Tips and Tricks and Clinical Outcome of Cryopreserved Human Amniotic Membrane Application for the Management of Medication-Related Osteonecrosis of the Jaw (MRONJ): A Pilot Study.

Medication-related osteonecrosis of the jaw (MRONJ) is a complication of certain pharmacological treatments such as bisphosphonates, denosumab, and angiogenesis inhibitors. There are currently no guidelines on its management, particularly in advanced stages. The human amniotic membrane (hAM) has low immunogenicity and exerts anti-inflammatory, antifibrotic, antimicrobial, antiviral, and analgesic effects. It is a source of stem cells and growth factors promoting tissue regeneration. hAM acts as an anatomical barrier with suitable mechanical properties (permeability, stability, elasticity, flexibility, and resorbability) to prevent the proliferation of fibrous tissue and promote early neovascularization at the surgical site. In oral surgery, hAM stimulates healing and facilitates the proliferation and differentiation of epithelial cells in the oral mucosa and therefore its regeneration. We proposed using cryopreserved hAM to eight patients suffering from cancer (11 lesions) with stage 2-3 MRONJ on a compassionate use basis. A collagen sponge was added in some cases to facilitate hAM grafting. One or three hAMs were applied and one patient had a reapplication. Three patients had complete closure of the surgical site with proper epithelialization at 2 weeks, and two of them maintained it until the last follow-up. At 1 week after surgery, three patients had partial wound dehiscence with partial healing 3 months later and two patients had complete wound dehiscence. hAM reapplication led to complete healing. All patients remained asymptomatic with excellent immediate significant pain relief, no infections, and a truly positive impact on the patients' quality of life. No adverse events occurred. At 6 months of follow-up, 80% of lesions had complete or partial wound healing (30 and 50%, respectively), while 62.5% of patients were in stage 3. Radiological evaluations found that 85.7% of patients had stable bone lesions (n = 5) or new bone formation (n = 1). One patient had a worsening MRONJ but remained asymptomatic. One patient did not attend his follow-up radiological examination. For the first time, this prospective pilot study extensively illustrates both the handling and surgical application of hAM in MRONJ, its possible association with a collagen sponge scaffold, its outcome at the site, the application of multiple hAM patches at the same time, and its reapplication.

Retrospective study of COVID-19 seroprevalence among tissue donors at the onset of the outbreak before implementation of strict lockdown measures in France.

Background The COVID-19 pandemic has altered organ and tissue donations as well as transplantation practices. SARS-CoV-2 serological tests could help in the selection of donors. We assessed COVID-19 seroprevalence in a population of tissue donors, at the onset of the outbreak in France, before systematic screening of donors for SARS-CoV-2 RNA. Methods 235 tissue donors at the Lille Tissue Bank between November 1, 2019 and March 16, 2020 were included. Archived serum samples were tested for SARS-CoV-2 antibodies using two FDA-approved kits. Results Most donors were at higher risks for severe COVID-19 illness including age over 65 years (142/235) and/or presence of co-morbidities (141/235). According to the COVID-19 risk assessment of transmission, 183 out of 235 tissue donors presented with a low risk level and 52 donors with an intermediate risk level of donor derived infection. Four out of the 235 (1.7%) tested specimens were positive for anti-SARS-CoV-2 antibodies: 2 donors with anti-N protein IgG and 2 other donors with anti-S protein total Ig. None of them had both type of antibodies. Conclusion Regarding the seroprevalence among tissue donors, we concluded that the transmission probability to recipient via tissue products was very low at the beginning of the outbreak.

How to improve donor skin availability: Pragmatic procedures to minimize the discard rate of cryopreserved allografts in skin banking.

