Biofilm Derived Oxylipin Mediated Autoimmune Response in Breast Implant Subjects

AbstractOver 10 million women worldwide have breast implants for breast cancer/prophylactic reconstruction or cosmetic augmentation. In recent years, a number of patients have described a constellation of symptoms that are believed to be related to their breast implants. This constellation of symptoms has been named Breast Implant Illness (BII). The symptoms described include chronic fatigue, joint pain, muscle pain and a host of other manifestations often associated with autoimmune illnesses. In this work, we report that bacterial biofilm is associated with BII. We postulate that the pathogenesis of BII is mediated via a host-pathogen interaction whereby the biofilm bacteria Staphylococcus epidermidis interacts with breast lipids to form the oxylipin 10-HOME. The oxylipin 10-HOME was found to activate CD4+ T cells to Th1 subtype. An increased abundance of CD4+Th1 was observed in the breast tissue of BII subjects. The identification of a mechanism of immune activation associated with BII via a biofilm enabled pathway provides insight into the pathogenesis for implant-associated autoimmune symptoms.

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Establishment and Characterization of Bacterial Infection of Breast Implants in a Murine Model

Aesthetic Surgery Journal ◽

10.1093/asj/sjz190 ◽

2019 ◽

Vol 40 (5) ◽

pp. 516-528 ◽

Cited By ~ 4

Author(s):

Jennifer N Walker ◽

Louis H Poppler ◽

Chloe L Pinkner ◽

Scott J Hultgren ◽

Terence M Myckatyn

Keyword(s):

Staphylococcus Epidermidis ◽

Breast Implant ◽

Breast Implants ◽

Surface Characteristics ◽

Implant Surface ◽

Colony Forming Units ◽

Common Causes ◽

The Impact ◽

Post Implantation

Abstract Background Staphylococcus epidermidis and Pseudomonas aeruginosa are the most common causes of Gram-positive and Gram-negative breast implant–associated infection. Little is known about how these bacteria infect breast implants as a function of implant surface characteristics and timing of infection. Objectives The aim of this work was to establish a mouse model for studying the impact of various conditions on breast implant infection. Methods Ninety-one mice were implanted with 273 breast implant shells and infected with S. epidermidis or P. aeruginosa. Smooth, microtextured, and macrotextured breast implant shells were implanted in each mouse. Bacterial inoculation occurred during implantation or 1 day later. Implants were retrieved 1 or 7 days later. Explanted breast implant shells were sonicated, cultured, and colony-forming units determined or analyzed with scanning electron microscopy. Results P. aeruginosa could be detected on all device surfaces at 1- and 7- days post infection (dpi), when mice were implanted and infected concurrently or when they were infected 1- day after implantation. However, P. aeruginosa infection was more robust on implant shells retrieved at 7 dpi and particularly on the macrotextured devices that were infected 1 day post implantation. S. epidermidis was mostly cleared from implants when mice were infected and implanted concurrently. Other the other hand, S. epidermidis could be detected on all device surfaces at 1 dpi and 2 days post implantation. However, S. epidermdis infection was suppressed by 7 dpi and 8 days post implantation. Conclusions S. epidermidis required higher inoculating doses to cause infection and was cleared within 7 days. P. aeruginosa infected at lower inoculating doses, with robust biofilms noted 7 days later.

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High-Throughput Screening for Small-Molecule Inhibitors of Staphylococcus epidermidis RP62a Biofilms

CrossRef Listing of Deleted DOIs ◽

10.1177/1087057113481499 ◽

2013 ◽

Vol 18 (7) ◽

pp. 820-829 ◽

Cited By ~ 5

Author(s):

Warunya Panmanee ◽

Deborah Taylor ◽

Chloe J. A. Shea ◽

Hong Tang ◽

Sandra Nelson ◽

...

