Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare T cell lymphoma in women with textured implants. Little is known about the cell of origin (COO) and whether the tumour immune microenvironment (TIME) is critical for BIA-ALCL survival. Single-cell RNA sequencing revealed BIA-ALCL cells were heterogeneous with unique gene profiles per patient and signature genes BATF3, SERPINS, TNFSFR8, and IL2RA. The COO is a CD4+ or CD8+ memory T cell identified through rearranged TCR and gene expression. The BIA-ALCL TIME included distinct myeloid clusters, dendritic cells (DCs), and monocytes, which may support lymphoma cells. Cytokines IL-13, IL-10, TNF and secretory PDL1 were increased in BIA-ALCL seroma, indicating an immunosuppressive TIME. Interactome analysis revealed a complex network among lymphoma cells, dominated by IL-13, IL-10, and TNF members. Endogenous CD8+ T cells exhibit higher checkpoint expression than benign seromas. No clonal relationship exists between BIA-ALCL and endogenous T cells. Tissue-archetype and gene-expression analysis revealed T-cell exclusion and immunosuppressive TIME in invasive disease. In summary, BIA-ALCL cells are diverse with markedly different TIME across stages. The TIME provides immunosuppressive signals to activated/exhausted T cells and homeostatic signals that promote BIA-ALCL proliferation. These new findings may offer novel therapeutic targets for advanced disease patients.

This paper is a response to the paper “Breast Implant Illness, Outcomes with Explantation, and Potential Etiologies, a Systematic Review and Meta-Analysis”. There are scientific inconsistencies and misleading statements in this paper that we felt needed to be addressed. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

BACKGROUND:Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare lymphoma associated with textured implants. Earlier detection and timely implant/capsulectomy reduce morbidity and improve outcomes. CD30 is a sensitive biomarker for BIA-ALCL; carbonic anhydrase IX (CA9) has been identified as a complementary marker in effusion samples. OBJECTIVES:To develop and evaluate a multiplex lateral flow assay (LFA) for CD30 and CA9 in peri-implant seroma fluid/effusions to support rapid clinical triage of suspected BIA-ALCL. METHODS:Recombinant CD30 and CA9 were spiked into benign seroma matrix to establish assay detection range under defined conditions. A retrospective cohort of 50 seroma samples (25 pathologically confirmed BIA-ALCL; 25 benign seromas) was tested. Performance was assessed by (i) visual interpretation and (ii) image-based quantification (test line/control line ratio, TL/CL) (iii) combined interpretation approach. Sensitivity, specificity, predictive values (study-conditional), and ROC/AUC were calculated. RESULTS:In matrix spike-in experiments, CD30 was detectable down to 500 pg/mL; CA9 was detectable down to 1000 pg/mL. In clinical samples, both CD30 and CA9 TL/CL were significantly higher in BIA-ALCL than benign seromas. Visual interpretation yielded 76% sensitivity and 88% specificity. Image-based interpretation increased sensitivity to 96% but reduced specificity to 80%. A prespecified combined interpretation approach maintained 96% sensitivity and 88% specificity (PPV 89%, NPV 96% within this case-control cohort). ROC analysis demonstrated AUC 0.96 for CD30 and 0.85 for CA9. CONCLUSIONS:In this retrospective cohort, a multiplex CD30/CA9 LFA distinguished BIA-ALCL from benign peri-implant seromas with high sensitivity and favorable study-conditional NPV, supporting feasibility as a rapid triage adjunct to prioritize confirmatory pathology. Prospective studies with standardized pre-analytics, blinded interpretation, and prevalence-representative cohorts are required to establish real-world predictive values and clinical utility.

