Browsing by Subject "Organ Transplantation"
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Item Open Access Bacteremia in solid organ transplant recipients as compared to immunocompetent patients: Acute phase cytokines and outcomes in a prospective, matched cohort study.(American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2021-06) Eichenberger, Emily M; Ruffin, Felicia; Dagher, Michael; Lerebours, Reginald; Jung, Sin-Ho; Sharma-Kuinkel, Batu; Macintyre, Andrew N; Thaden, Joshua T; Sinclair, Matthew; Hale, Lauren; Kohler, Celia; Palmer, Scott M; Alexander, Barbara D; Fowler, Vance G; Maskarinec, Stacey AWe undertook a prospective, matched cohort study of patients with Staphylococcus aureus bacteremia (SAB) and gram-negative bacteremia (GNB) to compare the characteristics, outcomes, and chemokine and cytokine response in transplant recipients to immunocompetent, nontransplant recipients. Fifty-five transplant recipients (GNB n = 29; SAB n = 26) and 225 nontransplant recipients (GNB n = 114; SAB n = 111) were included for clinical analysis. Transplant GNB had a significantly lower incidence of septic shock than nontransplant GNB (10.3% vs 30.7%, p = .03). Thirty-day mortality did not differ significantly between transplant and nontransplant recipients with GNB (10.3% vs 15.8%, p = .57) or SAB (0.0% vs 11.7%, p = .13). Next, transplant patients were matched 1:1 with nontransplant patients for the chemokine and cytokine analysis. Five cytokines and chemokines were significantly lower in transplant GNB vs nontransplant GNB: IL-2 (median [IQR]: 7.1 pg/ml [7.1, 7.1] vs 32.6 pg/ml [7.1, 88.0]; p = .001), MIP-1β (30.7 pg/ml [30.7, 30.7] vs 243.3 pg/ml [30.7, 344.4]; p = .001), IL-8 (32.0 pg/ml [5.6, 53.1] vs 59.1 pg/ml [39.2, 119.4]; p = .003), IL-15 (12.0 pg/ml [12.0, 12.0] vs 12.0 pg/ml [12.0, 126.7]; p = .03), and IFN-α (5.1 pg/mL [5.1, 5.1] vs 5.1 pg/ml [5.1, 26.3]; p = .04). Regulated upon Activation, Normal T Cell Expressed and Secreted (RANTES) was higher in transplant SAB vs nontransplant SAB (mean [SD]: 750.2 pg/ml [194.6] vs 656.5 pg/ml [147.6]; p = .046).Item Open Access Breakthrough invasive fungal infections: Who is at risk?(Mycoses, 2020-10) Jenks, Jeffrey D; Cornely, Oliver A; Chen, Sharon C-A; Thompson, George R; Hoenigl, MartinThe epidemiology of invasive fungal infections (IFIs) in immunocompromised individuals has changed over the last few decades, partially due to the increased use of antifungal agents to prevent IFIs. Although this strategy has resulted in an overall reduction in IFIs, a subset of patients develop breakthrough IFIs with substantial morbidity and mortality in this population. Here, we review the most significant risk factors for breakthrough IFIs in haematology patients, solid organ transplant recipients, and patients in the intensive care unit, focusing particularly on host factors, and highlight areas that require future investigation.Item Open Access Challenges in the Diagnosis and Management of Bacterial Lung Infections in Solid Organ Recipients: A Narrative Review.(International journal of molecular sciences, 2020-02) Carugati, Manuela; Morlacchi, Letizia Corinna; Peri, Anna Maria; Alagna, Laura; Rossetti, Valeria; Bandera, Alessandra; Gori, Andrea; Blasi, Francesco; Working Group, IfaltRespiratory infections pose a significant threat to the success of solid organ transplantation, and the diagnosis and management of these infections are challenging. The current narrative review addressed some of these challenges, based on evidence from the literature published in the last 20 years. Specifically, we focused our attention on (i) the obstacles to an etiologic diagnosis of respiratory infections among solid organ transplant recipients, (ii) the management of bacterial respiratory infections in an era characterized by increased antimicrobial resistance, and (iii) the development of antimicrobial stewardship programs dedicated to solid organ transplant recipients.Item Open Access Changing trends in mortality among solid organ transplant recipients hospitalized for COVID-19 during the course of the pandemic.