Extracellular Perinexal Separation Is a Principal Determinant of Cardiac Conduction.

BACKGROUND: Cardiac conduction is understood to occur through gap junctions. Recent evidence supports ephaptic coupling as another mechanism of electrical communication in the heart. Conduction via gap junctions predicts a direct relationship between conduction velocity (CV) and bulk extracellular resistance. By contrast, ephaptic theory is premised on the existence of a biphasic relationship between CV and the volume of specialized extracellular clefts within intercalated discs such as the perinexus. Our objective was to determine the relationship between ventricular CV and structural changes to micro- and nanoscale extracellular spaces. METHODS: Conduction and Cx43 (connexin43) protein expression were quantified from optically mapped guinea pig whole-heart preparations perfused with the osmotic agents albumin, mannitol, dextran 70 kDa, or dextran 2 MDa. Peak sodium current was quantified in isolated guinea pig ventricular myocytes. Extracellular resistance was quantified by impedance spectroscopy. Intercellular communication was assessed in a heterologous expression system with fluorescence recovery after photobleaching. Perinexal width was quantified from transmission electron micrographs. RESULTS: CV primarily in the transverse direction of propagation was significantly reduced by mannitol and increased by albumin and both dextrans. The combination of albumin and dextran 70 kDa decreased CV relative to albumin alone. Extracellular resistance was reduced by mannitol, unchanged by albumin, and increased by both dextrans. Cx43 expression and conductance and peak sodium currents were not significantly altered by the osmotic agents. In response to osmotic agents, perinexal width, in order of narrowest to widest, was albumin with dextran 70 kDa; albumin or dextran 2 MDa; dextran 70 kDa or no osmotic agent, and mannitol. When compared in the same order, CV was biphasically related to perinexal width. CONCLUSIONS: Cardiac conduction does not correlate with extracellular resistance but is biphasically related to perinexal separation, providing evidence that the relationship between CV and extracellular volume is determined by ephaptic mechanisms under conditions of normal gap junctional coupling.

Long-term Outcomes of Poly-4-Hydroxybutyrate (P4HB) in Aesthetic Breast Surgery.

BACKGROUND: Over the past decade, the use of poly-4-hydroxybutyrate (P4HB) in aesthetic breast surgery has grown in popularity. Published data on long-term outcomes, however, is scarce. OBJECTIVES: The purpose of this study was to assess long-term outcomes when using P4HB in various aesthetic breast procedures. METHODS: A retrospective review of all patients undergoing breast procedures with P4HB performed by the senior author (WPA) between July 2012 and March 2022. All patients with greater than one year of follow-up were evaluated, including demographics, surgical indications, complications, secondary procedures, and patient satisfaction. A Kruskal-Wallis test was performed to assess the stability of satisfaction over time. RESULTS: A total of 248 patients were evaluated. The mean follow-up length was 2.9 years (range, 1-9.3y). The most common surgical indication was breast ptosis, which comprised 68 percent (n=167) of patients. The overall complication rate was 8.0 percent (n=20), with an unplanned reoperation rate of 2.8 percent (n=7). Across the entire study population, the mean satisfaction score was 3.42 out of 4. When satisfaction scores were compared to follow-up length, Kruskal-Wallis test demonstrated no statistical differences (H = 18.2, p = 0.89, df = 2), suggesting stability of satisfaction over time. CONCLUSIONS: This study presents the senior author's entire experience with P4HB across a wide range of aesthetic breast procedures. With an average follow-up length of almost 3 years, P4HB appears to be both a safe and effective tool to support soft tissue in aesthetic breast surgery. Further, high patient satisfaction appears stable.

Enhancing Patient Outcomes in Aesthetic Breast Implant Procedures Using Proven Antimicrobial Breast Pocket Irrigations: A 20-Year Follow-up.

