Positive Recipients Research Articles

Risks of Tacrolimus and Paxlovid Therapy in SARS-CoV-2 Positive Transplant Recipients: A Case Discussion and Institutional Data Review

Abstract Introduction/Objective Transplant recipients maintained on immunosuppressants like tacrolimus continue to be at high risk for morbidity due to SARS-CoV-2 infection and are strong candidates for antiviral therapies. However, co- administration of the antiviral Paxlovid (nirmatrelvir/ritonavir) poses a significant risk to these patients due to ritonavir- mediated inhibition of CYP3A, an important mediator of tacrolimus metabolism. Consequently, Paxlovid therapy in post-organ transplant patients on tacrolimus requires careful consideration. Our investigation aims to assess the continuing risk posed by this drug-drug interaction and better understand clinical circumstances linked to critically high tacrolimus levels due to Paxlovid co-administration. Methods/Case Report We conducted a large-scale retrospective analysis of tacrolimus measurements at the University of Michigan Medicine beginning in January 2020. We also performed a detailed review of patients with critically high tacrolimus levels coinciding with Paxlovid administration. Results (if a Case Study enter NA) Of 39,752 tacrolimus measurements examined, 682 correspond to 329 patients with recent positive SARS-CoV-2 nucleic acid testing, and 37 correspond to 18 patients with documented Paxlovid co- administration. Patients receiving concurrent Paxlovid and tacrolimus demonstrate 1.6- and 1.8-fold higher mean tacrolimus levels (14.1 ng/mL, p = 3e-5) compared to other SARS-CoV-2 positive (8.7 ng/mL) and negative/untested (7.9 ng/mL) patients, respectively. Among SARS-CoV-2 patients, those prescribed Paxlovid are more likely to present with supratherapeutic tacrolimus levels (OR 4.1, 95% CI 1.6 – 10.7). A detailed case review of three organ transplant recipients presenting with tacrolimus levels >60 ng/mL and creatinine levels increased by 0.45 ± 0.27 mg/dL from baseline shows Paxlovid was prescribed at outside facilities, and regular tacrolimus dose was continued. Three other patients exhibited supratherapeutic tacrolimus levels (20 – 30 ng/mL), and creatinine levels increased by 0.41 ± 0.23 mg/dL from baseline despite dose reduction or cessation before initiating Paxlovid. Conclusion Our findings highlight the importance of communication between primary and tertiary care providers and caution when prescribing Paxlovid in populations managed with tacrolimus therapy.

406.2: Graft protein shows a distinct signature in donor-specific antibody positive kidney transplant recipients with antibody-mediated rejection.

406.2: Graft protein shows a distinct signature in donor-specific antibody positive kidney transplant recipients with antibody-mediated rejection.

P-569 Reciprocal expanded carrier screening for intended parents and gamete donors: experience of a global surrogacy support network

Abstract Study question Is expanded carrier screening an effective tool to identify carriers of clinically relevant genes and determine the reproductive risk between a donor and recipient pair? Summary answer This study has determined that there is a strong rationale for performing matching according to expanded carrier screening results, especially for gamete donor programs. What is known already Carrier screening (CS) identifies carriers of autosomal recessive (AR) and/or X-linked (XL) genetic conditions to establish reproductive risk. If both partners (egg and sperm providers) carry a pathogenic variant in the same gene (co-carriage), there is 25% risk that offspring will be affected. The same risk is present for egg providers who carry an XL disorder. In expanded carrier screening (ECS), many clinically relevant conditions are screened simultaneously using a single-panel approach. The implementation of ECS is becoming commonplace across gamete donor banks. Providing recipients with a matching panel is key in determining reproductive risk and suitable treatment options. Study design, size, duration In this retrospective review, data was collected for 104 gamete recipients and 31 gamete donors who underwent ECS between March 2021-January 2024. ECS was provided through a single genetic testing laboratory, using a whole exome sequencing (WES) platform. The panel used for the gamete donors/recipients consisted of approximately 500 AR genes; optional analysis of 66 X-Linked genes was available for biologically female donors/recipients. Participants/materials, setting, methods In total, 104 gamete recipients were screened against one or more donor(s) using the same ECS panel. All donors/recipients underwent testing in a clinical setting and received pre/post-test genetic counselling, where required. The testing laboratory provided the referring clinician with the results for each individual. Matching was overseen by My Surrogacy Journey and the relevant donor bank. Donor-recipient match reports were requested from the testing laboratory. Individual and matched reports were used for this review. Main results and the role of chance In total, 76.9% (80/104) of gamete recipients presented with a positive result in at least one clinically relevant gene that could have an impact on reproductive planning. Between the 80 positive gamete recipients, 177 gene variants were carried; variant classification was available for 132 variants (74.6%). The majority of gene variants carried were classified as pathogenic (59.9%), meaning that these variants are associated with causing disease. Most frequently, recipients were carriers of a variant in 1-3 genes (1 gene: 36.3%; 2 genes: 27.5%; 3 genes: 22.5%). In addition to this, 77.4% (24/31) of gamete donors were identified to carry a variant in at least one clinically relevant gene, which includes one egg donor (3.2%; 1/24) who was a carrier of an XL condition. This meant that despite the lack of co-carriage in the AR gene(s) of interest, the recipient could not proceed with this donor due to the associated risk (25%). Of the 43 recipients matched with a donor, 9.3% (4/43) showed a high reproductive risk (25%) due to their reciprocal matching results. This expanded carrier screening strategy demonstrates significant utility in identifying positive carrier status and supporting donor-recipient matching programmes by determining high risk reproductive pairs. Limitations, reasons for caution This study was retrospective in nature. The majority of recipients were Caucasian (∼80% of cases). Ethnic groups are not homogenous; there can be significant genetic, cultural, and environmental diversity between/within ethnic groups. Decision outcome data should be collected to improve this work. Wider implications of the findings The findings from this analysis suggest that there is a strong rationale for performing donor-recipient matching using an ECS approach. Increasing awareness and accessibility of ECS in this setting should be a global initiative, with the ultimate aim of reducing the burden of genetic disease in donor-conceived offspring. Trial registration number N/A

