8). Only 44 candidate instruments (20%) had any measurement properties reported by the included studies. Of these instruments, only 57% matched with at least one of the 7-criteria adapted SOMP table. CONCLUSION: We identified 220 candidate instruments used in the SDM literature amongst people with rheumatic and musculoskeletal diseases. Our classification of instruments showed evidence gaps and inconsistent reporting of measurement properties. The next steps for the OMERACT SDM Working Group are to match candidate instruments with Core Domains, assess feasibility and review validation studies of measurement instruments in rheumatic diseases or other conditions. Development and validation of new instruments may be required for some Core Domains.

Impact of concurrent glomerulonephritis on outcomes of diffuse alveolar haemorrhage in antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVES: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) commonly presents with diffuse alveolar haemorrhage (DAH) and/or glomerulonephritis. Patients who present with DAH but without kidney involvement have been understudied. METHODS: Patients with DAH diagnosed by bronchoscopy and attributed to AAV over 8.5 years were retrospectively identified through electronic medical records and bronchoscopy reporting software. Patients with end-stage kidney disease (ESKD) or prior kidney transplant were excluded. Characteristics, treatments, and outcomes were abstracted. RESULTS: 30 patients were identified with DAH secondary to AAV. Five with ESKD or prior kidney transplant, and one with concomitant anti-glomerular basement membrane disease, were excluded, leaving 24 patients for analysis. At the time of qualifying bronchoscopy, six patients had no apparent kidney involvement by AAV, while eight of 18 with kidney involvement required dialysis. Of the eight patients dialysed during the initial hospitalisation, four were declared to have ESKD and three died in the subsequent year (one of whom did both). None of the 16 patients without initial dialysis requirement developed kidney involvement requiring dialysis in the subsequent year, though three of the six without initial evidence of kidney involvement by AAV ultimately developed it. No patient without initial kidney involvement died during follow-up. CONCLUSIONS: In our cohort, patients with DAH due to AAV without initial kidney involvement did not develop kidney involvement requiring dialysis or die during the follow-up period, though half of patients without initial evidence of kidney involvement subsequently developed it. Larger studies are warranted to better characterise this population and guide medical management.

Urine and Plasma Complement Ba Levels During Disease Flares in Patients With Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis.

Introduction: Although the alternative complement pathway has been implicated in the pathogenesis of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), the specific nature of its involvement is unclear. This study measured levels of urine and plasma complement fragment Ba at multiple time points in a group of patients with AAV. Methods: The complement fragment Ba was measured by enzyme-linked immunosorbent assay in serial urine and plasma samples from 21 patients with AAV who developed a renal flare, 19 who developed a nonrenal flare, and 20 in long-term remission. Urine Ba levels were corrected for urine creatinine concentration. Changes in Ba levels were modeled using mixed linear-effect models. A logistic regression model was fit to predict a renal flare using Ba levels at the time of flare versus the nonrenal flare and long-term remission groups. Results: Data from 60 patients with AAV were used for this analysis; 53% were male, 93% were White, and 74% had antiproteinase3-ANCA. Urine Ba levels increased at renal flare (P < 0.001) but remained stable during a nonrenal flare or long-term remission. Plasma Ba levels were stable over time in all groups. Urine Ba levels predicted a renal flare with an area under the curve of 0.76 (P < 0.001), with a cutoff of 12.53 ng/mg urine creatinine yielding a sensitivity of 76.2% and a specificity of 68.4%. Conclusion: Urine Ba levels, but not plasma Ba levels, are increased at the time of a renal flare in AAV, suggesting intrarenal complement activation and highlighting the potential use of this biomarker for surveillance of active renal vasculitis.

2023 American College of Rheumatology and American Association of Hip and Knee Surgeons Clinical Practice Guideline for the Optimal Timing of Elective Hip or Knee Arthroplasty for Patients With Symptomatic Moderate-to-Severe Osteoarthritis or Advanced Symptomatic Osteonecrosis With Secondary Arthritis for Whom Nonoperative Therapy Is Ineffective.