Background/Objective: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) has affected more than 1700 women with textured breast implants. About 80% of patients present with fluid (seroma) around their implant. BIA-ALCL can be cured by surgery alone when confined to the seroma and lining of the peri-implant capsule. To address the need for early detection, we developed a rapid point of care (POC) lateral flow assay (LFA) to identify lymphoma in seromas. Methods: We compared 28 malignant seromas to 23 benign seromas using both ELISA and LFA. LFA test lines (TL) and control lines (CL) were visualized and measured with imaging software and the TL/CL ratio for each sample was calculated. Results: By visual exam, the sensitivity for detection of CA9 was 93% and specificity 78%, while the positive predictive value was 84% and negative predictive value 90%. Quantitative image analysis increased the positive predictive value to 96% while the negative predictive value reduced to 79%. Conclusions: We conclude that CA9 is a sensitive biomarker for detection and screening of patients for BIA-ALCL in patients who present with seromas of unknown etiology. The CA9 LFA can potentially replace ELISA, flow cytometry and other tests requiring specialized equipment, highly trained personnel, larger amounts of fluid and delay in diagnosis of BIA-ALCL.

BACKGROUND:Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) has affected more than 1700 women. Treatment morbidity is reduced and survival improved by early detection and removal of implant and capsule. OBJECTIVE:To address the need for early detection, we developed a multiplex lateral flow assay (LFA) for soluble IL-10 and CD30 in seromas surrounding implants. METHODS:The range of detection was determined with recombinant CD30 or IL-10 added to a benign seroma to simulate clinical conditions. Then clinical samples from 23 women with BIA-ALCL and 17 benign seromas were analyzed with a multiplex LFA detecting soluble IL-10 and CD30. RESULTS:When recombinant proteins were added to benign seromas, CD30 was detected down to a concentration of 0.5 ng/mL, and IL-10 could be detected to down to 5 ng/mL. Significant differences were found between CD30 and IL-10 test line/control line ratios (TL/CL) of 23 BIA-ALCL and 17 benign seromas. Visual inspection of LFAs resulted in 65% sensitivity, and improved to 87% with image analysis. CONCLUSIONS:We conclude that the multiplex IL-10/CD30 can detect BIA-ALCL with 100% specificity and 65% sensitivity in this group of 40 clinical seromas based on visual assessment of LFA strips. Sensitivity was improved to 87% with image analysis, which can provide a screening test for BIA-ALCL. The multiplex LFA demonstrated a perfect positive predictive value (100%), indicating that all positive results correctly identified BIA-ALCL cases. The negative predictive value of 99% can exclude BIA-ALCL. LEVEL OF EVIDENCE: 5 (DIAGNOSTIC):

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a recently identified T cell lymphoma that develops in women with textured breast implants and can have localised presentation (seroma-associated) or invasive disease (Stage II and above). Nevertheless, the mechanisms behind ALCL formation and the potential influence of the tumour microenvironment (TME) on ALCL's survival and growth in breast tissue remain unclear. To explore these questions, we examined the immunobiology of both ALCL and the endogenous immune cells present in both localised and invasive disease using a multimodal approach. We conducted a multi-centre national cohort study and collected breast implant seroma samples, including benign cases and BIA-ALCL cases at surgery. We used single-cell RNA sequencing (scRNAseq) and bulk RNA sequencing to characterise immune cells and ALCL cells from both localised and invasive disease. Bulk RNA sequencing was also conducted on samples from patients with cutaneous ALCL (pcALCL). We performed TCR-seq to explore their clonal relationships. Additionally, we analysed the microenvironment by measuring seroma cytokine and chemokine levels and conducted an interactome analysis to identify potential cell-cell interactions. We also performed targeted sequencing to detect mutations and utilised spatial multiplex immunohistochemistry to examine the spatial relationships between tumour and immune cells, as well as differences between invasive and non-invasive disease. scRNAseq data revealed that ALCL cells formed separate clusters, with distinct gene expression patterns observed between patients. ALCL cells expressed common gene signature genes such as BATF3, SERPIN family genes, TNFSFR8, and IL2RA; along with genes unique to each patient. Endogenous T cells from the BIA-ALCL seroma exhibited an activated or exhausted phenotype, along with immune checkpoints and endogenous T cell clonal expansion. In contrast, benign seroma endogenous T cells had a Th1/Th17 profile and limited T cell clonal expansion. Myeloid clusters were abundant in the BIA-ALCL seroma, but not in benign seroma. TME studies showed a significant increase in BIA-ALCL seroma for cytokines IL-13, TNF, IL-10, and secretory PDL-1. The single-cell interactome analysis using CellphoneDB revealed unique cell-cell interactions in the BIA-ALCL TME between tumour-tumour, tumour-myeloid DC, and tumour-CD8+ T effector memory cells. Mutational analysis revealed novel JAK1 mutations and STAT3 mutations along with chromosome 20 loss consistent with previous studies. Bulk RNAseq analysis revealed differences between BIA-ALCL and pcALCL with BIA-ALCL displaying a more inflamed immune TME. BIA-ALCL cells vary between patients and from the body's own immune cells. Additionally, BIA-ALCL seroma contains endogenous T cells with an exhausted profile and clonal expansion, along with higher levels of IFN-γ and TNF, suggesting these T cells are responding to antigens in the tumour microenvironment (TME). The TME also shows increased IL-13 and IL-10 levels, produced through interactions between tumour cells and myeloid cells. Bulk RNA sequencing and spatial analysis indicated that the invasive BIA-ALCL TME is less inflamed and more immune-excluded compared to non-invasive early-stage disease. This is the first study to perform an in-depth characterisation of BIA-ALCL using a multi-omics approach, and the results enhance our understanding of this rare lymphoma, offering potential for improved treatments.