(American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2022-01) Heldman, Madeleine R; Kates, Olivia S; Safa, Kassem; Kotton, Camille N; Georgia, Sarah J; Steinbrink, Julie M; Alexander, Barbara D; Hemmersbach-Miller, Marion; Blumberg, Emily A; Multani, Ashrit; Haydel, Brandy; La Hoz, Ricardo M; Moni, Lisset; Condor, Yesabeli; Flores, Sandra; Munoz, Carlos G; Guitierrez, Juan; Diaz, Esther I; Diaz, Daniela; Vianna, Rodrigo; Guerra, Giselle; Loebe, Matthias; Rakita, Robert M; Malinis, Maricar; Azar, Marwan M; Hemmige, Vagish; McCort, Margaret E; Chaudhry, Zohra S; Singh, Pooja P; Hughes Kramer, Kailey; Velioglu, Arzu; Yabu, Julie M; Morillis, Jose A; Mehta, Sapna A; Tanna, Sajal D; Ison, Michael G; Derenge, Ariella C; van Duin, David; Maximin, Adrienne; Gilbert, Carlene; Goldman, Jason D; Lease, Erika D; Fisher, Cynthia E; Limaye, Ajit P; UW COVID-19 SOT Study TeamMortality among patients hospitalized for COVID-19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID-19, we compared 28-day mortality between early 2020 (March 1, 2020-June 19, 2020) and late 2020 (June 20, 2020-December 31, 2020). Multivariable logistic regression was used to assess comorbidity-adjusted mortality. Time period of diagnosis was available for 1435/1616 (88.8%) SOTR and 971/1435 (67.7%) were hospitalized: 571/753 (75.8%) in early 2020 and 402/682 (58.9%) in late 2020 (p < .001). Crude 28-day mortality decreased between the early and late periods (112/571 [19.6%] vs. 55/402 [13.7%]) and remained lower in the late period even after adjusting for baseline comorbidities (aOR 0.67, 95% CI 0.46-0.98, p = .016). Between the early and late periods, the use of corticosteroids (≥6 mg dexamethasone/day) and remdesivir increased (62/571 [10.9%] vs. 243/402 [61.5%], p < .001 and 50/571 [8.8%] vs. 213/402 [52.2%], p < .001, respectively), and the use of hydroxychloroquine and IL-6/IL-6 receptor inhibitor decreased (329/571 [60.0%] vs. 4/492 [1.0%], p < .001 and 73/571 [12.8%] vs. 5/402 [1.2%], p < .001, respectively). Mortality among SOTR hospitalized for COVID-19 declined between early and late 2020, consistent with trends reported in the general population. The mechanism(s) underlying improved survival require further study.Item Open Access Emerging arboviruses and implications for pediatric transplantation: A review.(Pediatric transplantation, 2019-02) Freeman, Megan Culler; Coyne, Carolyn B; Green, Michael; Williams, John V; Silva, Laurie ARecent years have brought a rise in newly emergent viral infections, primarily in the form of previously known arthropod-transmitted viruses that have increased significantly in both incidence and geographical range. Of particular note are DENV, CHIKV, and ZIKV, which are transmitted mostly by Aedes species of mosquitoes that exhibit a wide and increasing global distribution. Being important pathogens for the general population, these viruses have the potential to be devastating in the international transplant community, with graft rejection and death as possible outcomes of infection. In this review, we discuss the current state of knowledge for these viruses as well as repercussions of infection in the solid organ and HSCT population, with a focus, when possible, on pediatric patients.Item Open Access Factors associated with mortality in transplant patients with invasive aspergillosis.