Solid Organ Transplantation Research Articles

Association between neuroimaging and clinical outcomes in individuals with central nervous system cryptococcosis.

The radiological manifestations of central nervous system (CNS) cryptococcosis are diverse and often subtle. There is heterogeneity on how different neuroimaging patterns impact prognosis. This study aims to assess the association between the neuroimaging and clinical outcomes of CNS cryptococcosis. All patients with CNS cryptococcosis between July 2017 and April 2023 who underwent brain magnetic resonance imaging (MRI) were included. The primary outcome was mortality during hospitalisation. Secondary outcomes were readmission, ventricular shunting, duration of hospitalisation and time to the first negative cerebrospinal fluid culture. We compared the outcomes for each of the five main radiological findings on the brain MRI scan. We included 46 proven CNS cryptococcosis cases. The two main comorbidity groups were HIV infection (20, 43%) and solid organ transplantation (10, 22%), respectively. Thirty-nine patients exhibited at least one radiological abnormality (85%), with the most common being meningeal enhancement (34, 74%). The mortality rates occurred at 11% (5/46) during hospitalisation. We found no significant disparities in mortality related to distinct radiological patterns. The presence of pseudocysts was significantly associated with the need for readmission (p = .027). The ventricular shunting was significantly associated with the presence of pseudocysts (p = .005) and hydrocephalus (p = .044). In this study, there is no association between brain MRI findings and mortality. Larger studies are needed to evaluate this important issue.

TTV and CMV viral load dynamics: Which emerges first during immunosuppression?

Novel biomarkers reflecting the degree of immunosuppression in transplant patients are required to ensure eventual personalized equilibrium between rejection and infection risks.With the above aim, Torque Teno Virus(TTV) viremia was precisely examined in a large cohort of transplanted immunocompromised patients (192 hematological and 60 solid organ transplant recipients) being monitored for Cytomegalovirus reactivation.TTV load was measured in 2612 plasma samples from 448 patients. The results revealed a significant increase in TTV viral load approximately 14 days following CMV reactivation/infection in solid organ transplant(SOT) patients. No recognizable difference in TTV load was noted among hematological patients during the entire timeframe analyzed. Furthermore, a temporal gap of approximately 30 days was noted between the viral load peaks reached by the two viruses, with Cytomegalovirus(CMV) preceding TTV.It was not possible to establish a correlation between CMV reactivation/infection and TTV viremia in hematological patients. On the other hand, the SOT patient cohort allowed us to analyze viral kinetics and draw intriguing conclusions. Taken together, the data suggest, to our knowledge for the first time, that CMV infection itself could potentially cause an increase in TTV load in the peripheral blood of patients undergoing immunosuppressive therapy.

Solid organ transplant patients do well after shoulder arthroplasty: a propensity matched analysis

Solid organ transplant (SOT) recipients are commonly prescribed immunosuppressive therapies which may predispose patients to higher infection and complication rates following total shoulder arthroplasty. This article aims to analyze the effects SOT and subsequent immunosuppressive regimens have on the functional and patient-reported outcomes of total shoulder arthroplasties. A single institution, multisurgeon retrospective case-control study investigating the functional and patient-reported outcomes of shoulder arthroplasty after SOT was conducted between the years of 2010 and 2020. To be included in the study, patients must have undergone SOT prior to primary total shoulder arthroplasty. A 4:1 match-paired control group lacking SOT prior to arthroplasty was then constructed. Thirty-four SOT patients (18 males and 16 females) and 136 control patients (77 male and 59 female) were included in the study. Patients were analyzed who underwent SOT prior to shoulder arthroplasty, with outcomes compared to controls that only underwent arthroplasty. The primary outcomes include range of motion and strength in forward elevation, external rotation, and internal rotation, and patient reported outcomes. There was no significant difference in improvement for range of motion and strength between the 2 cohorts, but within each cohort, improvement was statistically significant. In the SOT patients, forward elevation improved by 56° ± 52°, external rotation increased by 13° ± 20°, and internal rotation increased by 2 vertebral levels. In the non-SOT patients, forward elevation improved by 45° ± 51°, external rotation increased by 16° ± 25°, and internal rotation increased by 3 vertebral levels. SOT patients had equivocal visual analog scale pain and Simple Shoulder Test scores but lower American Shoulder and Elbow Surgeons (59±13 vs. 79±2; P=.002) and SANE (61±30 vs. 84±17; P<.001) scores than non-SOT patients. Complication rates were not significantly higher in the SOT group (15% vs. 6%; P=.05), but incidence of surgical revisions was not significantly different (SOT=3%; non-SOT=5%; P=.59). Shoulder arthroplasty is a safe, effective surgical intervention for improving shoulder function in patients with a history of SOT. Despite being on chronic immunosuppressive regimens, our solid organ transplants had comparable clinical outcomes and revision rates, but higher complication rates.

