PURPOSE: Current approaches to accurately identify immune-related adverse events (irAEs) in large retrospective studies are limited. Large language models (LLMs) offer a potential solution to this challenge, given their high performance in natural language comprehension tasks. Therefore, we investigated the use of an LLM to identify irAEs among hospitalized patients, comparing its performance with manual adjudication and International Classification of Disease (ICD) codes. METHODS: Hospital admissions of patients receiving immune checkpoint inhibitor (ICI) therapy at a single institution from February 5, 2011, to September 5, 2023, were individually reviewed and adjudicated for the presence of irAEs. ICD codes and an LLM with retrieval-augmented generation were applied to detect frequent irAEs (ICI-induced colitis, hepatitis, and pneumonitis) and the most fatal irAE (ICI-myocarditis) from electronic health records. The performance between ICD codes and LLM was compared via sensitivity and specificity with an α = .05, relative to the gold standard of manual adjudication. External validation was performed using a data set of hospital admissions from June 1, 2018, to May 31, 2019, from a second institution. RESULTS: Of the 7,555 admissions for patients on ICI therapy in the initial cohort, 2.0% were adjudicated to be due to ICI-colitis, 1.1% ICI-hepatitis, 0.7% ICI-pneumonitis, and 0.8% ICI-myocarditis. The LLM demonstrated higher sensitivity than ICD codes (94.7% v 68.7%), achieving significance for ICI-hepatitis ( P < .001), myocarditis ( P < .001), and pneumonitis ( P = .003) while yielding similar specificities (93.7% v 92.4%). The LLM spent an average of 9.53 seconds/chart in comparison with an estimated 15 minutes for adjudication. In the validation cohort (N = 1,270), the mean LLM sensitivity and specificity were 98.1% and 95.7%, respectively. CONCLUSION: LLMs are a useful tool for the detection of irAEs, outperforming ICD codes in sensitivity and adjudication in efficiency.

In the STOP-CA (Statins to Prevent the Cardiotoxicity From Anthracyclines) trial, atorvastatin preserved the left ventricular ejection fraction among patients with lymphoma treated with anthracyclines. The protective mechanisms are currently unclear. The aim of this study was to test the effect of atorvastatin on the anthracycline-associated increase in myocardial extracellular volume (ECV) using cardiac magnetic resonance imaging (MRI). Cardiac MRI with mapping was performed at baseline and at 12-month follow-up. ECV was calculated, and the primary endpoint was a ≥3% increase. Increases of ≥1 SD in native T1 and T2 times and ECV were secondary endpoints. The subgroup included 171 participants with paired cardiac MRI scans, and 127 had contrast scans of appropriate quality (median age 52 years, 47% women). The proportion of participants with ≥3% increases in ECV was lower in the atorvastatin compared with the placebo group (8% vs 29%; P = 0.002; OR: 0.20; 95% CI: 0.06 to 0.59). A ≥3% increase in ECV was associated with an 8.4% decrease in left ventricular ejection fraction at follow-up (95% CI: -6.31 to -10.38; P < 0.001). The proportion of participants with ≥1-SD increases in T1 and T2 times was statistically similar between groups at 12 months. At 24 months, there were fewer heart failure events among those without ≥3% increases in ECV (8% vs 24%; P = 0.054), though not statistically significantly. Compared with placebo, atorvastatin limited ECV expansion among participants with lymphoma undergoing anthracycline chemotherapy. This study is the first to provide mechanistic insight into statins' cardioprotective effects with anthracyclines. (Statins to Prevent the Cardiotoxicity From Anthracyclines [STOP-CA]; NCT02943590).

