Clinical presentation and treatment of Macroplastique® urethral exposures: a retrospective case series.

INTRODUCTION AND HYPOTHESIS: Manufacturers of Macroplastique® for urethral bulking have not previously reported exposures as potential complications. This study was aimed at identifying presenting symptoms, management, and outcomes in patients experiencing urethral or bladder exposures. METHODS: A retrospective case series from 2010 to 2019 was performed in an academic affiliated hospital system. Participants were 18-89 years old and received Macroplastique® urethral bulking for treatment of stress urinary incontinence. Charts were identified through diagnosis and procedure codes relating to injections of urethral bulking agents and foreign bodies in the bladder or urethra. Factors evaluated were patient history and presenting symptoms, diagnostic evaluation, treatment, and outcomes using frequency tables for categorical values and statistical distribution with median and interquartile ranges (IQR) for continuous variables. RESULTS: After review of 1,269 charts, 580 cases met the inclusion criteria and 14 Macroplastique® urethral exposures were identified. The median age at first presentation was 73.5 years (IQR57.5-79.7 years) with 48 months (IQR 22-78 months) as the median time to first presentation after last Macroplastique® injection. The median number of injection sessions was 2 (IQR 1-2.75 sessions) with a medium volume of 4.5 ml (IQR 2.75-9.0 ml). Presenting symptoms included urge incontinence (64.3%), stress urinary incontinence (57.1%), recurrent urinary tract infection (42.9%), urinary urgency (28.9%), urinary frequency (28.9%), urinary retention (14.3%), and interrupted flow (7.1%). Macroplastique® urethral exposures were extracted in 10 patients using blunt, sharp, or electrocautery excision. No complications after excision were identified and improvement in urinary symptoms was observed. CONCLUSION: Urethral bulking with Macroplastique® can lead to symptomatic urethral exposures.

Molecular characterization of hematopoietic stem cells after in vitro amplification on biomimetic 3D PDMS cell culture scaffolds.

Hematopoietic stem cell (HSC) transplantation is successfully applied since the late 1950s. However, its efficacy can be impaired by insufficient numbers of donor HSCs. A promising strategy to overcome this hurdle is the use of an advanced ex vivo culture system that supports the proliferation and, at the same time, maintains the pluripotency of HSCs. Therefore, we have developed artificial 3D bone marrow-like scaffolds made of polydimethylsiloxane (PDMS) that model the natural HSC niche in vitro. These 3D PDMS scaffolds in combination with an optimized HSC culture medium allow the amplification of high numbers of undifferentiated HSCs. After 14 days in vitro cell culture, we performed transcriptome and proteome analysis. Ingenuity pathway analysis indicated that the 3D PDMS cell culture scaffolds altered PI3K/AKT/mTOR pathways and activated SREBP, HIF1α and FOXO signaling, leading to metabolic adaptations, as judged by ELISA, Western blot and metabolic flux analysis. These molecular signaling pathways can promote the expansion of HSCs and are involved in the maintenance of their pluripotency. Thus, we have shown that the 3D PDMS scaffolds activate key molecular signaling pathways to amplify the numbers of undifferentiated HSCs ex vivo effectively.

Safety and efficacy of polydimethylsiloxane (Macroplastique®) in women with stress urinary incontinence: analysis of data from patients who completed three years follow-up.

INTRODUCTION AND HYPOTHESIS: This study aimed to report 3-year completed follow-up of the safety and efficacy of Macroplastique® (MPQ) in women with stress urinary incontinence (SUI) due to intrinsic sphincter deficiency (ISD). METHODS: This is a retrospective analysis of all women who completed 3-year follow-up post-MPQ injection(s) at ten medical centers. We used the ROSE registry data report of Macroplastique® [Macroplastique® Real-time Observation of Safety and Effectiveness (ROSE) registry P040050/PAS001 on 2017]. Subjective incontinence outcome and adverse effects were assessed. RESULTS: The study included all patients (n = 70) who completed 3-year follow-up after the last MPQ injection. Twenty-four of 70 (34%) patients had two injections; 21/70 (30%) patients reported Stamey grade 0 and 28/70 (40%) reported Stamey grade 1. The overall patient satisfaction was 68% who completed 3-year follow-up. The composite success rate (I-QoL, PGI-S, and Stamey grade improvement) was 51.4%. No serious adverse events (AE) were reported within the completed 3-year follow-up. CONCLUSIONS: MPQ was found to be safe and efficacious for the treatment of SUI secondary to ISD in women. The overall high satisfaction rate was sustained from baseline to 3 years post-injection. Most complications were minor and transient without sequelae.