Predictive value of the dynamics of absolute lymphocyte counts for 90-day mortality in ICU sepsis patients: a retrospective big data study

ObjectivesThe objective of the study was to assess the clinical predictive value of the dynamics of absolute lymphocyte count (ALC) for 90-day all-cause mortality in sepsis patients in intensive care...

Transcatheter Versus Surgical Aortic Valve Replacement in Recipients of Solid Organ Transplants and Liver Cirrhosis: A Propensity-Matched Analysis of National Readmission Data

Transcatheter aortic valve replacement (TAVR) continues to grow in the United States. There are limited data on recipients of solid organ transplant (SOT) and patients with liver cirrhosis who undergo aortic valve replacement (AVR). Our study aims to evaluate outcomes in these populations. Using the national readmission database (2016 to 2020), we identified recipients of SOT and patients with liver cirrhosis without previous liver transplants who were admitted for severe aortic stenosis and underwent either TAVR or surgical AVR (SAVR). We used multivariable regression for adjusted analysis and the propensity score matching model, implementing complete Mahalanobis distance matching within the Propensity Score Caliper (0.2) to match TAVR and SAVR cohorts for outcomes. Of 3,394 hospitalizations for AVR in recipients of SOT, 2,181 underwent TAVR, and 1,213 underwent SAVR. On propensity-matched analysis, SAVR was associated with more adverse events than was TAVR, including in-hospital mortality (5.2% vs 1.1%, adjusted odds ratio [aOR] 4.49, p <0.001), acute kidney injury (43.7% vs 10.2%, p <0.001), cardiogenic shock (9.0% vs 1.6%, p <0.001), sudden cardiac arrest (15.9 vs 6.0%, p <0.001), major adverse cardiac and cerebrovascular events (28% vs 10.4%, p <0.001), and net adverse events (72.8 vs 37.6%, p <0.001). A greater median length of stay (10 vs 2 days, p <0.001) and adjusted cost ($80,842 vs $57,014, p <0.001) were also observed. The readmission rates were the same for both cohorts after a 6-month follow-up. Similarly, in 14,763 hospitalizations for AVR in liver cirrhosis, 7,109 patients underwent TAVR, and 7,654 underwent SAVR. In propensity-matched cohorts (n = 2,341), SAVR was found to be associated with greater adverse events, including in-hospital mortality (19.8% vs 10%), stroke (6.7% vs 2%), acute kidney injury (67.7% vs 30.3%), cardiogenic shock (41.9% vs 19.9%), sudden cardiac arrest (31.8% vs 13.2%, aOR 2.89), major adverse cardiac and cerebrovascular events (66.2% vs 35.7%), and net adverse events (86% vs 59.5%) (p <0.001). A greater median length of stay (16 vs 3 days) and cost ($500,218 vs $263,383) were also observed (p <0.001). However, the rate of readmissions at 30-day (9% vs 11.1%) and 180-day intervals (33.4% vs 39.8%) was lower for the SAVR cohort (p <0.05). In recipients of SOT and patients with liver cirrhosis, SAVR is associated with greater short-term mortality, adverse events, and healthcare burden than is TAVR. TAVR is a relatively safer alternative to SAVR in these patient populations, although further studies are warranted to compare the long-term outcomes.