BACKGROUND: Capsular contracture (CC) remains the most common complication of implant-based aesthetic and reconstructive breast surgery. With subclinical infection proven to be the primary etiology, antimicrobial breast pocket irrigation has been recommended as the key step to reduce CC but has not been universally adopted. OBJECTIVES: The purpose of this study was to review the rates of CC observed when applying proven antimicrobial breast pocket irrigations. METHODS: Data from patients undergoing cosmetic breast augmentation were recorded prospectively from 1997 to 2017. The irrigation was performed with either a Betadine-containing (50% Betadine or "Betadine triple") or a non-Betadine triple antibiotic regimen. The database was assessed to determine the type of implant used, the incidence of CC, and possible contributing factors. The degree of CC was recorded according to the Baker classification. RESULTS: A 20-year prospective data collection yielded 2088 patients with 4176 implants; of these patients, 826 had textured implants and 1262 had smooth implants. The incidence of Grade III/IV CC was found to be 0.57% in all patients undergoing primary breast augmentation (1.21% in textured implants and 0.16% in smooth implants). CONCLUSIONS: This study constitutes the largest and longest review of CC in a controlled, single-surgeon setting. The incidence of CC is low and reinforces the efficacy/utility of antimicrobial breast pocket irrigation. Both the Betadine and non-Betadine antibiotic regimens were found to be effective, with the Betadine regimen being preferred. Universal adoption of Betadine-containing antimicrobial breast pocket irrigation is recommended to reduce CC and other device-associated infections.

US FDA Patient Decision Checklist for Breast Implants: Results of a Survey to Members of The Aesthetic Society, April 2022.

The US Food and Drug Administration (FDA), in response to concerns that patients undergoing breast implant surgery were not adequately informed about the risks of receiving an implanted medical device, mandated a Patient Decision Checklist (PDC) in October 2021. Breast implant manufactures communicated with plastic surgeons in 2022 regarding the use of the PDC as a condition for the sale of breast implants. Plastic surgeons voiced concerns over the accuracy of the content in the PDC and its confusing statements about the risk of adverse events associated with breast surgery. In April 2022, The Aesthetic Society developed a survey that was sent to its members regarding their experiences with the PDC. This was a 5-question survey, with 1 additional place for comments. The purpose of this survey was to develop data based on the 6-month experience of plastic surgeons with the PDC. A total of 206 Aesthetic Society members (9%) participated in the survey (1849 total active members in the United States). Patients deserve appropriate information prior to breast implant surgery to make an informed decision after reviewing the potential risks and benefits. The authors believe that there is still more work to be done to create an ideal PDC that is fair and balanced, scientifically describes risk incidence in a way that patients understand, and can be updated.

A Qualitative Study on the Experiences of Women With Breast Implant Illness.

BACKGROUND: Breast implant illness (BII) is a term used to describe physical and psychological symptoms experienced by some women following breast implant surgery. Few studies have examined the experiences of women with BII-a poorly understood condition with no clear cause or treatment. OBJECTIVES: The aim of this study was to explore women's experiences of BII, including symptoms, healthcare encounters, social media, and explant surgery. METHODS: Employing an exploratory qualitative methodology, researchers undertook semistructured interviews with 29 women who self-identified as having BII. Interviews were audio-recorded and transcribed verbatim. Data were analyzed by inductive thematic analysis. RESULTS: Thematic analysis of the interviews identified 6 themes: (1) symptoms without explanation; (2) invalidation and invisibility; (3) making the BII connection; (4) implant toxicity; (5) explant surgery: solution to suffering?; and (6) concealed information. BII was described as distressing and debilitating across multiple domains including relationships, work, identity, and physical and mental health, and symptoms were attributed to implant toxicity and immune system rejection of foreign objects. When their experience was not validated by healthcare professionals, many looked to social media for information, support, and understanding, and saw explant as their only chance of recovery. CONCLUSIONS: BII is disabling mentally and physically. Women with BII require support, understanding, and validation, and proactive treatment to prevent disability. With unclear pathophysiology, future research should examine how biopsychosocial approaches can be used to guide treatment, and how to best support women with BII, focusing on early detection and evidence-based education and intervention.

A Practical Guide to Managing Patients With Systemic Symptoms and Breast Implants.

