Ultrasonographic Identification of Shell Surface Types in Commercially Available Silicone Gel-Filled Breast Implants.

BACKGROUND: Breast implant safety issues have resulted in the need for global product recalls and medical device tracing. Conventional methods of breast implant tracing, have to date proven to be unsuccessful. This study aims to evaluate the effectiveness of high-resolution ultrasound (HRUS) screening in identifying implanted breast devices. METHODS: Data from 113 female patients undergoing preoperative ultrasound screening for secondary breast surgery between 2019 and 2022 was prospectively reviewed to evaluate the effectiveness of HRUS imaging with the aid of a sonographic surface catalog to identify the surface and brand type of implanted breast devices. To corroborate the findings and assess the reproducibility of the approach, further evaluations were replicated in New Zealand white rabbits and compared with the results found in humans. RESULTS: In the human recipients, implant surface and brand types were correctly identified by ultrasound imaging in 99% (112 of 113) and 96% (69 of 72) of the cases, either consultation-only or revision, respectively. This constituted an overall success rate of 98% (181 of 185). Furthermore, in a corroborating New Zealand white rabbit model where full-scale commercial implants were introduced and monitored over many months, from the total 28 analyzed, the surface was accurately identified in a total of 27 cases (the one failure being before generation of a sonograph surface catalogue), demonstrating an overall success rate of 96.4%. CONCLUSION: HRUS is, therefore, a valid and first-hand tool for breast implant imaging that can correctly evaluate both surface type and brand type alongside other variables such as implant placement, positioning, flipping, or rupture. CLINICAL RELEVANCE STATEMENT: HRUS is a valid and first-hand tool for the identification and traceability of breast implants that evaluates surface type and brand type. This low-cost, accessible, and reproducible practice provides patients with peace of mind and surgeons with a promising diagnostic tool.

Evaluation and comparison of pharmacokinetic profiles and safety of two extended-release buprenorphine formulations in common marmosets (Callithrix jacchus).

While sustained-release buprenorphine (BSR) is used as a long-lasting opioid analgesic in common marmosets (Callithrix jacchus), there are no published studies on pharmaceutical-grade extended-release buprenorphine options such as Ethiqa XR (EXR) for this species. However, BSR is a compounded product and has been reported to cause injection site reactions in multiple species, including marmosets. Additionally, now with the availability of EXR, a pharmaceutical-grade veterinary product, the use of BSR in laboratory animals is not compliant with the Guide for the Care and Use of Laboratory Animals (Guide) unless scientifically justified and approved by the IACUC. We compared pharmacokinetic and safety profiles of BSR (0.15 mg/kg) and EXR (0.1-0.2 mg/kg) administered subcutaneously to adult marmosets. Blood was collected by venipuncture of the saphenous vein at multiple time points (0.25-72 h) and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). EXR between 0.1 and 0.2 mg/kg resulted in a dose-dependent increase in Cmax (1.43-2.51 ng/mL) and were not statistically different from BSR (1.82 ng/mL). Tmax, lambdaz, and t1/2 were not statistically different between formulations. Mean plasma buprenorphine concentrations for BSR and EXR exceeded the therapeutic threshold (0.1 ng/mL) within 0.25 h and lasted for > 72 h. Mild sedation, but neither respiratory depression nor ataxia, was observed for both formulations. BSR injection sites had significantly higher histopathological scores compared to EXR. Video recordings for monitoring drug-induced behavioral changes showed increased animal activity levels after BSR and EXR versus saline controls. Norbuprenorphine, a buprenorphine metabolite associated with respiratory depression, was detected in the plasma after BSR and EXR administration as well as by in vitro liver microsome assays. In conclusion, we recommend using EXR over BSR as a long-lasting buprenorphine analgesic in marmosets because EXR is a pharmaceutical-grade formulation that is compliant with FDA guidelines and the Guide as well as exhibits comparable PK and safety profiles as BSR.

Pharmacokinetics of Single-Dose Intramuscular and Subcutaneous Injections of Buprenorphine in Common Marmosets (Callithrix jacchus).