Bladder neck and urethral erosions after Macroplastique injections.

AIMS: To evaluate the presentation, risk factors, diagnostic workup, management, and outcomes of Macroplastique (MPQ) erosions. METHODS: We performed a retrospective chart review of women experiencing MPQ erosion at two tertiary care centers (United States and United Kingdom). Data collected included age, presenting symptoms, parity, comorbidities, hormone replacement therapy, sexual activity, and smoking status. Previous surgical history, time from MPQ injection, urine culture results, and cystoscopic and imaging findings were also reviewed. Development of stress urinary incontinence (SUI) after MPQ removal and subsequent SUI treatments were recorded. RESULTS: From 2012 to 2018, 18 patients were identified with a median follow-up time of 24 months (interquartile range [IQR] 8-33). All patients presented with recurrent urinary tract infections (rUTI) and had cystoscopic evidence of MPQ erosion. The most common location of erosion was the bladder neck area (72%). Median time to presentation since MPQ injection was 14 months (IQR 11-35). The majority of patients (72%) had a previous history of anti-incontinence surgery. The overall success rate of endoscopic management defined as resolution of presenting symptoms including rUTI was 80%. The majority of patients (80%) developed recurrent SUI following MPQ resection with 33% requiring a subsequent autologous fascial sling placement. CONCLUSION: MPQ erosions present predominantly with UTI, sometimes years after the original injection, and may necessitate endoscopic management with satisfactory results in most patients. Following excision of MPQ, these patients are highly likely to experience SUI recurrence and need to be appropriately counseled. Some may require additional subsequent autologous fascial sling placement for treatment of their SUI symptoms.

Development and Characterization of A New Dimethicone Nanoemulsion and its Application for Electronic Gastroscopy Examination.

PURPOSE: Although the effective and safe medical defoamers, dimethicone (DM) and simethicone (SM) are widely used in electronic gastroscope examination (EGE), their preparations are presented in the form of suspensions or emulsions, these are untransparent or milk-like in appearance and can easily cause misdiagnosis as a result of an unclear field of vision if the doctor does not master the amount of defoamer or operates incorrectly. At the same time, it is also difficult to wash out the camera and pipeline, due to the large oil droplets of preparations. The purpose of this study was to develop a new clear and transparent oil in water (O/W) DM nanoemulsions (DMNs) and observe the effect of application in EGE. METHODS: The oil phase was chosen for its antifoaming activity and viscosity. The emulsifier and co-emulsifier were selected according to the solubility of the oil phase in them. The water titration method was used to make the pseudoternary phase diagrams of nanoemulsions and optimize the prescription composition. DM-in-water nanoemulsion was prepared by the low energy method and evaluated for appearance, antifoaming ability, droplet size, and stability. The effect of DMNs utilized in EGEs was also observed. RESULTS: The optimal formulation of DMNs contained CRH-40 as an emulsifier, PEG-400 as a co-emulsifier, DM as oil phase with the viscosity of 10 mPa.s, and their proportion was 4.5:4.5:1, respectively. DMNs obtained the average particle size of 67.98 nm with the polydispersity index (PDI) of 0.332, and 57.14% defoaming rate. The result of using an EGE showed that DMNs were superior in comparison to the emulsions with regard to the defoaming effect, visual clarity, and easy cleanup. CONCLUSION: DMNs were found to provide excellent visual clarity to its other preparations. The novel DMNs is a promising substitute for DM emulsions or suspensions in EGEs.

