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Item Histoplasmosis in Solid Organ Transplantation(MDPI, 2024-02-02) Barros, Nicolas; Wheat, L. Joseph; Medicine, School of MedicineHistoplasma capsulatum, the etiological agent for histoplasmosis, is a dimorphic fungus that grows as a mold in the environment and as a yeast in human tissues. It has a broad global distribution with shifting epidemiology during recent decades. While in immunocompetent individuals infection is usually self-resolving, solid organ transplant recipients are at increased risk of symptomatic disease with dissemination to extrapulmonary tissue. Diagnosis of histoplasmosis relies on direct observation of the pathogen (histopathology, cytopathology, and culture) or detection of antigens, antibodies, or nucleic acids. All transplant recipients with histoplasmosis warrant therapy, though the agent of choice and duration of therapy depends on the severity of disease. In the present article, we describe the pathogenesis, epidemiology, clinical manifestations and management of histoplasmosis in solid organ transplant recipients.Item A Large-Scale Bank of Organ Donor Bone Marrow and Matched Mesenchymal Stem Cells for Promoting Immunomodulation and Transplant Tolerance(Frontiers Media, 2021-02-26) Johnstone, Brian H.; Messner, Franka; Brandacher, Gerald; Woods, Erik J.; Medical and Molecular Genetics, School of MedicineInduction of immune tolerance for solid organ and vascular composite allografts is the Holy Grail for transplantation medicine. This would obviate the need for life-long immunosuppression which is associated with serious adverse outcomes, such as infections, cancers, and renal failure. Currently the most promising means of tolerance induction is through establishing a mixed chimeric state by transplantation of donor hematopoietic stem cells; however, with the exception of living donor renal transplantation, the mixed chimerism approach has not achieved durable immune tolerance on a large scale in preclinical or clinical trials with other solid organs or vascular composite allotransplants (VCA). Ossium Health has established a bank of cryopreserved bone marrow (BM), termed “hematopoietic progenitor cell (HPC), Marrow,” recovered from deceased organ donor vertebral bodies. This new source for hematopoietic cell transplant will be a valuable resource for treating hematological malignancies as well as for inducing transplant tolerance. In addition, we have discovered and developed a large source of mesenchymal stem (stromal) cells (MSC) tightly associated with the vertebral body bone fragment byproduct of the HPC, Marrow recovery process. Thus, these vertebral bone adherent MSC (vBA-MSC) are matched to the banked BM obtained from each donor, as opposed to third-party MSC, which enhances safety and potentially efficacy. Isolation and characterization of vBA-MSC from over 30 donors has demonstrated that the cells are no different than traditional BM-MSC; however, their abundance is >1,000-fold higher than obtainable from living donor BM aspirates. Based on our own unpublished data as well as reports published by others, MSC facilitate chimerism, especially at limiting hematopoietic stem and progenitor cell (HSPC) numbers and increase safety by controlling and/or preventing graft-vs.-host-disease (GvHD). Thus, vBA-MSC have the potential to facilitate mixed chimerism, promote complementary peripheral immunomodulatory functions and increase safety of BM infusions. Both HPC, Marrow and vBA-MSC have potential use in current VCA and solid organ transplant (SOT) tolerance clinical protocols that are amenable to “delayed tolerance.” Current trials with HPC, Marrow are planned with subsequent phases to include vBA-MSC for tolerance of both VCA and SOT.Item Mpox Perceptions and Vaccine Advocacy among the Healthcare Workers of Solid Organ Transplant Centers: A Multicenter, Cross-Sectional Survey in Saudi Arabia(MDPI, 2023-02-17) Alhasan, Khalid; Sallam, Malik; Aljamaan, Fadi; Ali, Tariq; Al-jedai, Ahmed; Nazmi, Ahmed; Ajlan, Aziza; Aleid, Hassan; Karar, Enaam; Al-Awwami, Moheeb; Almojalli, Hamad; Shah, Yaser Zahir; Mohammed, Amir Eltayeb Ismail; Barry, Mazin; Alsubaie, Sarah; Altheaby, Abdulrahman; Almaghrabi, Reem S.; Askandarani, Sumayah; Memish, Ziad A.; Al-Tawfiq, Jaffar A.; Broering, Dieter Clemens; Temsah, Mohamad-Hani; Medicine, School of MedicineBackground: In response to the global Mpox outbreaks, this survey aimed to assess the knowledge, perceptions, and advocacy of Mpox vaccines among solid organ transplant healthcare workers (HCWs) in Saudi Arabia. Methods: A cross-sectional survey was conducted among solid organ transplant HCWs in Saudi Arabia from 15 August to 5 September 2022. A total of 199 responses were received from participants primarily working in the kidney (54.8%) and liver (14.6%) transplant units. Results: The survey found that most participants were aware of the 2022 Mpox outbreak, but the majority were more concerned about COVID-19 than Mpox. While the majority of participants thought laboratory personnel and HCWs in direct contact with Mpox patients should receive the vaccine, less than 60% believed that all HCWs should be vaccinated. Additionally, over half of the participants lacked knowledge of animal-human transmission of the virus. Conclusion: The results highlight the need for increased education on Mpox among transplant HCWs in Saudi Arabia, particularly regarding the virus's transmission dynamics and vaccines. This education is crucial to improve HCWs' understanding of this emerging disease, especially given their vulnerability during the COVID-19 pandemic.Item Strongyloides stercoralis Infection in Solid Organ Transplant Patients Is Associated With Eosinophil Activation and Intestinal Inflammation: A Cross-sectional Study(Oxford University Press, 2020-12) Clark, Eva; Pritchard, Haley; Hemmige, Vagish; Restrepo, Alejandro; Bautista, Karla; Damania, Ashish; Ricciardi, Alessandra; Nutman, Thomas B.; Mejia, Rojelio; Medicine, School of MedicineBackground: Strongyloidiasis can cause devastating morbidity and death in immunosuppressed patients. Identification of reliable biomarkers for strongyloidiasis in immunosuppressed patients is critical for the prevention of severe disease. Methods: In this cross-sectional study of solid organ transplant (SOT) candidates and recipients, we quantified Strongyloides-specific IgG to the recombinant NIE-Strongyloides antigen and/or to a soluble extract of S. stercoralis somatic antigens ("crude antigen") using enzyme-linked immunosorbent assays (ELISAs). We also measured peripheral eosinophilia, 4 different eosinophil granule proteins, and intestinal fatty acid-binding protein (IFABP). Results: We evaluated serum biomarkers in 149 individuals; 77 (52%) pre-SOT and 72 (48%) post-SOT. Four percent (6/149) tested positive by NIE ELISA and 9.6% (11/114) by crude antigen ELISA (overall seropositivity of 9.4% [14/149]). Seropositive patients had higher absolute eosinophil counts (AECs) than seronegative patients (P = .004). AEC was positively correlated to the levels of eosinophil granule proteins eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO) (P < .05), while IFABP was positively related to the 2 other eosinophil granule proteins (major basic protein [MBP] and eosinophil-derived neurotoxin [EDN]; Spearman's r = 0.3090 and 0.3778, respectively; P < .05; multivariate analyses slopes = 0.70 and 2.83, respectively). Conclusions: This study suggests that, in SOT patients, strongyloidiasis triggers both eosinophilia and eosinophil activation, the latter being associated with intestinal inflammation. These data provide insight into the pathogenesis of S. stercoralis infection in the immunocompromised population at high risk of severe strongyloidiasis syndromes.