A Comparative Analysis of Local and Systemic Immunological Biomarkers in Females With Breast Implants and Capsular Contracture.

Background: The etiology of capsular contracture (CC), the most common complication following breast augmentation, remains unclear. Chronic, fibrotic inflammation resulting in excessive fibrosis has been proposed as a potential mechanism. Objectives: In this study, we aimed to investigate the relation between biomarkers that are associated with inflammation and fibrosis and the severity of CC. Methods: Fifty healthy females were categorized into 3 groups: females with no-to-mild CC (Baker 1-2; n = 15), females with severe CC (Baker 3-4; n = 20), and a control group awaiting breast augmentation (n = 15). We assessed 5 biomarkers (galectin-1 [Gal-1], interferon-ß [INF-ß], interferon-γ [INF-γ], interleukin-6 [IL-6], and tumor necrosis factor-α [TNF-α]) in breast implant capsules and serum samples. Results: No significant differences in intracapsular cytokine levels were observed between the Baker 1-2 and the Baker 3-4 groups, as the levels were generally low and, in some cases, almost undetectable. In the blood samples, no significant differences in Gal-1, INF-γ, IL-6, or TNF-α levels were found within the 3 groups. We identified significantly increased levels of INF-ß (P = .009) in the blood samples of females with severe CC, driven mainly by 3 extremely high values. Conclusions: The cytokines assessed in this study did not reflect the degree of CC among females with silicone breast implants. However, 3 females with severe CC, who all had prolonged silicone exposure, showed extremely elevated levels of INF-ß in their serum samples. This possible association between prolonged silicone exposure and systemic inflammation in some females should be further investigated.

COVID-19 burden differed by city districts and ethnicities during the pre-vaccination era in Amsterdam, the Netherlands.

Background: During the first wave of COVID-19 in Amsterdam, the Netherlands, a disproportional number of COVID-19 hospitalizations occurred in individuals with an ethnic minority background and in individuals living in city districts with a lower socioeconomic status (SES). In this study, we assessed whether these disparities continued throughout the second wave, when SARS-CoV-2 testing was available to anyone with symptoms but prior to the availability of COVID-19 vaccination. Methods: Surveillance data on all notified SARS-CoV-2 cases in Amsterdam between 15 June 2020 and 20 January 2021 were matched to municipal registration data to obtain the migration background of cases. Crude and directly age- and sex-standardized rates (DSR) of confirmed cases, hospitalizations, and deaths per 100,000 population were calculated overall, and by city districts, and migration backgrounds. Rate differences (RD) and rate ratios (RR) were calculated to compare DSR between city districts and migration backgrounds. We used multivariable Poisson regression to assess the association of city districts, migration backgrounds, age, and sex with rates of hospitalization. Results: A total of 53,584 SARS-CoV-2 cases (median age 35 years [IQR = 25-74]) were notified, of whom 1,113 (2.1%) were hospitalized and 297 (0.6%) deceased. DSR of notified infections, hospitalization, and deaths per 100,000 population were higher in lower SES peripheral city districts (South-East/North/New-West) than higher SES central districts (Central/West/South/East), with almost a 2-fold higher hospitalization DSR in peripheral compared to central districts (RR = 1.86, 95%CI = 1.74-1.97). Individuals with a non-European migration background also had a higher COVID-19 burden, particularly with respect to hospitalization rates, with a 4.5-fold higher DSR for individuals with a non-European background compared to ethnic-Dutch (RR 4.51, 95%CI = 4.37-4.65). City districts, migration backgrounds, male gender, and older age were independently associated with COVID-19 hospitalization rates. Discussion: Individuals with a non-European background and individuals living in city districts with lower SES continued to independently have the highest COVID-19 burden in the second wave of COVID-19 in Amsterdam, the Netherlands.

No association found between late-onset inflammatory adverse events after soft tissue filler injections and the adaptive immune system.

