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Allogeneic hematopoietic stem cell transplantation (alloSCT) is the cornerstone treatment for various hematopoietic disorders, but its utility is often compromised by chronic graft-versus-host disease (cGvHD), affecting skin integrity and leading to ulcer formations. Traditional treatments, including systemic and topical therapies, frequently fail in severe cases. This study retrospectively examines three patients with therapy-resistant ulcers due to cGvHD post-alloSCT treated at the University Hospital of Regensburg in 2023. We evaluated the therapeutic impact of human amniotic membrane (hAM) transplantation-a novel approach utilizing hAM's anti-inflammatory, anti-microbial, and anti-fibrotic properties for wound healing. Surgical debridement was followed by hAM application and routine follow-up. HAM transplantation led to complete wound closure in two out of three patients and a significant reduction in local pain and infection rates. The treatment alleviated the need for regular dressing changes within three months in two patients, demonstrating the hAM's efficacy in fostering rapid and sustained healing. The utilization of hAM represents a promising alternative for the management of refractory skin ulcers in cGvHD patients, particularly when conventional methods are inadequate.
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BACKGROUND: Late-stage pressure sore (PS) patients are particularly susceptible to osteomyelitis (OM), as bony prominences commonly constitute the focal point of the ulcer. There are lack of data regarding the associated factors and the clinical relevance of this diagnosis in the context of PS treatment. METHODS: This retrospective analysis investigated the clinical characteristics, blood markers indicative of infection in PS patients, and development of histologically evident OM. A total of 125 patient were included from 2014 to 2019. The patient records were especially scanned for histological diagnosis of OM. RESULTS: OM was detected in 39% (37/96) of the samples taken during the index procedure. OM prevalence increased to 56% (43/77) at the second and 70% (41/59) at the third debridement. Therefore, the diagnosis of OM was acquired during treatment in 35 cases. Patients diagnosed with initial OM presented significantly higher blood markers, indicative of infection upon admission. Only patients with consistent OM (three positive biopsies) showed higher flap revision rates. CONCLUSION: This study found no compelling evidence linking OM to worse clinical outcomes in PS patients. In the absence of elevated inflammatory markers, reducing bone biopsy frequency and adopting a less aggressive bone debridement approach may help prevent OM in PS patients.
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Introduction: Glutamine deficiency is a well-known feature of the tumor environment. Here we analyzed the impact of glutamine deprivation on human myeloid cell survival and function. Methods: Different types of myeloid cells were cultured in the absence or presence of glutamine and/or with L-methionine-S-sulfoximine (MSO), an irreversible glutamine synthetase (GS) inhibitor. GS expression was analyzed on mRNA and protein level. GS activity and the conversion of glutamate to glutamine by myeloid cells was followed by 13C tracing analyses. Results: The absence of extracellular glutamine only slightly affected postmitotic human monocyte to dendritic cell (DC) differentiation, function and survival. Similar results were obtained for monocyte-derived macrophages. In contrast, proliferation of the monocytic leukemia cell line THP-1 was significantly suppressed. While macrophages exhibited high constitutive GS expression, glutamine deprivation induced GS in DC and THP-1. Accordingly, proliferation of THP-1 was rescued by addition of the GS substrate glutamate and 13C tracing analyses revealed conversion of glutamate to glutamine. Supplementation with the GS inhibitor MSO reduced the survival of DC and macrophages and counteracted the proliferation rescue of THP-1 by glutamate. Discussion: Our results show that GS supports myeloid cell survival in a glutamine poor environment. Notably, in addition to suppressing proliferation and survival of tumor cells, the blockade of GS also targets immune cells such as DCs and macrophages.
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The good availability and the large content of adult stem cells in adipose tissue has made it one of the most interesting tissues in regenerative medicine. Although lipofilling is one of the most frequent procedures in plastic surgery, the method still struggles with high absorption rates and volume losses of up to 70%. Therefore, many efforts have been made to optimize liposuction and to process the harvested tissue in order to increase fat graft retention. Because of their immunomodulatory properties, their cytokine secretory activity, and their differentiation potential, enrichment with adipose tissue-derived stem cells was identified as a promising tool to promote transplant survival. Here, we review the important parameters for lipofilling optimization. Finally, we present a new method for the enrichment of lipoaspirate with adipose tissue-derived stem cells and discuss the parameters that contribute to fat graft survival.