Numerous studies have explored the possibility of an association between breast implants and systemic symptoms potentially linked to exposure to silicone. Some studies show no direct association whereas others provide insufficient scientific evidence to prove or disprove an association. Nonetheless, some patients with breast implants remain concerned about the possible role of their implants in systemic symptoms they may be experiencing. This paper provides a practical approach for plastic surgeons in managing patients with breast implants who present with systemic symptoms, including recommendations for patient counseling, clinical and laboratory assessment of symptoms, and/or referral. Integral components of patient counseling include listening attentively, providing unbiased information, and discussing the risks and benefits of options for evaluation and treatment. A thorough history and assessment of symptoms, including appropriate laboratory tests, may identify underlying conditions to expeditiously address patients' health issues through a specialist referral. Diagnosing and treating disorders that are causing a patient's symptoms, if unrelated to their implant, would avoid a potentially unnecessary surgery. Ultimately, better information is needed to reliably guide patients in an evidence-based fashion. Long-term follow-up of patients who are explanted to see what symptoms may or may not improve could be useful in educating patients. Control groups in studies prospectively following women with implants for development of systemic symptoms would also be useful because the symptoms reported are common in women without implants. Cases are presented to illustrate the recommendations for a practical approach toward management of women reporting systemic symptoms with breast implants.

Evaluating Postoperative Outcomes of Patients Undergoing Elective Procedures in an Ambulatory Surgery Center During the COVID-19 Pandemic.

BACKGROUND: Despite the rapid increase in the number of publications pertaining to COVID-19, there is a lack of data examining patient outcomes following elective procedures performed during this pandemic. OBJECTIVES: The purpose of this investigation was to examine the postoperative outcomes of patients who underwent elective procedures in an ambulatory surgery center during the COVID-19 pandemic, and to share the preoperative screening and patient selection protocol implemented in our center. METHODS: Elective procedures performed in an ambulatory surgery center between March 1, 2020 and April 16, 2020 were retrospectively reviewed. The primary outcomes were occurrence of COVID-19-related postoperative complications. These complications include pneumonia, stroke, myocardial infarction, and clotting disorders. The predictive variables analyzed in this study were age, American Society of Anesthesiologists score, specialty conducting the procedure, operating time, and the type of plastic and reconstructive surgery procedure being performed. RESULTS: A total of 300 consecutive electives cases were included in the study. The most common procedures were pain management (43.0%), gastrointestinal (26.0%), aesthetic (14.0%), orthopedic (10.3%), reconstructive (4.0%), otorhinolaryngology (2.0%), and gynecology (0.67%). The median age of the cohort was 54.6 years (range, 1-90 years) and the median procedure time was 47 minutes (range, 11-304 minutes). COVID-19-related symptoms or complications following the procedures were not observed in any of the patients or in the healthcare care personnel. CONCLUSIONS: In this cohort of 300 elective cases, we found no patients with COVID-19-related symptoms postoperatively. This suggests that with proper preoperative screening and patient selection, elective procedures can be safely performed in an ambulatory surgery center during this pandemic.

Commentary on: Understanding Breast Implant Illness.

BACKGROUND: Breast implant surgery is the most common plastic surgery procedure performed globally. A subset of women with breast implants report experiencing a myriad of disabling and distressing physical and psychological symptoms attributed to their implants. Social media groups have coined the condition "breast implant illness" (BII). Little to no scientific research currently exists for BII. OBJECTIVES: The aim of this study was to investigate the experiences of women with BII (both those with implants still in place and those who have explanted) and compare them with those of a control group of women with implants who do not report BII. METHODS: Women with self-reported BII and implants still in place (n = 51), self-reported BII who had explanted (n = 60), and women with implants in place without BII (n = 58) completed online self-report questionnaires about their symptoms, physical and mental health, health service use patterns, and lifestyle factors (eg, exercise, smoking, alcohol consumption). RESULTS: Women with BII, regardless of whether they had undergone explant surgery, reported experiencing more severe somatic symptoms, higher depression, anxiety and health anxiety, and poorer physical health than women without BII. CONCLUSIONS: These findings highlight the need for further investigation into the causes, risk factors, long-term effects, and potential interventions for women who experience BII.

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

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.

Why Do We Need Anatomical Implants? the Science and Rationale for Maintaining Their Availability and Use in Breast Surgery.

The choice between anatomical and round implants is an important decision in breast augmentation surgery; however, both have their place and the decision between them that should be made on a patient-by-patient basis, taking into account the patient's desires, anatomy, and surgical history. In some individuals, there are clear indications for using either anatomical or round devices, and there is good evidence that aesthetic outcomes are better with anatomical implants in some instances. When both types are an option, anatomical devices may offer increased flexibility and, despite a longer learning curve needed to properly manage them, they are associated with positive long-term outcomes and high levels of patient satisfaction. Concerns about implant rotation can be minimized with proper patient selection and surgical technique, and the overall complication rate may favor anatomical over round devices in appropriate patients. Breast implant-associated anaplastic large-cell lymphoma is an important issue, and while rare, it must be considered in the context of the entire patient risk profile. Both anatomical and round implants remain key elements of a complete surgical toolbox in breast augmentation. 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.