OBJECTIVE: To develop evidence-based consensus recommendations for the optimal timing of hip and knee arthroplasty to improve patient-important outcomes including, but not limited to, pain, function, infection, hospitalization, and death at 1 year for patients with symptomatic and radiographic moderate-to-severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis of the hip or knee who have previously attempted nonoperative therapy, and for whom nonoperative therapy was ineffective, and who have chosen to undergo elective hip or knee arthroplasty (collectively referred to as TJA). METHODS: We developed 13 clinically relevant population, intervention, comparator, outcomes (PICO) questions. After a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the quality of evidence (high, moderate, low, or very low), and evidence tables were created. A Voting Panel, including 13 physicians and patients, discussed the PICO questions until consensus was achieved on the direction (for/against) and strength (strong/conditional) of the recommendations. RESULTS: The panel conditionally recommended against delaying TJA to pursue additional nonoperative treatment including physical therapy, nonsteroidal antiinflammatory drugs, ambulatory aids, and intraarticular injections. It conditionally recommended delaying TJA for nicotine reduction or cessation. The panel conditionally recommended delay for better glycemic control for patients who have diabetes mellitus, although no specific measure or level was identified. There was consensus that obesity by itself was not a reason for delay, but that weight loss should be strongly encouraged, and the increase in operative risk should be discussed. The panel conditionally recommended against delay in patients who have severe deformity or bone loss, or in patients who have a neuropathic joint. Evidence for all recommendations was graded as low or very low quality. CONCLUSION: This guideline provides evidence-based recommendations regarding the optimal timing of TJA in patients who have symptomatic and radiographic moderate-to-severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis for whom nonoperative therapy was ineffective to improve patient-important outcomes, including pain, function, infection, hospitalization, and death at 1 year. We acknowledge that the evidence is of low quality primarily due to indirectness and hope future research will allow for further refinement of the recommendations.

2023 American College of Rheumatology and American Association of Hip and Knee Surgeons Clinical Practice Guideline for the Optimal Timing of Elective Hip or Knee Arthroplasty for Patients With Symptomatic Moderate-to-Severe Osteoarthritis or Advanced Symptomatic Osteonecrosis With Secondary Arthritis for Whom Nonoperative Therapy Is Ineffective.

OBJECTIVE: To develop evidence-based consensus recommendations for the optimal timing of hip and knee arthroplasty to improve patient-important outcomes including, but not limited to, pain, function, infection, hospitalization, and death at 1 year for patients with symptomatic and radiographic moderate-to-severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis of the hip or knee who have previously attempted nonoperative therapy, and for whom nonoperative therapy was ineffective, and who have chosen to undergo elective hip or knee arthroplasty (collectively referred to as TJA). METHODS: We developed 13 clinically relevant population, intervention, comparator, outcomes (PICO) questions. After a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the quality of evidence (high, moderate, low, or very low), and evidence tables were created. A Voting Panel, including 13 physicians and patients, discussed the PICO questions until consensus was achieved on the direction (for/against) and strength (strong/conditional) of the recommendations. RESULTS: The panel conditionally recommended against delaying TJA to pursue additional nonoperative treatment including physical therapy, nonsteroidal antiinflammatory drugs, ambulatory aids, and intraarticular injections. It conditionally recommended delaying TJA for nicotine reduction or cessation. The panel conditionally recommended delay for better glycemic control for patients who have diabetes mellitus, although no specific measure or level was identified. There was consensus that obesity by itself was not a reason for delay, but that weight loss should be strongly encouraged, and the increase in operative risk should be discussed. The panel conditionally recommended against delay in patients who have severe deformity or bone loss, or in patients who have a neuropathic joint. Evidence for all recommendations was graded as low or very low quality. CONCLUSION: This guideline provides evidence-based recommendations regarding the optimal timing of TJA in patients who have symptomatic and radiographic moderate-to-severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis for whom nonoperative therapy was ineffective to improve patient-important outcomes, including pain, function, infection, hospitalization, and death at 1 year. We acknowledge that the evidence is of low quality primarily due to indirectness and hope future research will allow for further refinement of the recommendations.

2023 American College of Rheumatology and American Association of Hip and Knee Surgeons Clinical Practice Guideline for the Optimal Timing of Elective Hip or Knee Arthroplasty for Patients With Symptomatic Moderate-to-Severe Osteoarthritis or Advanced Symptomatic Osteonecrosis With Secondary Arthritis for Whom Nonoperative Therapy Is Ineffective.