Approach for defining human adenovirus infection and disease for central review adjudication in clinical studies.

Pediatric allogeneic hematopoietic cell transplant (allo-HCT) recipients are at risk for morbidity and mortality from human adenovirus (HAdV). HAdV can be detected in an asymptomatic state, referred to as infection or with signs or symptoms of illness, referred to as disease. Standardized case definitions are needed to distinguish infection from disease and allow for consistent reporting in both observational cohort studies and therapeutic clinical trials. A working group of experts in virology, transplant infectious disease, and HCT was assembled to develop HAdV infection and disease definitions with the degree of certainty (i.e., possible, probable, and proven). Definitions were further refined through an iterative process and independently applied by two central review committees (CRCs) to 20 pediatric allo-HCT recipients with at least one HAdV-positive PCR. Initial HAdV infection and disease definitions were developed and updated through an iterative process after reviewing clinical and virological details for 81 subjects with at least one positive HAdV PCR detected in a clinical specimen. Independent application of final definitions to 20 HAdV positive allo-HCT recipients by two CRCs yielded similar number of HAdV infection or disease events but with variation of degree of certainty for some events. Application of definitions by a CRC for a study of HAdV infection and disease is feasible and can provide consistency in the assignment of outcomes. Definitions need further refinement to improve reproducibility and to provide guidance on determining clinical improvement or worsening after initial diagnosis of HAdV infection or disease.

Cytomegalovirus Reactivations in Allogeneic Hematopoietic Stem Cell Transplantation from HLA-Matched and Haploidentical Donors with Post-Transplantation Cyclophosphamide

Cytomegalovirus (CMV) reactivations cause significant morbidity in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. Graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy) is associated with an increased risk of CMV infections. Data are limited comparing HSCT with PTCy performed from matched sibling donors (MSDs), matched unrelated donors (MUDs), and haploidentical (Haplo) donors. In the present study, we aimed to characterize CMV reactivation and recurrence in patients with hematologic malignancies undergoing HSCT from MSD, MUD, and Haplo donors using PTCy as GVHD prophylaxis in the pre-letermovir era. We also analyzed risk factors of CMV reactivation, including GVHD as a time-dependent variable, on the incidence and mortality associated with CMV infections. We analyzed CMV reactivation in patients undergoing HSCT from 160 MSDs, 124 MUDs, and 82 Haplo donors from a single institution. Uniform GVHD prophylaxis with PTCy, sirolimus, and mycophenolate mofetil was given irrespective of donor type. Overall, 46% of patients had at least 1 CMV reactivation. The 1-year cumulative incidence of CMV infection was 39% for MSD, 44% for MUD, and 62% for Haplo donors (P < .001), with 96% of reactivations occurring before day +100. Multivariate analysis identified factors associated with the first CMV reactivation, including Haplo donor, positive recipient CMV serology, older patient age, and grade II-IV acute GVHD. The 1-year cumulative incidence of second reactivation from HSCT was 13%. Recipient CMV seropositivity, older patient age, and grade II-IV acute GVHD, but not type of donor, were identified as adverse factors for second CMV reactivation in multivariate analysis. The 1-year cumulative incidence of a third reactivation post HSCT was 4.4%. Ten cases of CMV disease were recorded, with no attributable deaths. Nevertheless, the risk for nonrelapse mortality was greater for patients who experienced CMV reactivation in multivariate time-dependent Cox model analysis. CMV reactivation is frequent in HSCT with PTCy in patients not receiving letermovir prophylaxis. Identified risk factors include the use of a Haplo donor, recipient CMV seropositivity, and grade II-IV acute GVHD. The prevalence of recurrent CMV reactivations is a noteworthy issue, especially after acute GVHD, warranting trials of secondary prophylaxis strategies.

