The Implant-Induced Foreign Body Response Is Limited by CD13-Dependent Regulation of Ubiquitination of Fusogenic Proteins.

Implanted medical devices, from artificial heart valves and arthroscopic joints to implantable sensors, often induce a foreign body response (FBR), a form of chronic inflammation resulting from the inflammatory reaction to a persistent foreign stimulus. The FBR is characterized by a subset of multinucleated giant cells (MGCs) formed by macrophage fusion, the foreign body giant cells (FBGCs), accompanied by inflammatory cytokines, matrix deposition, and eventually deleterious fibrotic implant encapsulation. Despite efforts to improve biocompatibility, implant-induced FBR persists, compromising the utility of devices and making efforts to control the FBR imperative for long-term function. Controlling macrophage fusion in FBGC formation presents a logical target to prevent implant failure, but the actual contribution of FBGCs to FBR-induced damage is controversial. CD13 is a molecular scaffold, and in vitro induction of CD13KO bone marrow progenitors generates many more MGCs than the wild type, suggesting that CD13 regulates macrophage fusion. In the mesh implant model of FBR, CD13KO mice produced significantly more peri-implant FBGCs with enhanced TGF-ß expression and increased collagen deposition versus the wild type. Prior to fusion, increased protrusion and microprotrusion formation accompanies hyperfusion in the absence of CD13. Expression of fusogenic proteins driving cell-cell fusion was aberrantly sustained at high levels in CD13KO MGCs, which we show is due to a novel CD13 function, to our knowledge, regulating ubiquitin/proteasomal protein degradation. We propose CD13 as a physiologic brake limiting aberrant macrophage fusion and the FBR, and it may be a novel therapeutic target to improve the success of implanted medical devices. Furthermore, our data directly implicate FBGCs in the detrimental fibrosis that characterizes the FBR.

Decoding the "Fingerprint" of Implant Materials: Insights into the Foreign Body Reaction.

Foreign body reaction (FBR) is a prevalent yet often overlooked pathological phenomenon, particularly within the field of biomedical implantation. The presence of FBR poses a heavy burden on both the medical and socioeconomic systems. This review seeks to elucidate the protein "fingerprint" of implant materials, which is generated by the physiochemical properties of the implant materials themselves. In this review, the activity of macrophages, the formation of foreign body giant cells (FBGCs), and the development of fibrosis capsules in the context of FBR are introduced. Additionally, the relationship between various implant materials and FBR is elucidated in detail, as is an overview of the existing approaches and technologies employed to alleviate FBR. Finally, the significance of implant components (metallic materials and non-metallic materials), surface CHEMISTRY (charge and wettability), and physical characteristics (topography, roughness, and stiffness) in establishing the protein "fingerprint" of implant materials is also well documented. In conclusion, this review aims to emphasize the importance of FBR on implant materials and provides the current perspectives and approaches in developing implant materials with anti-FBR properties.

Treating acid reflux without compressing the food passageway: 4-year safety and clinical outcomes with the RefluxStop device in a prospective multicenter study.

INTRODUCTION: RefluxStop is an implantable device for laparoscopic surgical treatment of gastroesophageal reflux disease (GERD) to restore and maintain lower esophageal sphincter and angle of His anatomy without encircling and putting pressure on the food passageway, thereby avoiding side effects such as dysphagia and bloating seen with traditional fundoplication. This study reports the clinical outcomes with RefluxStop at 4 years following implantation of the device. METHODS: A prospective, single arm, multicenter clinical investigation analyzing safety and effectiveness of the RefluxStop device in 50 patients with chronic GERD. RESULTS: Available data are presented for 44 patients at 4 years with the addition of three patients at 3 years carried forward. At 4 years, median GERD-HRQL score was 90% reduced compared to baseline. Two patients (2/44) used regular daily proton pump inhibitors (PPIs) despite subsequent 24-h pH monitoring off PPI therapy yielding normal results. There were no device-related adverse events (AEs), esophageal dilations, migrations, or explants during the entire study period. AEs reported between 1 and 4 years were as follows: one subject with heartburn and a pathologic pH result with device positioned too low at surgery; one subject with dysphagia, thus, 46/47 patients reported no dysphagia-related AEs between years 1 and 4. Two patients (2/47) were dissatisfied with treatment despite normal 24-h pH monitoring, of whom one had manometry-verified dysmotility at 6 months, indicating dissatisfaction for reasons other than acid reflux. CONCLUSION: These results confirm the excellent and already published 1-year results as stable in the long-term, supporting the safety and effectiveness of the RefluxStop device in treating GERD for over 4 years. GERD-HRQL score, pH testing, and PPI usage indicate treatment success without dysphagia or gas-bloating and only minimal incidence of other AEs. This favorably low rate of AEs is likely attributable to RefluxStop's dynamic physiologic interaction and non-encircling nature.