Keyword(s):

High Throughput ◽

Staphylococcus Epidermidis ◽

High Throughput Screening ◽

Laser Scanning ◽

Bacterial Biofilm ◽

Laser Scanning Microscopy ◽

Confocal Laser ◽

Response Curves ◽

Resazurin Assay ◽

Biofilm Bacteria

High-throughput screening (HTS) of 42 865 compounds was performed to identify compounds that inhibit formation of or kill Staphylococcus epidermidis RP62a biofilms. Three biological processes were assayed, including (1) growth of planktonic/biofilm bacteria, (2) assessment of metabolically active biofilm bacteria using a resazurin assay, and (3) assessment of biofilm biomass by crystal violet staining. After completing the three tiers (primary screening, hit confirmation, and dose-response curves), 352 compounds (representing ~0.8%) were selected as confirmed hit compounds from the HTS assay. The compounds were divided into groups based on their effectiveness on S. epidermidis biofilm properties. The majority of these affected both inhibition and killing of bacterial biofilm cultures. Only 16 of the confirmed hit compounds that have either an AC50 lower than 10 µM and/or Sconst ≥70 from those processed were selected for further study by confocal laser scanning microscopy (CLSM). The CLSM was used to evaluate the confirmed hit compounds on (1) inhibition of biofilm formation and (2) killing of preexisting S. epidermidis biofilms. Taken together, with further testing (e.g., disease-related conditions), such compounds may have applications as broad antimicrobial/antibiofilm use for prophylactic or therapeutic intervention to combat infections in surgical and intensive care clinics and battlefield settings.

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Comparative Analysis of Cytokines of Tumor Cell Lines, Malignant and Benign Effusions Around Breast Implants

Aesthetic Surgery Journal ◽

10.1093/asj/sjz243 ◽

2019 ◽

Vol 40 (6) ◽

pp. 630-637 ◽

Cited By ~ 3

Author(s):

Marshall E Kadin ◽

John Morgan ◽

Nick Kouttab ◽

Haiying Xu ◽

William P Adams ◽

...

Keyword(s):

Breast Implant ◽

Breast Implants ◽

Interferon Γ ◽

Textured Surface ◽

Malignant Cells ◽

Level Of Evidence ◽

Scar Contracture ◽

Ancillary Test ◽

Soluble Cd30 ◽

Insight Into

Abstract Background More than 700 women have developed an anaplastic large T cell lymphoma (ALCL) surrounding textured surface breast implants, termed breast implant–associated ALCL (BIA-ALCL). Most patients with BIA-ALCL present with an accumulation of fluid (delayed seroma) around the implant. However, benign seromas without malignant cells complicating scar contracture, implant rupture, trauma, infection, and other causes are more common. For proper patient management and to avoid unnecessary surgery, a simple diagnostic test to identify malignant seromas is desirable. Objectives The aim of this study was to develop an ancillary test for the diagnosis of malignant seromas and to gain insight into the nature of the malignant cells and their microenvironment. Methods We employed an immunologic assay on only 50 µL of aspirated seroma fluid. The assay measures 13 cytokines simultaneously by flow cytometry. To establish a baseline for clinical studies we measured cytokines secreted by BIA-ALCL and cutaneous ALCL lines. Results Our study of cell line culture supernatants, and 8 malignant compared with 9 benign seromas indicates that interleukin 9 (IL-9), IL-10, IL-13, IL-22, and/or interferon γ concentrations >1000 pg/mL distinguish malignant seromas from benign seromas. IL-6, known to be a driver of malignant cells, is also elevated in benign seromas and does not distinguish them from malignant seromas. Conclusions The cytokine assay introduced in this study can be used together with levels of soluble CD30 to identify malignant seromas. Validation of these findings in a larger prospective patient cohort is warranted. The unique pattern of cytokine expression in malignant effusions surrounding breast implants gives further insight into the pathogenesis and cells of origin of BIA-ALCL. Level of Evidence: 5

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Research Related to Capsular Contracture after Breast Augmentation for Cosmetic or Reconstructive Purposes

Revista de Chimie ◽

10.37358/rc.19.5.7180 ◽

2019 ◽

Vol 70 (5) ◽

pp. 1619-1624

Author(s):

Silviu Adrian Marinescu ◽

Dan Mircea Enescu ◽

Catalin Gheorghe Bejinariu ◽

Carmen Giuglea

Keyword(s):

