Immune Checkpoint Inhibitor-Associated Remitting Seronegative Symmetrical Synovitis With Pitting Edema: Description of a New Entity by CanRIO.

OBJECTIVE: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is characterized by symmetrical synovitis with pitting edema and negative rheumatoid factor (RF). It has been described in a setting of malignancy, suggesting a paraneoplastic association. With the increasing use of immune checkpoint inhibitors (ICIs) for the treatment of cancers and emergence of immune-related adverse events (irAEs), our objective was to identify and describe cases of ICI-associated RS3PE (ICI-RS3PE) and compare them to non-ICI-RS3PE. METHODS: The Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO) network is a collaboration of Canadian rheumatologists with experience in the management of patients with rheumatic irAEs (Rh-irAEs). Standardized data on adult patients with Rh-irAE have been collected as part of retrospective and prospective cohorts. In this study, detailed information on all cases of ICI-RS3PE from both cohorts were extracted and analyzed. RESULTS: We identified 11 cases of ICI-RS3PE. The most frequently observed malignancy was nonsmall cell lung cancer (4 of 11), followed by malignant melanoma (2 of 11) and cutaneous squamous cell carcinoma (2 of 11). The median time to onset of ICI-RS3PE was 26 weeks from ICI start and 52 weeks from diagnosis of malignancy. Seven patients had stable cancer prior to onset of ICI-RS3PE, 3 had partial response, and 1 had complete response. All patients received glucocorticoids. Conventional synthetic disease-modifying antirheumatic drugs (csDMARD) were needed in 10 patients. CONCLUSION: ICI-RS3PE may be an independent Rh-irAE, separate from paraneoplastic RS3PE. The symptoms of ICI-RS3PE responded well to glucocorticoids, but concomitant treatment with csDMARDs may be necessary.

Fracture risk and assessment in adults with cancer.

Individuals with cancer face unique risk factors for osteoporosis and fractures. Clinicians must consider the additive effects of cancer-specific factors, including treatment-induced bone loss, and premorbid fracture risk, utilizing FRAX score and bone mineral densitometry when available. Pharmacologic therapy should be offered as per cancer-specific guidelines, when available, or local general osteoporosis guidelines informed by clinical judgment and patient preferences. Our objective was to review and summarize the epidemiologic burden of osteoporotic fracture risk and fracture risk assessment in adults with cancer, and recommended treatment thresholds for cancer treatment-induced bone loss, with specific focus on breast, prostate, thyroid, gynecological, multiple myeloma, and hematopoietic stem cell transplant. This narrative review was informed by PubMed searches to July 25, 2022, that combined terms for cancer, stem cell transplantation, fracture, bone mineral density (BMD), trabecular bone score, FRAX, Garvan nomogram or fracture risk calculator, QFracture, prediction, and risk factors. The literature informs that cancer can impact bone health in numerous ways, leading to both systemic and localized decreases in BMD. Many cancer treatments can have detrimental effects on bone health. In particular, hormone deprivation therapies for hormone-responsive cancers such as breast cancer and prostate cancer, and hematopoietic stem cell transplant for hematologic malignancies, adversely affect bone turnover, resulting in osteoporosis and fractures. Surgical treatments such as hysterectomy with bilateral salpingo-oophorectomy for gynecological cancers can also lead to deleterious effects on bone health. Radiation therapy is well documented to cause localized bone loss and fractures. Few studies have validated the use of fracture risk prediction tools in the cancer population. Guidelines on cancer-specific treatment thresholds are limited, and major knowledge gaps still exist in fracture risk and fracture risk assessment in patients with cancer. Despite the limitations of current knowledge on fracture risk assessment and treatment thresholds in patients with cancer, clinicians must consider the additive effects of bone damaging factors to which these patients are exposed and their premorbid fracture risk profile. Pharmacologic treatment should be offered as per cancer-specific guidelines when available, or per local general osteoporosis guidelines, in accordance with clinical judgment and patient preferences.

Fracture rate increases after immune checkpoint inhibitor treatment: a potential new immune related adverse event.