SARS-CoV-2 Vaccination Rates and Uptake of Tixagevimab-Cilgavimab Among a Cohort of Pediatric Solid Organ Transplant Recipients.

There is a lack of data regarding SARS-CoV-2 vaccination rates and tixagevimab-cilgavimab (TC) uptake among pediatric solid organ transplant recipients. The purpose of our study was to assess these rates. We reviewed vaccination records of pediatric recipients of heart, kidney, and liver transplants at Mayo Clinic, Rochester, MN, who received a transplant between January 2011 and December 2021. All SARS-CoV-2 vaccines and doses of TC received on or before September 1, 2022, the date of approval of the bivalent SARS-CoV2 vaccine, were included. We also assessed whether patients had been seen by an infectious diseases physician (ID) in the preceding 6 months. Our study included 110 patients: 47 kidney, 36 heart, and 27 liver transplant recipients. All vaccine doses recorded were monovalent SARS-CoV-2 vaccines. Sixty-eight (61.8%) patients received at least one vaccine. This varied by age group, with f of≥12 years olds, 40.9% of 5-11 year olds and 14.3% of under 5 year olds (p=0.001). Seven patients (6.4%) were up-to-date (UTD) for age. There was no difference in UTD status by organ type (p=0.335). Patients who saw ID were significantly more likely to be UTD (13.2% versus 2.8%; p=0.047). Among those eligible, 14 (18.2%) received TC, with rates not different based on transplanted organ type (p=0.158) or whether they saw ID (p=0.273). Despite the availability of vaccines, nearly 40% of pediatric solid organ transplant recipients remained unvaccinated against SARS-CoV-2 at time of the bivalent vaccine release. Less than a fifth of eligible patients received TC. Strategies to increase uptake of SARS-CoV-2 vaccines as well as adjunctive agents among this vulnerable group should be further explored.

Daratumumab for De-sensitization of Donor Specific Antibodies: Is it a Quicker and Easier way?

Antibodies directed against donor-specific HLA loci (DSA) has been proved as a main culprit for graft rejection, more specifically in HLA mismatched and haplo-identical transplant settings. There is no standardized regimen to manage the presence of DSAs in allogeneic stem cell transplantations (allo-SCTs). Most widely regimen includes combination of rituximab (anti CD20 antibody), Immunoglobulin (IVIG), plasma exchange, and buffy coat infusion, which is costly and time-consuming. Daratumumab (anti CD38 monoclonal antibody) is an effective therapeutic agent to deplete plasma cells and hence, it has a potential to reduce DSA. It has been utilized widely in solid organ transplantation for this purpose. We used this agent in two haplo-identical transplant patients to eliminate or reduce DSA. We observed definite either reduction or elimination in DSA levels in these cases and we could perform haplo-identical transplantation without much delay and with successful primary engraftment in both scenarios. We emphasize that literature on real-world utilization of daratumumab in allo-SCTs is limited. However, it has been utilized widely in solid organ transplantation for this purpose. Our experience with daratumumab regarding effective reduction of DSA followed by successful engraftment might encourage its use in de-sensitization protocols without much delay in transplantation.

Candida auris cluster in a center with no previous infections associated with a single organ donor