Pre-transplant donor specific antibodies in ABO incompatible kidney transplantation - data from the Swiss transplant cohort study.

Living donor (LD) kidney transplantation in the setting of ABO blood group incompatibility (ABOi) has been previously reported to be associated with increased risk for antibody-mediated rejection (ABMR). It is however unclear if the presence of pre-transplant donor specific antibodies (DSA) works as an additive risk factor in the setting of ABOi and if DSA positive ABOi transplants have a significantly worse long-term outcome as compared with ABO compatible (ABOc) DSA positive transplants. We investigated the effect of pre-transplant DSA in the ABOi and ABOc setting on the risk of antibody-mediated rejection (ABMR) and graft loss in a cohort of 952 LD kidney transplants. We found a higher incidence of ABMR in ABOi transplants as compared to ABOc transplants but this did not significantly affect graft survival or overall survival which was similar in both groups. The presence of pre-transplant DSA was associated with a significantly increased risk of ABMR and graft loss both in the ABOi and ABOc setting. We could not detect an additional risk of DSA in the ABOi setting and outcomes were comparable between DSA positive ABOi and ABOc recipients. Furthermore, a combination of DSA directed at both Class I and Class II, as well as DSA with a high mean fluorescence intensity (MFI) showed the strongest relation to ABMR development and graft loss. The presence of pre-transplant DSA was associated with a significantly worse long-term outcome in both ABOi and ABOc LD kidney transplants and our results suggests that the risk associated with pre-transplant DSA is perhaps not augmented in the ABOi setting. Our study is the first to investigate the long-term effects of DSA in the ABOi setting and argues that pre-transplant DSA risk could potentially be evaluated similarly regardless of ABO compatibility status.

The first kidney transplantation in an HIV positive recipient in Slovakia.

Patients infected with human immunodeficiency virus (HIV) have long been considered unsuitable candidates for solid organ transplantation due to their poor prognosis. After the introduction of combination antiretroviral therapy, the survival of this group of patients improved significantly. HIV positive patients had been successfully transplanted for the last 18 years. HIV positive patients encounter very specific issues after transplantation, specifically related to drug interactions and higher rejection rates. Despite that, HIV positive patients have similar results to HIV negative patients post transplantation. We present the case of the first kidney transplantation in an HIV positive patient in Slovakia. The procedure was possible due to achange in legislation, as HIV positivity was an absolute contraindication for transplantation in Slovakia until October 2023. The aim of our case report is to draw attention to the possibility of kidney transplantation in an HIV positive patient and to the specific problems related to the preparation of an HIV positive patient for transplantation, post-transplant complications and the possibilities of their management (Fig. 6, Ref. 37). Keywords: kidney transplantation, HIV, human immunodeficiency virus, acute rejection, HAART, drug interaction.

Risk stratification of renal transplant recipients using routine parameters: Implication of learning from SARS-CoV-2 into transplant follow-up program.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a global pandemic that is associated with a high risk of morbidity and mortality among recipients of solid organ transplantation. In the course of acute SARS-CoV-2 infection, various laboratory markers have been identified as predictors for high risk of mortality. To risk stratify renal transplant recipients (RTxR) using general demographic parameters, comorbidities and routine laboratory markers for the severity of the disease and its outcomes. We believe that learning about these routinely moni tored parameters can help us plan better strategies for the RTxR follow-up program. This present study includes RTxR who acquired SARS-CoV-2 infection from March 2020 to February 2021. We recorded the basic demographics, comorbidities and routine laboratory markers. We investigated the impact of SARS-CoV-2 infection on RTxRs and risk-stratified the progression of disease severity and outcomes in terms of recovery or mortality. From 505 RTxRs in our renal transplant follow-up program, 29 (7.75%) RTxRs had PCR-positive SARS-CoV-2 infection. We recorded 8 deaths from SARS-CoV-2 infection giving an overall mortality rate of 1.6% but a significant 27.6% mortality in SARS-CoV-2 positive recipients. Age more than 68 years, non-Caucasian ethnicity and male gender were associated with a significant drop in survival probability; P ≤ 0.001. < 0.001 and < 0.0001 respectively. 87.5% of the deceased were diabetic; P ≤ 0.0.0001. Estimated glomerular filtration rate of less than 26 mL/min/1.73 m2, serum albumin less than 20 g/L, Hemoglobin less than 9.6 g/L and serum calcium less than 1.70 mmol/L were all associated with significantly increased risk of mortality; P = 0.0128, < 0.001, < 0.0001 and 0.0061 respectively. This study has identified some routinely used modifiable parameters in predicting a higher risk of mortality and morbidity. This knowledge can be used in RTxR follow-up programs by addressing these parameters early to help reduce the morbidity and mortality in RTxRs.