INTRODUCTION: T cell activation can lead to osteoporosis and while there are several case reports of fractures occurring after immune checkpoint inhibitor (ICI) use, to date, there are no population level studies looking at fracture risk related to ICI use. METHODS: Using Alberta Cancer Registry data, we identified all individuals treated with ICI for cancer between September 29, 2010, and March 31, 2019. Linked records from Alberta's healthcare administrative databases were assessed for the presence of fracture diagnostic codes in the year prior to and up to two years after ICI initiation. Fracture rate was stratified based on the time-period before and after ICI initiation. Fracture rates after ICI were compared to baseline. RESULTS: The study cohort consisted of 1600 ICI users (mean age 65.7 years, 60% male). Most patients were treated with an anti-PD-1 agent (73.9%). ICIs were initiated on average 707.8 days after cancer diagnosis. 76 (4.8%) individuals had a remote history of a major fracture, and 141 (8.8%) had been treated with an osteoporosis medication prior to ICI treatment. The fracture rate in the year prior to ICI initiation was 11.3 per 1000 patient-years. The fracture rate in the year after ICI initiation was significantly higher at 27.3 per 1000 patient-years. The fracture rate dropped to 17.6 per 1000 patient-years in the second year after ICI initiation. The incidence rate ratio of sustaining a major fracture in the year after compared to the year prior to ICI initiation was 2.43 (95% CI 1.34-4.27). CONCLUSIONS: Fracture risk may be increased in cancer patients early after initiation of ICI, and this may represent a novel immune-related adverse event.

Fractures and long-term mortality in cancer patients: a population-based cohort study.

We assessed post-fracture mortality in a population-based cohort of 122,045 individuals with cancers. Major fractures (hip, vertebrae, humerus, and forearm) were associated with early and long-term increased all-cause mortality. INTRODUCTION: Currently, there are no population-based data among cancer patients on post-fracture mortality risk across a broad range of cancer diagnoses. Our objective was to estimate the association of fracture with mortality in cancer survivors. METHODS: Using Manitoba Cancer Registry data from the province of Manitoba, Canada, we identified all women and men with cancer diagnosed between January 1, 1987, and March 31, 2014. We then linked cancer data to provincial healthcare administrative data and ascertained fractures after cancer diagnosis and mortality to March 31, 2015. Hazard ratios for all-cause mortality in those with versus without fracture were estimated from time-dependent Cox proportional hazards models adjusted for multiple covariates. RESULTS: The study cohort consisted of 122,045 cancer patients (median age 68 years, IQR 58-77, 49.2% female). During the median follow-up of 5.8 years from cancer diagnosis, we ascertained 7120 (5.8%) major fractures. All fracture sites, except for the forearm, were associated with increased mortality risk, even after multivariable adjustment. Excess mortality risk associated with a major fracture was greatest in the first year after fracture (HR 2.42, 95% CI 2.30-2.54) and remained significant > 5 years after fracture (HR 1.60, 95% CI 1.50-1.70) and for fractures occurring > 10 years after cancer diagnosis (HR 1.93, 95% CI 1.79-2.07). CONCLUSION: Fractures among cancer patients are associated with increased all-cause mortality. This excess risk is greatest in the first year and persists more than 5 years post-fracture; increased risk is also noted for fractures occurring up to and beyond 10 years after cancer diagnosis.

Preexisting autoimmune disease and immune-related adverse events associated with anti-PD-1 cancer immunotherapy: a national case series from the Canadian Research Group of Rheumatology in Immuno-Oncology.

