Contact allergy to the Dexcom G6 glucose monitoring system-Role of 2,2'-methylenebis(6-tert-butyl-4-methylphenol) monoacrylate in the new adhesive.

BACKGROUND: Skin reactions to the glucose monitoring systems Dexcom G5 and G6 have been rare. In 2019, the components of the adhesive were exchanged for better skin fixation. Since then, more and more patients experienced severe skin reactions. A few months ago, 2,2'-methylenebis(6-tert-butyl-4-methylphenol) monoacrylate (MBPA) was identified as a new component in the adhesive of the G6 model. Furthermore, it was suspected that isobornyl acrylate (IBOA) was also a component of the exchanged adhesive. OBJECTIVES: Our objective was to investigate if MBPA plays a major role in the increasing skin problems of patients without a history of IBOA-sensitization. Furthermore, our aim was to examine whether IBOA is contained in the newer model adhesive and may also contribute to allergic contact dermatitis (ACD). PATIENTS AND METHODS: Five patients with a newly occurred ACD caused by the glucose monitoring system Dexcom G6 were investigated. Patch testing including MBPA in three different concentrations, as well as IBOA, were performed. Gas chromatography-mass spectrometry of the newer system Dexcom G6 was carried out. RESULTS: All patients were shown to be sensitized to MBPA, while MBPA 0,5% showed the strongest reaction. On the other hand, IBOA was tested negative. CONCLUSION: In our study group, MBPA was observed to be the triggering allergen of the recently changed adhesive.

Bare Metal Stents on Resveratrol-Coated Balloons in Porcine Coronary and Peripheral Arteries.

Balloon angioplasty and stent implantation are standard techniques to reopen stenotic vessels. Often, balloons or stents coated with cytostatic drugs are used to prevent re-occlusion of the arteries. Resveratrol, which is known for its numerous beneficial effects on cardiovascular health, is used as an antioxidant additive on paclitaxel-coated balloon catheters. What is still unclear is whether resveratrol-only balloon coating in combination with a bare metal stent (BMS) also has positive effects on vascular healing. Here, we analyzed neointimal thickening, fibrin deposition, inflammation, vasa vasorum density, and reendothelialization after implantation of BMS via a resveratrol coated balloon approach in a porcine model. In general, resveratrol treatment did not result in significantly altered responses compared to the control group in peripheral arteries. In coronary arteries, an increase in vasa vasorum density became evident three days after resveratrol treatment compared to the control group and abolished up to day 7. Significant effects of the resveratrol treatment on the fibrin score or intima-media area were transient and restricted to either peripheral or coronary arteries. In conclusion, local single-dose resveratrol treatment via a resveratrol-only coated balloon and BMS approach did not lead to adverse systemic or local effects, but also no significant beneficial effects on vascular healing were detected in the current study.

Modern diabetes devices for continuous blood sugar measuring: Limitations due to contact allergies.

During the past years, diabetes diseases have increased significantly worldwide. However, new technologies such as continuous glucose measurement using a subcutaneous sensor are developing just as rapidly. A continuous improvement in insulin pump therapy is also contributing to an improved quality of life. A common feature of these modern devices for diabetes therapy is that they remain fixed in place on the skin for several days. In recent years, skin reactions, in particular pronounced contact dermatitis due to the devices and their adhesives have been increasingly reported. In particular, isobornyl acrylate, which used to be included in a glucose measurement sensor set, was identified as a main allergen. Development of contact allergy can result both in a necessity to quit the measuring system and in allergic cross-reactions to other systems.

Skin Reaction Report Form: Development and Design of a Standardized Report Form for Skin Reactions Due to Medical Devices for Diabetes Management.

BACKGROUND: Skin reactions due to medical devices for diabetes management have become a common problem in diabetes technology. There is a varying degree in how detailed skin reactions are described in scientific literature and diabetes practice, and no uniform structured documentation is given. Whereas most articles only describe findings, some others already document final diagnoses, such as contact dermatitis. Furthermore, inconsistent wordings for comparable issues were used. METHODS: A more detailed and standardized documentation, possibly facilitated by a generally accepted guideline for structured descriptions, of skin reactions could be helpful to enable better differentiations between the described skin reactions. Therefore, a report form to assess skin reactions due to medical devices in diabetes therapy was developed and will be presented in this article. RESULTS: The one-page report form is divided into four categories and a separate instruction paper. Beside general information the form includes the location, size, severity and duration of skin appearances, the grading of itching, and suspected diagnoses. CONCLUSION: A consistent use of the form in daily practice and clinical trials could facilitate a fast and standardized documentation and help to evaluate the occurrence and severity of different skin reactions due to medical devices in diabetes management.