High efficacy of a dimeticone-based pediculicide following a brief application: in vitro assays and randomized controlled investigator-blinded clinical trial.

BACKGROUND: Increasing resistance of head lice against neurotoxic agents and safety concerns have led to the search for treatment alternatives. Dimeticones with a physical mode of action are safe, and bear a reduced risk for the development of resistance. METHODS: We performed in vitro bioassays to assess pediculicidal and ovicidal activities of a new dimeticone-based product, and a randomized controlled clinical trial to assess efficacy, following 10 min application. Of 153 individuals screened, 100 participants with active head louse infestations were randomly assigned to treatment with either a dimeticone-based test product, or a 0.5% permethrin-based reference product (50 participants per group). Participants received two topical applications of either the test (10 min) or reference products (45 min) at days 0 and 7 or 8. Outcome measures included the efficacies of treatment and their safety, as well as global and local tolerability at baseline, and days 1, 7, and 10. RESULTS: After 10 min exposure, all lice treated with the dimeticone test product were classified as non-viable in the in vitro assay. Ovicidal activity after treatment of eggs with the dimeticone test product was 96.8%. In the clinical trial, 96 patients completed all study visits. In the full analysis set (FAS) population, on day 1 after one application, 98% of patients were cured in the test group, as compared to 84% cured in the reference group. All participants in both groups were free of head lice on day 10, following two applications (100% cure rate). In total, 42 adverse events (AEs) in 23 patients of both treatment groups were recorded, with the majority of AEs classified as mild. CONCLUSIONS: We have shown a high level of pediculicidal and ovicidal activity, and clinical efficacy and safety, of a brief application of a new dimeticone-based product. The short application time and reduced risk for the development of resistance are key drivers for improved patients' compliance. TRIAL REGISTRATION: EU Clinical Trials Register EudraCT  2016-004635-20 . Registered 14 November 2016.

Ureteral Obstruction After Endoscopic Treatment of Vesicoureteral Reflux: Does the Type of Injected Bulking Agent Matter?

PURPOSE OF REVIEW: Endoscopic injection of bulking agents for the treatment of vesicoureteral reflux (VUR) has become a therapeutic alternative to antibiotic prophylaxis and ureteral reimplantation. Although considered as a safe and efficient procedure, several studies have reported cases of ureteral obstruction (UO) after endoscopic correction of VUR. This review article evaluates the present VUR literature to estimate the incidence of UO following endoscopic injection of different substances, while also discussing the impact of injection technique and implant volume. RECENT FINDINGS: Twenty-five publications were identified that provided detailed information on 64 females and 32 males (age range, 7 months-48 years) that developed UO after endoscopic treatment of VUR using dextranomer/hyaluronic acid (Dx/HA), polyacrylate polyalcohol (PP), polydimethylsiloxane (PDMS), calcium hydroxyapatite (CaHA), polytetrafluoroethylene (PTFE), or collagen. There was some variation in the reported incidence of UO among these materials: Dx/HA (0.5-6.1%), PP (1.1-1.6%), PDMS (2.5-10.0%), CaHA (1.0%), and PTFE (0.3%). Postoperative UO was described following subureteric transurethral injection (STING), intraureteric hydrodistension implantation technique (HIT), combined HIT/STING and double HIT. The injected volume ranged widely, also depending on the type of bulking agent: Dx/HA (0.3-3.0 mL), PP (0.3-1.2 mL), PDMS (1.0-2.2 mL), CaHA (0.4-0.6 mL), and PTFE (1.5-2.0 mL). The timing of UO varied from immediately after the procedure to 63 months. Over half of patients showed asymptomatic hydroureteronephrosis on follow-up imaging, whereas the remaining presented with symptoms of acute UO or fever. UO remains a rare complication after endoscopic correction of VUR, generally reported in less than 1% of treated cases, which appears to be independent of the injected substance, volume, and technique. However, long-term follow-up is recommended as asymptomatic or delayed UO can occur, potentially leading to deterioration of renal function.