BACKGROUND: Limited data are available on the safety and efficacy of immune checkpoint inhibitors (ICI) in patients with preexisting autoimmune diseases (PAD). METHODS: Retrospective study of patients with PAD referred for rheumatologic evaluation prior to starting or during immunotherapy between January 2013 and July 2019 from 10 academic sites across Canada. Data were extracted by chart review using a standardized form. RESULTS: Twenty-seven patients with PAD on ICI therapy were identified. The most common PADs were rheumatoid arthritis (30%), psoriasis/psoriatic arthritis (30%), inflammatory bowel disease (IBD, 15%) and axial spondyloarthritis (11%), and the most frequently observed cancers were lung cancer and melanoma. All patients received anti-PD-1 therapies, and 2 received additional sequential anti-CTLA-4 therapy. PAD exacerbations occurred in 52% over a median (IQR) follow-up of 11.0 (6.0-17.5) months, with 14% being severe, 57% requiring corticosteroids, 50% requiring immunosuppression and 14% requiring ICI discontinuation. Flares were generally more frequent and severe in patients who previously required more intensive immunosuppression (i.e., biologics). Flares occurred despite background immunosuppression at the time of ICI initiation. In patients with preexisting psoriasis, IBD and axial spondyloarthritis, rheumatic immune-related adverse events (irAEs), mostly polyarthritis and tenosynovitis, were frequently observed. Tumor progression was not associated with exposure to immunosuppressive drugs before or after ICI initiation and was numerically less frequent in patients with irAEs. CONCLUSION: PAD exacerbations in the context of ICI treatment are common, although generally mild, and occur despite background immunosuppression. Exacerbations are more frequent and severe in patients on more intensive immunosuppressive therapies pre-immunotherapy.

Prior adherence to statins is a predictor of subsequent adherence and persistence to oral, but not parenteral, osteoporosis medications.

INTRODUCTION: Although bisphosphonates are effective for treating osteoporosis, patient adherence is variable. We conducted this study to determine if prior adherence with another medication used to treat chronic asymptomatic conditions predicts adherence with bisphosphonates. MATERIALS AND METHODS: Retrospective cohort study using linked population-level data for the entire Canadian province of Alberta between April 1, 2009 and March 31, 2017. We examined all new users of an oral or parenteral osteoporosis treatment over the age of 20 who had filled at least one statin prescription in the prior 12 months before the start date of the osteoporosis treatment. Adherence was defined based on medication possession ratio (MPR) and > = 80% was deemed good adherence. Persistence was defined as continuous treatment without an interruption of treatment for more than 56 days. RESULTS: Of 20,612 new users of oral bisphosphonates and 1538 new users of parenteral treatments, prior good adherence with statins was independently associated with both short term [adjusted Odds Ratio (aOR) 1.34 (95% CI 1.26-1.42) at 1 year] and long term [aOR 1.35 (1.20-1.51) at 5 years] adherence with oral bisphosphonates. However, there was no association between prior statin adherence and adherence [OR 0.94 (0.74, 1.20)] or persistence [(OR 0.96 (0.76, 1.22)] with parenteral osteoporosis therapies. Other factors associated with oral bisphosphonate adherence at 1 year included older age, history of bone mineral density scan, and history of pap smear. CONCLUSIONS: Prior adherence to statins is a predictor of subsequent short-term and long-term adherence and persistence with oral bisphosphonates but not parenteral osteoporosis therapies.

Asymptomatic bacteriuria is an independent predictor of urinary tract infections in an ambulatory cirrhotic population: a prospective evaluation.

BACKGROUND & AIMS: Asymptomatic bacteriuria (ASB) is a risk factor for urinary tract infections (UTIs) in many patients without liver disease. It remains unclear whether a diagnosis of ASB in an outpatient with cirrhosis could be utilized to predict the subsequent development of a UTI. We undertook this study to determine the prevalence and incidence of ASB in an outpatient population and its association with UTI. METHODS: We prospectively evaluated 108 adult outpatients with cirrhosis over a 6-month period. Monthly midstream urines (MSU) were performed to detect the occurrence of UTI and ASB (culture of ≥10(8) CFU/L of a urinary pathogen in the absence of UTI symptoms). RESULTS: Of 108 patients enrolled, 99 completed at least one MSU, for a total of 489 MSUs. Total follow-up was 44 person-years. The incidences of ASB and UTI were 181 and 250 per 1000 person-years, respectively. The prevalences of ASB and UTI on the first MSU were 5 and 1%, respectively. In total, 8% of patients developed an episode of ASB and 11% developed a UTI during the study period. Univariate predictors of UTI were female gender, primary biliary cirrhosis, number of previous UTIs and preceding ASB. Preceding ASB was the only independent predictor of UTI on multivariate analysis, with an odds ratio of 6.2 (1.1-34.3), P = 0.04. CONCLUSIONS: Cirrhotic patients have higher rates of ASB and UTI than reported in the general population. ASB is an independent predictor of UTI. Further studies are necessary to determine whether routine screening and antimicrobial treatment of ASB is warranted.