2732. Peri-Operative Antibiotic Management for Lung Transplant Recipients with Cystic Fibrosis

Abstract Background Lung transplant (LTx) recipients universally receive peri- and post-transplant antibiotics. Approaches to antibiotics for candidates with cystic fibrosis (CF) are institution specific. Little has been published about these practices. Routine LTx perioperative prophylaxis at our institution is 96 hours of vancomycin and cefepime with antibiotics then adjusted for positive intraoperative donor and recipient cultures. In recipients with CF, perioperative prophylaxis is determined pre-LTx to cover colonizing organisms isolated in culture from the 2 years before LTx, adjusted for intraoperative cultures, and administered for 14-21 days post-LTx. Our study aims to add to the current literature by describing our center’s experience with antibiotic management and outcomes in lung transplant recipients with CF to help guide best practices for prophylaxis strategies for this patient population. Methods We performed a retrospective chart review of patients with CF who underwent LTx from 3/1/2015-11/18/21 at our center and were colonized pre-LTx with MRSA, Pseudomonas aeruginosa, or Burkholderia cepacia complex. Peri- and post-operative antibiotic regimens, donor and recipient culture results, changes in antibiotic therapy post-LTx, and duration of antibiotic therapy were documented. Outcomes included rehospitalization, isolation in culture of the prophylaxis-targeted organisms post-LTx, and mortality, within 6 months of LTx. Results Nineteen incidents of LTx were included in this study. Pre-LTx colonizing organisms and antibiotics administered are outlined in table 1. Prophylaxis-targeted organisms were infrequently isolated in culture after LTx (table 2), with 7/19 (36.8%) developing post-transplant infection with prior colonizing organisms. Four (21.1%) recipients developed post-LTx Clostridioides difficile infection. One (5.3%) recipient died within 6 months post-LTx. Conclusion LTx recipients with CF who received targeted perioperative prophylaxis for pre-LTx colonizing organisms infrequently developed post-LTx culture positivity with the same bacteria including none during the antimicrobial prophylaxis period. Future prospective studies are needed to determine optimal antibiotic duration of peri-LTx antibiotics in this patient population. Disclosures All Authors: No reported disclosures

Hepatitis B virus reactivation in hepatitis B core antibody positive lung transplant recipients

BackgroundSolid organ transplant recipients with resolved hepatitis B (HBV) infection are at risk for reactivation, however, most of the studies have focused on kidney transplant recipients and have short to intermediate term follow up. Risk factors for reactivation are also uncertain, with some studies suggesting surface antibody (anti-HBs) may be protective. MethodsThis retrospective single center study aimed to assess the risk of HBV reactivation (HBVr) in lung transplant recipients with prior HBV infection as well as the value of anti-HBs titers in predicting HBVr. Surface antigen (HBsAg) negative, core antibody (anti-HBc) positive adult lung and heart-lung SOTR from 2005 to 2019 were included. The primary outcome was HBVr after transplant, defined as seroreversion to HBsAg positivity. The secondary outcome compared anti-HBs titers at transplant and at posttransplant month 12. ResultsThe cohort included 38 lung and heart-lung recipients with anti-HBc positive, HBsAg negative pretransplant serology. Reactivation occurred in 3 of 38 (8%) at 49, 69 and 94 months posttransplant. Two (5% of cohort) subjects died as a consequence of HBVr. Two of the 3 HBVr patients had anti-HBs titers >10 IU/ml at transplant and one had anti-HBs >100 IU/ml at time of HBV reactivation. We did not find a statistically significant decrease in anti-HBs titers one year after transplant in subjects with baseline anti-HBs>10 IU/ml. ConclusionThe prolonged time to reactivation highlights the lifelong risk. The 8% rate of reactivation and 5% mortality support a preferred strategy of indefinite HBV antiviral prophylaxis over monitoring in anti-HBc positive lung recipients.

