Conservative surgical approach towards placenta accreta spectrum disorders for uterine preservation.

OBJECTIVE: We previously described a technique for repair of the myometrial defect at repeat Caesarean section which increases residual myometrial thickness thereby potentially reducing future niche-related complications. Here we describe how this technique can be modified for use for placenta accreta spectrum disorders, in line with emerging evidence that this is more a disorder of myometrial deficiency than morbid adherence. DESIGN: The surgical performance of peripartum hysterectomy was compared with that of the modified technique in all women having repeat Caesarean delivery for placenta accreta spectrum disorder in a tertiary unit in Singapore between December 2019 and October 2021. METHODS: Modification of the original technique involved the systematic delivery of the placenta starting from its most posterior attachment after uterine exteriorization. This is followed by the identification, mobilization, and apposition of the boundaries of myometrial defects as described previously. RESULTS: Ten women had Caesarean hysterectomy and ten had Caesarean section using the modified approach. Age and gestational age at delivery were similar for the two groups. Women in the modified technique group had had fewer prior Caesarean sections and had a lower body mass index. Operating time, estimated blood loss and need for transfusion were all lower in the myometrial repair group but without statistical significance. There were no visceral injuries in the repair group but there was one bladder injury in the hysterectomy group. CONCLUSION: The modified approach provides an effective alternative to peripartum hysterectomy with favourable surgical profile and allows uterine conservation with restoration of myometrial thickness.

A comparison of in vitro cytotoxicity assays in medical device regulatory studies.

Medical device biocompatibility testing is used to evaluate the risk of adverse effects on tissues from exposure to leachates/extracts. A battery of tests is typically recommended in accordance with regulatory standards to determine if the device is biocompatible. In vitro cytotoxicity, a key element of the standards, is a required endpoint for all types of medical devices. Each validated cytotoxicity method has different methodology and acceptance criteria that could influence the selection of a specific test. In addition, some guidances are more specific than others as to the recommended test methods. For example, the International Organization for Standardization (ISO1) cites preference for quantitative methods (e.g., tetrazolium (MTT/XTT), neutral red (NR), or colony formation assays (CFA)) over qualitative methods (e.g., elution, agar overlay/diffusion, or direct), while a recent ISO standard for contact lens/lens care solutions specifically requires a qualitative direct test. Qualitative methods are described in United States Pharmacopeia (USP) while quantitative CFAs are listed in Japan guidance. The aim of this review is to compare the methodologies such as test article preparation, test conditions, and criteria for six cytotoxicity methods recommended in regulatory standards in order to inform decisions on which method(s) to select during the medical device safety evaluation.

A review of the surgical management of heel pressure ulcers in the 21st century.

Heel ulceration, most frequently the result of prolonged pressure because of patient immobility, can range from the trivial to the life threatening. Whilst the vast majority of heel pressure ulcers (PUs) are superficial and involve the skin (stages I and II) or underlying fat (stage III), between 10% and 20% will involve deeper tissues, either muscle, tendon or bone (stage IV). These stage IV heel PUs represent a major health and economic burden and can be difficult to treat. The worst outcomes are seen in those with large ulcers, compromised peripheral arterial supply, osteomyelitis and associated comorbidities. Whilst the mainstay of management of stage I-III heel pressure ulceration centres on offloading and appropriate wound care, successful healing in stage IV PUs is often only possible with surgical intervention. Such intervention includes simple debridement, partial or total calcanectomy, arterial revascularisation in the context of coexisting peripheral vascular disease or using free tissue flaps. Amputation may be required for failed surgical intervention, or as a definitive first-line procedure in certain high-risk or poor prognosis patient groups. This review provides an overview of heel PUs, alongside a comprehensive literature review detailing the surgical interventions available when managing such patients.

Design and development of an in vitro tear replenishment system.

Understanding the cellular and molecular mechanisms of the corneal tissue and translating them into effective therapies requires organotypic culture systems that can better model the physiological conditions of the front of the eye. Human corneal in vitro models currently exist, however, the lack of tear replenishment limits corneal in vitro models' ability to accurately simulate the physiological environment of the human cornea. The tear replenishment system (TRS), a micro-fluidic device, was developed to mimic the in vivo tear replenishment in the human eye in an in vitro corneal model. The TRS is capable of generating adjustable intermittent flow from 0.1 µL in every cycle. The TRS is a sterilizable device that is designed to fit standard 6-well cell culture plates. Experiments with the corneal models demonstrated that exposure to the TRS did not damage the integrity of the stratified cell culture. Contact lenses "worn" by the in vitro corneal model also remained moist at all times and the cytotoxicity of BAK could also be verified using this model. These in vitro results confirmed that the TRS presents novel avenues to assess lens-solution biocompatibility and drug delivery systems in a physiologically relevant milieu.

Development of a curved, stratified, in vitro model to assess ocular biocompatibility.

PURPOSE: To further improve in vitro models of the cornea, this study focused on the creation of a three-dimensional, stratified, curved epithelium; and the subsequent characterization and evaluation of its suitability as a model for biocompatibility testing. METHODS: Immortalized human corneal epithelial cells were grown to confluency on curved cellulose filters for seven days, and were then differentiated and stratified using an air-liquid interface for seven days before testing. Varying concentrations of a commercial ophthalmic solution containing benzalkonium chloride (BAK), a known cytotoxic agent, and two relevant ocular surfactants were tested on the model. A whole balafilcon A lens soaked in phosphate buffered saline (BA PBS) was also used to assess biocompatibility and verify the validity of the model. Viability assays as well as flow cytometry were performed on the cells to investigate changes in cell death and integrin expression. RESULTS: The reconstructed curved corneal epithelium was composed of 3-5 layers of cells. Increasing concentrations of BAK showed dose-dependent decreased cell viability and increased integrin expression and cell death. No significant change in viability was observed in the presence of the surfactants. As expected, the BA PBS combination appeared to be very biocompatible with no adverse change in cell viability or integrin expression. CONCLUSIONS: The stratified, curved, epithelial model proved to be sensitive to distinct changes in cytotoxicity and is suitable for continued assessment for biocompatibility testing of contact lenses. Our results showed that flow cytometry can provide a quantitative measure of the cell response to biomaterials or cytotoxic compounds for both the supernatant and adherent cell populations. As a specifically designed in vitro model of the corneal epithelium, this quantitative model for biocompatibility at the ocular surface may help improve our understanding of cell-material interactions and reduce the use of animal testing.