Immune checkpoint inhibitors (ICIs) deliver prominent anti-tumor efficacy across multiple malignancies, yet ICI-associated myocarditis represents a life-threatening adverse event requiring standardized management. Updated from the 2022 version, these recommendations integrate up-to-date domestic and international real-world data and emerging evidence concerning bispecific antibody-related cardiac injury, thymic imaging grading, artificial intelligence-assisted early screening, and optimized second-line immunosuppressive regimens. These recommendations provide standardized practical guidance for prevention, early recognition and individualized intervention to improve patient outcomes.

To report diagnosis and treatment of a patient with rectal cancer and synchronous liver metastases,accompanied by severe coronary artery stenosis and cardiac insufficiency,and to provide a reference for clinical decision-making in such cases through introducing the treatment contradiction,the choice of systemic treatment plan and the timing of operation,and the final outcome.After definitive diagnosis,the patient received systemic therapy with cetuximab+irinotecan+oxaliplatin+raltitrexed,and along with oral medication to improve cardiac function,followed by elective coronary revascularization.After revascularization,the cardiac function of patient was fully improved.And the tumor lesion was effectively controlled after antitumor therapy.Once the cardiac condition of patient stabilized,two-stage surgical resection of the primary rectal cancer and liver metastases was performed,ultimately achieving tumor-free status,and discharged.

Immune checkpoint inhibitors (ICIs) have prolonged cancer survival but exacerbated atherosclerotic cardiovascular disease (ASCVD). This research aims to interrogate the underlying mechanism of ICIs-related atherosclerotic progression and the potential protective effect of Red Yeast Rice (RYR) on it. A tumor-bearing atherosclerotic (TB-AS) mouse model was established by subcutaneously injecting MC38 cells in male ApoE-/- mice fed a high-fat diet (HFD). Intraperitoneal anti-PD-1 antibody (αPD-1) with/without dietary RYR supplementation was administered during the model. Serum was separated for lipid and inflammation evaluation. Plaque assessment was quantified by histological staining. Bone marrow-derived macrophages (BMDMs) were isolated, incubated in growth medium containing 5% serum from the mice model, and treated with ox-LDL and RYR. Cell viability was accessed by CCK8 assay. Lipid staining was employed to assess lipid droplet accumulation. The apoptosis and polarization of BMDMs were analyzed using flow cytometry. Cytokine levels were determined by luminex multiplex assay. And finally, western blot was conducted for mechanism investigation. αPD-1 significantly increased atherosclerotic lesion area, plaque lipid content, and macrophage/T-cell infiltration versus untreated TB-AS controls. These effects coincided with elevated pro-inflammatory cytokines/chemokines and reduced anti-inflammatory mediators. RYR co-treatment attenuated these αPD-1-induced pro-atherogenic changes. In vitro, compared with serum from TB-AS mice, BMDMs cultured with serum from αPD-1-treated TB-AS mice exhibited reduced cell viability, elevated pro-inflammatory cytokine levels in culture supernatants, enhanced M1 polarization, and increased apoptosis levels. All these phenotypic changes were reversed by RYR treatment. Mechanistically, RYR significantly inhibited the RhoA-mediated activation of NF-κB and MAPK signaling, thereby suppressing the αPD-1-induced inflammatory response in BMDMs. αPD-1 promotes ASCVD progression by enhancing macrophage inflammation and T-cell recruitment within plaques. RYR mitigates these effects through RhoA inhibition, suggesting its therapeutic potential for improving cardiovascular outcomes in ICIs-treated cancer patients with ASCVD.