BACKGROUND: To date, it is unknown why some individuals develop late-onset inflammatory adverse events after treatment with fillers. These events may result from various factors, including an immunological response of the adaptive immune system. OBJECTIVE: In a pilot study, we looked for evidence that is there a relation between late-onset inflammatory adverse events and the presence of immune cells surrounding the injected filler. METHODS AND MATERIALS: We included 47 patients, of whom 20 experienced late-onset inflammatory adverse events to different fillers (inflammatory group) and 27 who did not (reference group). A biopsy was taken from the area of the adverse event. Hematoxylin-eosin staining and immunohistochemistry analysis with CD3 (T-cells) and CD68 (macrophages) on paraffin tissue sections was used to assess the biopsies. RESULTS: Immune cells were found in biopsies obtained from 18 of 47 patients: Nine biopsies from the inflammation group and nine from the reference group. All these 18 cases showed CD68-positive immune cells. Virtually no CD3-positive immune cells were found. CONCLUSION: Our results indicate that there is no T-cell activity in biopsies from areas with late-onset adverse events after filler injections. The macrophages found in the biopsies are probably not responsible for the inflammatory response.

Bacterial Contamination Is Involved in the Etiology of Soft-Tissue Filler, Late-Onset, Inflammatory Adverse Events.

BACKGROUND: The treatment algorithm in late-onset inflammatory adverse events with soft-tissue fillers depends primarily on the assumed causative factor: immunologic or bacterial. METHODS: The authors included 29 patients, 13 of whom experienced late-onset inflammatory adverse events to fillers (inflammatory group) and 16 who did not (reference group). Biopsies were acquired from both groups with an 18-G needle. Before taking the biopsy, the authors acquired skin swabs for 25 of the 29 patients. The IS-pro method-a new and very sensitive method to detect microbiota-was used. This is a novel broad-range polymerase chain reaction technique based on length and sequence variations of the 16S to 23S ribosomal interspacer region. IS-pro can detect bacteria at low abundances and identify them up to species level. To exclude contamination from skin microbiota, the authors compared the microbiota found on skin swabs with that found in the corresponding biopsies. RESULTS: A high level of Gram-positive bacteria was found in biopsies of soft-tissue fillers, predominantly in patients from the inflammation group. This suggests that these bacteria were introduced during the primary filler injection treatment. The composition of the microbiota on the skin differed markedly from that in the filler, indicating that contamination during the sampling process did not influence results. CONCLUSIONS: Bacteria adherent to soft-tissue fillers or bacteremia probably play a causative role in adverse events. Contamination of samples in the biopsies with skin microbiota was excluded. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Patient-reported systemic symptoms in women with silicone breast implants: a descriptive cohort study.

OBJECTIVE: An unknown portion of women with silicone breast implants (SBI) report development of systemic symptoms, recently named as 'breast implant illness (BII)'. We aim to describe the symptoms and characteristics of women with SBI reporting these systemic symptoms and compare the clinical course of women who chose to keep their implants, to women who had their implants removed. DESIGN: Observational cohort study. SETTING: Specialised BII out-patient clinic at Amsterdam UMC, the Netherlands, from 2011 to 2020. PARTICIPANTS: All women presenting to the BII clinic with SBI and systemic symptoms. RESULTS: 467 women were included for baseline analyses and 398 women for follow-up. Most frequently reported systemic symptoms at baseline included fatigue (88%), arthralgia (71%), morning stiffness (59%), myalgia (48%), cognitive impairment (33%), peripheral neurological symptoms (30%) and lymphadenopathy (22%). Furthermore, 56% reported pre-existing allergies at baseline and positive antinuclear antibodies were observed in 23%. At follow-up with a median of 3.3 years (IQR 2-4), 152 women had their implants removed on clinical grounds. Symptoms improved significantly in 65 women (43%), improved moderately in 37 women (24%), did not change in 37 women (24%) and deteriorated in 13 women (9%). Women who underwent explantation showed more improvement of their systemic symptoms compared with women who did not (OR 2.9, 95% CI 1.3 to 6.2). Additionally, women who underwent explantation within 10 years after implantation improved significantly better than women who got the implants removed after 10 years (p=0.007). Lastly, local symptoms decreased from 75% to 34% after implant removal (p<0.0001). CONCLUSION: Most women with SBI who developed systemic symptoms experienced improvement after explantation, especially when removed within 10 years after implantation. Early recognition of the pattern of systemic symptoms in women with SBI is important and implant removal should be considered.