Optimizing Breast Pocket Irrigation: The Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) Era.

BACKGROUND: Specific antimicrobial breast pocket irrigations have been proven over the past 20 years to reduce the incidence of capsular contracture by a factor of 10, and the emergence of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) and its link to bacteria/technique has created renewed interest in different antimicrobial breast pocket preparation agents. Our previous studies have identified that both Betadine-containing and non-Betadine-containing antimicrobial irrigations provide excellent broad-spectrum bacterial coverage. The current science of BIA-ALCL has implicated the Gram-negative microbiome as a key in pathogenesis. OBJECTIVES: The aim of this study was to revisit the antimicrobial effectiveness of clinically utilized Betadine and non-Betadine solutions, along with other antimicrobial agents that have not yet been tested, against multiple organisms, including additional common Gram-negative bacteria associated with chronic breast implant infections/inflammation. METHODS: Current and new antimicrobial breast irrigations were tested via standard techniques for bactericidal activity against multiple Gram-positive and Gram-negative strains. Test results are detailed and clinical recommendations for current antimicrobial irrigations are provided. RESULTS: Betadine-containing irrigations were found to be superior according to the testing performed. CONCLUSIONS: There are quite few misconceptions with regard to antimicrobial breast pocket irrigation. These are discussed and final evidence-based recommendations for practice are given.

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

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.

The Tissue-Based Triad in Augmentation Mastopexy: Single-Stage Technical Refinements.

BACKGROUND: The number of patients seeking augmentation mastopexy has increased over the last several decades. The conflicting goals of augmentation (tissue expansion) and mastopexy (tissue reduction) have led to higher revision rates, decreased patient satisfaction, and pending litigation. Some have even argued for staging of all augmentation mastopexy procedures. OBJECTIVES: The goal of this study was to review the senior author's (W.P.A.) process-oriented approach to single-stage augmentation mastopexy and to detail the technical framework to produce reliable, reproducible, safe results in a 1-stage augmentation mastopexy. METHODS: A prospectively collected patient database from January 2007 until January 2018 was reviewed. All single-stage augmentation mastopexy patients were evaluated, including patient demographics, operative details, complications, and outcomes. RESULTS: A total of 251 patients were evaluated. Mean follow-up was 16.9 months, average patient age was 38.0 years, and average implant size was 285.8 cc. A total of 9 (3.6%) patients required reoperation and only 2 (0.8%) required explantation. Fourteen (5.6%) patients developed delayed wound healing that responded to local wound care alone. CONCLUSIONS: Utilization of a safe and reliable processed approach to single-stage augmentation mastopexy is highly predictable with low reoperation rates. The technical refinements presented have led to increased consistency in delivering high-quality results to patients in a procedure fraught with challenges.

Betadine and Breast Implants.

In the fourth quarter of 2017, the US FDA reviewed and approved a request by one of the breast implant manufacturers for a change in the Directions for Use (DFU) that removed warnings regarding the use of Betadine (povidone-iodine [PI] 10% solution, 1% available iodine [Purdue Frederick Company, Stamford, CT], also available in generic formulations [Aplicare, Inc., Meriden, CT]). Previously, in 2000, there were concerns by the FDA that PI would degrade the silicone elastomer shell. This change in the DFU represents an important advance that will benefit patients through the permitted use of PI to reduce the risk of bacterial contamination of implant surfaces. What was formerly an off-label practice can be openly practiced by plastic surgeons as an anti-infective and biofilm-mitigation strategy. PI has an ideal spectrum effect for gram-positive and gram-negative organisms. Gram-positive organisms have been linked to capsular contracture and gram-negative Ralstonia picketti to breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). R picketti is resistant to aminoglycoside antibiotics, but it is susceptible to at least a 50% solution of PI. We believe that the strategy of antisepsis and biofilm mitigation is an integral part of a contemporary approach for breast augmentation. This is beneficial regarding reduction of the risk of surgical infection, capsular contracture, and BIA-ALCL. Outcome data so far indicate that antibiotics/anti-infectives seem to reduce the incidence of these adverse events that lead to reoperation and increased costs. It behooves plastic surgeons to take all actionable steps that enhance the quality of breast implant outcomes and reduce the rate of reoperation.

