Interdisciplinary Healthcare Team Experience of Carboplatin and Oxaliplatin Desensitizations in a Tertiary Referral University Hospital.

Purpose: Repeated exposure to platinum compounds increases the risk of immunoglobulin E-mediated immediate hypersensitivity reactions (HSR). To date, many different desensitization protocols with varying success rates have been reported. The presented study is aimed at disseminating the real-world experience of an interdisciplinary healthcare team focusing on platin desensitization. Patients and Methods: This is a cross-sectional, retrospective study of 7 female patients with carboplatin- or oxaliplatin-induced HSRs. After a discussion with the oncologist and the patient, desensitization protocols were performed by a team consisting of an allergy and immunology specialist, a clinical pharmacist, and a nurse. Clinical data were extracted from the patients' medical records, and HSRs were reviewed and classified by an allergist according to severity and type. Results: Twenty-five desensitization protocols were carried out for patients with carboplatin- or oxaliplatin-induced HSRs (N=4 and N=3, respectively; age range: 54-66). Two of the patients did not experience any HSR during a total of 8 desensitization cycles. The other patients had grade 1-3 HSRs on 15 cycles, which were successfully managed by oxygen and/or pharmacological interventions and infusions were resumed at a lower rate after stabilization of the patient. Compared to baseline, serum tryptase levels were elevated during HSRs (4.77±0.21 vs 9.50±1.71, P=0.028). Conclusion: All the patients were able to finish the treatment protocol and receive full chemotherapeutic doses. Interdisciplinary teams may facilitate the preparation and administration of platinum-based chemotherapeutics and increase the success rates of desensitization protocols for platin-based chemotherapy, where the concentration and application of drugs differ from standard procedure.

Age-related changes in the immunomodulatory effects of human dental pulp derived mesenchymal stem cells on the CD4+ T cell subsets.

Mesenchymal stem cells (MSCs) are powerful immunomodulatory cells. The effects of the aging on these abilities of MSCs have not been adequately clarified. In this study, alterations in immunomodulatory abilities of MSCs caused by aging were investigated. For this, dental pulp (DP) MSCs and peripheral blood mononuclear cells (PBMCs) of elderly and young donors were co-cultured age-matched and cross. We detected that the effects of DP-MSCs on Th1 and Th2 cells and their specific cytokines IFN-γ and IL-4 are not affected by aging. However, we observed that young and elderly DP-MSCs have different effects on Th17 and Treg cells. Th17 frequencies of young and elderly PBMCs were significantly increased only by young DP-MSCs, in contrast, Treg frequencies were significantly increased by elderly DP-MSCs. IL-6, IL-17a and HGF levels of both young and elderly PBMCs showed a significant increase only by young DP-MSCs, but TGF-ß levels were significantly increased only by elderly DP-MSCs. The oral cavity is home to a rich microflora. The interactions of dental tissues with this microflora can lead them to acquire different epigenetic modifications. Aging can affect the microflora composition of the oral cavity and change this process in different directions. According to our findings, DP-MSCs are effective cells in the regulation of CD4+ T cells, and their effects on Th1 and Th2 cells were not affected by aging. However, pleiotropic molecules IL-6 and HGF expressions, which are important in dental and bone tissue regeneration, decreased significantly in elderly DP-MSCs. This situation may have indirectly made a difference in the modulation effects of young and elderly DP-MSCs on the Th17 and Treg cells.

Necrotizing Fasciitis in Paroxysmal Nocturnal Hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, progressive, and life-threatening hematopoietic stem cell disorder characterized by complement-mediated intravascular hemolysis and a prothrombotic state. Patients with PNH might have slightly increased risk of infections due to complement-associated defects subsequent to CD59 deficiency. Here, we report a rare case of a 65-year-old male patient with necrotic ulcers on both legs, where the recognition of pancytopenia and microthrombi led to the diagnosis of PNH based on FLAER (FLuorescent AERolysin) flow cytometric analysis. He was subsequently started on eculizumab therapy, with starting and maintenance doses set as per drug labelling. Progression of the patient's leg ulcers during follow-up, with fulminant tissue destruction, purulent discharge, and necrotic patches, led to a later diagnosis of necrotizing fasciitis due to Pseudomonas aeruginosa and Klebsiella pneumonia infection. Courses of broad-spectrum antibiotics, surgical debridement, and superficial skin grafting were applied with successful effect during ongoing eculizumab therapy. This case highlights the point that it is important to maintain treatment of underlying disorders such as PNH in the presence of life-threatening infections like NF.