Medical artificial intelligence (AI) offers transformative potential for earlier disease detection, equitable access, and safer, more consistent care. However, its advancement depends on large-scale, multimodal, and longitudinal clinical data, which are highly sensitive and difficult to share under increasingly strict privacy and regulatory constraints. Federated learning—based on local training with gradient or parameter sharing—has emerged as a partial response to these challenges, yet it continues to face important limitations, including reliance on centralized aggregation, communication overhead, and reduced efficiency in heterogeneous settings. This perspective outlines a conceptual framework for rethinking collaboration in medical AI. We introduce the forward-looking notion of a data–model network, a model-centric paradigm that shifts collaboration from direct data exchange toward structured model interaction. In this framework, healthcare institutions train models locally and exchange model artifacts—such as parameters, distilled representations, or weak-to-strong generalizations—within a decentralized ecosystem, without transferring raw patient data. This theoretical model highlights how model-centric interaction can enable collective learning across heterogeneous clinical environments while preserving data sovereignty and embedding privacy protection by design. At the same time, we emphasize that this paradigm entails its own trade-offs and implementation challenges, including governance complexity, knowledge incompleteness, and trust management. By articulating these opportunities and limitations, this perspective argues that privacy-aware collaboration architectures can reposition privacy compliance from a constraint into a potential driver of innovation in medical AI—without presenting it as a panacea.

Radiation-induced heart disease (RIHD) is a form of cardiotoxicity caused by radioactive substances or radiotherapy, and represents a common long-term complication after thoracic malignancy radiotherapy. RIHD onset is insidious, progression is slow, and significantly affects patients’ long-term quality of life. The pathophysiological mechanisms of RIHD involve multiple pathways, including endothelial cell injury, oxidative stress, inflammatory response, and myocardial fibrosis, ultimately leading to pericarditis, coronary artery disease, valvular heart disease, cardiac dysfunction, and conduction abnormalities, etc. Widespread use of immune checkpoint inhibitors (ICIs) in thoracic tumors, especially the combination of radiotherapy and ICIs, has introduced new changes in cardiac risk. This article reviews the epidemiological characteristics of RIHD, potential molecular targets, clinical manifestations, and treatment options. It also summarizes the value of imaging, electrocardiography, and biomarkers in RIHD monitoring, as well as the cardiac risks associated with combined radiotherapy and immunotherapy. Furthermore, multidisciplinary management strategies and preventive approaches are discussed, aiming to provide a reference for individualized management of RIHD patients in clinical practice.

BACKGROUND:Immune checkpoint inhibitor-associated myocarditis (ICIAM) poses significant challenges for cancer immunotherapy, particularly regarding the safety and efficacy of immune checkpoint blockade (ICB) rechallenge. METHODS:The present study analyzed 23 cases of ICIAM by integrating longitudinal clinical data with single-cell RNA sequencing and T-cell receptor profiling of peripheral blood mononuclear cells (PBMCs) obtained from three representative patients before and after ICB rechallenge. The single-cell cohort comprised two patients who experienced recurrent irAEs upon rechallenge and one patient who did not develop recurrent irAEs. RESULTS:Among 12 patients (52%) who experienced recurrent irAEs upon rechallenge, myocarditis recurrence occurred in 8 cases, with most (88%) presenting as grade 1- significantly milder than initial episodes (p=0.046). Single-cell analysis revealed that the patient who did not develop recurrent irAEs exhibited a high proportion of effector CD8+ T cells with high TRAV19 expression (CD8 Teff TRAV19), a TCR Vα family associated with SARS-CoV-2 reactivity. In contrast, patients who experienced recurrent irAEs lacked this expanded population. Rechallenge during myocarditis course was associated with higher recurrent irAEs risk (OR=14.0, 95%CI:1.3-147.4, p=0.027). Despite recurrence, tumor response was preserved, with a median progression-free survival (mPFS) of 8.5 months and no significant outcome difference between patients with and without post-rechallenge irAEs. CONCLUSION:ICB rechallenge is feasible in selected ICIAM patients, with most recurrent myocarditis cases being milder. Our exploratory single-cell analysis reveals that a high proportion of CD8 Teff TRAV19 was present in the patient protected from recurrence but absent in those who relapsed, suggesting that pre-existing virus specific memory T cells may modulate recurrent irAEs risk via antigen-specific niche occupation. While limited by sample size, these findings generate the hypothesis that T-cell repertoire composition could inform patient selection for ICB rechallenge, a concept warranting validation in larger cohorts.