Prevalence of osteoporosis and factors associated with bone density in HIV-positive kidney transplant candidates and recipients from an HIV-positive donor

Background: Studies show a high prevalence of osteoporosis and fracture risk in kidney transplant candidates and recipients. However, little is known about the prevalence of osteoporosis among transplant recipients and candidates living with HIV. Objective: To determine the prevalence of osteopenia and osteoporosis and investigate the socio-demographic and nutritional factors associated with BMD in HIV-positive transplant candidates and recipients from an HIV-positive donor. Methods: In this cross-sectional study, 20 HIV- positive transplant recipients and 36 transplant candidates on haemodialysis (HD) and awaiting transplantation had BMD and body composition measured by dual-energy X-ray absorptiometry (DEXA). Vitamin D status was measured using serum 25-hydroxyvitamin D [25(OH)D]. Dietary Vitamin D and calcium intake was obtained from a single 24-hour recall. Results: Participants were mainly black African (92.9%), male (55.4%) with a mean age of 43.8 ± 8.3 years. Serum 25(OH)D levels were low for the group as a whole, with a mean of 22.04 ± 12.74 ng/ml. Osteoporosis was more prevalent amongst transplant recipients (20.0%) than transplant candidates (13.9%). Conversely, osteopenia was present amongst transplant candidates (27.8%). T-scores strongly correlated positively, with lean mass and BMD of the spine (r = 0.707, p = 0.007), and moderately, with each side of the total hip BMD (r = 0.455, p = 0.007 and r = 0.420, p = 0.007). There was a significant positive association between dietary calcium and all BMD sites in transplant recipients only. Conclusion: The prevalence of osteoporosis was similar, and in some cases, lower than in transplant recipients elsewhere. Lean mass was positively associated with BMD, and in transplant recipients, dietary calcium intake was positively associated with BMD emphasising the role of diet and exercise in preserving BMD.

Risk Factors for CMV Infection, Including HLA Disparity and Ptcy Transplant in the Era of Letermovir Prophylaxis

Reports suggest that post-transplant cyclophosphamide (PTCy) for haploidentical and HLA-matched sibling donor allogeneic stem cell transplant (allo-SCT) is associated with a higher incidence of cytomegalovirus (CMV) infection than calcineurin inhibitor (CNI) for HLA-matched sibling donor allo-SCT. Prophylactic letermovir has been shown effective for CMV seropositive patients, based on the data mostly before the FDA approval of letermovir (2017). We reevaluated the risk of CMV infection in PTCy transplants. We retrospectively analyzed 175 patients after allo-SCT between May 2019-May 2022). CMV infection was monitored at least for the first year by serostatus, viral load over 500 IU/mL, and/or evidence of CMV end-organ disease. Univariate and multivariate Cox regression analyses were used for the factors, including CMV serostatus, use of letermovir, GVHD prophylaxis, and HLA disparities, to affect the risk of CMV infection and graft-versus-host disease (GVHD)-free relapse-free survival (GRFS). Cumulative incidence curves were used to visualize the incidence of CMV infection stratified by HLA match and PTCY use. A landmark analysis at Day +100 was used for GRFS, where patients who had CMV infection beyond Day +100 (N=13) were assigned to the no-infection group. Of the 175 patients, 108 received HLA-matched donors with GVHD prophylaxis, either CNI (N=70) or PTCy (N=38), while 67 received HLA mismatched donors with either CNI (n=6) or PTCy (N=66) ( Table). Letermovir was given to 137 patients (CMV IgG positive N=130, negative N=7) but not to 38 patients (CMV IgG positive N=12, negative N=26). CMV infection occurred in 28 patients (CMV IgG positive N= 28, CMV IgG negative N=0) before or after Day +100 (N=15 or N=13, respectively). CMV IgG positive recipients not receiving letermovir demonstrated a higher risk of infection by Day +100 than those receiving letermovir (Hazard ratio (HR) 10.1 (95% confidence interval (CI) 3.6-28.6), p&amp;lt;0.01). All 13 infections after Day +100 occurred after the cessation of letermovir (median: 82.9 days after cessation). On univariate analysis, PTCy and HLA mismatch donors increased the risk of CMV infection. The risk of infection by Day +100 increased with PTCy (p=0.07). The risk of infection after Day +100 increased with HLA mismatch donors (p=0.05). In addition, it was confirmed that HLA mismatch allo-SCT with PTCy increased the risk of CMV infection over matched allo-SCT with CNI ( Figure, HR 4.6 (95% CI 1.6-11.9), p&amp;lt;0.01), while HLA match allo-SCT with PTCy did not (p=0.3) (Figure 1). The trend was similar when analyzed only in the case of CMV infection by Day +100 (p&amp;lt;0.05) and after Day +100 (p=0.1). In the 130 CMV IgG seropositive patients who received letermovir, multivariate analysis showed that HLA mismatch donors with PTCy increased the risk of CMV infection over HLA match allo-SCT with CNI. When analyzed only for acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome with letermovir (N=91), HLA mismatch transplant with PTCy increased the risk of CMV infection over HLA match transplant with CNI (p=0.05), but not for HLA match transplant with PTCy. Landmark analysis demonstrated better GRFS in the PTCy group than the CNI group and in patients who received PTCy with CMV infection than those who received CNI without CMV infection (p&amp;lt;0.01). PTCy increased the incidence of CMV infection in HLA mismatch allo-SCT by D+100 but not HLA match allo-SCT in the era of letermovir prophylaxis. Patients with PTCy transplant who overcome CMV infection have improved GRFS, possibly due to the increased graft-versus-leukemia effect. Further analysis is required to confirm the difference in the incidence of CMV infection between HLA match and mismatch transplant with PTCy and to assess the significance of late CMV (after Day +100) infection on GRFS.