Efficacy and safety of polydimethylsiloxane injection (Macroplastique® ) for the treatment of female stress urinary incontinence: results of a series of 85 patients with ≥3 years of follow-up.

OBJECTIVE: To assess the long-term efficacy and safety of polydimethylsiloxane injection (Macroplastique® , Cogentix Medical, Orangeburg, New York, USA) for the treatment of female stress urinary incontinence (SUI), with a minimum follow-up of 3 years. PATIENTS AND METHODS: This is an observational analytical prospective cohort study conducted in a single uro-gynaecological unit. All consecutive women with urodynamically confirmed pure SUI treated with the Macroplastique procedure, were included. Data regarding patient outcomes (International Consultation on Incontinence Questionnaire-Short Form, Patient Global Impression of Improvement, and patient satisfaction scores), objective cure rates, and adverse events were collected during follow-up. Uni- and multivariable analyses were performed to investigate outcomes. Multiple logistic regression was performed to identify factors involved in the risk of failure of the procedures or recurrence of SUI. RESULTS: In all, 85 women had the Macroplastique procedure. At the 3-year follow-up, all 85 (100%) patients were available for the evaluation. We did not find any significant change in the surgical outcomes during this time. At 3 years after surgery, 42 of 85 patients (49%) declared themselves cured (P = 0.67). Similarly, at the 3-year evaluation, 40 of 85 patients (47%) were objectively cured. There was no significant deterioration of objective cure rates over time (P = 0.3). A history of radical pelvic surgery and a low surgeon's skill were significantly associated with the risk of failure of Macroplastique. The multivariate analysis confirmed these findings; a previous history of radical pelvic surgery and a low surgeon's skill independently predicted the subjective and objective failure of Macroplastique. CONCLUSIONS: The 3-year results of this study showed that Macroplastique could be an acceptable alternative for the treatment of SUI with stable results over time and a negligible complication rate.

Silicone pneumonitis, diffuse alveolar hemorrhage and acute respiratory distress syndrome from gluteal silicone injections.

Fatal complications from illegal cosmetic injection of nonmedical-grade liquid silicone (polydimethylsiloxane) by unlicensed providers are becoming more common. Silicone embolization syndrome (SES) can rapidly progress to pneumonitis and diffuse alveolar hemorrhage. Prompt and aggressive management with high-dose steroids and lung-protective ventilation strategies to minimize acute respiratory distress syndrome (ARDS) can be lifesaving. We present the case of a patient presenting with abdominal pain and shortness of breath who quickly developed respiratory failure. The patient recently had received bilateral gluteal silicone injections from an unlicensed provider.

Periurethral Mass Mimicking Neoplasm After Injection of Macroplastique for Postprostatectomy Stress Incontinence: A Pitfall on 18F-FDG PET/CT.

A 64-year-old man underwent initial F-FDG PET/CT staging for gastric cardia adenocarcinoma, which showed the primary gastric tumor, several bone metastases, and high uptake in a periurethral mass mimicking pelvic neoplasm developed after injection of polydimethylsiloxane (Macroplastique) urethral bulking agent 6 years ago for postprostatectomy stress urinary incontinence. This case showed a very rare complication of silicon particle injection therapy, and the intense uptake is likely due to granulomatous reaction around the implant.

Filler migration and extensive lesions after lip augmentation: Adverse effects of polydimethylsiloxane filler.

Polydimethylsiloxane (PDMS), also called liquid silicone, belongs to a group of polymeric compounds that are commonly referred to as silicones. These filling agents have been used as injectable filler for soft tissue augmentation. There are limited experiences about management of the severe complications related to filler migration associated with PDMS injection. We present a 35-year-old female with severe erythema, edema over her cheeks and neck, and multiple irregularities following cosmetic lip augmentation with PDMS. Further studies are required for management of this complicated case of PDMS injection.