BackgroundThis study explores the "wave-off" mechanism in healthcare, in which physicians implicitly discourage patient revisits to manage high workloads. Understanding this mechanism is critical for balancing workload management and patient-centered care, as it highlights how physician discretion shapes patient behavior and operational efficiency.MethodsWe analyze 200,426 outpatient records from a cardiology department to investigate the relationship between physician workload and the likelihood of patient revisits. We introduce a novel metric, Sample Entropy, to quantify patient "stickiness," or the propensity to revisit. We examine physician behaviors-such as referrals for diagnostic examinations and medication prescribing-to identify strategies used to modulate patient flow. Statistical analyses assess the impact of workload on revisit patterns and the mechanisms driving the wave-off effect.ResultsHigher physician workloads are significantly associated with reduced short-term patient revisits. Physicians manage workload by prescribing more medications and referring fewer diagnostic examinations, laboratory tests, particularly for patients with higher stickiness as measured by Sample Entropy. These behaviors alleviate short-term workload pressure but risk long-term inefficiencies, potentially reflecting bounded rationality in clinical decision-making.ConclusionsThe wave-off mechanism illustrates a trade-off between immediate workload relief and long-term operational performance. While it helps physicians address short-term capacity constraints, it may undermine optimal long-term patient care and system efficiency. This study highlights the operational and behavioral implications of physician-driven demand modulation, including the subtle yet consequential phenomenon of physician-reduced demand, in which patients are implicitly discouraged from revisiting due to workload-driven adjustments in care delivery.

Objective To investigate predictive value of soluble growth stimulation-expressed gene 2 protein(sST2),cardiac troponin T(cTnT),and creatine kinase-myocardial band(CK-MB)for steroid resistance and prognosis in patients with immune checkpoint inhibitor-associated myocarditis(ICIAM).Methods A total of 28 patients with ICIAM were prospectively enrolled from March 2023 to February 2024 at Zhongshan Hospital,Fudan University.All participants were divided into the steroid-resistant ICIAM(srICIAM)group and the non-srICIAM group.Baseline serum levels of sST2,cTnT and CK-MB were detected prior to treatment initiation.ROC curve analysis was applied to evaluate the predictive value of these biomarkers,and Kaplan-Meier survival analysis was performed to explore the relationship between sST2 and all-cause mortality.Results Baseline sST2,cTnT,and CK-MB levels were significantly higher in the srICIAM group(n=15)than in the non-srICIAM group(n=13,P＜0.05).Combination of cTnT and sST2 improved predictive performance for srICIAM(AUC=0.857,sensitivity 0.714,specificity 1.000).After 6 months of follow-up,the high sST2 group had a significantly higher all-cause mortality than the low sST2 group(P=0.016).Conclusions The combination of sST2 and cTnT could effectively predict srICIAM,and elevated sST2 is associated with increased higher all-cause mortality in ICIAM patients,providing a basis for early risk stratification and treatment optimization.

Immune checkpoint inhibitors (ICIs) have revolutionized treatment strategies for cancer; however, some fatal cardiovascular immune-related adverse events, such as myocarditis, limit their clinical application. Here, we report a case of ICI-associated autoimmune dilated cardiomyopathy, which has not been previously reported in the literature. A 63-year-old man with hepatic malignancy treated with envafolimab developed heart failure because of envafolimab-induced autoimmune dilated cardiomyopathy. Endomyocardial biopsy revealed a very small amount of lymphocyte infiltration, which was consistent with the manifestations of dilated cardiomyopathy. After the initiation of heart failure therapy according to the 2021 European Society of Cardiology Guidelines for the diagnosis and treatment of acute and chronic heart failure, he was recovering well and discharged. To our knowledge, this is the first case of dilated cardiomyopathy in a patient treated with envafolimab by subcutaneous injection.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of patients with lung cancer, including improving their survival rates. Immune checkpoint inhibitor-associated myocardial infarction is a rare but serious complication of using ICIs. We here present a case of a 70-year-old man who developed ICI-associated myocardial infarction, underwent percutaneous coronary stent implantation, and subsequently received standard oral medication. Chemotherapy was resumed after tumor progression was identified, at which time a review of coronary computed tomography angiography showed no stent stenosis. Strengthening the education and supervision of patients with cancer receiving ICIs and identifying and managing ICI-associated atherosclerosis in a timely manner is therefore necessary.

