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International myeloma working group immunotherapy committee recommendation on sequencing immunotherapy for treatment of multiple myeloma

T-cell redirecting therapy (TCRT), specifically chimeric antigen receptor T-cell therapy (CAR T-cells) and bispecific T-cell engagers (TCEs) represent a remarkable advance in the treatment of multiple myeloma (MM). There are several products available around the world and several more in development targeting primarily B-cell maturation antigen (BCMA) and G protein–coupled receptor class C group 5 member D (GRPC5D). The relatively rapid availability of multiple immunotherapies brings the necessity to understand how a certain agent may affect the safety and efficacy of a subsequent immunotherapy so MM physicians and patients can aim at optimal sequential use of these therapies. The International Myeloma Working Group conveyed panel of experts to review patient and disease-related factors affecting efficacy and safety of immunotherapy, summarize existing information on sequencing therapy and provide a series of core recommendations.

Speculating suitability of partial adrenalectomy for lateralized primary aldosteronism: With emphasis on partial and complete success as optimistic outcomes

Primary aldosteronism (PA) is the most common secondary hypertension. The best treatment for a lateralized PA is unilateral adrenalectomy. Recent studies explored partial adrenalectomy (pAdx) to reduce the risk of adrenal insufficiency. However, in cases involving multiple aldosterone-producing micronodules/nodules (mAPM/mAPN), pAdx cannot completely remove all origins of excess aldosterone and might not resolve hypertension. CYP11B2 immunohistochemical staining helps HISTALDO (Histopathology of PA) diagnosis, and adrenal specimens were categorized into various groups accordingly. To determine whether pAdx should be considered for lateralized PA, we focused on the success rate of classical (black + grey group) versus non-classical (white group) lateralized PA, and the percentage of co-existing mAPM/mAPN in lateralized PA. The visible tumor in imaging could be either non-functional (incidentaloma; white group), or with concurrent surrounding mAPM/mAPN (grey group) causing hypertension. Among 445 patients who underwent unilateral adrenalectomy, 390 were diagnosed with lateralized PA. There were 63 (30.73%) in the black, 79 (38.54%) in the grey, 63 (30.73%) in the white group. The overall complete clinical success rate was 51.28% in our lateralized PA patients; with 65.08% in the black, 50.63% in the grey, and 26.98% in the white group. The overall partial clinical success rate was 38.54%; with 28.57% in the black, 34.18% in the grey, and 53.97% in the white group. Were pAdx performed, significantly lower success rates would be achieved, especially for lateralized PA patients of the grey and white groups. We speculate that unilateral pAdx is not an appropriate option for the majority of lateralized PA patients.

Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies

Transcriptional dysregulation is a hallmark of cancer initiation and progression, driven by genetic and epigenetic alterations. Enhancer reprogramming has emerged as a pivotal driver of carcinogenesis, with cancer cells often relying on aberrant transcriptional programs. The advent of high-throughput sequencing technologies has provided critical insights into enhancer reprogramming events and their role in malignancy. While targeting enhancers presents a promising therapeutic strategy, significant challenges remain. These include the off-target effects of enhancer-targeting technologies, the complexity and redundancy of enhancer networks, and the dynamic nature of enhancer reprogramming, which may contribute to therapeutic resistance. This review comprehensively encapsulates the structural attributes of enhancers, delineates the mechanisms underlying their dysregulation in malignant transformation, and evaluates the therapeutic opportunities and limitations associated with targeting enhancers in cancer.

Engineering bone/cartilage organoids: strategy, progress, and application

The concept and development of bone/cartilage organoids are rapidly gaining momentum, providing opportunities for both fundamental and translational research in bone biology. Bone/cartilage organoids, essentially miniature bone/cartilage tissues grown in vitro, enable the study of complex cellular interactions, biological processes, and disease pathology in a representative and controlled environment. This review provides a comprehensive and up-to-date overview of the field, focusing on the strategies for bone/cartilage organoid construction strategies, progresses in the research, and potential applications. We delve into the significance of selecting appropriate cells, matrix gels, cytokines/inducers, and construction techniques. Moreover, we explore the role of bone/cartilage organoids in advancing our understanding of bone/cartilage reconstruction, disease modeling, drug screening, disease prevention, and treatment strategies. While acknowledging the potential of these organoids, we discuss the inherent challenges and limitations in the field and propose potential solutions, including the use of bioprinting for organoid induction, AI for improved screening processes, and the exploration of assembloids for more complex, multicellular bone/cartilage organoids models. We believe that with continuous refinement and standardization, bone/cartilage organoids can profoundly impact patient-specific therapeutic interventions and lead the way in regenerative medicine.

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