Optimal ultrasonic treatment frequency and duration parameters were used to detect the pathogenic bacteria of orthopedic implant-associated infection by ultrasonic oscillation.

INTRUDUCTON: The most accurate method for detecting the pathogen of orthopedic implant-associated infections (OIAIs) is sonication fluid (SF). However, the frequency and duration of ultrasound significantly influence the number and activity of microorganisms. Currently, there is no consensus on the selection of these two parameters. Through this study, the choice of these two parameters is clarified. METHODS: We established five ultrasonic groups (40kHz/10min, 40kHz/5min, 40 kHz/1min, 20kHz/5min, and 10kHz/5min) based on previous literature. OIAIs models were then developed and applied to ultrasound group treatment. Subsequently, we evaluated the efficiency of bacteria removal by conducting SEM and crystal violet staining. The number of live bacteria in the SF was determined using plate colony count and live/dead bacteria staining. RESULTS: The results of crystal violet staining revealed that both the 40kHz/5min group and the 40kHz/10min group exhibited a significantly higher bacterial clearance rate compared to the other groups. However, there was no significant difference between the two groups. Additionally, the results of plate colony count and fluorescence staining of live and dead bacteria indicated that the number of live bacteria in the 40kHz/5min SF group was significantly higher than in the other groups. CONCLUSION: 40kHz/5min ultrasound is the most beneficial for the detection of pathogenic bacteria on the surface of orthopedic implants.

A rare case of bilateral malignant glaucoma after cataract surgery with capsular tension ring implantation: a case report.

BACKGROUND: Bilateral malignant glaucoma induced by a capsular tension ring associated with ring-shaped cysts of the ciliary body post-cataract surgery is rare. Herein, we present a case to highlight the possibility of capsular tension ring-induced malignant glaucoma. CASE PRESENTATION: A 59-year-old woman underwent phacoemulsification combined with capsular tension ring implantation for cataracts and zonular fibre laxity in both eyes. Upon admission, annular ciliary masses were detected in both eyes using ultrasound biomicroscopy. Two months post-surgery, the patient experienced vision deterioration, high intraocular pressure, and an axial shallowing anterior chamber in the right eye, and responded poorly to traditional anti-glaucoma medication. Ten days later, similar symptoms appeared in the left eye. Ultrasound biomicroscopy detected contact between the ciliary body and the capsular tension ring. Subsequently, malignant glaucoma was diagnosed. Anterior and posterior capsulotomies performed peripheral to intraocular lens optics using neodymium: YAG laser restored communication and alleviated the symptoms. A one-year follow-up revealed stable intraocular pressure and anterior chamber in both eyes. CONCLUSIONS: This is the first case report of bilateral malignant glaucoma after cataract surgery induced by capsular tension ring, which is associated with bilateral ring-shaped cysts of the ciliary body. Blockage between the ciliary body and capsular tension ring was confirmed using ultrasound biomicroscopy.

Brain-implanted conductors amplify radiofrequency fields in rodents: Advantages and risks.