The Use of Poly-4-Hydroxybutyrate (P4HB) Scaffold in the Ptotic Breast: A Multicenter Clinical Study.

BACKGROUND: Mastopexy and reduction mammaplasty are often limited by the patient's poor native soft tissue quality, resulting in ptosis recurrence and loss of rejuvenated surgical results. Surgical scaffolds and acellular dermal matrices are used in these procedures to provide physical and mechanical stabilization of weakened or compromised tissue. GalaFLEX scaffold, made from poly-4-hydroxybutyrate (P4HB), is a next-generation product for soft tissue reinforcement that resorbs gradually while aiding tissue regeneration to achieve excellent outcomes. OBJECTIVES: To assess the clinical performance of GalaFLEX scaffold in soft tissue reinforcement during elective mastopexy and reduction mammaplasty. METHODS: This multicenter, single-arm, observational study assessed product performance and outcomes of GalaFLEX scaffold when used in breast surgery. Outcomes included ptosis correction and maintenance, associated adverse events, patient and surgeon satisfaction, and mammographic and ultrasound imaging evaluation. RESULTS: At 6 centers in the US, 62 of 69 enrolled patients were treated. Of this population, 89.7% had successful ptosis correction and maintenance at 1 year, with high patient and surgeon satisfaction for breast shape, droop/sag of the breast, and maintenance of results at 1 year. There were 5 adverse events deemed related to the device (8.0%), including nerve pain, breast swelling, ptosis, and 2 instances of asymmetry. CONCLUSIONS: GalaFLEX scaffold safely and successfully supports and elevates breast tissue in mastopexy and reduction mammaplasty, with maintained support at 1 year. Surgeon and patient satisfaction were high. No mammogram or ultrasound interference was detected.

What's Your Micromort? A Patient-Oriented Analysis of Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL).

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) continues to be a rare and elusive malignancy. Because BIA-ALCL does not behave like traditional lymphomas, additional research needs to be conducted to further delineate the lymphoproliferative nature of BIA-ALCL. An estimated 35 million women worldwide have breast implants and the total reported deaths from BIA-ALCL is 12 to date. The term micromort was introduced in 1979 by Ronald Howard as a person's risk of dying as 1 in a million. Drinking 0.5 L of wine or walking 17 miles all increase your risk of death by 1 micromort. Risk of death from BIA-ALCL is 0.4 micromorts for a woman having bilateral breast implants. This information is important for counseling new patients and those presenting with delayed onset seromas.

Clinical Evaluation of Shaped Gel Breast Implant Rotation Using High-Resolution Ultrasound.

Background: Clinical trials have demonstrated through core and independent studies that anatomical devices are safe and effective with low complication rates. The rotation rate of shaped breast implants in the literature is 0 to 8.2%. Currently there are no studies evaluating the efficacy of in office ultrasound or clinical rotation vs actual rotation rates seen on high-resolution ultrasound (HRUS). Objectives: The purpose of the study is to demonstrate the ease and reliability of HRUS for evaluating the rotation rate of 2 different brands of anatomic implants and to correlate this with the presumed clinical rate, as well as independent evaluators assessments. Methods: A total of 69 patients were followed up at routine intervals and were evaluated for rotation. Any implant rotated past >30° off of midline (outside 5-7 o'clock) was considered to be rotated. To determine if radiographic rotation was clinically evident, 20 composite patient photos were blindly evaluated. Results: A random total of 69 patients underwent bilateral augmentation mammoplasty with form stable anatimic gel implants using 138 implants. Twenty-nine of the 69 (42%) patients and 37 of the 138 (27%) implants were found to be rotated-using HRUS. Eight of the 69 (12%) patients had bilateral rotations. Independent evaluators were able to identify two of 12 (17%) possible rotations, or 2 rotations in 40 (5%) total implants. Conclusions: Anatomic form stable gel implants are actually rotated up to 25 times more frequently than previously thought, but these rotations do not translate into clinically significant sequela. High-resolution ultrasound is a simple alternative for breast implant surveillance and is better accepted by patients than magnetic resonance imaging (MRI). The clinical value of HRUS is also discussed and recommendations for FDA implant labeling changes are provided in this article. Level of Evidence: 4