Osteosarcoma and Ewing sarcoma patients face a significant risk of cardiotoxicity as defined by left ventricular dysfunction and heart failure (HF). This study sought to evaluate the association between age at sarcoma diagnosis and incident HF. A retrospective cohort study was performed at the largest sarcoma center in the Netherlands among patients with an osteosarcoma or Ewing sarcoma. All patients were diagnosed and treated over a 36-year period (1982-2018) and followed until August 2021. Incident HF was adjudicated through the universal definition of heart failure. Determinants including age at diagnosis, doxorubicin dose, and cardiovascular risk factors were entered as fixed or time-dependent covariates into a cause-specific Cox model to assess their impact on incident HF. The study population consisted of 528 patients with a median age at diagnosis of 19 years (Q1-Q3: 15-30 years). Over a median follow-up time of 13.2 years (Q1-Q3: 12.5-14.9 years), 18 patients developed HF with an estimated cumulative incidence of 5.9% (95% CI: 2.8%-9.1%). In a multivariable model, age at diagnosis (HR: 1.23; 95% CI: 1.06-1.43) per 5-year increase, doxorubicin dose per 10-mg/m² increase (HR: 1.13; 95% CI: 1.03-1.24), and female sex (HR: 3.17; 95% CI: 1.11-9.10) were associated with HF. In a large cohort of sarcoma patients, we found that patients diagnosed at an older age are more prone to develop HF.

Contrast-induced encephalopathy (CIE) is a rare complication of coronary angiography (CAG) caused by a direct neurotoxic reaction to iodinated contrast medium. Contrast-induced encephalopathy can result in a variety of neurological symptoms following within minutes to hours after contrast injection. It manifests most frequently as transient cortical blindness, headache, or confusion. In the majority of known cases, symptoms completely resolve solely with supportive care. We present a case where CIE takes a more dramatic course. A 67-year-old woman was scheduled for elective CAG, due to progressive typical chest pain. Within minutes after injection of iso-osmolar iodinated contrast medium, the patient showed a sudden decline in consciousness while all other vital functions remained normal. Shortly, after the patient was admitted to the intensive care unit due to acute-onset coma and respiratory insufficiency. A computed tomography scan of the brain showed bilateral cerebral oedema, which in combination with the development of symptoms after contrast injection led to the diagnosis of CIE. Remarkable decrease of cerebral oedema was observed 1 day later and slowly clinical recovery ensued. After 23 days, the patient was discharged from the cardiology ward. Follow-up at the outpatient clinic showed no lasting neurological deficits. While most symptoms of CIE are relatively mild and transient in nature, we describe a more devastating course that occurred with the use of only a low quantity of iso-osmolar contrast medium. We emphasize that even the more severe manifestations of CIE can develop at any dosage, and with all types of iodinated contrast medium.

Background: While it is broadly accepted that ageing is associated with impairment of coronary microvascular function, little is known about the underlying mechanisms.Aims: We investigated age‐related changes in coronary microvascular structure in patients with stable angina without epicardial coronary stenoses.Methods: In an analysis of the IDEAL registry, a total of 165 vessels without coronary stenosis were interrogated with combined pressure/Doppler guidewires. We calculated diastolic microvascular conductance (DMVC) and backward expansion wave (BEW), and compared them between age tertiles. We calculated the prevalence of CMD, defined by reduced coronary flow reserve (CFR), and the prevalence of low BEW and low DMVC in each group.Results: The three study groups were defined as having 37–53, 54–66, and 67–77 years of age, respectively. Oldest (3rd tertile) patients showed lower hyperemic flow velocity (46.7 ± 14.4 vs. 45.1 ± 12.4 vs. 38.4 ± 11.5 cm s⁻¹, p = 0.019), lower DMVC (1.90 ± 0.71 vs. 1.44 ± 0.56 vs. 1.37 ± 0.67 cm s⁻¹ mmHg⁻¹, p < 0.001) and lower BEW intensity (5.9 [2.9–8.4] vs. 4.8 [2.9–6.8] vs. 4.4 [3.4–6.3] × 10⁶ W m⁻² s⁻¹, p = 0.094). Older age was independently associated with lower BEW intensity (B: −0.10, 95% confidence interval [CI]: −0.17 to −0.09, p = 0.021) and DMVC (B: −0.25 95% CI: −0.45 to −0.09, p = 0.027). In patients with CFR < 2.5, the prevalence of BEW intensity and DMVC below the 25th percentile increased with age (25.0% vs. 52.0% vs. 72.7%, p = 0.010).Conclusions: Ageing is independently associated with structural microcirculatory remodeling that is reflected in BEW intensity and DMVC measurements, and with an increased prevalence of structural CMD. These results are important to understand non‐obstructive mechanisms of myocardial ischemia in the elderly.