The implanted glucose monitoring system Eversense: An alternative for diabetes patients with isobornyl acrylate allergy.

BACKGROUND: Some patients with diabetes develop skin reactions when using systems for continuous glucose monitoring (CGM) or insulin pumps. Regular usage and long wearing periods lead not only to skin irritation, but also to allergic contact dermatitis. It has been shown that allergens such as isobornyl acrylate (IBOA) are present in the plastic housing and also in the adhesives of medical devices used for diabetes treatment. OBJECTIVES: To evaluate the IBOA content of all parts of a newly introduced, implanted CGM system (Eversense) to check whether this can be an alternative for IBOA-sensitized patients. METHODS: The IBOA content of the implanted sensor itself (n = 3), the transmitter (n = 3), and two different types of adhesive (white adhesive [n = 4] and clear adhesive [n = 4]) was measured by gas chromatography/mass spectrometry. RESULTS: No IBOA was found in any part of this CGM system. CONCLUSIONS: Patients with an IBOA allergy may be able to use this implanted CGM system.

Usage of Hydrocolloid-Based Plasters in Patients Who Have Developed Allergic Contact Dermatitis to Isobornyl Acrylate While Using Continuous Glucose Monitoring Systems.

BACKGROUND: Continuous glucose monitoring (CGM) systems replace more and more capillary self-monitoring of blood glucose by patients with diabetes. However, at least a subset of patients experience adverse skin reactions such as severe allergic contact dermatitis (ACD) after prolonged usage of CGM systems. A major allergen isobornyl acrylate (IBOA) has been identified recently. OBJECTIVES: After developing an ACD, patients have difficulties in continuing the usage of their CGM system (and also of, eg, certain patch pumps). Most of such patients look for possibilities to continue the usage of, eg, a CGM system that requires intermittent scanning (iscCGM, Freestyle Libre). PATIENTS AND METHODS: Eight patients with a known ACD were supplied with different hydrocolloid-based plasters (n = 5 with Hansaplast blister plaster, n = 2 with Cutimed Hydro B from BSN, and n = 1 with Stomahesive baseplate from Convatec). They attached these plasters to their skin underneath their iscCGM system. RESULTS: All patients were able to continue the usage of this iscCGM system when using such plasters. CONCLUSION: Patients with ACD benefit from the usage of such plasters; however, some limitations have to be acknowledged.

Documentation of Skin-Related Issues Associated with Continuous Glucose Monitoring Use in the Scientific Literature.

Background: The average wear time of continuous glucose monitoring (CGM) systems steadily increased over the last years. Increased wear times are likely achieved by using adhesives with a longer adherence time, which may have a more pronounced effect on the skin than adhesives with shorter adherence time. Methods: In this project, a structured literature search was performed to assess how potential skin-related issues with CGM usage have been reported in scientific literature in the last 5 years. The literature search was performed with four search terms in the PubMed database. Results: In sum, 279 articles were analyzed. Skin-related issues were mentioned in 19.0% of articles (53 out of 279). With respect to articles mentioning skin-related issues, CGM performance or efficacy was the study's main topic of most of these studies, whereas the minority used CGM as "add-on" to assess other objectives. There was a varying degree in how detailed skin-related issues were described and no uniform structured documentation was given. While some articles only described findings, other articles already documented final diagnoses, such as contact dermatitis. Furthermore, inconsistent wordings for comparable issues were used. The most frequent issues were pain, itching, erythema, bleeding, bruising, and allergic reactions. Conclusion: To draw possible conclusions about the occurrence of skin-related issues during CGM use, more reports about skin-related issues in scientific literature are needed. A more detailed and uniformly structured documentation, possibly facilitated by a generally accepted guideline for structured descriptions, of skin-related issues could be helpful to enable clear differentiations between the described skin reactions.

Evaluation of Isobornyl Acrylate Content in Medical Devices for Diabetes Treatment.

Background: Along with increased usage of continuous glucose monitors, flash glucose monitors, and patch pumps by patients with diabetes, the frequency of skin reactions has also increased. Skin irritation and itching can be annoying to users. However, more serious contact allergies to one or more components of the adhesives or plastic material of the housing of the devices can become lifelong. Redness and itchiness are so strong that patients can no longer use a particular system. In August 2017, a major culprit allergen, isobornyl acrylate (IBOA), was identified for these more serious reactions. Objectives: Our objective was to evaluate IBOA content in different medical products. Methods: The plastic material used for the housing of the Freestyle Libre (n = 3), Dexcom G6 (n = 3), and Enlite (n = 4) was analyzed for IBOA content by gas chromatography-mass spectrometry. Adhesives of the different systems were also analyzed. Results: IBOA was found in the housings of Freestyle Libre and Enlite sensor, but not in the Dexcom G6. Conclusions: Patients with an IBOA allergy should consider switching to a medical product without IBOA. Furthermore, removal of IBOA from devices that contact the skin is encouraged.