Over the past few decades, daily exposure to radiofrequency (RF) fields has been increasing due to the rapid development of wireless and medical imaging technologies. Under extreme circumstances, exposure to very strong RF energy can lead to heating of body tissue, even resulting in tissue injury. The presence of implanted devices, moreover, can amplify RF effects on surrounding tissue. Therefore, it is important to understand the interactions of RF fields with tissue in the presence of implants, in order to establish appropriate wireless safety protocols, and also to extend the benefits of medical imaging to increasing numbers of people with implanted medical devices. This study explored the neurological effects of RF exposure in rodents implanted with neuronal recording electrodes. We exposed freely moving and anesthetized rats and mice to 950 MHz RF energy while monitoring their brain activity, temperature, and behavior. We found that RF exposure could induce fast onset firing of single neurons without heat injury. In addition, brain implants enhanced the effect of RF stimulation resulting in reversible behavioral changes. Using an optical temperature measurement system, we found greater than tenfold increase in brain temperature in the vicinity of the implant. On the one hand, our results underline the importance of careful safety assessment for brain-implanted devices, but on the other hand, we also show that metal implants may be used for neurostimulation if brain temperature can be kept within safe limits.

A literature review and expert consensus statement on diagnostics in suspected metal implant allergy.

BACKGROUND: Although rare, allergic reactions to metal implants represent a diagnostic challenge in view of missing guidelines. OBJECTIVES: To develop an European expert consensus on characteristics of metal allergy reactions and the utility of various diagnostic tools in suspected metal implant allergy. METHODS: A nominal group technique (NGT) was applied to develop consensus statements. Initially an online literature database was created on a secure server to enable a comprehensive information. Twenty-three statements were formulated on potential aspects of metal implant allergy with a focus on diagnostics and grouped into five domains. For the consensus development, the panel of 12 experts initially did refine and reformulate those statements that were ambiguous or had unclear wording. By face-to-face (9/12) or virtual participation (3/12), an anonymous online voting was performed. RESULTS: Consensus (≥80% of agreement) was reached in 20/23 statements. The panel agreed that implant allergy despite being rare should be considered in case of persistent unexplained symptoms. It was, however, recommended to allow adequate time for resolution of symptoms associated with healing and integration of an implant. Obtaining questionnaire-aided standardized medical history and standardized scoring of patient outcomes was also considered an important step by all experts There was broad consensus regarding the utility/performance of patch testing with additional late reading. It was recognized that the lymphocyte transformation test (LTT) has to many limitations to be generally recommended. Prior to orthopaedic implant, allergy screening of patients without a history of potential allergy to implant components was not recommended. CONCLUSIONS: Using an expert consensus process, statements concerning allergy diagnostics in suspected metal implant allergy were created. Areas of nonconsensus were identified, stressing uncertainty among the experts around topics such as preoperative testing in assumed allergy, histological correlate of periimplant allergy and in vitro testing, which underscores the need for further research.

Ventriculo-gallbladder shunt: case series and literature review.

BACKGROUND: The ventriculoperitoneal shunt (VPS) is the gold-standard surgical technique to treat hypertensive hydrocephalus; however, it may fail in 20 to 70% of cases. The present study shows an alternative for patients with contraindications to VPS. METHODS: A case series of nine patients. The medical records of all patients under 17 years of age who underwent ventriculo-gallbladder (VGB) shunt at a pediatric hospital from January 2014 to October 2022 were reviewed. RESULTS: There were 6 (66.7%) males and 3 (33.3%) females. The average age of 73.6 months or 6.1 years at the time of surgery. They had undergone, on average, 5.1 VPS reviews before the VGB shunt. Five (55.5%) had complications of VGB shunt: infection (11.1%), atony (11.1%), hypodrainage (11.1%), and ventriculoenteric fistula (22.2%); all these patients got better at surgical reapproach, and in two of them, the VGB shunt was re-implanted. CONCLUSION: This case series shows a lower risk of death and a similar risk of complications compared to other alternative shunts. This article spotlighted VGB as a viable alternative when VPS fails or has contraindications.

Metal implant allergy: A retrospective cohort analysis at a university allergy practice.