Background: Candida auris is an opportunistic pathogen reported in the US since 2016. C. auris infections (CAI) are frequently healthcare-associated, but only one case of donor-derived CAI in a lung transplant recipient has been reported (PMID 28520901). We describe a cluster of two CAIs at a single center in South Carolina occurring in 2 different recipients from the same solid organ transplant donor. Methods: We describe two cases of invasive CAIs occurring in an academic medical center without prior CAI in Charleston, SC in October 2023. C. auris was identified using Bruker MALDI-TOF and confirmed by the state health department. Results: Patient 1: 40-49 year-old male underwent heart transplantation on day 19 from admission complicated by growth of C. auris on post-op day #15 from a drain. He was readmitted post-op days 22-63 with positive blood cultures for C. auris and underwent re-operation with debridement and hardware removal. C. auris pericarditis required multiple returns to the OR (Figure). He was discharged on micafungin/posaconazole with plans for long-term antifungal therapy. Patient 2: 50-59 year-old male underwent liver and kidney transplantation on day 25 from admission from the same donor as Patient 1 in a separate hospital complex. His course was complicated by possible infected biloma not amendable to drainage and C. auris/C. glabrata fungemia, which was further complicated by abdominal wall collection cultures growing C. auris on post-operative day 35 on washout. He was managed with dual micafungin/posaconazole however, he died of unrelated causes at 93 days after transplant (Figure). Investigation: The donor for both recipients was a 10-19 year-old male who suffered brain death after trauma and was hospitalized for 56 days prior to procurement in Atlanta, GA without known CAI. Airway cultures at the time of organ procurement were positive for rare Pseudomonas and light unidentified yeast of multiple morphologies; urine cultures also grew 40,000 cfu/ml un-identified yeast. Screening of 35 and 4 inpatients in units exposed to patients 1 &amp; 2, respectively, with axilla/groin PCR was negative (Figure). A third organ recipient for this donor (kidney) at our center was identified and had negative urine fungus cultures. Conclusions: Despite no definitive link to a known donor infection, this cluster of CAI occurring simultaneously in 2 patients in separate hospitals/units at a single center with no known prior cases represents likely donor-derived CAI. Our experience suggests that organ procurement organizations should consider improved screening techniques for C. auris in donor cultures.Disclosure: Scott Curry: Consultant- Ferring; Abbott Diagnostics- Speaker honorarium

Bexarotene Induce Differentiation of Myeloid-Derived Suppressor Cells through Arg-1 Signalling Pathway

BackgroundCellular therapy has emerged as a promising strategy to minimize the use of conventional immunosuppressive drugs and ultimately induce long-term graft survival. Myeloid-derived suppressor cells (MDSCs) can be used for immunosuppressive treatment of solid organ transplants. MethodsGranular macrophage colony-stimulating factor (GM-CSF) and bexarotene, an X receptor-selective retinoid, were used for in vitro MDSC induction. Cell phenotypes were detected using flow cytometry, while mRNA was detected via real-time PCR. A mouse skin transplantation model was used to verify the inhibitory effects of this treatment. ResultsThe combination of GM-CSF and bexarotene-induced MDSC differentiation. MDSCs induce immune tolerance by inhibiting T-cell proliferation, influencing cytokine secretion, and inducing T-cell transformation into Treg cells. Combination treatment significantly up-regulated Arg-1 expression in MDSCs. The Arg-1 inhibitor nor-NOHA neutralized the immunosuppressive activity of MDSCs, suggesting the involvement of Arg-1 in MDSC-mediated immunosuppression. GM-CSF and bexarotene-induced MDSCs prolong graft survival in mouse skin transplants, exhibiting in vivo immunosuppressive effects. ConclusionsA new method for inducing MDSCs is presented. The combination of GM-CSF and bexarotene induces MDSCs with remarkable regulatory functions. Adoptive transfer of the induced MDSCs extended allograft survival. These results suggest that MDSCs can potentially be used in future clinical transplants to inhibit rejection, reduce adverse events, and induce operative tolerance.