Late inflammatory reactions in patients with soft tissue fillers after SARS-CoV-2 infection and vaccination: A systematic review of the literature.

INTRODUCTION: Soft tissue fillers are used for cosmetic and reconstructive purposes, and soft tissue filler procedures are among the most common nonsurgical procedures in the USA. Although soft tissue filler procedures are relatively quick and safe, adverse events such as late inflammatory reactions have been reported with every filler product. Infections and vaccinations have been proposed as potential triggers for late inflammatory reactions (LIRs), and it is therefore not surprising that these adverse events have been reported after SARS-CoV-2 infection and vaccination. Therefore, this review aims to give a detailed overview of these cases. MATERIALS AND METHODS: A literature search was undertaken on LIRs in patients with a history of soft tissue filler use after SARS-CoV-2 infection or vaccination. This systematic review was reported according to the PRISMA guidelines. We searched the electronic database PubMed from January 2020 to August 2021. Data on patient characteristics, filler characteristics, clinical findings, and treatment options were included. RESULTS: This review included 7 articles with a total of 19 patients with LIRs after SARS-CoV-2 infection or vaccination. Three patients with postinfection LIRs and 16 patients with postvaccination LIRs were reported. These LIRS mainly occurred in females who had HA injections for cosmetic purposes. Three patients with postinfection LIRs had symptoms of facial swelling and/or lip angioedema in a matter of weeks. Sixteen patients reported reactions after SARS-CoV-2 vaccination (13 following Moderna vaccination and 3 after Pfizer vaccination, after both the first and second doses) from 13 hours up to three weeks. These patients presented with similar clinical symptoms as patients with postinfection LIRs. All patients were treated in a conservative manner. DISCUSSION: This review shows a relationship between LIRs and SARS-CoV-2 infection and vaccination. In the case of vaccination, these adverse events have been reported only after Moderna and Pfizer vaccinations. The reported adverse events are generally minor and self-limiting, and we encourage patients with soft tissue fillers to participate in vaccination programs.

Capsular Contracture in Breast Implant Surgery: Where Are We Now and Where Are We Going?

Capsular contracture is the leading complication after surgery with breast implants. A lot of progress has been made investigating this complication over the years, and knowledge has been gained on this complication. Currently, the exact cause for capsular contracture is still unclear. It has been hypothesized that immunobiological factors (i.e., immunological and bacterial factors) and several risk factors play a central role in its development. In this paper, we give an overview of the known immunological factors that have been investigated in contracted and non-contracted capsules, as well as the role of bacterial formation around breast implants. We also report on risk factors that might increase the risk of capsular development. Lastly, it provides the latest research on this matter and discusses future perspectives as follow-up research is needed to unravel the pathogenic process leading to capsular contracture. This knowledge is of interest to establish medical therapies in order to prevent such side effects. Overall, capsular contracture seems to be a multifactorial condition consisting of several risk factors. LEVEL OF EVIDENCE V: 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 .

Increased risk of late-onset, immune-mediated, adverse reactions related to dermal fillers in patients bearing HLA-B*08 and DRB1*03 haplotypes.

Even though manufacturers claim that the dermal fillers are nontoxic and nonimmunogenic, adverse events may occur. Clinically and histologically, most of the late onset adverse events present as an inflammatory response. To assess whether HLA polymorphisms are associated with late-onset inflammatory adverse events related to dermal fillers. A total of 211 patients were included, of whom 129 experienced late-onset inflammatory adverse events to different fillers (Inflammation group) and 82 who did not (Reference group). Patients completed a standardized questionnaire and provided a blood sample or oral swap for HLA testing. The study population consisted of 188 (89%) women and 23 (11%) men. The two study groups were similar in the distributions of filler type, location of injecting, allergy, autoimmune disease, gender, age, ethnicity, and smoking status. Of the 211 patients in the sample, 25 had the combination of HLA subtype-B*08 and HLA subtype-DRB1*03. This was 16.3% of the inflammatory group and 4.9% of the reference group. This combination of HLA subtypes was associated with an almost 4-fold increase in the odds of developing immune mediated adverse events (odds ratio = 3.79, 95% CI 1.25-11.48). Genetic polymorphisms such as HLA combinations may identify patients at risk of developing late onset immune mediated adverse events to dermal fillers.