Resveratrol-Coated Balloon Catheters in Porcine Coronary and Peripheral Arteries.

Angioplasty aiming at vascular dilatation causes endothelial denudation and induces complex inflammatory responses that affect vascular healing, including delayed reendothelialization and excessive neointima proliferation. Resveratrol is known for multiple beneficial effects on the vessel wall after systemic treatment or sustained release from a stent. It is also used as an additive on drug-coated balloon catheters (DCB). In this study, the effect of a single dose of resveratrol, three days to four weeks after administration as a balloon coating during angioplasty, was investigated. Sixteen pigs underwent angioplasty with resveratrol-coated or uncoated balloon catheters in coronary and peripheral arteries. Vessels were overstretched by approximately 20% to enhance vessel wall injury and to produce persistent vessel wall irritation. A significantly reduced number of micro vessels and macrophages in the adventitia, as well as an improved reendothelialization of the vessel lumen, were observed in resveratrol-treated peripheral arteries. The coronaries had a much higher injury score compared to peripheral vessels. Resveratrol-dependent reduction of macrophages, micro vessels or acceleration of reendothelialization was not evident in the coronary vessels. Additionally, no significant effect on neointima proliferation and inflammation score in either vessel territory was observed as a result of resveratrol treatment. In conclusion, the results suggest that resveratrol diminishes the inflammatory response and promotes vascular healing in peripheral arteries. These same effects are absent in more severely injured coronary arteries.

The Dexcom glucose monitoring system-An isobornyl acrylate-free alternative for diabetic patients.

BACKGROUND: Glucose monitoring systems, for example, Freestyle Libre (Abott) and Dexcom (Nintamed), are increasingly being used instead of conventional blood sugar measurement. However, many patients have experienced adverse skin reactions such as severe allergic contact dermatitis (ACD). Finally, in August 2017, the culprit allergen in Freestyle Libre, isobornyl acrylate (IBOA), was identified. OBJECTIVES: After patients have developed ACD, it is recommended that they no longer use their glucose monitoring systems. Thus, it is important to find an alternative IBOA-free device. PATIENTS AND METHODS: Five patients presented with ACD caused by Freestyle Libre. Each was patch tested with allergens from the baseline series and from a plastics and glues series, and additionally with IBOA 0.1% pet. Gas chromatography-mass spectrometry (GC/MS) of the Freestyle Libre sensor and the Dexcom sensor was performed. The Dexcom sensor remained on the skin of all patients for at least 2 days. RESULTS: All patients were sensitized to IBOA. GC/MS showed the presence of IBOA in the Freestyle Libre sensor, whereas the Dexcom sensor was IBOA-free. None of the patients had skin reactions to the Dexcom sensor. CONCLUSIONS: Patients with Freestyle Libre and IBOA allergy may use the Dexcom sensor as an alternative for glucose monitoring.

Drug Distribution and Basic Pharmacology of Paclitaxel/Resveratrol-Coated Balloon Catheters.

PURPOSE: To experimentally investigate a new homogenously paclitaxel/resveratrol-coated balloon catheter in terms of transport of the coating to the treated tissue and local effects including histology and functional tests. METHODS: Adherence of the coating to the balloon was explored by in vitro simulation of its passage to the lesion. Paclitaxel and resveratrol transfer to the vessel wall was investigated in porcine coronary and peripheral arteries. Matrix-assisted laser desorption/ionization (MALDI) was used for direct microscopic visualization of paclitaxel in arterial tissue. Inhibition of neointimal proliferation and tolerance of complete coating and resveratrol-only coating was investigated in pigs 4 weeks after treatment, and the effect of resveratrol on inflammation and healing after 3 and 7 days. RESULTS: Drug loss on the way to the lesion was < 10% of dose, while 65 ± 13% was detected at the site of balloon inflation. After treatment similar proportions of drug were detected in coronary and peripheral arteries, i.e., 7.4 ± 4.6% of dose or 125 ± 74 ng/mg tissue. MALDI showed circumferential deposition. Inhibition of neointimal proliferation by paclitaxel/resveratrol coating was significant (p = 0.001) whereas resveratrol-only coating did not inhibit neointimal proliferation. During the first week after treatment of peripheral arteries with resveratrol-only balloons, we observed nominally less inflammation and fibrin deposition along with a significant macrophage reduction and more pronounced re-endothelialization. No safety issues emerged including left ventricular ejection fraction for detection of potential distal embolization after high-dose treatment of coronary arteries. CONCLUSIONS: Paclitaxel/resveratrol-coated balloons were effective and safe in animal studies. Beyond acting as excipient resveratrol may contribute to vascular healing.