Background:. Standard breast reduction dressings such as Prineo are used to cover surgical wounds, in combination with a binder or support bra. The Prevena Restor BellaForm is a negative pressure wound therapy dressing that covers the entirety of the breast mound and is purported to provide further support and reduce swelling. The aim of this study was to compare the Restor to standard-of-care dressings. Methods:. The study was a randomized control trial of women undergoing bilateral breast reduction with one breast being dressed with the Prevena Restor BellaForm dressing and the other having standard of care (Prineo). Outcomes measured were drain outputs, postoperative length of stay, quality of scarring, patient preference for dressings, and adverse events. Follow-up was at 1, 2–6, and 26 weeks. Results:. The results show a reduction in postoperative days 1 and 2 average drain output on the Restor side compared with standard dressings. Patient-reported outcome measures showed less bruising. There was no difference in postoperative length of stay and no difference in appearance of scars at the 26-week follow-up period. One patient required removal of the dressing due to irritation and one patient required assistance with resealing of the vacuum. Conclusions:. We have shown benefits to drain output and comfort using close incisional negative pressure therapy in breast reduction mammaplasty. We plan to continue to investigate close incisional negative pressure therapy in larger comparative trials for other breast procedures including implant-based reconstruction, where a reduction in drain output could be of great benefit to both healing and reduction of infection risk.

Introduction: The rising weight of Australians threatens to overwhelm health resources with its associated morbidity and chronic disease. We have established and scaled a novel model to target weight management for adults utilising the principles of integrated care. Methods: A new model of integrated care was established to provide access to all aspects of weight management. A general practitioner unskilled in the assessment and management of weight and metabolic disease paired with a dietician forms the frontline assessment for patients. Novel pathways for treatment including the use of health maintenance programs combining medical and allied health were developed. Patients also had access to new medical therapies and potential bariatric surgery. Patients were encouraged to commit to a 12 month program, regardless of the therapy prescribed. Results: A total of 224 patients have been assessed between July 2022 and March 2023. Preliminary data on weight loss and cost effectiveness will be presented. The majority of patients were managed through introduction of an improved diet, encouragement of exercise and identification and treatment of psychological drivers to weight gain. Conclusions: This model supports the use of a GP led community based approach to sustained weight reduction.