Although buprenorphine is the most frequently used opioid analgesic in common marmosets (Callithrix jacchus), there is limited information in the literature supporting current dosing regimens used for this species. The purpose of this study was to determine the pharmacokinetic profiles of single-dose buprenorphine HCl administered intramuscularly (IM) at 0.01 mg/kg in 6 adult marmosets (1.8 to 12.8 y old; 2 males, 4 females) and subcutaneously (SQ) at 0.01 mg/kg in 6 adult marmo- sets (2.3-4.4 y old; 3 males, 3 females) by mass spectrometry. Blood was collected at multiple time points from 0.25 to 24 h from unsedated animals following a hybrid sparse-serial sampling design. The maximal observed plasma concentration of buprenorphine (Cmax ) administered IM (2.57 ± 0.95 ng/mL) was significantly higher than administered SQ (1.47 ± 0.61 ng/mL). However, the time to Cmax (Tmax) was not statistically different between routes (17.4 ± 6 min for IM and 19.8 ± 7.8 min for SQ). The time of the last quantifiable concentration of buprenorphine was 5 ± 1.67 h for IM compared with 6.33 ± 1.51 h for SQ, which was not statistically different. The mean buprenorphine plasma concentration-time curves were used to propose a dosing frequency of 4 to 6 h for buprenorphine at 0.01 mg/kg IM or SQ based on a theoretical therapeutic plasma concentration threshold of 0.1 ng/mL. Based on the mean pharmacokinetic parameters and plasma-concentration time curves, both IM and SQ routes of buprenorphine at this dose provide a rapid increase in the plasma concentration of buprenorphine above the therapeutic threshold, and may be more effective for acute rather than long-lasting analgesia. Further studies are needed to examine repeated dosing regimens and the efficacy of buprenorphine in common marmosets.

The surface topography of silicone breast implants mediates the foreign body response in mice, rabbits and humans.

Silicone is widely used in chronic implants and is generally perceived to be safe. However, textured breast implants have been associated with immune-related complications, including malignancies. Here, by examining for up to one year the foreign body response and capsular fibrosis triggered by miniaturized or full-scale clinically approved breast implants with different surface topography (average roughness, 0-90 µm) placed in the mammary fat pads of mice or rabbits, respectively, we show that surface topography mediates immune responses to the implants. We also show that the surface surrounding human breast implants collected during revision surgeries also differentially alters the individual's immune responses to the implant. Moreover, miniaturized implants with an average roughness of 4 µm can largely suppress the foreign body response and fibrosis (but not in T-cell-deficient mice), and that tissue surrounding these implants displayed higher levels of immunosuppressive FOXP3+ regulatory T cells. Our findings suggest that, amongst the topographies investigated, implants with an average roughness of 4 µm provoke the least amount of inflammation and foreign body response.

Endothelial siRNA delivery in nonhuman primates using ionizable low-molecular weight polymeric nanoparticles.

Dysfunctional endothelial cells contribute to the pathophysiology of many diseases, including vascular disease, stroke, hypertension, atherosclerosis, organ failure, diabetes, retinopathy, and cancer. Toward the goal of creating a new RNA-based therapy to correct aberrant endothelial cell gene expression in humans, efficient gene silencing in the endothelium of nonhuman primates was achieved by delivering small interfering RNA (siRNA) with 7C1, a low-molecular weight, ionizable polymer that forms nanoparticles. After a single intravenous administration of 1 mg of siRNA per kilogram of animal, 7C1 nanoparticles delivering Tie2 siRNA caused Tie2 mRNA levels to decrease by approximately 80% in the endothelium of the lung. Significant decreases in Tie2 mRNA were also found in the heart, retina, kidney, pancreas, and bone. Blood chemistry and liver function analysis before and after treatment all showed protein and enzyme concentrations within the normal reference ranges. Furthermore, after controlling for siRNA-specific effects, no significant increases in inflammatory cytokine concentrations were found in the serum. Similarly, no gross lesions or significant underlying pathologies were observed after histological examination of nonhuman primate tissues. This study is the first demonstration of endothelial gene silencing in multiple nonhuman primate organs using systemically administered siRNA nanoparticles and highlights the potential of this approach for the treatment of disease in humans.

Lung Lobe Torsion in an Adult Male Common Marmoset (Callithrix jacchus).

A 6-y-old, intact, pair-housed male common marmoset (Callithrix jacchus) presented with acute onset dyspnea and tachypnea immediately after sedation with alfaxalone; a history of gradual weight loss initiated the examination under sedation. Thoracic radiographs revealed significant right-lung consolidation, with a vesicular gas pattern in the right caudodorsal lung field, pleural effusion, and dorsal displacement of the heart. The marmoset was euthanized due to his unstable condition and poor prognosis. At necropsy, the cranial and middle lobes of the right lung were homogenously dark red-brown, enlarged, edematous, and twisted around the longitudinal axis at the hilus. The left lung lobes were pale pink and slightly edematous. In light of the clinical and gross necropsy findings, acute torsion of the right cranial and middle lung lobes was diagnosed. Predisposing conditions for lung lobe torsion include trauma, neoplasia, pulmonary disease, previous thoracic surgery, and diaphragmatic hernia, but none of these applied to this case. Initial therapy for lung lobe torsion is to stabilize the patient and treat for underlying conditions, with prompt surgical resection as the treatment of choice. To our knowledge, this report is the first description of lung lobe torsion in an experimentally unmanipulated New World NHP.