Further Evidence of Severe Allergic Contact Dermatitis From Isobornyl Acrylate While Using a Continuous Glucose Monitoring System.

In the past decade, new diabetes technologies, including continuous glucose monitoring (CGM) systems, support patients with diabetes in their daily struggle with achieving a good glucose control. However, shortly after the first CGM systems appeared on the market, also the first concerns about adverse skin reactions were raised. Most patients claimed to suffer from (sometimes severe) skin irritation, or even allergy, which they related to the (acrylate-based) adhesive part of the device. For a long time the actual substance that caused these skin reactions with, for example, the Flash Glucose Monitoring system (iscCGM; Freestyle® Libre) could not be identified; however, recently Belgian and Swedish dermatologists reported that the majority of their patients that have developed a contact-allergic while using iscCGM react sensitively to a specific acrylate, that is, isobornyl acrylate (IBOA). Subsequently they showed by means of gas chromatography-mass spectrometry that this substance is present in the case of the glucose sensor attached by an adhesive to the skin. We report three additional cases from Germany, including a 10-year-old boy, suffering from severe allergic contact dermatitis to IBOA.

Protective Function of Ahnak1 in Vascular Healing after Wire Injury.

AIM: Vascular remodeling following injury substantially accounts for restenosis and adverse clinical outcomes. In this study, we investigated the role of the giant scaffold protein Ahnak1 in vascular healing after endothelial denudation of the murine femoral artery. METHODS: The spatiotemporal expression pattern of Ahnak1 and Ahnak2 was examined using specific antibodies and real-time quantitative PCR. Following wire-mediated endothelial injury of Ahnak1-deficient mice and wild-type (WT) littermates, the processes of vascular healing were analyzed. RESULTS: Ahnak1 and Ahnak2 showed a mutually exclusive vascular expression pattern, with Ahnak1 being expressed in the endothelium and Ahnak2 in the medial cells in naïve WT arteries. After injury, a marked increase of Ahnak1- and Ahnak2-positive cells at the lesion site became evident. Both proteins showed a strong upregulation in neointimal cells 14 days after injury. Ahnak1-deficient mice showed delayed vascular healing and dramatically impaired re-endothelialization that resulted in prolonged adverse vascular remodeling, when compared to the WT littermates. CONCLUSION: The large scaffold and adaptor proteins Ahnak1 and Ahnak2 exhibit differential expression patterns and functions in naïve and injured arteries. Ahnak1 plays a nonredundant protective role in vascular healing.

In vivo biocompatibility assessment of poly (ether imide) electrospun scaffolds.

Poly(ether imide) (PEI), which can be chemically functionalized with biologically active ligands, has emerged as a potential biomaterial for medical implants. Electrospun PEI scaffolds have shown advantageous properties, such as enhanced endothelial cell adherence, proliferation and low platelet adhesion in in vitro experiments. In this study, the in vivo behaviour of electrospun PEI scaffolds and PEI films was examined in a murine subcutaneous implantation model. Electrospun PEI scaffolds and films were surgically implanted subcutaneously in the dorsae of mice. The surrounding subcutaneous tissue response was examined via histopathological examination at 7 and 28 days after implantation. No serious adverse events were observed for both types of PEI implants. The presence of macrophages or foreign body giant cells in the vicinity of the implants and the formation of a fibrous capsule indicated a normal foreign body reaction towards PEI films and scaffolds. Capsule thickness and inflammatory infiltration cells significantly decreased for PEI scaffolds during days 7-28 while remaining unchanged for PEI films. The infiltration of cells into the implant was observed for PEI scaffolds 7 days after implantation and remained stable until 28 days of implantation. Additionally some, but not all, PEI scaffold implants induced the formation of functional blood vessels in the vicinity of the implants. Conclusively, this study demonstrates the in vivo biocompatibility of PEI implants, with favourable properties of electrospun PEI scaffolds regarding tissue integration and wound healing. Copyright © 2015 John Wiley & Sons, Ltd.