Assessment of Efficacy and Irritation of Ingenol Mebutate Gel 0.015% Used With or Without Dimethicone Lotion for Treatment of Actinic Keratosis on the Face.

Background: Ingenol mebutate gel 0.015% provides high clearance rates for actinic keratosis (AK) on the face and scalp but causes transient local skin responses (LSRs).

Objective: This study sought to determine whether the application of 1% dimethicone would decrease ingenol mebutate-associated LSRs and/or affect efficacy during the treatment of multiple AKs on the face.

Methods: Ingenol mebutate gel 0.015% was applied for 3 days to two 25 cm2 areas, each containing 3 to 8 AKs on the face of each subject, followed by application of 1% dimethicone lotion in an investigator-blinded manner to one randomly selected AK-containing area until LSRs were no longer present.

Results: In total, 20 subjects were enrolled and completed the study. Topical 1% dimethicone lotion applied during and after treatment of facial AK with ingenol mebutate gel 0.015% reduced mean total LSR scores at days 8 and 15 compared with ingenol mebutate gel only, although the difference was not statistically significant. Efficacy was equivalent between the two treatment arms.

Limitations: The study evaluated a relatively small number of subjects, all of whom were white.

Conclusions: The application of 1% dimethicone following ingenol mebutate gel 0.015% produced a trend toward lower severity of some LSRs, with no difference in efficacy.

J Drugs Dermatol. 2017;16(5):432-436.

Cytotoxicity of GuttaFlow Bioseal, GuttaFlow2, MTA Fillapex, and AH Plus on Human Periodontal Ligament Stem Cells.

INTRODUCTION: The aim of the present study was to evaluate the in vitro cytotoxicity of endodontic sealers (GuttaFlow Bioseal, GuttaFlow2, and MTA Fillapex) on human periodontal ligament stem cells (hPDLSCs). As a reference, AH Plus was compared with the more recent endodontic sealers regarding cell viability and cell attachment. METHODS: Biological testing was carried out in vitro on hPDLSCs. Cell viability assay was performed by using eluates from each endodontic sealer. To assess cell morphology and attachment to the different sealers, the hPDLSCs were directly seeded onto the material surfaces and analyzed by scanning electron microscopy. Chemical composition of the sealers was determined by energy-dispersive x-ray, and eluates were analyzed by inductively coupled plasma mass spectrometry. Statistical differences were assessed by analysis of variance and Tukey test (P < .05). RESULTS: Cell viability was evident after 24 hours in the presence of GuttaFlow Bioseal and GuttaFlow 2 but not in the case of AH Plus or MTA Fillapex. At 168 hours, GuttaFlow Bioseal and GuttaFlow 2 exhibited high and moderate cell viability, respectively, whereas AH Plus and MTA Fillapex revealed low rates of cell cell viability (P < .001). Finally, scanning electron microscopy studies revealed a high degree of proliferation, cell spreading, and attachment, especially when using GuttaFlow Bioseal disks. CONCLUSIONS: GuttaFlow Bioseal and GuttaFlow2 showed lower cytotoxicity than MTA Fillapex and AH plus. Further in vitro and in vivo investigations are required to confirm the suitability of GuttaFlow Bioseal for clinical application.

Para-Urethral Injections with Urolastic® for Treatment of Female Stress Urinary Incontinence: Subjective Improvement and Safety.

INTRODUCTION: Female stress urinary incontinence (SUI) is often treated surgically. Urethral bulking agents are a minimally invasive alternative, especially in patients suffering from intrinsic sphincter deficiency, but often with limited long-term efficacy. Urolastic® is a non-deformable, non-resorbable silicone elastomer that is used as an injectable. Its properties might result in a more durable response after injection. If this durability factor can be combined with a low complication rate, this can become a useful treatment option. We therefore assessed the subjective improvement and safety after treatment with Urolastic®. MATERIALS AND METHODS: In 2 Dutch hospitals, 65 patients were treated with Urolastic®. The subjective improvement was assessed and the medical charts were reviewed for complications that appeared during the follow-up period. The complications were classified using the Clavien-Dindo classification. RESULTS: We found that 76-88% of the patients showed subjective improvement at 12-25 months follow-up. The rate of improvement experienced was 50-70%. The rate of complications classified as Clavien-Dindo >II was 24-33%. The 12 patients with 75-100% subjective improvement after 2 months, showed 85% improvement after a median of 25 months. CONCLUSIONS: With careful patient selection, Urolastic® seems to be a safe, durable and effective treatment option for female SUI.