Background: Concern of metal sensitization in pre- and postsurgical evaluation is growing, with the recent guidelines remaining the criterion standard for consideration of patch testing. Information remains scarce on surgical screening in the groups of patients who reported a history of metal sensitivity versus those with no reported history. Objective: The objective of this study was to assess the utility of patch testing in surgical candidates based on reported metal allergy history. The secondary objective was to evaluate the utility and outcomes in postsurgical patch testing. Methods: Nine hundred and thirty-one patient charts of patients with the diagnosis of "contact dermatitis" who underwent an evaluation at a single allergy clinic site between January 2013 and December 2022 were identified and reviewed as part of a retrospective chart review study. Patients were included in subgroups based on the time of patch testing and history of reported metal allergy. Results: In all, 67 patients underwent patch testing, 10 (14.9%) of whom were surgical candidates without a history of metal sensitivity, 31 (46.2%) of whom were surgical candidates with a history of metal sensitivity, and 26 (38.8%) of whom were postsurgical patients. Twenty-nine (43.3%) of patients had positive patch testing results, with only one (10%) in the presurgical group, 17 (54.8%) in the presurgical with a history of metal sensitivity, and 11 (42.3%) in the postsurgical group. Zero patients in our cohort without metal sensitivity who were undergoing the Nuss procedure had positive reactions on patch testing, whereas two of four (50%) with reported metal sensitivity who were undergoing the Nuss procedure had positive relevant metal reactions. Conclusion: Ambiguity in the utility of patch testing for surgical decision making remains, despite common utilization. Recent guidelines along with coordination of care among the surgeon, allergist, and patient remains the criterion standard of care.

Instrumentation failure following pediatric spine deformity growth-sparing surgery using traditional growing rods or vertical expandable prosthetic titanium ribs.

BACKGROUND: Instrumentation failure (IF) is a major complication associated with growth-sparing surgery for pediatric spinal deformities; however, studies focusing on IF following each surgical procedure are lacking. We aimed to evaluate the incidence, timing, and rates of unplanned return to the operating room (UPROR) associated with IF following each surgical procedure in growth-sparing surgeries using traditional growing rods (TGRs) and vertical expandable prosthetic titanium ribs (VEPTRs). METHODS: We reviewed 1,139 surgical procedures documented in a Japanese multicenter database from 2015 to 2017. Of these, 544 TGR and 455 VEPTR procedures were included for evaluation on a per-surgery basis. IF was defined as the occurrence of an implant-related complication requiring revision surgery. RESULTS: The surgery-based incidences of IF requiring revision surgery in the TGR and VEPTR groups were 4.3% and 4.0%, respectively, with no significant intergroup difference. Remarkably, there was a negative correlation between IF incidence per surgical procedure and the number of lengthening surgeries in both groups. In addition, rod breakage in the TGR group and anchor-related complications in the VEPTR group tended to occur relatively early in the treatment course. The surgery-based rates of UPROR due to IF in the TGR and VEPTR groups were 2.0% and 1.5%, respectively, showing no statistically significant difference. CONCLUSIONS: We found that IF, such as anchor related-complications and rod breakage, occurs more frequently earlier in the course of lengthening surgeries. This finding may help in patient counseling and highlights the importance of close postoperative follow-up to detect IF and improve outcomes.

The Role of Revision Total Joint Arthroplasty for Periprosthetic Fractures With Unstable Implants.

The management of periprosthetic fractures with unstable prosthetic implants is a challenging and commonly encountered problem. It is important to address the many current issues and controversies regarding the treatment of periprosthetic fractures with revision total joint arthroplasty. Key strategies to optimize surgical decision making around the use of arthroplasty and management of complications following these complex injuries will be addressed.

Management of Implant Extrusion following Thyroplasty for Vocal Fold Paralysis: A Case Report.

The most widely used laryngeal surgery technique for patients with vocal fold paralysis is medialization thyroplasty. Materials such as Gore-Tex, silastic, and hydroxyapatite are often used, and the most worrisome possible complication is extrusion of the implant. A 36-year-old female patient with a history of pediatric cardiac surgery was diagnosed with left vocal cord paralysis after an episode of upper respiratory infection with a working diagnosis of subclinical left vocal cord paralysis following cardiac surgery. She underwent medialization thyroplasty with a Gore-Tex implant under local anesthesia. On the 21st postoperative day, she presented with sudden-onset hoarseness and dysphagia due to Gore-Tex implant extrusion. The implant was removed and augmentation of the left vocal cord with adipose tissue was performed. Only 14 cases of Gore-Tex implant extrusion have been described in the literature so far. The aim of this case report was not only to show one possible complication when using a Gore-Tex implant but also to present fat augmentation as one of the solutions for revision medialization and salvage treatment, with sustained long-term results.