Reduced Blood Culture Use in High-Volume Lung Transplant MICU Following a Stewardship Program, Northern California, 2021–2023

Introduction: There is a need to optimize blood culture (BC) utilization among hospitalized adults. A previous study showed an evidence-based BC algorithm improved BC utilization in a medical intensive care unit (MICU) at a large academic center. Our aim is to evaluate the impact of an intervention based on this algorithm on blood culture utilization in the MICU at Stanford Health Care, a referral center known for its high volume of solid organ transplants. Methods: We conducted a before-after study evaluating the impact of a BC diagnostic stewardship program in the MICU at Stanford Health Care, a 20-bed unit with an average of 20% lung transplant patients per day. All patients ≥18 years of age admitted to the unit during the study period were included. We adopted a previously published evidence-based algorithm detailing syndromes with low and high risk for bacteremia, which was referenced during patient rounds. Additionally, education and feedback to providers about BC utilization and indication inappropriateness was performed during leadership meetings every other month. We performed an interrupted time series analysis using historical data 17 months before the implementation of the blood culture stewardship program on April 1, 2022 and 8 months after. We assessed changes on BC utilization adjusted to patient days and crude mortality rate during the same period as a balancing measure. Results: Before the implementation of the program, the median BC utilization was 216 per 1,000 patient days (range 150–250 per 1,000 patient days). Following the introduction of the program, there was a significant decrease in blood culture utilization by 5% (95% CI -10% to -1%, p=.02; Figure 1). Post-intervention, the blood culture stabilized, with no significant increase observed (0.09% increase, 95% CI -0.7% to 1%, p=.81). The mortality rate, prior to the implementation of the program, had shown a significant downward trend of 1.4% over time (95% CI -3% to -0.2%, p=.02). After the intervention, a nonsignificant decrease of 8% was observed (95% CI -44% to 27%, p=.62; Figure 2), followed by a nonsignificant upward trend of 6% (95% CI -1% to 13%, p=.10). Conclusion: We observed a significant reduction in BC utilization after implementing the BC diagnostic stewardship program in a MICU frequented by a high number of lung transplant patients.

A Case of Disseminated Cryptococcus in an HIV-Positive Patient

A 69-year-old male with a history of untreated Human Immunodeficiency Virus (HIV) was admitted to the emergency department for symptoms such as cough, shortness of breath, lethargy, and weight loss. His physical examination revealed severe wasting, oral thrush, and hypoxia. Chest imaging revealed cavitary lesions and blood work showed an absolute CD4 count of 23 cells/mm3. An IR-guided biopsy revealed abundant necrosis and scattered narrow-based fungal organisms consistent with Cryptococcus neoformans infection. The patient was treated with liposomal amphotericin B and flucytosine. Due to the increased risk of Immune Reconstitution Inflammatory Syndrome (IRIS), HIV treatment was deferred. The patient deteriorated, transitioned to comfort care, and unfortunately expired. INTRODUCTION Cryptococcus neoformans is a ubiquitous environmental yeast and a leading cause of invasive fungal infection in humans with significant morbidity and mortality that affects both immunocompetent and immune-compromised hosts.1,2 Globally, there are approximately 1 million cases of AIDS-related cryptococcosis each year, leading to over 600,000 deaths. This represents a prevalence of 6.0% (95% CI 5.8–6.2) among people with a CD4 cell count of less than 100 cells per uL.2 The transmission mode is by inhalation of microscopic fungus (desiccated yeast or spores). Immunosuppression is the strongest risk factor for disease development, including HIV infection, stem cell and solid organ transplantation, prolonged immunosuppressive therapy, invasive medical procedures, hematological malignancies, advanced age, and prematurity.1,2,3 Treatment usually involves a fungicidal regimen of IV liposomal amphotericin B, plus flucytosine followed by oral fluconazole.4,5 Overall, 90-day all-cause mortality in patients with cryptococcal infection is 19.4%. Mortality rates are significantly higher in HIV/transplant patients at 90 days (41.7% versus 8.3%, p = 0.017) and one year (41.7% versus 12.5%, p = 0.047).6,7 This case describes a 69-year-old HIV-positive patient who presented with multisystemic manifestations and cavitary lung lesions with blood and cerebrospinal fluid (CSF) findings of cryptococcal antigen and positive fungal culture and lung biopsy confirmation of Cryptococcus.

The performance of bronchoalveolar lavage Aspergillus PCR testing in solid organ transplant recipients with invasive pulmonary aspergillosis.

