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As tumor mutational burden (TMB) has been approved as a predictive biomarker for immune checkpoint inhibitors (ICIs), next-generation sequencing (NGS) TMB panels are being increasingly used clinically. However, only a few of them have been validated in clinical trials or authorized by administration. The harmonization and standardization of TMB panels are thus essential for clinical implementation. In this review, preanalytic, sequencing, bioinformatics and interpretative factors are summarized to provide a comprehensive picture of how the different factors affect the estimation of panel-based TMB. Among the factors, poor DNA quality, improper formalin fixation and residual germline variants after filtration may overestimate TMB, while low tumor purity may decrease the sensitivity of the TMB panel. In addition, a small panel size leads to more variability when comparing with true TMB values detected by whole-exome sequencing (WES). A panel covering a genomic region of more than 1Mb is more stable for harmonization and standardization. Because the TMB estimate reflects the sum of effects from multiple factors, deliberation based on laboratory and specimen quality, as well as clinical information, is essential for decision making.

Background Despite the advances of therapies, multiple myeloma (MM) remains an incurable hematological cancer that most patients experience relapse. Tumor angiogenesis is strongly correlated with cancer relapse. Human leukocyte antigen G (HLA-G) has been known as a molecule to suppress angiogenesis. We aimed to investigate whether soluble HLA-G (sHLA-G) was involved in the relapse of MM. Methods We first investigated the dynamics of serum sHLA-G, vascular endothelial growth factor (VEGF) and interleukin 6 (IL-6) in 57 successfully treated MM patients undergoing remission and relapse. The interactions among these angiogenesis-related targets (sHLA-G, VEGF and IL-6) were examined in vitro. Their expression at different oxygen concentrations was investigated using a xenograft animal model by intra-bone marrow and skin grafts with myeloma cells. Results We found that HLA-G protein degradation augmented angiogenesis. Soluble HLA-G directly inhibited vasculature formation in vitro. Mechanistically, HLA-G expression was regulated by hypoxia-inducible factor-1α (HIF-1α) in MM cells under hypoxia. We thus developed two mouse models of myeloma xenografts in intra-bone marrow (BM) and underneath the skin, and found a strong correlation between HLA-G and HIF-1α expressions in hypoxic BM, but not in oxygenated tissues. Yet when stimulated with IL-6, both HLA-G and HIF-1α could be targeted to ubiquitin-mediated degradation via PARKIN. Conclusion These results highlight the importance of sHLA-G in angiogenesis at different phases of multiple myeloma. The experimental evidence that sHLA-G as an angiogenesis suppressor in MM may be useful for future development of novel therapies to prevent relapse.

Background Cardiac involvement in diffuse large B-cell lymphoma (DLBCL) is rare but often complicated by life-threatening arrhythmias, conduction disturbances, and heart failure. Electrocardiography (ECG) is essential for early recognition and guiding intervention. Objectives To characterize ECG manifestations of cardiac-involved DLBCL and evaluate strategies for managing associated cardiac complications. Methods This study is a retrospective institutional case series conducted at MacKay Memorial Hospital from 2010 to 2025. We reviewed five patients with histologically confirmed primary or secondary cardiac DLBCL. Data on tumor location, ECG and echocardiographic findings, cardioprotective and anti-arrhythmic therapy, chemotherapy regimens, and outcomes were analyzed to correlate electrical abnormalities with anatomical involvement and therapeutic response. Results ECG patterns varied according to tumor distribution. Right atrial involvement was often associated with atrial tachycardia or atrial fibrillation. Pericardial infiltration produced low-voltage QRS complexes and electrical alternans in cases of massive effusion, whereas minimal effusion preserved normal sinus rhythm. Myocardial infiltration appeared to increase the risk of ventricular tachycardia and high-grade atrioventricular block, which is supported by the previous research about the reentry circuits at tumor–myocardium interfaces. Chemotherapy remains the principal therapeutic approach for cardiac DLBCL; however, our limited observations suggest that integrating anti-arrhythmic and cardioprotective therapy may improve chemotherapy tolerance. Successful arrhythmia control frequently correlated with improved clinical outcomes. However, the optimal use of anthracycline-based regimens in cardiac DLBCL remains uncertain and warrants further investigation. Conclusions Our findings highlight the importance of early recognition and multidisciplinary management for cardiac complications in the patients with cardiac-involved DLBCL. Cardioprotective strategies, anti-arrhythmic management, and careful chemotherapy selection are crucial to balance oncologic efficacy with cardiovascular safety.

Immune thrombocytopenia purpura (ITP) is initially treated with steroids, but TPO‐RAs such as eltrombopag are used for chronic cases. Though effective, eltrombopag has been linked to thromboembolic events, with cerebral venous thrombosis (CVT) being a rare complication. A 20‐year‐old woman with ITP developed severe headaches, nausea, and vomiting five days after starting eltrombopag. CT scans revealed a dense clot in the right transverse sinus, indicating CVT. Lab data showed elevated platelet counts and D‐dimer levels. MRV confirmed CVT, leading to the discontinuation of eltrombopag and initiation of anticoagulant therapy. Recurring thrombocytopenia necessitated further treatment adjustments, including rituximab and cyclosporine, resulting in improved platelet counts and CVT resolution. This case highlighted that CVT is a serious but rare side effect of eltrombopag in ITP patients. Early detection, prompt anticoagulation, and cautious TPO‐RA management are crucial for preventing thromboembolic events.