Background: A recent association between breast implants and the development of anaplastic large-cell lymphoma (ALCL) has been observed. The purpose of this study was to identify whether bacterial biofilm is present in breast implant–associated ALCL and, if so, to compare the bacterial microbiome to nontumor capsule samples from breast implants with contracture. Methods: Twenty-six breast implant–associated ALCL samples were analyzed for the presence of biofilm by real-time quantitative polymerase chain reaction, next-generation sequencing, fluorescent in situ hybridization, and scanning electron microscopy, and compared to 62 nontumor capsule specimens. Results: Both the breast implant–associated ALCL and nontumor capsule samples yielded high mean numbers of bacteria (breast implant–associated ALCL, 4.7 × 10⁶ cells/mg of tissue; capsule, 4.9 × 10⁶ cells/mg of tissue). Analysis of the microbiome in breast implant–associated ALCL specimens showed significant differences with species identified in nontumor capsule specimens. There was a significantly greater proportion of Ralstonia spp. present in ALCL specimens compared with nontumor capsule specimens (p < 0.05). In contrast, significantly more Staphylococcus spp. were found associated with nontumor capsule specimens compared with breast implant–associated ALCL specimens (p < 0.001). Bacterial biofilm was visualized both on scanning electron microscopy and fluorescent in situ hybridization. Conclusions: This novel finding of bacterial biofilm and a distinct microbiome in breast implant–associated ALCL samples points to a possible infectious contributing cause. Breast implants are widely used in both reconstructive and aesthetic surgery, and strategies to reduce their contamination should be more widely studied and practiced. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, V.

Background: Sialic acid, a key component of both human milk oligosaccharides and neural tissues, may be a conditional nutrient during periods of rapid brain growth. Objective: We tested the hypothesis that variations in the sialic acid content of a formula milk would influence early learning behavior and gene expression of enzymes involved in sialic acid metabolism in piglets. Design: Piglets (n = 54) were allocated to 1 of 4 groups fed sow milk replacer supplemented with increasing amounts of sialic acid as casein glycomacropeptide for 35 d. Learning performance and memory were assessed with the use of easy and difficult visual cues in an 8-arm radial maze. Brain ganglioside and sialoprotein concentrations and mRNA expression of 2 learning-associated genes (ST8SIA4 and GNE) were measured. Results: In both tests, the supplemented groups learned in significantly fewer trials than did the control group, with a dose-response relation for the difficult task (P = 0.018) but not the easy task. In the hippocampus, significant dose-response relations were observed between amount of sialic acid supplementation and mRNA levels of ST8SIA4 (P = 0.002) and GNE (P = 0.004), corresponding with proportionate increases in protein-bound sialic acid concentrations in the frontal cortex. Conclusions: Feeding a protein-bound source of sialic acid during early development enhanced learning and increased expression of 2 genes associated with learning in developing piglets. Sialic acid in mammalian milks could play a role in cognitive development.

Biofilm infection of breast implants significantly potentiates capsular contracture. This study investigated whether chronic biofilm infection could promote T-cell hyperplasia. In the pig study, 12 textured and 12 smooth implants were inserted into three adult pigs. Implants were left in situ for a mean period of 8.75 months. In the human study, 57 capsules from patients with Baker grade IV contracture were collected prospectively over a 4-year period. Biofilm and surrounding lymphocytes were analyzed using culture, nucleic acid, and visualization techniques. In the pig study, all samples were positive for bacterial biofilm. There was a significant correlation between the bacterial numbers and grade of capsular contracture (p = 0.04). Quantitative real-time polymerase chain reaction showed that all lymphocytes were significantly more numerous on textured compared with smooth implants (p < 0.001). T cells accounted for the majority of the lymphocytic infiltrate. Imaging confirmed the presence of activated lymphocytes. In the human study, all capsules were positive for biofilm. Analysis of lymphocyte numbers showed a T-cell predominance (p < 0.001). There was a significant linear correlation between the number of T and B cells and the number of detected bacteria (p < 0.001). Subset analysis showed a significantly higher number of bacteria for polyurethane implants (p < 0.005). Chronic biofilm infection around breast prostheses produces an increased T-cell response both in the pig and in humans. A possible link between bacterial biofilm and T-cell hyperplasia is significant in light of breast implant-associated anaplastic large-cell lymphoma. Risk, V.

Capsular contracture remains the most common complication following breast augmentation surgery, and evidence suggests that bacterial biofilm on the implant surface is responsible. The authors investigated whether the interaction of bacterial biofilm with implants independently determines progression to capsule formation. They also studied the rate of bacterial growth and adhesion to implants. Sixteen adult female pigs had 121 breast implants inserted. Sixty-six implants-23 smooth and 43 textured-were inoculated with a human strain of Staphylococcus epidermidis and received no other treatment. After an average period of 19 weeks, Baker grading was performed and implants were retrieved. For the in vitro study, samples underwent both quantitative bacterial analysis and imaging using confocal laser scanning and scanning electron microscopy. At explantation, there was no significant difference (p = 1.0) in the presence of capsular contracture (Baker grade III and IV) between smooth (83 percent) and textured implants (84 percent). Biofilm was confirmed on 60 of the 66 capsules. Capsules from smooth and textured implants had the same number of infecting bacteria (textured: 3.01 × 10 bacteria/g; smooth: 3.00 × 10 bacteria/g). In vitro, the surface of textured implants showed 11-, 43-, and 72-fold more bacteria at 2, 6, and 24 hours, respectively, compared with smooth implants (p < 0.001). These findings were confirmed by imaging analysis. These results show that textured implants develop a significantly higher load of bacterial biofilm in comparison with smooth implants. Furthermore, in vivo, once a threshold of biofilm forms on either smooth or textured implant surfaces, there seems to be an equal propensity to progress to capsular contracture.

Pseudomonas aeruginosaairway infection is the leading cause of morbidity and mortality in cystic fibrosis (CF) patients. Variousin vitromodels have been developed to studyP. aeruginosapathobiology in the CF lung. In this study we produced a modified artificial-sputum medium (ASMDM) more closely resembling CF sputum than previous models, and extended previous work by using strain PAO1 arrays to examine the global transcription profiles ofP. aeruginosastrain UCBPP-PA14 under early exponential-phase and stationary-phase growth. In early exponential phase, 38/39 nutrition-related genes were upregulated in line with data from previousin vitromodels using UCBPP-PA14. Additionally, 23 type III secretion system (T3SS) genes, several anaerobic respiration genes and 24 quorum-sensing (QS)-related genes were upregulated in ASMDM, suggesting enhanced virulence factor expression and priming for anaerobic growth and biofilm formation. Under stationary phase growth in ASMDM, macroscopic clumps resembling microcolonies were evident in UCBPP-PA14 and CF strains, and over 40 potentially important genes were differentially expressed relative to stationary-phase growth in Luria broth. Most notably, QS-related and T3SS genes were downregulated in ASMDM, and iron-acquisition and assimilatory nitrate reductase genes were upregulated, simulating the iron-depleted, microaerophilic/anaerobic environment of CF sputum. ASMDM thus appears to be highly suitable for gene expression studies ofP. aeruginosain CF.