Breast Augmentation ◽

Cell Lymphoma ◽

Breast Implant ◽

Capsular Contracture ◽

Breast Implants ◽

Large Cell ◽

Upward Trend ◽

Silicone Breast Implants ◽

Number Of Patients ◽

Alloplastic Breast Reconstruction

The upward trend of patients opting for elective breast augmentation, as well as the large number of patients benefiting from alloplastic breast reconstruction, require further studies on the safety profile of these techniques. Without any doubt, the incidence of Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) has drawn attention to the possible unknown complications characteristic of these procedures, creating the context of further studies devoted to this issue. The present research examines the capsular contracture rate on a group of 253 patients between 2015 and 2019, also proposing a scoring system based on the integration of the main diagnostic criteria related to the capsular contracture. The results of the literature review indicate that a lower incidence of capsular contracture could be achieved by using the newest techniques in the field involving the application of chemical substances on the surface of the latest generation of silicone breast implants.

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Is Breast Implant Associated Autoimmune Disorders Independent of Silicone?

Proceedings of IMPRS ◽

10.18060/24774 ◽

2020 ◽

Vol 3 ◽

Author(s):

Lily Suh ◽

Connor Drake ◽

Imran Khan ◽

Colby Neumann ◽

Aladdin Hassanein ◽

...

Keyword(s):

Prophylactic Mastectomy ◽

Breast Implant ◽

Breast Implants ◽

Orthopedic Implants ◽

Epidemiological Studies ◽

Autoimmune Disorders ◽

Bacterial Biofilm ◽

Inert Material ◽

Search Term ◽

Increased Risk

Background: Breast implant illness (BII) is a systemic autoimmune complication associated with breast implants. Breast implants are used for cosmetic augmentation, reconstructive surgery post-breast cancer treatment, or for prophylactic mastectomy. Thus, these implants are important for quality of life of the subjects. Through this work, we sought to characterize breast implant associated autoimmune disorders and discuss possible causes for its etiology. Methods: The PubMed and OVID databases were interrogated from 1990-2020 using a query strategy including search term combinations of “implants”, “breast implant illness”, “autoimmune”, “systemic illness”. Results: BII includes a spectrum of autoimmune symptoms such as fatigue, myalgias/arthralgias, dry eyes/mouth, and rash. Review of epidemiological studies in the past thirty years exhibited evidence affirming an association between breast implants and autoimmune diseases. The most commonly recognized were Sjogren’s, rheumatoid arthritis, systemic sclerosis, and Raynaud’s syndrome. Explantation resulted in alleviation of symptoms in over 50% patients, strengthening the hypothesis associating breast implants to these problems. Studies have shown silicone is a biologically inert material and unlikely to be the cause of these symptoms. This is supported by the fact that increased risk of autoimmune disease was also reported in patients with other implantable biomaterials such as orthopedic implants. Recent studies conducted by our group and other researchers shed light on a possible role of bacterial biofilm and subsequent host-pathogen interactions as a confounding factor to this problem. Conclusion: BII could be dependent on biofilm infection and the microenvironment around the implants. Should explantation of the implant continue to be the gold standard for treatment, or should more research be done to treat the underlying cause? The true pathophysiology behind these complaints must be further investigated so that accurate treatment regimens other than explantation can be developed. Translational significance of these studies is not limited to breast implants but extends to other implants as well.

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Intraoperative Assessment of Endogenous Microbiota in the Breast

Revista Brasileira de Ginecologia e Obstetrícia / RBGO Gynecology and Obstetrics ◽

10.1055/s-0041-1736300 ◽

2021 ◽

Vol 43 (10) ◽

pp. 759-764

Author(s):

Henrique Stachon ◽

Vanessa Amoroso ◽

Cicero Urban ◽

Pamela Bioni ◽

Cleverton Spautz ◽

...

Keyword(s):