Osteoporotic fractures: an unrecognized adverse event of immune checkpoint inhibitors?

The widespread use of immune checkpoint inhibitors (ICIs) in clinical practice has broadened our understanding of their immune-related adverse events (irAEs). IrAEs, including musculoskeletal adverse events, remain a significant concern. While ICI-associated arthritis is a well-documented musculoskeletal side effect of ICI therapy, the direct effects of ICIs on bone in patients with cancer are poorly understood. There is emerging evidence to support the hypothesis that ICIs adversely impact bone turnover and can lead to osteoporosis and fragility fractures, which are not currently recognized as irAEs.

Elevated CK from immune checkpoint inhibitor- related hypophysitis: a case report.

Immune checkpoint inhibitors (ICIs), have emerged to the forefront of management for various advanced cancers, such as melanoma, lung cancer and renal cell carcinoma. Immune checkpoints such as CTLA-4 and PD-1 serve to inhibit T cell activation and signaling; therefore through blockade of these pathways, ICIs promote anti-tumour immune activation. However, as a result of T cell disinhibition, ICIs have been reported to cause immune related adverse events (irAEs) affecting numerous organ systems. One of the most serious and potentially life-threatening irAE is inflammatory myositis. Myositis, which generally presents with progressive proximal muscle weakness and elevated serum creatine kinase (CK), has been reported in <1% of patients who have received ICI therapy. A rare cause of elevated CK is adrenal insufficiency, which has been reported in up to 6% of ICI users. Here we report a case of ICI-related hypophysitis related myopathy that was initially misdiagnosed as ICI-associated inflammatory myositis. This case illustrates the importance of considering a wide differential when assessing hyperCKemia in the setting of ICI use.

Case report: hypertrophic osteoarthropathy improves with immune checkpoint inhibitor therapy.

We report a case of a 66 year-old male with recurrent stage IIIA non-small cell lung cancer (NSCLC) and no prior arthritis or bone disease who developed hypertrophic osteoarthropathy (HOA) prior to immunotherapy treatment. Approximately one month after the first durvalumab infusion and without other interventions for symptom management, the patient reported improvements to his hand pain, with complete resolution of symptoms after five durvalumab treatments. Repeat x-ray after nine cycles of durvalumab showed decreased periosteal thickening of the phalanges bilaterally. He had no evidence of recurrent NSCLC based on serial computed tomography one year after durvalumab initiation. To our knowledge, there are no documented reports on the isolated effect of immune-checkpoint inhibitor (ICI) therapy on HOA. This case suggests that durvalumab may have a positive role in the management of HOA in NSCLC patients. Further research is needed to better understand the interaction of ICIs, HOA and other paraneoplastic syndromes.

False-positive Findings of Large Vessel Vasculitis on FDG-PET in Patients Treated With Immune Checkpoint Inhibitors.