Evaluation of risk factors for cytomegalovirus DNAemia after end of regular prophylaxis after heart transplantation.

Cytomegalovirus (CMV) infections after heart transplantation (HTx) can cause cardiac allograft vasculopathy. Consequently, monitoring and prophylaxis for cytomegalovirus deoxyribonucleic acid(CMV-DNAemia) within the first weeks after HTx is recommended. All patients who underwent HTx between September 2010 and 2021 surviving the first 90 days (n = 196) were retrospectively reviewed. The patients were divided on the prevalence of CMV-DNAemia during the first postoperative year after the end of the prophylaxis. A total of n = 35 (20.1%) developed CMV-DNAemia (CMV group) and were compared to patients without CMV-DNAemia (controls, n = 139). The remaining patients (n = 22) were excluded due to incomplete data. Positive donors and negative recipients (D+/R-) and negative donors and positive recipients(D-/R+) serology was significantly increased and D-/R- decreased in the CMV group (p < .01). Furthermore, the mean age was 57.7 ± 8.7 years but only 53.6 ± 10.0 years for controls (p = .03). Additionally, the intensive care unit(p = .02) and total hospital stay (p = .03) after HTx were approximately 50% longer. Interestingly, the incidence of CMV-DNAemia during prophylaxis was only numerically increased in the CMV group (5.7%, respectively,0.7%, p = .10), the same effect was also observed for postoperative infections. Multivariate analyses confirmed that D+/R- and D-/R+CMV immunoglobulin Gmatch were independent risk factors for postprophylaxis CMV-DNAemia. Our data should raise awareness of CMV-DNAemia after the termination of regular prophylaxis, as this affects one in five HTx patients. Especially old recipients as well as D+/R- and D-/R+ serology share an elevated risk of late CMV-DNAemia. For these patients, prolongation, or repetition of CMV prophylaxis, including antiviral drugs and CMV immunoglobulins, may be considered.

311.1: Pushing the boundaries - Leading change in Australian organ donation and transplantation: First HIV positive donor to HIV positive recipient.

311.1: Pushing the boundaries - Leading change in Australian organ donation and transplantation: First HIV positive donor to HIV positive recipient.

What Went Right? A Mixed-Methods Study of Positive Feedback Data in a Hospital-Wide Mortality Review Survey.

Toxic work culture contributes to healthcare worker burnout and attrition, but little is known about how healthcare organizations can systematically create and promote a culture of civility and collegiality. To analyze peer-to-peer positive feedback collected as part of a systematized mortality review survey to identify themes and recognition dynamics that can inform positive organizational culture change. Convergent mixed-methods study design. A total of 388 physicians, 212 registered nurses, 64 advanced practice providers, and 1 respiratory therapist at four non-profit hospitals (2 academic and 2 community). Providing optional positive feedback in the mortality review survey. Key themes and subthemes that emerged from positive feedback data, associations between key themes and positive feedback respondent characteristics, and recognition dynamics between positive feedback respondents and recipients. Approximately 20% of healthcare workers provided positive feedback. Three key themes emerged among responses with free text comments: (1) providing extraordinary patient and family-centered care; (2) demonstrating self-possession and mastery; and (3) exhibiting empathic peer support and effective team collaboration. Compared to other specialties, most positive feedback from medicine (70.2%), neurology (65.2%), hospice and palliative medicine (64.3%), and surgery (58.8%) focused on providing extraordinary patient and family-centered care (p = 0.02), whereas emergency medicine (59.1%) comments predominantly focused on demonstrating self-possession and mastery (p = 0.06). Registered nurses (40.2%) provided multidirectional positive feedback more often than other clinician types in the hospital hierarchy (p < 0.001). Analysis of positive feedback from a mortality review survey provided meaningful insights into a health system's culture of teamwork and values related to civility and collegiality when providing end-of-life care. Systematic collection and sharing of positive feedback is feasible and has the potential to promote positive culture change and improve healthcare worker well-being.