BACKGROUND:Immune checkpoint inhibitor associated myocarditis (ICIAM) is a drug-induced myocarditis characterized by the infiltration of immune cells into cardiac. However, the mechanisms are unknown and effective drug therapies are lacking in clinical practice. This study aims to explore the relationship between plasma metabolites and the treatment of ICIAM. METHODS:Human plasma metabolites were analyzed using untargeted metabolomics for characteristic metabolites. For in vivo experiments, Male Balb/c mice were divided into six groups: PBS, L-Kynurenine, cTNI+PD-1 inhibitor (ICIs), ICIs+L-Kynurenine, ICIs+RO8191, ICIs+RO8191+L-Kynurenine. On day 21 post-modeling, echocardiography, ELISA and histopathology were employed to evaluate the therapeutic effect of L-Kynurenine. Flow cytometry was used to determine the proportion of immune cells in the heart and spleen. Bulk-RNAseq was conducted to analyze differential genes, and q-PCR, immunofluorescence and western blot were performed for validation experiments. RESULTS:Untargeted metabolomics verified that indoleamine 2,3 dioxygenase-1 (IDO1)-derived L-Kynurenine level was higher in the serum of ICIAM compared to non-ICIAM patients. Meanwhile, in vitro and in vivo experiments showed that L-Kynurenine exhibited a therapeutic ability in ICIAM by inhibiting the pro-inflammatory polarization of immune cells and the secretion of pro-inflammatory cytokines. Mechanistically, L-Kynurenine improved cardiac functions majorly by the inhibition of the JAK1/STAT3 signaling pathway. CONCLUSION:L-Kynurenine exhibits significant therapeutic potential in ICIAM. The multi-roles of L-Kynurenine in regulating immune responses make it possible to be used as a targeted drug for ICIAM therapy.

Background and purpose:With the widespread application of immune checkpoint inhibitors (ICIs) in cancer treatment, the associated risk of developing atherosclerotic cardiovascular injury is increasing. However, the risk of cardiovascular disease after ICI treatment in patients with both coronary artery disease and malignancy remains unclear. This study aimed to investigate whether ICI treatment is associated with an increased risk of major adverse cardiovascular events (MACE) in these high-risk patients. Methods:This single-center, retrospective cohort study included 93 patients diagnosed with coronary heart disease and malignant tumors who received ICIs or non-ICIs therapy. The primary outcome was MACE, defined as a composite of cardiogenic death, heart failure, non-fatal acute coronary syndrome, and non-fatal ischemic stroke. The association between baseline clinical parameters, including ICI exposure, and the incidence of MACE was evaluated. Results:During a median follow-up of 14 months, MACE occurred in 32.50% of ICIs-treated patients, with a median time to event of 4 months (2.0-8.5 months), compared to 11.32% and 15.5 months (7.8-27.0 months) in non-ICIs patients. Additionally, all-cause mortality occurred in 12.50% of the ICIs-treated group and 13.21% of the non-ICIs group. Traditional cardiovascular risk factors were not associated with MACE in patients with or without ICI treatment. Multivariable regression analyses revealed an increased risk of developing MACE following ICIs therapy (hazard ration [HR]: 2.86, 95% confidence interval [95% CI]: 1.01-8.11; P = 0.048). Conclusions:Our findings show that ICIs therapy may be independently associated with an increased risk of MACE in patients with coronary heart disease and malignancy. Further larger-scale studies are needed to validate the potential cardiotoxic risk associated with ICIs.