Invasive aspergillosis affects solid organ transplant (SOT) recipients, carrying a high risk of mortality and morbidity in this population. Rapid and accurate diagnosis is essential to ensure the initiation of correct antifungal therapy. We aimed to evaluate the performance of the bronchoalveolar lavage (BAL) Eurofins Viracor Aspergillus PCR (AspPCR) in diagnosing invasive pulmonary aspergillosis (IPA) in SOT recipients. We conducted a multicenter retrospective study of SOT recipients in Arizona from February 2019 to December 2022 who had AspPCR done at the time of the clinical encounter. Probable IPA was defined as a positive BAL culture with Aspergillus spp. with clinical and imaging findings of IPA per EORTC/MSGERC criteria. Ninety-nine SOT recipients with 131 encounters with BAL AspPCR testing were included. The median age was 66, the majority were White, non-Hispanics (60%), and males (66%). Among the participants, 93 lung transplant recipients with 87 of the encounters received antifungal prophylaxis active against Aspergillus spp. Sixty-four encounters had BAL galactomannan (GM), all of which had BAL GM <1 OD, and one case had a serum GM of 10 OD. Nine cases met the definition of IPA. The sensitivity of the BAL AspPCR was 67% (95% CI 30%-93%), and the specificity was 98% (95% CI 93%-99%). BAL AspPCR had moderate sensitivity and high specificity in identifying IPA in our cohort of SOT recipients. Further studies in populations with a higher prevalence of IPA are needed to evaluate the performance of this test.

Effectiveness of ceftazidime/avibactam as a continuous infusion in critically ill patients with OXA-48-producing Klebsiella pneumoniae infection

Introduction. Ceftazidime/avibactam, a novel beta-lactam antibiotic, demonstrates time-dependent bacterial killing; thus, new reports advocate its administration as a continuous infusion, as opposed to bolus or prolonged infusion application. Methods. Critically ill COVID-19 patients (n=10) superinfected with OXA-48-producing Klebsiella pneumoniae susceptible to ceftazidime/avibactam were treated with ceftazidime/avibactam as a continuous infusion for an average of 10 days. The treatment regimen included an initial loading dose, followed by a continuous infusion of ceftazidime/avibactam. These patients were immunocompromised because of severe COVID-19, treatment with corticosteroids, and some solid organ transplant recipients (n=2), all with high disease severity scores. Discussion. Considering the published literature to this date, this is the one of first reports describing the real-life results of using a continuous infusion of ceftazidime/avibactam in the treatment of OXA-48-producing K. pneumoniae superinfection in critically ill COVID-19 patients. Microbiological effectiveness of treatment, evidenced by negativization of microbiological samples, was achieved in eight cases (80%) overall, but in patients with sepsis and urinary tract infection, the cure rate was 100%. Conclusion. The reasons for the low treatment success rates in pneumonia caused by OXA-48-producing K. pneumoniae could be explained by the concurrent severe COVID-19 pneumonia.

Cytomegalovirus infection risk with alemtuzumab therapy in hematological malignancies: a retrospective cohort study in the non-transplant setting

Alemtuzumab is a potent lymphocyte-depleting immunotherapy used in solid organ transplan­tation (SOT), that is increasingly being applied in diverse lymphoproliferative disorders (LPDs). However, a significant toxicity limiting expanded usage is cytomegalovirus (CMV) infection, for which standardized preventive strategies exist in SOT but not in LPDs due to a poor understanding of infection risk in this population, with early LPD studies largely limited to stem cell transplantation. Using one of the most diverse arrays of LPDs studied to date, our retrospective cohort study of non-transplant patients receiving alemtuzumab over a ten-year period at a large regional cancer center examines the incidence and clinical profile of infected patients. Among 24 patients, we identified a composite CMV infection rate of 42% with a symptomatic rate of 21%. We also noted significant variations in preventive strategies, which alongside a high infection rate presents an opportunity to improve outcomes through further work in standardization.