OBJECTIVE: To develop evidence-based consensus recommendations for the optimal timing of hip and knee arthroplasty to improve patient-important outcomes including, but not limited to, pain, function, infection, hospitalization, and death at 1 year for patients with symptomatic and radiographic moderate-to-severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis of the hip or knee who have previously attempted nonoperative therapy, and for whom nonoperative therapy was ineffective, and who have chosen to undergo elective hip or knee arthroplasty (collectively referred to as TJA). METHODS: We developed 13 clinically relevant population, intervention, comparator, outcomes (PICO) questions. After a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the quality of evidence (high, moderate, low, or very low), and evidence tables were created. A Voting Panel, including 13 physicians and patients, discussed the PICO questions until consensus was achieved on the direction (for/against) and strength (strong/conditional) of the recommendations. RESULTS: The panel conditionally recommended against delaying TJA to pursue additional nonoperative treatment including physical therapy, nonsteroidal antiinflammatory drugs, ambulatory aids, and intraarticular injections. It conditionally recommended delaying TJA for nicotine reduction or cessation. The panel conditionally recommended delay for better glycemic control for patients who have diabetes mellitus, although no specific measure or level was identified. There was consensus that obesity by itself was not a reason for delay, but that weight loss should be strongly encouraged, and the increase in operative risk should be discussed. The panel conditionally recommended against delay in patients who have severe deformity or bone loss, or in patients who have a neuropathic joint. Evidence for all recommendations was graded as low or very low quality. CONCLUSION: This guideline provides evidence-based recommendations regarding the optimal timing of TJA in patients who have symptomatic and radiographic moderate-to-severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis for whom nonoperative therapy was ineffective to improve patient-important outcomes, including pain, function, infection, hospitalization, and death at 1 year. We acknowledge that the evidence is of low quality primarily due to indirectness and hope future research will allow for further refinement of the recommendations.

Plasma Exchange for ANCA-Associated Vasculitis: An International Survey of Patient Preferences.

Rationale & Objective: We sought to elicit patient preferences regarding the use of plasma exchange in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and its tradeoffs of risk of kidney failure and risk of serious infection. Study Design: Patient survey. Setting & Participants: The online survey was circulated to adults with AAV via kidney and vasculitis networks in Canada, the United Kingdom, and the United States. Outcomes: Respondents reviewed the estimated 1-year risks of kidney failure and serious infection in AAV with and without plasma exchange across 5 serum creatinine categories (150, 250, 350, 450, and 600 µmol/L). For each scenario, participants indicated whether or not they would choose plasma exchange. Analytical Approach: Responses were assessed with multilevel multivariable logistic regression models to identify predictors of respondent choice regarding treatment with plasma exchange. Results: The 470 respondents from the 13 countries (United States 61.7%, United Kingdom 20.0%, Canada 13.8%, and other countries 4.5%) had a mean age of 58.6 (SD 14.3) years, 70.2% women. Respondents were more likely to choose plasma exchange in scenarios at high risk of kidney failure and serious infection (creatinine level of 350 or 450 µmol/L) compared with lower risk scenarios or the highest risk scenario. However, 145 (30.9%) chose plasma exchange across all scenarios, whereas 80 (17.0%) declined plasma exchange across all scenarios. Respondents from the United Kingdom (OR, 2.61; 95% CI, 1.09-6.22) who received previous dialysis (OR, 2.70; 95% CI, 1.12-6.52) or received previous plasma exchange (OR, 5.62; 95% CI, 2.72-11.61) were more likely to choose plasma exchange, whereas older respondents (OR, 0.98; 95% CI, 0.96-0.99 per 1 year increase) were less likely. Limitations: Unclear generalizability to non-English-speaking, older, and less health literate adults, possible responder bias, survivor bias, lack of individualized risk assessments for kidney failure, and serious infection. Conclusions: Patients with AAV do not express a consistent choice for plasma exchange, which highlights the need for shared decision making.

Immune checkpoint inhibitor-induced hepatitis injury: risk factors, outcomes, and impact on survival.

PURPOSE: Immune checkpoint inhibitors (ICIs) are associated with a unique set of immune-related adverse events (irAEs). Few studies have evaluated the risk factors and outcomes of patients who develop ICI-induced hepatitis (ICIH). METHODS: We utilized an institutional database of patients with advanced cancers treated with ICI to identify patients with ICIH. irAEs were graded using the Common Terminology Criteria for Adverse Events v4. Overall survival (OS) was calculated from the date of ICI to death from any cause or the date of the last follow-up. OS with 95% confidence intervals were estimated using the Kaplan-Meier method and stratified by the occurrence of ICIH. RESULTS: We identified 1096 patients treated with ICI. The most common ICIs were PD1/L1 (n = 774) and CTLA-4 inhibitors (n = 195). ICIH occurred among 64 (6%) patients: severity was < grade 3 in 30 and ≥ grade 3 in 24 patients (3.1% overall). Median time to ICIH was 63 days. ICIH was more frequent in women (p = 0.038), in patients treated with combination ICIs (p < 0.001), and when given as first-line therapy (p = 0.018). Occurrence of ICIH was associated with significantly longer OS, median 37.0 months (95% CI 21.4, NR) compared to 11.3 months (95% CI 10, 13, p < 0.001); there was no difference in OS between patients with ≥ grade 3 ICIH vs grade 1-2. CONCLUSIONS: Female sex, combination immunotherapy, and the first line of immunotherapy were associated with ICIH. Patients with ICIH had improved clinical survival compared to those that did not develop ICIH. There is a need for prospective further studies to confirm our findings.