Staphylococcus Epidermidis ◽

Breast Tissue ◽

Breast Surgery ◽

Breast Implant ◽

Brain Heart Infusion ◽

Breast Implants ◽

Large Cell ◽

Aeromonas Salmonicida ◽

Staphylococcus Hominis ◽

Near Future

Abstract Objective: Breast surgery is considered a clean surgery; however, the rates of infection range between 3 and 15%. The objective of the present study was to intraoperatively investigate the presence of autochthonous microbiota in the breast. Methods: Pieces of breast tissue collected from 49 patients who underwent elective breast surgery (reconstructive, diagnostic, or oncologic) were cultured. The pieces of breast tissue were approximately 1 cm in diameter and were removed from the retroareolar area, medial quadrant, and lateral quadrant. Each piece of tissue was incubated in brain heart infusion (BHI) broth for 7 days at 37°C, and in cases in which the medium became turbid due to microorganism growth, the samples were placed in Petri dishes for culturing and isolating strains and for identifying species using an automated counter. Results: Microorganism growth was observed in the samples of 10 of the 49 patients (20.4%) and in 11 of the 218 pieces of tissue (5%). The detected species were Staphylococcus lugdunensis, Staphylococcus hominis, Staphylococcus epidermidis, Sphingomonas paucimobilis, and Aeromonas salmonicida. No patient with positive samples had clinical infection postoperatively. Conclusion: The presence of these bacteria in breast tissue in approximately 20% of the patients in this series suggests that breast surgery should be considered a potential source of contamination that may have implications for adverse reactions to breast implants and should be studied in the near future for their oncological implications in breast implant-associated large-cell lymphoma etiology.

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Autoimmune / Inflammatory Syndrome Induced by Adjuvants (Asia Syndrome) Associated with Silicone Breast Implant Rupture

Archives of Breast Cancer ◽

10.32768/abc.202182156-161 ◽

2021 ◽

pp. 156-161

Author(s):

Ivie Braga De Paula ◽

Erica Araujo Santiago

Keyword(s):

Clinical Symptoms ◽

Breast Implant ◽

Memory Loss ◽

Breast Implants ◽

Chronic Fatigue ◽

Surgical Removal ◽

Neurological Manifestations ◽

Silicone Breast Implant ◽

Cognitive Disturbances ◽

Inflammatory Syndrome

Background: Autoimmune/inflammatory syndrome (ASIA) constitutes a set of related immune mediated diseases that share a common clinical picture and a history of a previous exposure to an adjuvant agent. From a clinical standpoint, patients present with none specific manifestations such as myalgia, arthralgia, chronic fatigue and dry mouth as well as neurological manifestations such as cognitive disturbances, memory loss and neurologic disabilities. .Case presentation: A previously healthy 25-year-old patient who underwent breast augmentation 3 years ago, with an asymptomatic rupture of the silicone breast implant, presented with three major criteria of ASIA, and improved after bilateral implant removal. She also had pleuritis and pericarditis, rarely described in such disease. A literature review on complications related to breast implants, their questionable relationship to the onset of autoimmune pathologies, and basic aspects of the diagnosis and management of ASIA was carried out. Conclusion: The silicone presented in breast implants should be considered as an adjuvant, with the potential to cause chronic stimulation to the immune system. This can lead to systemic manifestations that can be severe in patients genetically predisposed and potentially not reversible even after surgical removal of the implants. When facing patients with breast implants and systemic clinical symptoms, lymph node disorders, neurological manifestations, or serositis as in the case presented, without other defined etiology, the possibility of ASIA should be considered in the differential diagnosis.

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Revisiting an Aspergillus flavus Strain Isolated from an Egyptian Sugarcane Field in 1930

Microorganisms ◽

10.3390/microorganisms8111633 ◽

2020 ◽

Vol 8 (11) ◽

pp. 1633

Author(s):

Mohamed F. Abdallah ◽

Kris Audenaert ◽

Sarah De Saeger ◽

Jos Houbraken

Keyword(s):