B-Cell Lymphoma Arising From a Nasal Implant: A Brief Clinical Study.

Continuous exposure to foreign substances initiates a sustained inflammatory reaction in the body, and subsequent chronic inflammation is recognized as one of the causes of lymphoma. Most lymphomas caused by foreign bodies are composed of 2 major phenotypes. Diffuse large B-cell lymphoma arising from metallic prosthesis, also called metallic implant-associated lymphoma and T-cell phenotype anaplastic large cell lymphoma, commonly associated with breast implants. Augmentation rhinoplasty is often performed to improve the esthetics of the nasal dorsum and various synthetic materials have been used as implants. The occurrence of lymphoma originating from a nasal implant is scarcely documented, and even more uncommon is its manifestation as epstein-barr virus (EBV)-negative extranodal marginal zone lymphoma. Here, the authors describe a rare case of B-cell lymphoma of the nose and nasolacrimal duct in a 49-year-old woman who underwent rhinoplasty with a silicone implant 20 years ago.

An Update on Implant-Associated Malignancies and Their Biocompatibility.

Implanted medical devices are widely used across various medical specialties for numerous applications, ranging from cardiovascular supports to orthopedic prostheses and cosmetic enhancements. However, recent observations have raised concerns about the potential of these implants to induce malignancies in the tissues surrounding them. There have been several case reports documenting the occurrence of cancers adjacent to these devices, prompting a closer examination of their safety. This review delves into the epidemiology, clinical presentations, pathological findings, and hypothesized mechanisms of carcinogenesis related to implanted devices. It also explores how the surgical domain and the intrinsic properties and biocompatibility of the implants might influence the development of these rare but serious malignancies. Understanding these associations is crucial for assessing the risks associated with the use of medical implants, and for developing strategies to mitigate potential adverse outcomes.

Environmental, Microbiological, and Immunological Features of Bacterial Biofilms Associated with Implanted Medical Devices.

The spread of biofilms on medical implants represents one of the principal triggers of persistent and chronic infections in clinical settings, and it has been the subject of many studies in the past few years, with most of them focused on prosthetic joint infections. We review here recent works on biofilm formation and microbial colonization on a large variety of indwelling devices, ranging from heart valves and pacemakers to urological and breast implants and from biliary stents and endoscopic tubes to contact lenses and neurosurgical implants. We focus on bacterial abundance and distribution across different devices and body sites and on the role of environmental features, such as the presence of fluid flow and properties of the implant surface, as well as on the interplay between bacterial colonization and the response of the human immune system.

Submuscular Buttock Augmentation With Silicone Implants in 80 Female Patients.

BACKGROUND: Over the past 4 decades, gluteal augmentation has increased enormously in popularity, and numerous techniques have been developed to provide patients with the best possible outcomes. The submuscular technique has been shown to be a reliable option for a broad cohort of patients. OBJECTIVES: The main objective of this retrospective study was to describe the characteristics and clinical outcomes of a group of patients who underwent gluteal augmentation by the submuscular technique. METHODS: A retrospective analysis was conducted on 80 female patients who underwent submuscular gluteal augmentation with silicone implants between August 2019 and May 2022. All of the patients were operated on by the authors of the present study. RESULTS: Information about patient demographics, implants, complications, and treatments was analyzed. Moreover, the satisfaction of the patients was assessed by means of a short survey. The most frequent complication was wound dehiscence. Only 7 patients required surgical revisions, and 2 required isolated antibiotic therapy. All complications were effectively addressed and no implants had to be removed. Furthermore, the retrospective analysis revealed a noteworthy association between the size of the implant and the occurrence of complications. CONCLUSIONS: The submuscular method provides the best aesthetic results and adequate safety for patients. It significantly minimizes the possibility of complications, such as fluid collection due to muscle fiber dissection or implant exposure/extrusion.

A review of wear debris in thumb base joint implants.