(Clin Infect Dis, 2010-06-15) Baddley, John W; Andes, David R; Marr, Kieren A; Kontoyiannis, Dimitrios P; Alexander, Barbara D; Kauffman, Carol A; Oster, Robert A; Anaissie, Elias J; Walsh, Thomas J; Schuster, Mindy G; Wingard, John R; Patterson, Thomas F; Ito, James I; Williams, O Dale; Chiller, Tom; Pappas, Peter GBACKGROUND: Invasive aspergillosis (IA) is an important cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. The purpose of this study was to evaluate factors associated with mortality in transplant patients with IA. METHODS: Transplant patients from 23 US centers were enrolled from March 2001 to October 2005 as part of the Transplant Associated Infection Surveillance Network. IA cases were identified prospectively in this cohort through March 2006, and data were collected. Factors associated with 12-week all-cause mortality were determined by logistic regression analysis and Cox proportional hazards regression. RESULTS: Six-hundred forty-two cases of proven or probable IA were evaluated, of which 317 (49.4%) died by the study endpoint. All-cause mortality was greater in HSCT patients (239 [57.5%] of 415) than in SOT patients (78 [34.4%] of 227; P<.001). Independent poor prognostic factors in HSCT patients were neutropenia, renal insufficiency, hepatic insufficiency, early-onset IA, proven IA, and methylprednisolone use. In contrast, white race was associated with decreased risk of death. Among SOT patients, hepatic insufficiency, malnutrition, and central nervous system disease were poor prognostic indicators, whereas prednisone use was associated with decreased risk of death. Among HSCT or SOT patients who received antifungal therapy, use of an amphotericin B preparation as part of initial therapy was associated with increased risk of death. CONCLUSIONS: There are multiple variables associated with survival in transplant patients with IA. Understanding these prognostic factors may assist in the development of treatment algorithms and clinical trials.Item Open Access Healthcare resource use among solid organ transplant recipients hospitalized with COVID-19.(Clinical transplantation, 2021-02) Heldman, Madeleine R; Kates, Olivia S; Haydel, Brandy M; Florman, Sander S; Rana, Meenakshi M; Chaudhry, Zohra S; Ramesh, Mayur S; Safa, Kassem; Kotton, Camille N; Blumberg, Emily A; Besharatian, Behdad D; Tanna, Sajal D; Ison, Michael G; Malinis, Maricar; Azar, Marwan M; Rakita, Robert M; Morillas, Jose A; Majeed, Aneela; Sait, Afrah S; Spaggiari, Mario; Hemmige, Vagish; Mehta, Sapna A; Neumann, Henry; Badami, Abbasali; Jeng, Amy; Goldman, Jason D; Lala, Anuradha; Hemmersbach-Miller, Marion; McCort, Margaret E; Bajrovic, Valida; Ortiz-Bautista, Carlos; Friedman-Moraco, Rachel; Sehgal, Sameep; Lease, Erika D; Limaye, Ajit P; Fisher, Cynthia EItem Open Access Human Leukocyte Antigen Sensitization in Solid Organ Transplantation: A Primer on Terminology, Testing, and Clinical Significance for the Apheresis Practitioner.(Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy, 2017-10) Abbes, Sarah; Metjian, Ara; Gray, Alice; Martinu, Tereza; Snyder, Laurie; Chen, Dong-Feng; Ellis, Matthew; Arepally, Gowthami M; Onwuemene, OluwatoyosiThe human leukocyte antigen (HLA) system is an important immunologic barrier that must be considered for successful solid organ transplantation. Formation of donor-specific HLA antibodies in solid organ transplantation is an important cause of allograft injury and may contribute to recipient morbidity and mortality. Therapeutic plasma exchange is often requested to lower HLA antibody levels prior to or after transplantation and for management of HLA antibodies in the context of organ rejection. In this review, we summarize the current terminology, laboratory testing, and clinical significance of HLA sensitization in the solid organ transplant population. Furthermore, to illustrate applications of HLA testing in clinical practice, we summarize our own lung and kidney institutional protocols for managing HLA antibodies in the peri-transplant setting.Item Open Access Immunosuppression in solid organ transplant recipients with Covid-19: More data, but still complicated.