BACKGROUND:Bacterial contamination of implants has been linked to biofilm formation and subsequent infection, capsular contracture, and breast implant-associated anaplastic large cell lymphoma. Reducing contamination during implant insertion should therefore reduce biofilm formation disease sequelae. OBJECTIVES:The aim of this study was to compare levels of contamination between preventative techniques. METHODS:A model to simulate the passage of implants through a skin incision was designed that utilized a sterile textured polyvinyl plastic sheet contaminated with Staphylococcus epidermidis. In the first stage of the polyvinyl contamination model, implants were subject to infection-mitigation techniques and passed through the incision, then placed onto horse blood agar plates and incubated for 24 hours. In the second stage of the study the same contamination was applied to human abdominal wall specimens. A 5 cm incision was made through skin and fat, then implants were passed through and levels of contamination were measured as described. RESULTS:Smooth implants grew a mean of 95 colony-forming units (CFUs; approximately 1 CFU/cm2) and textured implants grew 86 CFUs (also approximately 1 CFU/cm2). CFU counts were analyzed by the Mann-Whitney U-test which showed no significant difference between implant types (P < .05); independent-sample t-tests showed a significant difference. The dependent-variable techniques were then compared as groups by one-way analysis of variance, which also showed a significant reduction compared with the control group (P < .01). CONCLUSIONS:This in vitro study has shown the effectiveness of antiseptic rinse and skin/implant barrier techniques for reducing bacterial contamination of breast implants at the time of insertion.

Background: A delayed seroma around breast implants is the most common clinical presentation of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). Interleukin-9 (IL-9), IL-10, and IL-13 concentrations are significantly higher in BIA-ALCL than in benign seromas, offering a means to distinguish between these conditions. Objectives: The aim of this research was to test the ability of a lateral flow assay (LFA) to detect high concentrations of IL-9 rapidly. In addition, the authors compared CD30 and IL-9 LFAs for distinguishing BIA-ALCL from benign seromas. Methods: Samples of 26 seromas (15 benign, 11 malignant) were tested on in-house-prepared LFA strips for IL-9 and CD30. Nanoparticle-conjugated antibodies specific to IL-9 and CD30 were used for detection. The intensity of both the test line (TL) and a control line (CL) were analyzed and the TL/CL ratio was calculated. IL-9 protein and IL-9 transcription factor PU.1 were stained in BIA-ALCL lines and clinical samples. Results: The IL-9 LFA could reliably distinguish BIA-ALCL from benign seromas when the IL-9 concentration was >10 ng/ml. The CD30 LFA was positive in all 11 malignant cases. In 1 case with only faint CD30 and IL-10 TLs, the IL-9 LFA was clearly positive. Immunohistochemistry showed that IL-9 and PU.1 were present in tumor cells in BIA-ALCL lines and clinical samples. Conclusions: Concentrations of IL-9 >10 ng/ml reliably distinguished BIA-ALCL from benign seromas. Moreover, the IL-9 LFA could detect BIA-ALCL when both the CD30 and IL-10 LFAs were not definitive, suggesting a multiplex LFA measuring IL-9, CD30, and IL-10 might be more effective in detecting BIA-ALCL in selected cases.

Objectives: Biofilm is the major challenge in chronic wound management. Instilling a wound cleansing solution aids in wound bed cleaning and infectious pathogen elimination. Negative pressure wound therapy (NPWT) improves the wound-healing process. This study investigated the efficacy of two antimicrobials (Vashe Wound Cleanser and Prontosan Wound Irrigation Solution) against a multispecies bacterial biofilm with or without NPWT in an in vitro wound model. Methods; A mixed multispecies biofilm containing Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pyogenes, and Acinetobacter baumannii was developed and verified by scanning electron microscopy and fluorescent in situ hybridization. The efficacy of Vashe and Prontosan against multispecies biofilm with or without NPWT was evaluated by colony-forming unit (cfu) of each species and total bacterial number, and visually confirmed by live/dead stain and confocal microscopy. Results: Prontosan reduced biofilm cell numbers significantly: 6 instils over 24 h resulting in 3.86 +/- 0.14 cfu log10 reduction without NPWT and 4.75 +/- 0.13 cfu log10 reduction combined with NPWT (P < 0.01) and 12 instils over 48 h resulting in 5.24 +/- 0.11 cfu log10 reduction without NPWT and biofilm eradication with NPWT (P < 0.001). NPWT alone or combined with Vashe failed to reduce multispecies biofilm numbers significantly over 24 or 48 h. Conclusions: Prontosan significantly reduced biofilm cell numbers, with better efficacy over 48 than 24 h, emphasizing the necessity for persistent and robust treatment. NPWT enhanced the effectiveness of Prontosan instillation. However, NPWT alone or combined with Vashe showed limited efficacy and difficulty when combating the multispecies biofilm in vitro.