Aspergillus Flavus ◽

Short Communication ◽

Aflatoxin Contamination ◽

Type B ◽

Prevention Strategies ◽

Sugarcane Field ◽

Host Pathogen Interaction ◽

Sugarcane Crop ◽

Insight Into ◽

Shed Light

The aflatoxin type B and G producer Aspergillus novoparasiticus was described in 2012 and was firstly reported from sputum, hospital air (Brazil), and soil (Colombia). Later, several survey studies reported the occurrence of this species in different foods and other agricultural commodities from several countries worldwide. This short communication reports on an old fungal strain (CBS 108.30), isolated from Pseudococcus sacchari (grey sugarcane mealybug) from an Egyptian sugarcane field in (or before) 1930. This strain was initially identified as Aspergillus flavus; however, using the latest taxonomy schemes, the strain is, in fact, A. novoparasiticus. These data and previous reports indicate that A. novoparasiticus is strongly associated with sugarcane, and pre-harvest biocontrol approaches with non-toxigenic A. novoparasiticus strains are likely to be more successful than those using non-toxigenic A. flavus strains. Further studies on the association between A. novoparasiticus and Pseudococcus sacchari might shed light on the distribution (and aflatoxin contamination) of this species in sugarcane. Additionally, the interaction between A. novoparasiticus, Pseudococcus sacchari, and sugarcane crop under different scenarios of climate change will be critical in order to get more insight into the host–pathogen interaction and host resistance and propose appropriate prevention strategies to decrease mycotoxin contamination and crop loss due to A. novoparasiticus attack.

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Mycobacterium tuberculosis adhesins: potential biomarkers as anti-tuberculosis therapeutic and diagnostic targets

Microbiology ◽

10.1099/mic.0.082206-0 ◽

2014 ◽

Vol 160 (9) ◽

pp. 1821-1831 ◽

Cited By ~ 22

Author(s):

Viveshree S. Govender ◽

Saiyur Ramsugit ◽

Manormoney Pillay

Keyword(s):

Immune Response ◽

Mycobacterium Tuberculosis ◽

Control Strategies ◽

Host Cells ◽

Tuberculosis Control ◽

Surface Molecules ◽

Host Pathogen Interaction ◽

Bacterial Aggregation ◽

Insight Into

Adhesion to host cells is a precursor to host colonization and evasion of the host immune response. Conversely, it triggers the induction of the immune response, a process vital to the host’s defence against infection. Adhesins are microbial cell surface molecules or structures that mediate the attachment of the microbe to host cells and thus the host–pathogen interaction. They also play a crucial role in bacterial aggregation and biofilm formation. In this review, we discuss the role of adhesins in the pathogenesis of the aetiological agent of tuberculosis, Mycobacterium tuberculosis. We also provide insight into the structure and characteristics of some of the characterized and putative M. tuberculosis adhesins. Finally, we examine the potential of adhesins as targets for the development of tuberculosis control strategies.

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Granzyme B Is a Biomarker for Suspicion of Malignant Seromas Around Breast Implants

Aesthetic Surgery Journal ◽

10.1093/asj/sjaa302 ◽

2020 ◽

Author(s):

Marshall E Kadin ◽

John Morgan ◽

Haiying Xu ◽

Caroline Glicksman ◽

David Sieber ◽

...

Keyword(s):

Early Detection ◽

Tumor Cells ◽

Breast Implant ◽

Granzyme B ◽

Breast Implants ◽

Large Cell ◽

Target Cells ◽

Cytotoxic Lymphocytes ◽

Tumor Cell Death ◽

Level Of Evidence

Abstract Background Granzyme B (GrB) is a serine protease secreted, along with pore-forming perforin, by cytotoxic lymphocytes to mediate apoptosis in target cells. GrB has been detected in tumor cells associated with systemic and breast implant–associated anaplastic large cell lymphoma (BIA-ALCL) but its potential use for detection of early BIA-ALCL has not been fully investigated. Objectives Prompted by the increased incidence of BIA-ALCL, the aim of this study was to assess GrB as a new biomarker to detect early disease in malignant seromas and to better understand the nature of the neoplastic cell. Methods A Human XL Cytokine Discovery Magnetic Luminex 45-plex Fixed Panel Performance Assay was used to compare cytokine levels in cell culture supernatants of BIA-ALCL and other T-cell lymphomas, as well as malignant and benign seromas surrounding breast implants. Immunohistochemistry was employed to localize GrB to cells in seromas and capsular infiltrates. Results Differences in GrB concentrations between malignant and benign seromas were significant (P < 0.001). GrB was found in and around apoptotic tumor cells, suggesting that the protease may be involved in tumor cell death. Conclusions GrB is a useful marker for early detection of malignant seromas and to identify tumor cells in seromas and capsular infiltrates. Because there is an overlap between the lowest concentrations of soluble GrB in malignant seromas and the highest concentrations of GrB in benign seromas, it is recommended that GrB be used only as part of a panel of biomarkers for the screening and early detection of BIA-ALCL. Level of Evidence: 5

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