BACKGROUND AND AIMS:Immune checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process that causes ICI myocarditis can manifest concurrent generalized myositis, myasthenia-like syndrome, and respiratory muscle failure. Prognostic factors for this 'cardiomyotoxicity' are lacking. The main aim of this study was to determine predictors and construct a risk score associated with negative outcomes in patients admitted for ICI myocarditis. METHODS:A multicentre registry collected data retrospectively from 17 countries between 2014 and 2023. A multivariable Cox regression model was used to determine risk factors for the primary composite outcome: time to severe arrhythmia, heart failure, respiratory muscle failure, and/or cardiomyotoxicity-related death. Covariates included demographics, comorbidities, cardiomuscular symptoms, diagnostics, and treatments. Time-dependent covariates were used, and missing data were imputed. A point-based prognostic risk score was derived and externally validated. RESULTS:In 748 patients (67% male, age 23-94 years), 30-day incidence of the primary composite outcome, cardiomyotoxic death, and overall death were 33%, 13%, and 17%, respectively. By multivariable analysis, the primary composite outcome was associated with active thymoma (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.7-7.7), presence of cardiomuscular symptoms (HR 2.6 [1.5-4.2]), low QRS voltage on presenting electrocardiogram (HR for ≤0.5 mV vs >1 mV 1.9 [1.1-3.1]), left ventricular ejection fraction (LVEF) < 50% (HR 1.7 [1.1-2.6]), and incremental troponin elevation (HR 1.8 [1.4-2.4], 2.9 [1.8-4.7], and 4.6 [2.3-9.3], for 20, 200, and 2000-fold above upper reference limit, respectively). A prognostic risk score developed using these parameters showed good performance; 30-day primary outcome incidence increased gradually from 4% (risk score = 0) to 81% (risk score ≥ 4). This risk score was externally validated in two independent French and US cohorts. This risk score was used prospectively in the external French cohort to identify low-risk patients who were managed with no immunosuppression resulting in no cardiomyotoxic events. CONCLUSIONS:ICI-associated myocarditis can manifest with high morbidity and mortality. Myocarditis severity is associated with magnitude of troponin, thymoma, low QRS voltage, depressed LVEF, and cardiomuscular symptoms. A risk score incorporating these features performed well. CLINICAL TRIAL REGISTRATION:NCT04294771 and NCT05454527.
The number of patients with inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), continues to increase in many countries and regions. With recent rapid advances in medical therapies targeting intestinal inflammation, the number of patients with long-term disease duration is also increasing. It is well-recognized that longstanding IBD carries an increased risk of developing gastrointestinal (GI) neoplasia, particularly colorectal cancer. However, compared to sporadic GI tumors, IBD-associated GI tumors are relatively rare, and even among specialists in GI diseases, opportunities to encounter such cases remain limited. In light of this situation, the Japanese Society for Cancer of the Colon and Rectum (JSCCR), in collaboration with the Japanese Inflammatory Bowel Disease Research Group (funded by the Japan Sciences Research Grant for Research on Intractable Diseases affiliated with the Ministry of Health, Labour, and Welfare) launched the Guideline Development Committee for IBD-associated Gastrointestinal Tumors in 2021, with the aim of establishing clinical practice guidelines to support the diagnosis and management of these tumors. The committee-comprising experts in gastroenterology, surgery, pathology, guideline development, and literature review-conducted extensive discussions and successfully published the first Japanese edition of the guidelines in July 2024. We believe that the current edition provides the best possible guidance based on presently available knowledge. Furthermore, the guideline development process highlighted several key issues to be addressed in future research and clinical practice. We are pleased to present here the English version of the JSCCR Guidelines 2024 for the Clinical Practice of IBD-associated Intestinal Neoplasia.
Background and study aims:Indigo carmine chromoendoscopy (IC) enhances diagnosis of early gastric cancer (EGC), but its clinical application is limited by procedure complexity and time. We developed a deep-learning system using a cycle-consistent generative adversarial network (CycleGAN) to generate virtual IC images from white-light endoscopy (WLE) and evaluated visibility of EGC in video-based virtual IC in a pilot study. Patients and methods:We collected 4,096 endoscopic still images (2,089 WLE, 2,007 real IC) from 262 patients with gastric neoplasms. A CycleGAN model was trained to convert WLE into virtual IC images, and videos with 512 × 512 pixels at 30 frames per second were generated for five EGC cases. For each case, WLE, real IC, and virtual IC videos were prepared and evaluated by 16 endoscopists (6 experts, 10 non-experts). Visibility relative to WLE was rated using a 7-point Likert-type scale (-3 to +3), with positive values indicating improved visibility. Results:A total of 160 evaluations were performed. Median [IQR] visibility score was 1 [0-2)] for real IC and 0 [-1 to 1] for virtual IC ( P < 0.001). In virtual IC, 46.3% of cases achieved a score of +1 or higher. Scores significantly varied by endoscope system ( P < 0.001). Conclusions:Virtual IC improved visibility compared with WLE in nearly half the assessments, although its efficacy did not equal real IC. Optimizing performance for specific endoscope systems may enhance its clinical utility as a practical alternative for improving EGC detection.