The nineteenth century bore witness to a remarkable proliferation of reconstructive literature in Europe, based on procedures originally described in India and Italy. Despite the publication of a successful forehead flap in England in 1816, texts exclusively dedicated to the field of plastic surgery were relatively scarce in the English-speaking world. The authors sought to identify the first English textbook entirely devoted to plastic surgery. A comprehensive examination was undertaken, spanning various databases encompassing medical, medical humanities and historical domains (PubMed, MEDLINE, Web of Science, Anthropology, JSTOR, Encyclopedia of Ancient History), as well as an extensive perusal of materials housed in the State Library of Victoria, the University of Melbourne and the HathiTrust Digital Library. The scope of this search was confined to publications predating Harold Gillies' influential 1920 textbook. Within this vast literary landscape, an Australian surgeon named William Moore emerged as a figure of notable significance, authoring the first textbook of plastic surgery in English in 1899. Moore's legacy as a pioneering surgeon ahead of his era is undeniable. Yet, various factors conspired to obscure his rightful place in the annals of surgical history.

BACKGROUND:Broad evidence supports the use of antiseptic pocket rinse in breast implant surgery to minimize the risk of capsular contracture or other complications. However, there is limited consensus or standardization of antiseptic rinse in practice. OBJECTIVES:In this preliminary study, we sought to determine contemporary trends in antiseptic rinse use in primary breast implant surgery based on Australian Breast Device Registry (ABDR) data, and whether these trends align with the suggestions of the 14-point plan. This further served as a feasibility study for subsequent comparison of antiseptic rinse effects on clinical outcomes. METHODS:Institutional ethics approval was obtained and national ABDR data for primary breast implant surgery from 2015 to 2020 were analyzed for the use and type of antiseptic rinse. The surgeon-reported data were homogenized with regard to terminology and categorized by major trends, and the literature was reviewed. RESULTS:We analyzed data for 37,143 patients, totaling 73,935 primary implants. Antiseptic rinse included povidone-iodine (PVP-I) in 35,859 (48.5%), no antiseptic use in 24,216 (32.8%), other concentrations of PVP-I in 4200 (5.7%), and Betadine triple antibiotic in 1831 implants (2.5%). Multiple other antiseptic permutations were noted in 7004 implants (9.5%). CONCLUSIONS:The majority (56.7%) of Australian practitioners utilize previously described antiseptic pocket irrigation solutions that align with the 14-point plan. A third (32.8%), however, do not record any antiseptic pocket irrigation. These findings will permit a subsequent (ongoing) study of outcomes comparing PVP-I pocket rinse to no antiseptic pocket rinse, which will likely constitute the largest study of its kind.

Hexanucleotide repeat expansions (HREs) in the chromosome 9 open reading frame 72 (C9orf72) gene are the most frequent genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Both are debilitating neurodegenerative conditions affecting either motor neurons (ALS) in the brain and spinal cord or neurons in the frontal and/or temporal cortical lobes (FTD). HREs undergo repeat-associated non-ATG (RAN) translation on both sense and anti-sense strands, generating five distinct dipeptide repeat proteins (DPRs), poly-GA, -GR, -GP, -PA and -PR. Perturbed proteostasis is well-recognised in ALS pathogenesis, including processes affecting the endoplasmic reticulum (ER) and Golgi compartments. However, these mechanisms have not been well characterised for C9orf72-mediated ALS/FTD. In this study we demonstrate that C9orf72 DPRs polyGA, polyGR and polyGP (× 40 repeats) disrupt secretory protein transport from the ER to the Golgi apparatus in neuronal cells. Consistent with this finding, these DPRs also induce fragmentation of the Golgi apparatus, activate ER stress, and inhibit the formation of the omegasome, the precursor of the autophagosome that originates from ER membranes. We also demonstrate Golgi fragmentation in cells undergoing RAN translation that express polyGP. Furthermore, dysregulated ER-Golgi transport was confirmed in C9orf72 patient dermal fibroblasts. Evidence of aberrant ER-derived vesicles in spinal cord motor neurons from C9orf72 ALS patients compared to controls was also obtained. These data thus confirm that ER proteostasis and ER-Golgi transport is perturbed in C9orf72-ALS in the absence of protein over-expression. Hence this study identifies novel molecular mechanisms associated with the ER and Golgi compartments induced by the C9orf72 HRE.