ObjectiveTo investigate the improvement effect of Necrostatin-1 (Nec-1) on mouse models with immune checkpoint inhibitor (ICI) -associated myocarditis (ICIAM) and potential mechanism. MethodsTen male BALB/c mice aged 6-8 weeks were selected to construct the ICIAM models. The echocardiography and serum myocardial injury markers were used to assess cardiac function of mice. The levels of inflammatory markers including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Hematoxylin-eosin (HE) staining was used to evaluate myocardial inflammation, and Masson staining was used to evaluate myocardial fibrosis. The expressions of myocardial necroptosis proteins including receptor-interacting protein kinase 1 (RIP1), RIP3, mixed lineage kinase domain-like protein (MLKL) and their phosphorylated forms were detected by Western blotting. The spleen lymphocytes were extracted and co-cultured with HL-1 cell line. Cell viability was measured by cell counting kit-8 (CCK-8). The release of reactive oxygen species (ROS) and changes of mitochondrial membrane potential were observed. RIP1, RIP3, MLKL and their phosphorylated forms were determined. The levels of markers of oxidative stress, including malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), were measured. ResultsNec-1 significantly improved the cardiac function injury of mice induced by ICI, and inhibited the release of TNF-α and IL-1β in plasma of ICIAM mice (P＜0.001); inhibited expressions of phosphorylated RIP1, RIP3 and MLKL (P＜0.05); decreased MDA activity, and increased SOD and GSH-Px activity (P＜0.001). In HL-1 cells, Nec-1 intervention inhibited the RIP1-RIP3-MLKL pathway (P＜0.05), improved decrease of the cell viability induced by lymphocytes (P＜0.001), decreased ROS release, increased mitochondrial membrane potential, inhibited MDA activity, and increased SOD and GSH-Px activities (P＜0.001). ConclusionsNecroptosis plays an important role in the occurrence and development of ICIAM，but Nec-1 could alleviate the progression of ICIAM by inhibiting necroptosis induced by oxidative stress in cardiomyocytes; RIP1 maybe a new target in treatment of ICIAM.

ObjectiveTo develop a risk assessment scale for immune checkpoint inhibitor (ICI)-associated myocarditis based on multidisciplinary collaboration, and to evaluate its diagnostic performance. MethodsBased on multidisciplinary cooperation, integrating clinical experience from oncology and cardiology, literature data, and patient conditions, a risk assessment scale for ICI-associated myocarditis was developed. A total of 101 patients with malignancies who received immunotherapy at Zhongshan Hospital, Fudan University, from October 2020 to October 2024 were included as the validation cohort. Patients were stratified into low-risk (0-1 point), medium-risk (2-4 points), and high-risk (≥5 points) groups based on their scale scores. The association between pretictive risk stratifications and actual assessment results was assessed using the Cox proportional hazards regression model. The predictive value of the scale for ICI-associated myocarditis was evaluated using receiver operating characteristic (ROC) curve. Agreement between the scale scores and actual assessment results was assessed using Cohen’s Kappa coefficient. ResultsBased on the scale pretictive results, 28(27.7%), 8(7.9%), 65(64.4%) patients were at low risk, medium risk, and high risk for ICI-related myocarditis, respectively; however, 46(45.5%), 8(7.9%), 47(46.5%) were at low risk, medium risk, and high risk actually. Kaplan-Meier survival analysis showed that the cumulative incidence of ICI-related myocarditis in the high-risk group was significantly higher than that in the medium- and low-risk groups (P＜0.05). In the multivariable-adjusted Cox proportional hazards model, the ICI-related myocarditis risk in high-risk group was about 4 times that in the low-risk group. ROC curve analysis demonstrated that the average area under the curve (AUC) for predicting ICI-related myocarditis was 0.81, with an accuracy of 0.74. The Cohen’s Kappa coefficient was 0.55, indicating moderate agreement. In the actual high-risk group, no patient was predicted to be at low risk; in the actual low-risk group, 16 patients were predicted to be at high risk. ConclusionsThis risk assessment scale for ICI-associated myocarditis shows high predictive performance. It provides oncologists with a simple yet effective multidisciplinary diagnostic reference tool, potentially enhancing early identification of ICI-associated myocarditis.

In the evolving tapestry of medical science,the traditional boundaries between disciplines are being reimagined,resulting in the rise of innovative paradigms that bridge previously disconnected areas of research.