Prospective assessment of pre-existing and de novo anti-HLA IgE in kidney, liver, lung and heart transplantation.

Antibody mediated rejection (ABMR) is a major factor limiting outcome after organ transplantation. Anti-HLA donor-specific antibodies (DSA) of the IgG isotype are mainly responsible for ABMR. Recently DSA of the IgE isotype were demonstrated in murine models as well as in a small cohort of sensitized transplant recipients. In the present study, we aimed to determine the frequency of pre-existing and de novo anti-HLA IgE antibodies in a cohort of 105 solid organ transplant recipients. We prospectively measured anti-HLA IgE antibodies in a cohort of kidney (n=60), liver, heart and lung (n=15 each) transplant recipients before and within one-year after transplantation, employing a single-antigen bead assay for HLA class I and class II antigens. Functional activity of anti-HLA IgE antibodies was assessed by an in vitro mediator release assay. Antibodies of the IgG1-4 subclasses and Th1 and Th2 cytokines were measured in anti-HLA IgE positive patients. Pre-existing anti-HLA IgE antibodies were detected in 10% of renal recipients (including 3.3% IgE-DSA) and in 4.4% of non-renal solid organ transplant recipients (heart, liver and lung cohort). Anti-HLA IgE occurred only in patients that were positive for anti-HLA IgG, and most IgE positive patients had had a previous transplant. Only a small fraction of patients developed de novo anti-HLA IgE antibodies (1.7% of kidney recipients and 4.4% of non-renal recipients), whereas no de novo IgE-DSA was detected. IgG subclass antibodies showed a distinct pattern in patients who were positive for anti-HLA IgE. Moreover, patients with anti-HLA IgE showed elevated Th2 and also Th1 cytokine levels. Serum from IgE positive recipients led to degranulation of basophils in vitro, demonstrating functionality of anti-HLA IgE. These data demonstrate that anti-HLA IgE antibodies occur at low frequency in kidney, liver, heart and lung transplant recipients. Anti-HLA IgE development is associated with sensitization at the IgG level, in particular through previous transplants and distinct IgG subclasses. Taken together, HLA specific IgE sensitization is a new phenomenon in solid organ transplant recipients whose potential relevance for allograft injury requires further investigation.

The impact of COVID-19 infection on heart transplant function

BackgroundHeart transplant recipients are a subset of immunocompromised patients at particularly high risk of morbidity and mortality from COVID-19. Acute effects of the viral infection have been well-described in the literature but the chronic effects persisting after recovery from infection have not. The aim of this study is to determine the impact of COVID-19 on heart transplant function both during and after recovery from acute infection.MethodsWe retrospectively analyzed the data of 32 heart transplant recipients at the University of Texas Medical Branch (UTMB). Echocardiograms of patients with documented COVID-19 infection were analyzed at three time points including pre-infection, peri-infection, and post-infection. Echocardiograms of patients without history of infection were analyzed as control. Left Ventricular Ejection Fraction (LVEF) and presence or absence of valvular insufficiency were collected from echocardiograms to assess systolic and valvular function.Results2 out of 10 COVID-19 positive heart transplant recipients had decreases in LVEF below 20% during the peri-infection period, and one of these patients passed away from complications of infection. Despite this, mean LVEF was not significantly different at peri-infection (p = .3, 95% CI − 11.5 to 27.6) or post-infection (p = .6, 95% CI − 3.6 to 5.8) time points when compared to pre-infection. A statistically significant increase in valvular dysfunction was found among COVID-19 positive patients without documented history of valvular dysfunction on pre-infection echocardiograms (p = .01, 95% CI 19.3% to 96.4%). COVID-19 negative heart transplant recipients did not experience statistically significant changes in LVEF 1, 2, or 3 years after baseline echocardiogram.ConclusionCOVID-19 may induce myocardial dysfunction resulting in decreased systolic function and valvular dysfunction among heart transplant recipients. Severity of systolic dysfunction may be a useful prognostic indicator among this patient population. More research must be conducted to fully elucidate the effects of COVID-19 infection on heart transplant recipients.

Evaluation of the relationship between de-novo DSA development and CXCR5+PD-1+CD8+ T cells and PD-1/PD-L1 mRNA expression in kidney transplant recipients.

