The Impact of Breast Implant Cohesivity on Rippling and Revision Procedures in 2-Stage Prepectoral Breast Reconstruction.

Background: Rippling remains one of the most common complications following prepectoral implant-based reconstruction (IBR). Objectives: The purpose of this study was to assess how implant cohesivity, a measure of elasticity and form stability, affects the incidence of rippling in prepectoral IBR. Methods: We performed a retrospective cohort study of 2-stage prepectoral IBR performed between January 2020 and June 2022 at the Brigham and Women's Hospital and Dana-Farber Cancer Institute, comparing outcomes in patients who received Allergan Natrelle least cohesive, moderately cohesive, and most cohesive silicone gel implants. Outcomes of interest were rippling and reoperation for fat grafting. Results: A total of 129 patients were identified, of whom 52 had the least cohesive implants, 24 had the moderately cohesive implants, and 53 patients had the most cohesive implants. The mean follow-up time was 463 (±220) days. A decreased incidence of rippling was seen with moderately cohesive (odds ratio [OR] 0.30, P < .05) and most cohesive (OR 0.39, P < .05) implants. Third stage reoperation for fat grafting was less frequent in patients with the most cohesive implant (OR 0.07, P < .05). In subgroup analyses, the patients with the most cohesive implant, who did not receive fat grafting at the time of initial implant placement, did not require reoperation for fat grafting (0%). Conclusions: The use of highly cohesive implants in prepectoral IBR is associated with decreased rippling and fewer reoperations for fat grafting.

Genotype/Phenotype Interactions and First Steps Toward Targeted Therapy for Sphingosine Phosphate Lyase Insufficiency Syndrome.

Sphingosine-1-phosphate lyase insufficiency syndrome (SPLIS) is a rare metabolic disorder caused by a deficiency in sphingosine-1-phosphate lyase (SPL), the final enzyme in the sphingolipid degradative pathway. Inactivating mutations of SGPL1-the gene encoding SPL-lead to a deficiency of its downstream products, and buildup of sphingolipid intermediates, including its bioactive substrate, sphingosine-1-phosphate (S1P), the latter causing lymphopenia, a hallmark of the disease. Other manifestations of SPLIS include nephrotic syndrome, neuronal defects, and adrenal insufficiency, but their pathogenesis remains unknown. In this report, we describe the correlation between SGPL1 genotypes, age at diagnosis, and patient outcome. Vitamin B6 serves as a cofactor for SPL. B6 supplementation may aid some SPLIS patients by overcoming poor binding kinetics and promoting proper folding and stability of mutant SPL proteins. However, this approach remains limited to patients with a susceptible allele. Gene therapy represents a potential targeted therapy for SPLIS patients harboring B6-unresponsive missense mutations, truncations, deletions, and splice-site mutations. When Sgpl1 knockout (SPLKO) mice that model SPLIS were treated with adeno-associated virus (AAV)-mediated SGPL1 gene therapy, they showed profound improvement in survival and kidney and neurological function compared to untreated SPLKO mice. Thus, gene therapy appears promising as a universal, potentially curative treatment for SPLIS.