PCR Characterization of Microbiota on Contracted and Non-Contracted Breast Capsules.

BACKGROUND: The aetiology of capsular contracture around breast implants remains unclear. The leading theory is that a subclinical infection around the implant plays a role in the development of capsular contractions. Several studies found associations between the presence of bacteria and the occurrence of capsular contraction. However, it is unclear whether detected bacteria originate from the breast capsule, breast glandular tissue or skin contamination. Moreover, this has never been investigated with molecular techniques. The aim of this study was to assess the bacterial microbiota on breast capsules, glandular tissue and skin using a highly sensitive PCR assay. MATERIALS AND METHODS: Fifty breast capsules were collected during implant removal or replacement. Ten specimens of glandular breast tissue and breast skin were collected in females who were undergoing reduction mammoplasty. A sample specimen (4 mm) was sterilely obtained from all tissues. All specimens were analysed by IS-pro, a 16S-23S interspace region-based PCR assay. RESULTS: Low numbers of Staphylococcus spp. (four species in four capsules) were found on breast capsules. There was no difference in bacterial presence between normal and contracted capsules. The skin of the breast-harboured Streptococcus spp. and Staphylococcus spp. while the glandular tissue was sterile. CONCLUSION: The low numbers of bacteria found on the capsules are most likely caused by contamination during capsule removal. More and larger studies are needed to investigate the bacterial presence on breast capsules using a PCR assay. This is the first study in which breast capsules have been studied using a highly sensitive PCR assay. 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 .

Poly Implant Prothèse Silicone Breast Explants: Chemical Analysis of Silicone Gel and Implant Shell.

BACKGROUND: Poly Implant Prothèse (PIP) silicone breast implants were removed from the market between 2010 and 2012 because of the use of nonmedical grade silicone filler. The chemical and physico-chemical properties of PIP implants have been analyzed by several groups. In addition, our previous study illustrated that PIP implant shells were more permeable. Therefore, we analyzed the chemical composition of the envelope and gel of PIP silicone breast explants. Also, the composition of absorbed material into the implant was analyzed. METHODS: This study was conducted on 3 PIP implants explanted from 2 patients. The envelope was analyzed using Raman microscopy, whereas the gel was analyzed using near-infrared spectra, nuclear magnetic resonance spectroscopy, and gas chromatography coupled to mass spectrometry. Absorbed material was investigated with Fourier-transform infrared spectroscopy and sodium dodecyl sulfate polyacrylamide gel electrophoresis. RESULTS: The 3 implants appeared to be Rofil implants, and all implants displayed a yellow color. None of the envelope showed a barrier layer. Amounts of D4, D5, and D6 were found to be below 100 ppm. Water was found in all 3 implants and also proteins were absorbed into the implants. CONCLUSIONS: The current study shows that the analyzed implants originate from the manufacturer Rofil but have PIP1 hallmarks. Apparently, these are own brand labeling implants. The presence of water and proteins in the explants indicate exchange of small and large molecules into the explants, even in the implant with a visually intact envelope. Because of the PIP1 hallmarks of the Rofil implants, patients with such implants are advised to be counseled by their physicians.

Distal Pole Resection of the Scaphoid for the Treatment of Scaphotrapeziotrapezoid Osteoarthritis.

BACKGROUND: Distal pole resection of the scaphoid is one of the surgical techniques applied for the treatment of painful scaphotrapeziotrapezoid osteoarthritis (STT-OA). METHODS: In this retrospective study, we evaluated midterm outcomes in a consecutive series of patients who underwent distal pole resection of the scaphoid: 13 patients (15 wrists) with a mean follow-up of 4.1 years. We examined objective functional and patient-reported outcome measures. In addition, we assessed the degree of dorsal intercalated segment instability (DISI) and postoperative complications. RESULTS: All patients scored within a normal range on objective functional and patient-reported outcome measures. We observed a mild postoperative DISI deformity with an average lunocapitate angle of 22° (range, 0°-44°), which did not correlate with pain scores. In the opposite wrists, with and without STT-OA, the average lunocapitate angle was 6° (range, 0°-20°). CONCLUSIONS: According to this study, midterm results for distal pole resection of the scaphoid are satisfactory.