(Transplant infectious disease : an official journal of the Transplantation Society, 2021-08) Heldman, Madeleine R; Kates, Olivia S; Fisher, Cynthia E; Limaye, Ajit P"Outcomes of COVID-19 in solid organ transplant (SOT) recipients: a matched cohort study" by Pereira et al found similar 28 day mortality among hospitalized SOT recipients and comorbidity matched controls, shedding light on the relationship between immunosuppression and Covid-19 outcomes.Item Open Access Infective endocarditis and solid organ transplantation: Only worse outcomes during initial transplantation hospitalization.(American heart journal, 2021-10) Eichenberger, Emily M; Dagher, Michael; Sinclair, Matthew R; Maskarinec, Stacey A; Fowler, Vance G; Federspiel, Jerome JBackground
The epidemiology, and outcome of infective endocarditis (IE) among solid organ transplant (SOT) recipients is unknown.Methods
We used data from the 2013-2018 Nationwide Readmissions Database (NRD). IE- and SOT-associated hospitalizations were identified using diagnosis and procedure codes. Outcomes included inpatient mortality, length of stay, and inpatient costs. Adjusted analyses were performed using weighted regression models.Results
A total of 99,052 IE-associated hospitalizations, corresponding to a weighted national estimate of 193,164, were included for analysis. Of these, 794 (weighted n = 1,574) were associated with transplant history (SOT-IE). Mortality was not significantly different between SOT-IE and non-SOT-IE (17.2% vs. 15.8%, adjusted relative risk [aRR]: 0.86, 95% confidence interval [CI] [0.71, 1.03]), and fewer SOT-IE patients underwent valve repair or replacement than non-SOT-IE (12.5% vs. 16.2%, aRR 0.82, 95% CI [0.71, 0.95]). We then compared outcomes of patients diagnosed with IE during their index transplant hospitalization (index-SOT-IE) to patients without IE during their transplant hospitalization (index-SOT). Index-SOT-IE occurred most frequently among heart transplant recipients (45.1%), and was associated with greater mortality (27.1% vs. 2.3%, aRR 6.07, 95% CI [3.32, 11.11]).Conclusion
Dual diagnosis of SOT and IE was associated with worse outcomes among SOT recipients during index hospitalization, but not overall among patients with IE.Item Open Access The role of B cells in solid organ transplantation.(Semin Immunol, 2012-04) Kwun, Jean; Bulut, Pinar; Kim, Eugenia; Dar, Wasim; Oh, Byoungchol; Ruhil, Ravi; Iwakoshi, Neal; Knechtle, Stuart JThe role of antibodies in chronic injury to organ transplants has been suggested for many years, but recently emphasized by new data. We have observed that when immunosuppressive potency decreases either by intentional weaning of maintenance agents or due to homeostatic repopulation after immune cell depletion, the threshold of B cell activation may be lowered. In human transplant recipients the result may be donor-specific antibody, C4d+ injury, and chronic rejection. This scenario has precise parallels in a rhesus monkey renal allograft model in which T cells are depleted with CD3 immunotoxin, or in a CD52-T cell transgenic mouse model using alemtuzumab to deplete T cells. Such animal models may be useful for the testing of therapeutic strategies to prevent DSA. We agree with others who suggest that weaning of immunosuppression may place transplant recipients at risk of chronic antibody-mediated rejection, and that strategies to prevent this scenario are needed if we are to improve long-term graft and patient outcomes in transplantation. We believe that animal models will play a crucial role in defining the pathophysiology of antibody-mediated rejection and in developing effective therapies to prevent graft injury. Two such animal models are described herein.