Two Cases of Suspected Rejection of Polydimethylsiloxane Urethral Bulking Agent.

We report the cases of 2 women who had urethral bulking injections with polydimethylsiloxane for stress urinary incontinence with intrinsic sphincter deficiency and reported initial improvement of symptoms followed by rapid return of stress urinary incontinence several weeks later associated with extrusion of the bulking material. We hypothesize this unique adverse outcome could represent immune rejection of this urethral bulking agent.

Nonabsorbable urethral bulking agent - clinical effectiveness and late complications rates in the treatment of recurrent stress urinary incontinence after 2 years of follow-up.

OBJECTIVE: Those patients who failed to achieve continence after a procedure aimed to correct it, require a special attitude and precise management due to the sophisticated anatomical and functional field of interest. The purpose of the present study was to assess long-term clinical efficacy and evaluate the frequency and severity of any complications related to recurrent stress urinary incontinence treatment with a non-absorbable bulking agent periurethral injections. STUDY DESIGN: Between February 2012-September 2013, 66 patients with recurrent stress urinary incontinence were treated with Urolastic in the tertiary referral gynecologic department. The efficacy of the procedure was assessed objectively at each follow-up visit, scheduled at two, six weeks and 3, 6, 12 and 24 months after primary procedure. Material was injected under local anesthesia according to the manufacturer's instructions, at 10, 2, 4 and 8 o'clock positions with 0.5-1.25ccm per spot. Statistical analyses were performed with Statistica package version 8.0 (StatSoft Inc., Tulsa, OK, USA). A p value <0.05 was considered statistically significant. RESULTS: Objective success rate at 24 months was found in 32.7% of patients, including 22.4% patients who were completely dry. The efficacy of Urolastic, when considering the intention to treat, is 24.2% and 16.7%, respectively. In 4.5% patients an oval shaped material was found inside the bladder. Overall, complications were observed in 17 (25.8%) patients. CONCLUSIONS: Although only 30% of patients will benefit from Urolastic injection on the long-term basis it seems to be a safe procedure in the treatment of recurrent stress urinary incontinence.

Inflammatory responses of primary human dendritic cells towards polydimethylsiloxane and polytetrafluoroethylene.

Although frequently used as implants materials, both polydimethylsiloxane (PDMS) and polytetrafluoroethylene (PTFE) are often associated with adverse effects including foreign body responses. Dendritic cells (DC) are crucial for the initiation of immune reactions and could also play a role in foreign body associated inflammations. Therefore, the interaction of DC with PDMS and PTFE was investigated regarding their capacity to induce undesired cell activation. Medical grade PDMS and PTFE films were embedded into polystyrene PS inserts via injection molding to prevent the DC from migrating below the substrate and thereby, interacting not only with the test sample but also with the culture vessel material. The viability, the expression of co-stimulatory molecules, and the cytokine/chemokine profiles were determined after 24 hours incubation of the DC with PDMS or PTFE. Blank PS inserts and tissue culture polystyrene (TCP) served as reference materials. The viability of DC was not substantially influenced after incubation with PDMS and PTFE. However, both polymers induced DC activation indicated by the upregulation of co-stimulatory molecules. The release profiles of 14 soluble inflammatory mediators showed substantial differences between PDMS, PTFE, PS, and TCP. This study showed the potential of PTFE and PDMS to activate primary human dendritic cells, which could be an explanation for the often observed inflammatory events associated with the implantation of these polymers.