The Influence of Radiotherapy on the Mechanical Properties of Silicone Breast Implants.

BACKGROUND: Silicone breast implants have been used for decades for cosmetic breast augmentation or reconstruction after mastectomy. In selected cases, postmastectomy adjuvant radiotherapy is given with the breast implants in situ. Previous clinical studies have shown that radiotherapy may lead to complications such as capsular contracture and infection and that removal of the implant may be required. Yet, the effect of radiotherapy on silicone breast implants themselves is unknown. The aim of this study was to investigate if irradiation of breast implants influences their mechanical properties. METHODS: This was an ex vivo study on 32 ready-to-use silicone breast implants (Mentor and Silimed). Half of the implants of each brand were irradiated with 1 × 60 Gy, the other half were not irradiated. Tensile, mechanical hysteresis, and rheology tests were performed. Differences in mechanical properties between the irradiated and nonirradiated implants were determined. RESULTS: No significant differences were found in tensile strength, mechanical hysteresis, and rheological properties between irradiated and nonirradiated implants. CONCLUSIONS: Breast implants' mechanical properties for these 2 brands were not significantly affected after single-dose irradiation in an ex vivo setting.

Risk factors for developing capsular contracture in women after breast implant surgery: A systematic review of the literature.

BACKGROUND: Capsular contracture is the most frequent complication in breast augmentation or reconstruction with breast implants. The exact mechanism for this complication is not completely understood. Yet, it is most likely to be a multifactorial condition. Several patient-, surgery-, and implant-specific risk factors have been related to cause capsular contracture. This review aims to provide a clear overview of all risk factors for capsular contracture. METHODS: A systematic literature review was performed focusing on patient-, surgery-, and/or implant-related factors related to capsular contracture in breast implants. PubMed, Embase, and Wiley/Cochrane Library databases were searched for relevant articles published from inception up to October 20, 2016. The included studies were assessed for the following main variables: study characteristics, patient characteristics, indication for surgery, type of surgery, implant characteristics, and other characteristics. RESULTS: Data on the risk factors for the development of capsular contracture were retrieved from 40 studies. A presumptive increased risk in the development of capsular contracture is shown for the following variables: longer duration of follow-up, breast reconstructive surgery in patients with a history of breast cancer, subglandular implant placement, postoperative hematoma, and a textured implant surface. There is little, weak, or no evidence for the association of other factors with capsular contracture. This review also shows a large heterogeneity between studies and within the definition of capsular contracture. CONCLUSION: This review provides an overview of the relationship between patient-, surgery-, and implant-specific risk factors in the development of capsular contracture.

The aetiopathogenesis of capsular contracture: A systematic review of the literature.

BACKGROUND: Capsular contracture is the most frequent complication after breast augmentation or reconstruction with breast implants. The immune system plays a prominent role in capsular contracture formation, albeit to an unknown extent. Bacterial contamination in situ has been hypothesized to be causative for capsular contracture. How this relates to the immunological processes involved is unknown. This article aims to provide an overview of immunological and bacterial factors involved in development of capsular contracture. MATERIALS AND METHODS: We undertook a systematic literature review focused on immunological factors and microbiota in relation to capsular contraction around implants. This systematic review was performed in accordance with the PRISMA guidelines. PubMed, EMBASE, and the Cochrane databases were searched from inception up to October 2016. Included studies were assessed for the following variables: subject characteristics, number of capsules, primary indication for surgery, surgical procedure, follow-up or implant duration, study methods, type of antibiotics or medical therapies and outcomes related to microbiota and immunological factors. RESULTS: Data on immunological factors and bacterial contamination were retrieved from 64 included studies. Notably the presence of macrophages and Staphylococcus epidermidis within capsules was often associated with capsular contracture. CONCLUSION: This review provides a clear overview of the immunological factors associated with capsular contracture and provides a hypothetical immunological model for development of the disease. Furthermore, an overview of bacterial contamination and associations with capsular contracture has been provided. Follow-up research may result in clinical recommendations to prevent capsular contracture.