AIM: Polymers and metals, such as polyethylene (PE) and cobalt chrome (CoCr), are common materials used in thumb-based joint implants, also known as CMC (Carpometacarpal) arthroplasty. The purpose of this review was to investigate the reported failure modes related to wear debris from these type of materials in CMC implants. The impact of wear debris on clinical outcomes of CMC implants was also examined. Potential adverse wear conditions and inflammatory particle characteristics were also considered. METHOD: A literature search was performed using PRISMA guidelines and 55 studies were reviewed including 49 cohort studies and 6 case studies. Of the 55 studies, 38/55 (69%) focused on metal-on-polyethylene devices, followed by metal-on-metal (35%), and metal-on-bone (4%). RESULTS: The summarized data was used to determine the frequency of failure modes potentially related to wear debris from metals and/or polymers. The most commonly reported incidents potentially relating to debris were implant loosening (7.1%), osteolysis (1.2%) and metallosis (0.6%). Interestingly the reported mechanisms behind osteolysis and loosening greatly varied. Inflammatory reactions, while rare, were generally attributed to metallic debris from metal-on-metal devices. Mechanisms of adverse wear conditions included implant malpositioning, over-tensioning, high loading for active patients, third-body debris, and polyethylene wear-through. No specific examination of debris particle characterization was found, pointing to a gap in the literature. CONCLUSION: This review underscores the types of failure modes associated with wear debris in CMC implants. It was found that failure rates and adverse wear conditions of CMC implants of any design are low and the exact relationship between wear debris and implant incidences, such as osteolysis and loosening remains uncertain. The authors note that further research and specific characterization is required to understand the relationship between debris and implant failure.

IQGAP1-mediated mechanical signaling promotes the foreign body response to biomedical implants.

The aim of this study was to further elucidate the molecular mechanisms that mediate pathologic foreign body response (FBR) to biomedical implants. The longevity of biomedical implants is limited by the FBR, which leads to implant failure and patient morbidity. Since the specific molecular mechanisms underlying fibrotic responses to biomedical implants have yet to be fully described, there are currently no targeted approaches to reduce pathologic FBR. We utilized proteomics analysis of human FBR samples to identify potential molecular targets for therapeutic inhibition of FBR. We then employed a murine model of FBR to further evaluate the role of this potential target. We performed histological and immunohistochemical analysis on the murine FBR capsule tissue, as well as single-cell RNA sequencing (scRNA-seq) on cells isolated from the capsules. We identified IQ motif containing GTPase activating protein 1 (IQGAP1) as the most promising of several targets, serving as a central molecular mediator in human and murine FBR compared to control subcutaneous tissue. IQGAP1-deficient mice displayed a significantly reduced FBR compared to wild-type mice as evidenced by lower levels of collagen deposition and maturity. Our scRNA-seq analysis revealed that decreasing IQGAP1 resulted in diminished transcription of mechanotransduction, inflammation, and fibrosis-related genes, which was confirmed on the protein level with immunofluorescent staining. The deficiency of IQGAP1 significantly attenuates FBR by deactivating downstream mechanotransduction signaling, inflammation, and fibrotic pathways. IQGAP1 may be a promising target for rational therapeutic design to mitigate pathologic FBR around biomedical implants.

Glaucoma management in patients with penetrating keratoplasty or keratoprosthesis.

PURPOSE OF REVIEW: Advances in surgical techniques and postoperative care have significantly improved rates of short-term complications following keratoplasty; however, glaucoma remains a highly prevalent long-term and potentially devastating complication for postkeratoplasty patients. In this review, we provide an overview of recent literature on glaucoma management in patients who have undergone penetrating keratoplasty or the Boston keratoprosthesis type I (KPro) implantation. RECENT FINDINGS: New research suggests an inflammatory cause underlying glaucoma following KPro. Accurate IOP measurement is difficult in patients postkeratoplasty; study of objective techniques such as PDCT or Tono-Pen in penetrating keratoplasty eyes and trans-palpebral Diaton tonometry in KPro eyes have shown promising results. Early glaucoma surgical intervention should be considered for patients undergoing penetrating keratoplasty and KPro. SUMMARY: Patients who have undergone penetrating keratoplasty or implantation of the Boston keratoprosthesis type I should be monitored frequently for elevated intraocular pressure and for other signs of glaucomatous optic nerve damage. Intraocular pressure elevation should be treated promptly either medically or surgically while minimizing risk to the corneal graft. Further research into inflammatory causes and other treatment modalities is promising for the long-term visual success in these patients.