Fluorine-18 fluorodeoxygluocose positron emission tomography (FDG-PET) is increasingly used in the evaluation of response to immune checkpoint inhibitor (ICI) therapy. Incidental findings of increased vessel wall uptake may prompt the concern for ICI-induced large vessel vasculitis (LVV). Precise radiographic and clinical evaluation is required to determine if this represents true vasculitis, as use of immune suppression and ICI discontinuation can have significant impacts on patient outcomes. We performed a retrospective case analysis of 4 consecutive patients referred to 2 rheumatology clinics treated with ICI with incidental findings of LVV on FDG-PET, reviewing their clinical course and radiographic findings. All 4 cases had FDG-PET scans for routine oncology indications and had no associated clinical features of LVV. One patient was treated with corticosteroids and no patients developed any clinical evidence of vasculitis during a mean follow-up period of 17 months (range: 7-33 mo). All FDG-PET images reporting LVV underwent a standardized analysis to identify any technical issues or concerns with interpretation. In review of imaging, 3 of the cases may have been due to delayed tracer to scan interval leading to misinterpretation of vascular uptake as suspected LVV. Recognition of technical pitfalls in FDG-PET interpretation is crucial to inform the need for immunosuppression and the safety of continued ICI therapy.

Targeted Coaching to Improve Osteoporosis Therapy Adherence: A Single Arm Variation of the C-STOP Study.

BACKGROUND: In this pre-planned variation of the Comparing Strategies Targeting Osteoporosis to Prevent Fractures After an Upper Extremity Fracture (C-STOP) trial, we investigated whether adherence-specific coaching by the case manager (CM) further improved the adherence and persistence rates compared to those seen in the C-STOP trial. METHODS: We conducted a prospective observational cohort study of community-dwelling adults 50 years or older who suffered an upper-extremity fracture and were not previously treated with osteoporosis medications, to assess whether a well-trained CM can partner with patients to improve adherence to and persistence with oral bisphosphonate intake. The primary outcome was adherence (taking > 80% of prescribed doses) to oral bisphosphonate intake at 12 months after study enrollment. Secondary outcomes included primary adherence to and 12-month persistence with oral bisphosphonate and calcium and vitamin D supplement intake at 12 months. RESULTS: The study cohort consisted of 84 participants, of which 30 were prescribed an oral bisphosphonate. Twenty-two (73.3%) started treatment within 3 months. The adherence rate at 12 months was 77.3%. The persistence rate at 12 months was 95.5%. Of those not prescribed an oral bisphosphonate, 62.8% were taking supplemental calcium and 93.0% were taking supplemental vitamin D at 12 months. Depression was a significant predictor of 12-month non-adherence (adjusted odds ratio, 9.8; 95% confidence interval, 1.2-81.5). CONCLUSIONS: Adherence-specific coaching by a CM did not further improve the level of medication adherence achieved in the original C-STOP study. Importantly, these results can inform adherence in future intervention studies.

Doctor Versus Artificial Intelligence: Patient and Physician Evaluation of Large Language Model Responses to Rheumatology Patient Questions in a Cross-Sectional Study.

OBJECTIVE: The objective of the current study was to assess the quality of large language model (LLM) chatbot versus physician-generated responses to patient-generated rheumatology questions. METHODS: We conducted a single-center cross-sectional survey of rheumatology patients (n = 17) in Edmonton, Alberta, Canada. Patients evaluated LLM chatbot versus physician-generated responses for comprehensiveness and readability, with four rheumatologists also evaluating accuracy by using a Likert scale from 1 to 10 (1 being poor, 10 being excellent). RESULTS: Patients rated no significant difference between artificial intelligence (AI) and physician-generated responses in comprehensiveness (mean 7.12 ± SD 0.99 vs 7.52 ± 1.16; P = 0.1962) or readability (7.90 ± 0.90 vs 7.80 ± 0.75; P = 0.5905). Rheumatologists rated AI responses significantly poorer than physician responses on comprehensiveness (AI 5.52 ± 2.13 vs physician 8.76 ± 1.07; P < 0.0001), readability (AI 7.85 ± 0.92 vs physician 8.75 ± 0.57; P = 0.0003), and accuracy (AI 6.48 ± 2.07 vs physician 9.08 ± 0.64; P < 0.0001). The proportion of preference to AI- versus physician-generated responses by patients and physicians was 0.45 ± 0.18 and 0.15 ± 0.08, respectively (P = 0.0106). After learning that one answer for each question was AI generated, patients were able to correctly identify AI-generated answers at a lower proportion compared to physicians (0.49 ± 0.26 vs 0.97 ± 0.04; P = 0.0183). The average word count of AI answers was 69.10 ± 25.35 words, as compared to 98.83 ± 34.58 words for physician-generated responses (P = 0.0008). CONCLUSION: Rheumatology patients rated AI-generated responses to patient questions similarly to physician-generated responses in terms of comprehensiveness, readability, and overall preference. However, rheumatologists rated AI responses significantly poorer than physician-generated responses, suggesting that LLM chatbot responses are inferior to physician responses, a difference that patients may not be aware of.

