Anti-CD19-directed chimeric antigen receptor (CAR) T-cell therapy yields durable remissions in up to 40% of patients with chemoresistant aggressive B-cell non-Hodgkin lymphoma (NHL), a group of patients expected only to survive on average 6 months. Although longer follow-up is needed to define durability, CD19 CAR T cells are demonstrating similar promise in other B-NHL subtypes such as mantle cell lymphoma and the indolent B-cell NHLs. This transformative therapy, however, remains hamstrung by its associated toxicities of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, as well as by mechanisms of resistance and relapse and accessibility. find more To address these limitations, studies are underway to investigate toxicity prevention and mitigation strategies and the development of safer CARs, combination strategies to overcome T-cell exhaustion and dual antigen targeting to combat antigen loss, and alternative cell sources to address cost and manufacturing inefficiencies and resomanufacturing inefficiencies and resolve issues surrounding T-cell fitness.

Immunotherapy with T cells engineered to express a chimeric antigen receptor (CAR T cells) is reshaping the management of patients with relapsed or refractory B-cell malignancies. High efficacy of CD19-targeted CAR T cells has been reported in children and adults with B-cell acute lymphoblastic leukemia (B-ALL), with complete responses without detectable minimal residual disease occurring in approximately 80% to 90% of patients. This led to the approval of tisagenlecleucel (Kymriah) by the Food and Drug Administration based on the results of the ELIANA trial. Although CD19 CAR T-cell therapy may be curative in children, responses are short-lived in most adult B-ALL patients. In addition, CAR T-cell therapy can be associated with severe, potentially life-threatening, toxicities, such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. Here, we review the recent advances in CAR T-cell therapy for R/R B-ALL and discuss strategies to improve its efficacy while minimizing toxing toxicities.

The US Food and Drug Administration has approved 3 chimeric antigen receptor (CAR) T-cell therapies. For continued breakthroughs, novel CAR designs are needed. This includes different antigen-binding domains such as antigen-ligand binding partners and variable lymphocyte receptors. Another recent advancement in CAR design is Boolean logic gates that can minimize on-target, off-tumor toxicities. Recent studies on the optimization of costimulatory signaling have also shown how CAR design can impact function. By using specific signaling pathways and transcription factors, CARs can impact T-cell gene expression to enhance function. By using these techniques, the promise of CAR T-cell therapies for solid tumors can be fulfilled.

The US Food and Drug Administration has approved 3 chimeric antigen receptor (CAR) T-cell therapies. For continued breakthroughs, novel CAR designs are needed. This includes different antigen-binding domains such as antigen-ligand binding partners and variable lymphocyte receptors. Another recent advancement in CAR design is Boolean logic gates that can minimize on-target, off-tumor toxicities. Recent studies on the optimization of costimulatory signaling have also shown how CAR design can impact function. By using specific signaling pathways and transcription factors, CARs can impact T-cell gene expression to enhance function. By using these techniques, the promise of CAR T-cell therapies for solid tumors can be fulfilled.

This study examined the relations between subjective stress and strategies for coping with stress (emotion control strategies and self-compassion), as well as the relations between emotional distress and fatigue.

The study used a cross-sectional survey design. Participants were 170 women aged 24 to 82 years with diagnoses of breast cancer stages I to III who were 1 to 12 months postchemotherapy, with no current evidence of disease and no previous cancer diagnosis. Participants were recruited by consecutive sampling, and the overall response rate was 85%.

Higher subjective stress was associated with higher emotional control (r = 0.23, P < 0.01), and both were associated with higher emotional distress (r = 0.63, P < 0.001; r = 0.20, P < 0.05). Lower self-compassion was associated with higher emotional distress (r = -0.20, P < 0.05). Fatigue exhibited a high association with emotional distress (r = 0.67, P < 0.001), which increased as subjective stress increased. Older age was associated with emotional control (r = 0.16, P < 0.05), whereas younger age was associated with emotional distress. Time elapsed since chemotherapy was negatively associated with both emotional distress (r = -0.19, P < 0.05) and fatigue (r = -0.18, P < 0.05). A strong positive association emerged between fatigue and emotional distress (r = 0.67, P < 0.001).

The results of this study underline the importance of self-compassion as a coping strategy to decrease emotional distress among breast cancer survivors.

The results of this study underline the importance of self-compassion as a coping strategy to decrease emotional distress among breast cancer survivors.The last medical act many emergency physicians must do in the context of caring for a dying patient and mourning relatives is to issue a medical death certificate (MDC). The physician is charged with filling in the MDC in cases that do not involve judicial certification. Ethical conflicts and doubts about the cause of death are common when MDCs are issued in emergencies. This paper analyzes the main ethical and legal issues related to MDCs in this setting. The ethical precepts to bear in mind when a conflict or doubt arises are loyalty to the patient, truthfulness, doing no harm, and using public resources wisely. Physician management of processes surrounding death in the emergency department can be improved by providing staff with better training so that they understand how and when to issue a MDC and what legal requirements are involved.