Assessing the Predictive Value of Methicillin-Resistant Staphylococcus aureus Nares Colonization Among Transplant Recipients and Patients With Neutropenia.

Methicillin-resistant Staphylococcus aureus (MRSA) nares screening has been shown to be a powerful antibiotic stewardship tool for MRSA infections within 7 days of screening across a variety of anatomical locations given the high negative predictive value (NPV). However, the utility outside of 7 days and among transplant recipients and patients with neutropenia is less clear. This was a retrospective cohort study across Veterans Affairs medical centers in the United States from 1 January 2007 to 1 January 2023 of patients tested for MRSA colonization and who had a subsequent positive bacterial culture within 28 days of MRSA sc---reening. Sensitivity, specificity, positive predictive value, and NPV were calculated across different time points and anatomical culture locations. The cohort consisted of 686 174 patients, 6 277 437 MRSA nares tests, and 2 446 766 positive bacterial cultures within 28 days of MRSA testing. The NPV of MRSA nares screening for ruling out a MRSA infection within 28 days was 95.8% across all anatomical culture sites. The NPV was 97.9% among patients with neutropenia and 97.5% in solid organ and hemopoietic stem cell transplant recipients. MRSA nares screening can reliably be used for de-escalation of anti-MRSA therapy within 28 days of bacterial culture for all patients, including solid organ and hematopoietic transplant recipients and patients with neutropenia.

Multicenter Analysis of Valganciclovir Prophylaxis in Pediatric Solid Organ Transplant Recipients.

Valganciclovir is the only approved antiviral for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation (SOT). Additional approaches may be needed to improve outcomes. A multicenter retrospective study from 2016 to 2019 was conducted of pediatric SOT recipients in whom at least 3 months of valganciclovir prophylaxis was planned. Episodes of CMV DNA in blood (DNAemia), CMV disease, drug-related toxicities, as well as other infections in the first year posttransplant and demographic and clinical data were collected. CMV DNAemia in the first year after prophylaxis or during prophylaxis (breakthrough) was analyzed by multivariate hazard models. Among the 749 patients enrolled, 131 (17.5%) had CMV DNAemia at any time in the first year; 85 (11.4%) had breakthrough DNAemia, and 46 (6.1%) had DNAemia after prophylaxis. CMV disease occurred in 30 (4%). In a multivariate model, liver transplantation compared to kidney or heart, intermediate or high risk based on donor/recipient serologies, neutropenia, and valganciclovir dose modifications attributed to toxicity were associated with increased risk of total and/or breakthrough DNAemia. Bacteremia was also associated with increased hazard ratio for CMV DNAemia. In a separate multivariate analysis, rejection occurred more often in those with breakthrough CMV DNAemia (P = .002); liver transplants, specifically, had increased rejection if CMV DNAemia occurred in the first year (P = .004). These associations may be bidirectional as rejection may contribute to infection risk. CMV DNAemia in the first year posttransplantation occurs despite valganciclovir prophylaxis and is associated with medication toxicity, bacteremia, and rejection. Pediatric studies of newer antivirals, especially in higher-risk subpopulations, appear to be warranted.

BI08 Delivery of stratified skin cancer surveillance in solid-organ transplant recipients: development of a consensus statement on behalf of the British Society for Skin Care in Immunosuppressed Individuals

BI08 Delivery of stratified skin cancer surveillance in solid-organ transplant recipients: development of a consensus statement on behalf of the British Society for Skin Care in Immunosuppressed Individuals

Impact of blood donation biovigilance and transfusion-transmitted infections on organ transplantation.

Over 118 million blood donations are collected globally each year. Recipients of blood products include those who experience major trauma or surgery, have acute blood loss and anemia, or impaired bone marrow function. Solid organ transplant recipients often require transfusion of blood products which places them at risk of transfusion-associated adverse events including transfusion-transmitted infection. National hemovigilance networks have documented low rates of transfusion-transmitted infection in the general population. Incidence transfusion-transmitted infection continues to occur in solid organ transplant patients and arises mainly from existing gaps in blood donor biovigilance processes. Emerging infectious diseases have highlighted existing gaps in the donor-recipient pathway to administering safe blood products. This article reviews the current process and regulatory oversight of blood donor biovigilance, including donor screening and microbiological testing, highlights cases of transfusion-transmitted infection documented in the literature, and addresses ways in which biovigilance may be improved, with a focus on the impact of solid organ transplantation.

