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Abstract Introduction This report outlines the evaluation of physiotherapist‐led prehabilitation/rehabilitation for recipients of chimeric antigen receptor T (CAR‐T) cell therapy. Methods A hybrid approach was used, incorporating in‐person assessment of quality of life and functional capacity (6‐min walk test and timed sit‐to‐stand test), and a personalised home exercise programme with remotely delivered physiotherapist support pre/post‐admission. Results Functional deficits were prevalent at referral for CAR‐T. Prehabilitation and rehabilitation were highly acceptable to patients, and improvements in functional capacity were documented pre‐admission. Conclusion This data highlights the importance of pre‐CAR‐T functional assessment and prehabilitation to optimise preparation and recovery.

Background We used a proliferating ligand (APRIL) to construct a ligand-based third generation chimeric antigen receptor (CAR) able to target two myeloma antigens, B-cell maturation antigen (BCMA) and transmembrane activator and CAML interactor.Methods The APRIL CAR was evaluated in a Phase 1 clinical trial (NCT03287804, AUTO2) in patients with relapsed, refractory multiple myeloma. Eleven patients received 13 doses, the first 15×106 CARs, and subsequent patients received 75,225,600 and 900×106 CARs in a 3+3 escalation design.Results The APRIL CAR was well tolerated. Five (45.5%) patients developed Grade 1 cytokine release syndrome and there was no neurotoxicity. However, responses were only observed in 45.5% patients (1×very good partial response, 3×partial response, 1×minimal response). Exploring the mechanistic basis for poor responses, we then compared the APRIL CAR to two other BCMA CARs in a series of in vitro assays, observing reduced interleukin-2 secretion and lack of sustained tumor control by APRIL CAR regardless of transduction method or co-stimulatory domain. There was also impaired interferon signaling of APRIL CAR and no evidence of autoactivation. Thus focusing on APRIL itself, we confirmed similar affinity to BCMA and protein stability in comparison to BCMA CAR binders but reduced binding by cell-expressed APRIL to soluble BCMA and reduced avidity to tumor cells. This indicated either suboptimal folding or stability of membrane-bound APRIL attenuating CAR activation.Conclusions The APRIL CAR was well tolerated, but the clinical responses observed in AUTO2 were disappointing. Subsequently, when comparing the APRIL CAR to other BCMA CARs, we observed in vitro functional deficiencies due to reduced target binding by cell-expressed ligand.

Breast reconstruction is highly complex, requiring navigation of not only clinical and operative realities, but of patient expectations as well. The authors sought to identify historical art pieces that exhibit breast asymmetries and deformities for comparison with photographs of breast reconstruction patients seen at the clinic of the senior author (S.O.P.) to demonstrate that achievement of perfect breast cosmesis is challenging in both breast reconstruction and in the classical arts. Open access libraries and Creative Commons images were reviewed to identify appropriate works of art from various time periods and geographic locations. Following artwork selection, photographs of breast reconstruction patients were reviewed and paired with selected artworks exhibiting cosmetically similar breasts. A total of 8 pieces of selected historic art were found to have at least 1 matching patient photograph, with 9 correlative patient photographs ultimately chosen. Common breast asymmetries and deformities identified included ptosis, asymmetric chest wall placement, asymmetric nipple placement, and absence of the nipple. This review identified diverse artworks of varying styles spanning vast expanses of both geography and time that exhibited breast deformities and asymmetries commonly encountered in patients seeking revision of breast reconstruction. This underscores that creating the cosmetically ideal breast is difficult both in the operating room and the art studio. Importantly, the authors emphasized that the arts frequently celebrate that which is considered beautiful, although to the trained eye of a plastic surgeon that which is considered beautiful is often classified as dysmorphic or asymmetric. [ABSTRACT FROM AUTHOR]