Cutaneous immune-related adverse events caused by immune checkpoint inhibitors are among the earliest and most common adverse reactions during tumor immunotherapy, resulting in substantial physical and psychological distress for patients. In severe cases, delayed or non-standard treatment may lead to life-threatening complications. The clinical manifestations of cutaneous immune-related adverse events are diverse and complex; considerable uncertainty exists regarding their diagnosis and management, including whether to discontinue tumor immunotherapy. This consensus provides a systematic analysis, comprehensive evaluation, and recommendations on the classification, clinical presentation, and treatment of cutaneous immune-related adverse events, as well as guidance concerning whether tumor immunotherapy should be discontinued. Emphasis is placed on the fact that immune-related adverse events often affect multiple organs and systems. Therefore, clinical assessments should extend beyond cutaneous involvement to include potential complications affecting the heart, lungs, endocrine system, and digestive system.

Steroid-resistant immune checkpoint inhibitor (ICI)-associated myocarditis (ICIAM) is rare, with no effective therapy. We present a case of successfully managed steroid-resistant ICIAM, demonstrating an effective treatment for this life-threatening complication. A 77-year-old woman with intrahepatic cholangiocarcinoma developed myocardial injury after two doses of ICI treatment. There was a rebound in troponin T during corticosteroid therapy; consequently, the patient was treated with tofacitinib combined with mycophenolate mofetil as second-line immunosuppressive therapy. Outcomes improved and anti-tumor treatment was rechallenged. The early administration of second-line immunosuppressive therapy is crucial for good outcomes with steroid-resistant ICIAM and the subsequent rechallenge of anti-tumor therapy.

Advent of immune checkpoint inhibitors (ICIs) has renovated onco-immunotherapy, with around 50% of cancer patients suitable for the treatment. However, patients treated by ICIs are in jeopardy for immune-related adverse events (irAEs) that attack any organ including the heart. ICIs-induced myocarditis (ICIIM) is an uncommon but possibly fatal irAE. With the increasing use of ICIs and improved diagnosis of this disease, the incidence of ICIIM is growing rapidly. In this review, we briefly overview roles of T cells and their immune checkpoints, and categorize the pathogenic process of ICIIM into three stages (upstream, midstream and downstream), with addressing recent research progress on the pathogenic mechanisms in each stage, particularly focusing on the downstream core pathogenic components and potential therapeutics for this disease.

Background and purpose: Outcomes for cancer patients with steroid-resistant immune checkpoint inhibitor-associated myocarditis (srICIAM) are poor. Intensified immunosuppressive therapies, including tofacitinib, a novel Janus kinase (JAK) inhibitor, may have some therapeutic benefits. However, due to the lack of sufficient clinical data, the effectiveness of such treatments and their impact on cardiovascular outcomes remain unclear. This study aimed to investigate the therapeutic effect of tofacitinib on srICIAM. Methods: This retrospective case-control study included 36 malignant tumor patients who received immune checkpoint inhibitor treatment at Zhongshan Hospital affiliated to Fudan University from July 2019 to May 2022 and developed srICIAM. Patients receiving corticosteroids in combination with tofacitinib were assigned to the tofacitinib group (n=19), while those not treated with tofacitinib were allocated to the control group (n=17). The study compared clinical characteristics, laboratory findings, and imaging results between the two groups. Additionally, follow-up was conducted to monitor the incidence of cardiovascular endpoints in these patients. The research plan was approved by the Ethics Committee of Zhongshan Hospital Affiliated to Fudan University (Approval Number: B2021-275R). This study was conducted in accordance with the ethical guidelines of the Helsinki Declaration. Results: Compared to the control group, and with no significant difference in the cumulative dose and duration of corticosteroids (P<0.05), the tofacitinib group showed a shorter myocarditis recovery time (median recovery time: 86.5 days vs 126.5 days, P=0.021). The myocarditis-related mortality rate was significantly lower in the tofacitinib group than in the control group (5% vs 35%, P=0.025). Conclusion: Tofacitinib may reduce mortality and promote cardiac recovery in srICIAM patients without impeding the anti-tumor effect. It may become one of the potential treatment strategies in the future.