Outcome of Pneumocystis pneumonia in transplant and non-transplant HIV-negative immunocompromised patients.

Previous studies showed HIV-negative immunocompromised patients are susceptible to Pneumocystis pneumonia (PCP). However, the PCP outcome has not been compared among HIV-negative immunocompromised patients. In this retrospective cohort study at the University Health Network, we included all HIV-negative immunocompromised patients who fulfilled the European Organization for Research and Treatment of Cancer (EORTC) PCP diagnosis criteria from December 2018 to December 2019. We compared the demographics, comorbidities, course of illness, and PCP outcome (28-day mortality and composite outcome [i.e., death or intensive care unit (ICU) admission]) between solid organ transplant (SOT) and non-SOT patients. Of 160 non-HIV patients with PCP diagnoses, 118 patients fulfilled EORTC criteria (76 males [64.4%], median [range] age: 65.5 [21-87] years). PCP presentation in SOT recipients (n=14) was more severe than non-SOT patients (n=104): acute presentation (onset <7 days before admission: 11/14 [78.6%] vs. 51/104 [56%], p=.037), shortness of breath (100% vs. 75/104 [74.3%], p=.037), median [range] O2 saturation (88% [75%, 99%] vs. 92%[70%, 99%], p=.040), and supplemental O2 requirement (12/14 [85.7%] vs. 59/104 [56.7%], p=.044). The mortality [4/14, (28.6%) vs. 15/104 (14.4%), p=.176], ICU admission (10/14 [71.4%] vs. 18/104 [17.3%], p<.0001), and mechanical ventilation (8/14 [57.1%] vs. 18/104 [17.3%], p=.0007) in SOT patients was different from non-SOT patients. In multivariable analysis, SOT recipients were at greater risk of composite outcome than non-SOT patients (aOR [CI95%]: 12.25 [3.08-48.62], p<.001). PCP presentation and outcomes in SOT recipients are more severe than in non-SOT patients. Further studies are required to explore the biological reasons for this difference.

Comparison of COVID-19 Hospitalization and Death Between Solid Organ Transplant Recipients and the General Population in Canada, 2020-2022.

Solid organ transplant recipients have a high risk of severe outcomes from SARS-CoV-2 infection. A comprehensive understanding of the impact of the COVID-19 pandemic across multiple waves in the solid organ transplant population and how this compares to the general population is limited. We conducted a population-based cohort study using linked administrative healthcare databases from Ontario, Canada to answer this question. We included 15 306 solid organ transplant recipients and 12 160 904 individuals from the general population. Our primary outcome was the rate (per 100 person-years) of severe COVID-19 (ie, hospitalization or death with a positive SARS-CoV-2 test) occurring between January 25, 2020, and November 30, 2022. Compared with the general population, solid organ transplant recipients had almost a 6 times higher rate of severe COVID-19 (20.39 versus 3.44 per 100 person-years), with almost 5.5 times as high a rate of death alone (4.19 versus 0.77 per 100 person-years). Transplant recipients with severe COVID-19 were substantially younger (60.1 versus 66.5 y) and had more comorbidities. The rate of severe COVID-19 declined over time in the solid organ transplant population, with an incidence rate of 41.25 per 100 person-years in the first wave (January 25, 2020, to August 31, 2020) and 18.41 in the seventh wave (June 19, 2022, to November 30, 2022, Omicron era). Solid organ transplant recipients remain at high risk of severe outcomes when they are infected with SARS-CoV-2. Resources and strategies to mitigate the impact of SARS-CoV-2 exposure are needed in this vulnerable patient population.