The relationship between the Follicular Cytotoxic T cell subgroup and expression levels of PD1/PD-L1 genes and the development of donor specific antibody (DSA) is unknown. In this study, we aimed to examine CD8+CXCR5+PD-1+ follicular cytotoxic T cell levels and expression levels of PD1/PD-L1 genes in peripheral blood lymphocytes in de-novo DSA positive and negative kidney transplant recipients (KTR). In our study, expression of PD-1/ PD-L1 genes by Real-Time Quantitative PCR method and CD8+CXCR5+PD-1+ T cell expression levels by flow cytometric method were obtained from peripheral blood samples. 63 participants were included in the study (de-novo DSA positive recipients (n=22, group 1), de-novo DSA negative recipients (n=20, group 2) and healthy control (n=21, group 3). All patients had negative PRA before kidney transplantation. Expression (%) levels of target cells were evaluated by flow cytometry method. IBM SPSS Statistics for Windows Version 22 and R.3.3.2 software were used to evaluate the data. The demographic data of the groups were similar. PD-1 mRNA expression was higher in de-novo DSA positive KTR than negative (respectively, 1.03±.29/.82±.15, p: .001). CD8+CXCR5+PD-1+ T cell expression levels were found to be higher in the de-novo DSA positive group than in the negative group and similar to the healthy group (respectively, 3.06±1.98/.52±.40, p:.001, 3.06±1.98/2.78±.59, p:.62). The percentage of CD8+CXCR5+PD-1+ expressing T cells was significantly lower in the HLA-Class II+ group than other groups (HLA CI/II/ I+II, respectively, 3.63±2.72/1.65±.50/3.68±1.67, p: .04). In our study, a significant relationship was found between DSA formation and PD-1 mRNA level and CD8+CXCR5+PD-1+ follicular cytotoxic T cell in KTR.

Is Transplantation With Coronavirus Disease 2019–Positive Donor Lungs Safe? A US Nationwide Analysis

BackgroundSince the beginning of the pandemic, coronavirus disease 2019 (COVID-19) has caused debilitating lung failure in many patients. Practitioners have understandably been hesitant to use lungs from donors with COVID-19 for transplantation. This study aimed to analyze the characteristics and short-term outcomes of lung transplantation from donors with recent positive COVID-19 testing results. MethodsLung transplantations performed between January 2020 and June 2022 were queried from the United Network for Organ Sharing database. Pediatric, multiorgan, and repeat lung transplantations were excluded. Propensity scoring matched recipients of lungs from donors with recent positive COVID-19 testing results to recipients of lungs from donors with negative COVID-19 testing results, and comparisons of 30-day mortality, 3-month mortality, and perioperative outcomes were performed. ResultsA total of 5270 patients underwent lung transplantation during the study dates, including 51 patients who received lungs from donors with recent positive COVID-19 testing results. Forty-five recipients of lungs from donors with recent positive COVID-19 testing results were matched with 135 recipients of lungs from donors with negative COVID-19 testing results. After matching, there was no difference in 30-day (log-rank P = .42) and 3-month (log-rank P = .42) mortality. The incidence of other perioperative complications was similar between the groups. ConclusionsThe 30-day and 3-month survival outcomes were similar between recipients of lungs from donors with recent positive COVID-19 testing results and recipients of lungs from donors with negative COVID-19 testing results. This finding suggests that highly selected COVID-19–positive donors without evidence of active infection may be safely considered for lung transplantation. Further studies should explore long-term outcomes to provide reassurance about the safety of this practice.

A modified perioperative regimen for deceased donor kidney transplantation in presensitized recipients without prior desensitization therapy.

Renal transplantation in HLA-presensitized recipients entails an increased risk of antibody-mediated rejection (AMR) and graft loss. There is currently no accepted standard treatment protocol that can help transplant surgeons safely perform deceased donor (DD) kidney transplantation in presensitized patients without pretransplant desensitization. Fifty-one panel-reactive antibody (PRA)-positive recipients and 62 PRA-negative retransplant recipients (control) who received DD renal transplantation were included. Patients in the presensitized group (donor-specific antibody [DSA]-positive, n=25; DSA-negative, n=26) without desensitization received a modified perioperative treatment starting on day 0 or -1 with rituximab, thymoglobulin, and low daily doses of intravenous immunoglobulin (IVIG, 10-20 g/d, for 14 days). Plasmapheresis was performed once before surgery in DSA-positive recipients. The median follow-up time was 51 months in the presensitized group and 41 months in the control group. The incidence of early acute rejection (AR) and AMR (including mixed rejection) was 35.3% and 13.7% in the presensitized group, respectively, significantly higher than in the control group (14.5% and 1.6%, respectively). Within the presensitized group, the DSA-positive subgroup had more AMR than the DSA-negative subgroup (24.0% vs. 3.8%), but the incidence of T cell-mediated rejection was comparable (20.0% vs. 23.4%). In the presensitized group, all rejections were successfully reversed, and graft function remained stable during follow-up. The 1-year and 3-year survival rates of the grafts and recipients in this group were 98.0%. With a modified IVIG-based perioperative regimen, excellent intermediate-term graft and recipient survival outcomes can be achieved in presensitized patients who received DD kidney transplantation without prior desensitization.