BACKGROUND: Microbial contamination of human skin allografts is a frequent cause of allograft discard. Our purpose was to evaluate the discard rate of skin bank contaminated allografts and specific procedures used to reduce allograft contamination without affecting safety. METHODS: We conducted at the Lille Tissue Bank a retrospective study of all deceased donors (n = 104) harvested from January 2018 to December 2018. Skin procurement was split into 3 zones: the back of the body and the two legs that were processed separately. It represented 433 cryopreserved skin allograft pouches of approximatively 500 cm² each. Donors were almost equally split between brain-dead (53%, 55/104) and cadaveric (47%, 49/104) donors. RESULTS: Out of all donors, 42 (40.5%) had at least one sampling zone with a positive microbiological test resulting in 106 (24%) contaminated skin pouches. The contamination rate did not vary according to the harvested zone or type of donor. Traumatic deaths showed significantly less contamination rates than other death types (p < 0.05). Contamination rate decreased with time spent in the antibiotic solution. The risk of having contaminated allografts was five-fold higher when the skin spent less than 96 h in the antibiotic cocktail (p < 0.05). According to our validation protocol, most donors (32/42, 76%) had skin allografts contaminated with bacteria (mainly Staphylococcus spp) compatible with clinical use. No recipient infection was recorded as a result of skin graft contaminated with saprophytic or non-pathogenic germs. By harvesting 3 separate zones per donor, the total surface area for clinical use increased by 53% for contaminated donors. Overall, the proportion of contamination-related discarded allografts was 3.2% (14/433 of pouches). CONCLUSION: Few simple pragmatic measures (including skin incubation in the antibiotic bath for at least 96 h at 4 °C, splitting the skin harvesting areas to minimize the risk of cross-infection and clinical use of allografts contaminated with saprophytic and non-pathogenic germs) can reduce the discard rate of contaminated allografts without affecting clinical safety.

Benefits of cryopreserved human amniotic membranes in association with conventional treatments in the management of full-thickness burns.

The use of split-thickness skin autografts (STSA) with dermal substitutes is the gold standard treatment for third-degree burn patients. In this article, we tested whether cryopreserved amniotic membranes could be beneficial to the current treatments for full-thickness burns. Swines were subjected to standardised full-thickness burn injuries, and then were randomly assigned to treatments: (a) STSA alone; (b) STSA associated with the dermal substitute, Matriderm; (c) STSA plus human amniotic membrane (HAM); and (d) STSA associated with Matriderm plus HAM. Clinical and histological assessments were performed over time. We also reported the clinical use of HAM in one patient. The addition of HAM to classic treatments reduced scar contraction. In the presence of HAM, skin wound healing displayed high elasticity and histological examination showed a dense network of long elastic fibres. The presence of HAM increased dermal neovascularization, but no effect was observed on the recruitment of inflammatory cells to the wound. Moreover, the use of HAM with classical treatments in one human patient revealed a clear benefit in terms of elasticity. These results give initial evidence to consider the clinical application of HAM to avoid post-burn contractures and therefore facilitate functional recovery after deep burn injury.

Direct regulatory immune activity of lactic acid bacteria on Der p 1-pulsed dendritic cells from allergic patients.

BACKGROUND: Lactic acid bacteria (LAB) are suggested to play a regulatory role in the development of allergic reactions. However, their potential effects on dendritic cells (DCs) directing the immune polarization remain unclear. OBJECTIVE: The immunologic effect of Lactobacillus plantarum NCIMB 8826 (LAB1) on monocyte-derived dendritic cells (MD-DCs) from patients allergic to house dust mite was evaluated. METHODS: MD-DCs were stimulated for 24 hours with the related allergen Der p 1 in the presence or absence of LAB1. Cell-surface markers were assessed by means of FACS analysis, and the key polarizing cytokines IL-12 and IL-10 were quantified. The subsequent regulatory effect of pulsed MD-DCs on naive or memory T cells was evaluated by determining the T-cell cytokine profile. RESULTS: LAB1 induced the maturation of MD-DCs, even if pulsed with Der p 1. Interestingly, after incubation with LAB1 and Der p 1, MD-DCs produced higher amounts of IL-12 than Der p 1-pulsed DCs. Indeed, the T H 2 cytokine (IL-4 and IL-5) production observed when naive or memory autologous T cells were cocultured with Der p 1-pulsed MD-DCs was highly reduced in the presence of LAB1. Finally, in contrast to naive or memory T cells exposed once to Der p 1-pulsed DCs, T cells stimulated by MD-DCs pulsed with Der p 1 and LAB1 failed to produce T H 2 cytokines in response to a new stimulation with Der p 1-pulsed DCs. CONCLUSION: Thus in the presence of LAB1, MD-DCs from allergic patients tend to reorientate the T-cell response toward a beneficial T H 1 profile.