The Utility of Laboratory Investigations for the Assessment and Management of Rheumatic Immune Related Adverse Events.

Immune checkpoint inhibitors (ICIs) have greatly improved survival of several cancers with historically very poor prognosis. ICIs act by stimulating the patient's own immune system to fight cancer. Simultaneously, this immune activation can lead to immune-related adverse events (irAEs), including rheumatic manifestations (Rh-irAEs). Rh-irAEs mimic primary rheumatic diseases including arthritis, polymyalgia rheumatica, myositis, vasculitis, sarcoidosis, and sicca. This article summarizes the latest evidence regarding the utility of laboratory investigations in Rh-irAEs.

FRAX predicts cardiovascular risk in women undergoing osteoporosis screening: the Manitoba bone mineral density registry.

Osteoporosis and cardiovascular disease (CVD) are highly prevalent in older women, with increasing evidence for shared risk factors and pathogenesis. Although FRAX was developed for the assessment of fracture risk, we hypothesized that it might also provide information on CVD risk. To test the ability of the FRAX tool and FRAX-defined risk factors to predict incident CVD in women undergoing osteoporosis screening with DXA, we performed a retrospective prognostic cohort study which included women aged 50 yr or older with a baseline DXA scan in the Manitoba Bone Mineral Density Registry between March 31, 1999 and March 31, 2018. FRAX scores for major osteoporotic fracture (MOF) were calculated on all participants. Incident MOF and major adverse CV events (MACE; hospitalized acute myocardial infarction [AMI], hospitalized non-hemorrhagic cerebrovascular disease [CVA], or all-cause death) were ascertained from linkage to population-based healthcare data. The study population comprised 59 696 women (mean age 65.7 ± 9.4 yr). Over mean 8.7 yr of observation, 6021 (10.1%) had MOF, 12 277 women (20.6%) had MACE, 2274 (3.8%) had AMI, 2061 (3.5%) had CVA, and 10 253 (17.2%) died. MACE rates per 1000 person-years by FRAX risk categories low (10-yr predicted MOF <10%), moderate (10%-19.9%) and high (≥20%) were 13.5, 34.0, and 64.6, respectively. Although weaker than the association with incident MOF, increasing FRAX quintile was associated with increasing risk for MACE (all P-trend <.001), even after excluding prior CVD and adjusting for age. HR for MACE per SD increase in FRAX was 1.99 (95%CI, 1.96-2.02). All FRAX-defined risk factors (except parental hip fracture and lower BMI) were independently associated with higher non-death CV events. Although FRAX is intended for fracture risk prediction, it has predictive value for cardiovascular risk.

Association of vertebral fractures with worsening degenerative changes of the spine: a longitudinal study.