Capsular contracture (CC) is one of the most common postoperative complications associated with breast implant-associated infections. The mechanisms that lead to CC remain poorly understood. Plasma is an ideal biospecimen for early proteomics biomarker discovery. However, as high-abundance proteins mask signals from low-abundance proteins, identifying novel or specific proteins as biomarkers for a particular disease has been hampered. Here, we employed depletion of high-abundance plasma proteins followed by Tandem Mass Tag (TMT)-based quantitative proteomics to compare 10 healthy control patients against 10 breast implant CC patients. A total of 450 proteins were identified from these samples. Among them, 16 proteins were significantly differentially expressed in which 5 proteins were upregulated and 11 downregulated in breast implant CC patients compared to healthy controls. Gene Ontology enrichment analysis revealed that proteins related to cell, cellular processes and catalytic activity were highest in the cellular component, biological process, and molecular function categories, respectively. Further, pathway analysis revealed that inflammatory responses, focal adhesion, platelet activation, and complement and coagulation cascades were enriched pathways. The differentially abundant proteins from TMT-based quantitative proteomics have the potential to provide important information for future mechanistic studies and in the development of breast implant CC biomarkers.

Abstract Staphylococcus aureus biofilms are tolerant to antibiotics and disinfectants. Staphylococci cell walls, principally composed of peptidoglycan, are a key target for antimicrobial agents. S. aureus proteomics and cell walls, grown as planktonic organisms, 3-day hydrated biofilm, 12-day hydrated biofilm and 12-day dry surface biofilm (DSB) were analysed. High-throughput tandem mass tag-based mass spectrometry showed upregulation of proteins involved in cell wall synthesis in biofilms compared to planktonic growth. Bacterial cell wall width (measured by transmission electron microscopy) and peptidoglycan production (detected using a silkworm larva plasma system) increased with biofilm culture duration (P < 0.001) and dehydration (P = 0.002). Similarly, disinfectant tolerance was greatest in DSB, followed by 12-day hydrated biofilm, then 3-day biofilm and least in planktonic bacteria, suggesting cell wall is one of the key determinants for S. aureus biofilm biocide resistance. Our findings shed light on possible new target to combat biofilm-related infections and hospital dry surface biofilms.

Intra-radicular infection theory assumes that when an infected tooth is extracted, the main source of infection is removed and any residual contaminating bacteria are killed by the immune response, then normal healing ensues. This study investigated whether bacteria and bacterial biofilms persisted in deep bone space following tooth extraction. The study was conducted on two adult male patients seeking dental implant therapy in a private practice setting. The cases presented as (1) A single-tooth with a chronic lesion in the anterior maxilla and (2) As a mandibular full-arch where the few remaining teeth presented endodontic/periodontic lesions, while odsteolytic/osteosclerotic lesions persisted in the edentulous, apparently healed bone. Bone fragments were obtained during full-flap, sterile surgical debridement/osteotomy, for Scanning Electron Microscopy (SEM) and pyrosequencing analysis. SEM images visually confirmed the presence of bacteria and bacterial biofilms in deep apparently healed bone space in health and disease. The extraction of diseased teeth did not result in the spontaneous resolution of pathologically altered bone surfaces. Severely sclerotic bone in both cases required multiple surgical debridements to attain a vascularised health margin beyond sclerotic encapsulation with reconnection to stem-cell-rich periosteum. The clinical effect of debridement was microbial population shift, with histologic regeneration of internal osseous architecture and bone quality, according to habitat fitness. Longitudinal same-site intracommunity extinctions and additions were corroborated by SEM and microbiome analysis, together with clinical and radiographic evidence. The circumvention of resident pathogenic bacterial biofilms before implant deployment becomes a method-protocol for biofilm-based osseointegration, improving outcomes and reducing re-operations.