Vertebral compression fractures (VFs) and spinal degeneration are both common causes of back pain, particularly in older adults. Previous cross-sectional studies have shown a potential association between these entities, but there is limited evidence on the role of VFs in spinal degeneration. In this longitudinal study, we evaluated the association between prevalent VFs and the subsequent progression of facet joint osteoarthritis (FJOA) and intervertebral disc height narrowing (DHN), using data from the Framingham Heart Study Offspring and Third Generation Multi-Detector Computed Tomography study. Summary indices representing the total burden of each spinal parameter (VFs, DHN and FJOA) were calculated for each individual. We hypothesized that prevalent VFs are associated with worsening spinal degeneration. 370 (31%) of 1197 participants, had a baseline (prevalent) VF. The change in summary index of DHN over the follow-up period was significantly higher in those with versus without prevalent VF (difference in change in DHN 0.38, 95% CI 0.18 to 0.59, P<.001), but the change in summary index of FJOA was similar between those with and without prevalent VF. However, once adjusted for age, sex, cohort, smoking status, body mass index, and baseline DHN, the change in summary index of DHN did not differ by prevalent VF status. There was a modestly higher change in the FJOA summary index in those with prevalent VFs compared to those without in the fully adjusted model (difference in change in FJOA 0.62, 95% CI -0.01 to 1.24, P=.054), driven primarily by those with severe (grade 3) VF (difference in change in FJOA 4.48, 95% CI 1.99 to 6.97). Moreover, there was greater change in the summary index of FJOA with increasing severity of prevalent VF (linear trend P=.005). Beyond the established morbidity and mortality associated with VFs, our study suggests that VFs may also lead to worsening spine osteoarthritis.

Vertebral compression fractures and spinal degeneration are both common causes of back pain. Previous studies have shown a potential link between these two entities, but it is not clear if one leads to the other. In this study, we examined the relationship between vertebral compression fractures and future progression of spinal degeneration. In this study of 1197 participants, those who had a vertebral compression fracture at the start of the study developed more spinal degeneration over 6 years of follow-up. There was an association between higher number and/or severity of vertebral compression fractures at the start of the study and worse spinal degeneration over the follow-up period. This study shows that vertebral compression fractures may lead to worsening spinal degeneration.

Elevated Troponin T in Immune-Checkpoint Inhibitor Myositis: A Case of Mistaken Myocarditis.

A patient with metastatic renal cell carcinoma on axitinib and pembrolizumab had elevated high-sensitivity cardiac troponin T and normal high-sensitivity cardiac troponin I with unremarkable cardiac investigations. A noncardiac cause (myositis) was the likely cause for cardiac troponin T elevation. Cardiac troponin I may be a more appropriate marker to support a myocarditis diagnosis with concurrent myositis.

Fracture Risk Prediction Using the Fracture Risk Assessment Tool in Individuals With Cancer.

Importance: The Fracture Risk Assessment Tool (FRAX) is a fracture risk prediction tool for 10-year probability of major osteoporotic fracture (MOF) and hip fracture in the general population. Whether FRAX is useful in individuals with cancer is uncertain. Objective: To determine the performance of FRAX for predicting incident fractures in individuals with cancer. Design, Setting, and Participants: This retrospective population-based cohort study included residents of Manitoba, Canada, with and without cancer diagnoses from 1987 to 2014. Diagnoses were identified through the Manitoba Cancer Registry. Incident fractures to March 31, 2021, were identified in population-based health care data. Data analysis occurred between January and March 2023. Main Outcomes and Measures: FRAX scores were computed for those with bone mineral density (BMD) results that were recorded in the Manitoba BMD Registry. Results: This study included 9877 individuals with cancer (mean [SD] age, 67.1 [11.2] years; 8693 [88.0%] female) and 45 877 individuals in the noncancer cohort (mean [SD] age, 66.2 [10.2] years; 41 656 [90.8%] female). Compared to individuals without cancer, those with cancer had higher rates of incident MOF (14.5 vs 12.9 per 1000 person-years; P < .001) and hip fracture (4.2 vs 3.5 per 1000 person-years; P = .002). In the cancer cohort, FRAX with BMD results were associated with incident MOF (HR per SD increase, 1.84 [95% CI, 1.74-1.95]) and hip fracture (HR per SD increase, 3.61 [95% CI, 3.13-4.15]). In the cancer cohort, calibration slopes for FRAX with BMD were 1.03 for MOFs and 0.97 for hip fractures. Conclusions and Relevance: In this retrospective cohort study, FRAX with BMD showed good stratification and calibration for predicting incident fractures in patients with cancer. These results suggest that FRAX with BMD can be a reliable tool for predicting incident fractures in individuals with cancer.