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The determination of panel reactive antibodies (cPRA) scores plays a critical role in assessing the immunological compatibility between organ transplant recipients and potential donors. Traditional cPRA methods focus on a limited number of HLA loci using physical cytotoxicity tests. However, advancements such as the Luminex single antigen (LSA) assay, which uses mean fluorescence intensity (MFI) of individualised HLA antigens for antibody evaluation, provide a foundation for a more precise assessment. We developed cPRAdictor, a novel cPRA calculation tool using a large series of HLA-type individuals in France with NGS. cPRAdictor was applied to a cohort of 5962 kidney transplant candidates in Paris. We analysed how extending the range of HLA specificities could affect cPRA values. Implementing cPRAdictor revealed and allowed quantification of the significant discrepancies in cPRA values that appeared when HLA loci C and DP, and antigen-specific antibodies were taken into account. Notably, over 43% of the immunised transplant candidates showed an increase in calculated cPRA values when considering C/DP loci and antigen-specific antibodies, negatively impacting their eligibility and prioritisation in the transplantation programme. These findings highlight the necessity of revisiting cPRA calculation methodologies to include a broader spectrum of immunological data, as more exhaustive and precise information regarding anti-HLA antibodies in patients' sera and donor and recipient HLA typing are available prospectively. This will strongly improve both accuracy and equity at the organ allocation step, especially for highly sensitised candidates for whom organ offers are very limited in number.

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The national transplant law in Colombia, Law 1805 of 2016, modified the Colombian legislation regarding how a person accesses an organ transplant, but above all, it changed the donor figure, establishing the term derived from the presumptive consent right. This term implies a person's hypothetical willingness to be an organ donor as a manifestation of solidarity and charity towards another person in a situation of need and vulnerability concerning his/her health and the dimensions that define it. In the following text, seven moments are considered fundamental facts when constructing a culture about the value of healthcare in the national transplant policy in Colombia.

La Ley Nacional de Trasplantes en Colombia, Ley 1805 de 2016, modificó la legislación colombiana en cuanto a cómo se accede a un trasplante de órganos, pero, sobre todo, cambió la figura de donatario y dispuso el término derivado del derecho del consentimiento presuntivo. Este define la hipotética voluntad de una persona de ser donante de órganos como manifestación de solidaridad y beneficencia con otra persona en situación de necesidad y vulnerabilidad relacionada con su salud y las dimensiones que la definen. En el siguiente texto se presentan siete momentos que se consideran hechos fundamentales en la construcción de una cultura del valor de la atención en salud en la política nacional de trasplantes de Colombia.

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Routine screening of organ donors to detect human immunodeficiency virus (HIV) infection has detected the rare transmission of the virus through organ transplantation. However, despite routine screening, HIV transmission remains a risk in organ transplantation since, unlike tissues, solid organs cannot be processed, disinfected, or modified to inactivate infectious pathogens. A case of possible transmission of HIV by organ transplant is described below, from a previously seronegative donor to two recipients.

El examen de rutina de los donantes de órganos para detectar la infección por el virus de la inmunodeficiencia humana (HIV) ha hecho que la transmisión del virus mediante el trasplante de órganos sea poco común. Sin embargo, a pesar de las pruebas de detección de rutina, la transmisión del HIV continúa siendo un riesgo del trasplante de órganos ya que, a diferencia de los tejidos, los órganos sólidos no se pueden procesar, desinfectar, ni modificar para inactivar patógenos infecciosos. A continuación, se describe un caso de posible transmisión de HIV por trasplante de órganos de un donante previamente seronegativo a dos de sus receptores.

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Although pediatric organ donation represents a small proportion of overall organ donation, children and adolescents make a significant contribution to the pool of donated organs. In this study 252 solid organs were collected from children and adolescent. Two hundred and two recipients benefited from 62 pediatric organ donors, with a recipient/donor ratio of 3.3.

BACKGROUND: Pediatric organ donors represent a small but important portion of the deceased donor pool, helping both children and adults in the transplant waitlist. Despite this, pediatric donation remains an overlooked subject of research. METHODS: Retrospective, single­center, descriptive study. All brain death patients under 18 years old who were admitted to the Intensive Care Unit (ICU) between January 1st, 2006, and December 31st, 2021, and who were eligible for organ donation were included. RESULTS: Between January 2006 and December 2021, 200 children/adolescent died in the ICU. From those, 62 patients (31%) were considered eligible for organ donation. The mean age of the donors at the time of death was 8.8 years. Sixty­three per cent were male. The most frequent cause of death was traumatic brain injury (n = 36). Two hundred and fifty organs were collected benefitting 202 persons with a recipient/donor ratio of 3.3. Kidneys were the most frequent organ donated (n = 116), followed by liver (n = 56) and heart (n = 34). The median number of organs donated per child was four, with a minimum of 1 organ and maximum of 8. CONCLUSIONS: Pediatric organ donation represents a small proportion of overall organ donation, but children and adolescents have important impact on the lives they save. The field of pediatric organ donation needs more research to better understand the contribution of the pediatric population to both adults and children who wait for an organ.

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Solid organ transplantation has progressed rapidly over the decades from the first experimental procedures to its role in the modern era as an established treatment for end-stage organ disease. Solid organ transplantation including liver, kidney, pancreas, heart, and lung transplantation, is the definitive option for many patients, but despite the advances that have been made, there are still significant challenges in meeting the demand for viable donor grafts. Furthermore, post-operatively, the recipient faces several hurdles, including poor early outcomes like primary graft dysfunction and acute and chronic forms of graft rejection. In an effort to address these issues, innovations in organ engineering and treatment have been developed. This review covers efforts made to expand the donor pool including bioengineering techniques and the use of ex vivo graft perfusion. It also covers modifications and treatments that have been trialed, in addition to research efforts in both abdominal organs and thoracic organs. Overall, this article discusses recent innovations in machine perfusion and organ bioengineering with the aim of improving and increasing the quality of donor organs.

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BACKGROUND: Life with end-stage organ failure is accompanied by an accumulation of traumatic medical or surgical experiences. Despite recovery after solid organ transplantation (SOT), many children and adolescents develop post-traumatic stress symptoms (PTSS). PTSS remain underappreciated as a major comorbidity in SOT programs, despite their association with decreased quality of life. METHODS: We conducted a retrospective, cross-sectional study of 86 pediatric SOT recipients (17 heart, 44 kidney, and 25 liver) to evaluate potential determinants of PTSS. Trauma symptoms were measured by the Child Trauma Screening Questionnaire (CTSQ). Demographic, baseline, and contemporaneous factors were tested for independent association with CTSQ scores. RESULTS: The median post-transplant CTSQ score was 2 (IQR 1-4), and 22% were identified as high risk (score ≥5) for PTSD. Higher CTSQ scores were independently associated with the number of ICU days within the previous 12 months, the number of medications (complexity), and involvement with foster care in the primary model (R2 [adj.] = 0.26). The addition of the Family Impact Module improved the overall model (R2 [adj.] = 0.33), wherein higher family functioning was independently associated with lower CTSQ scores. An exploratory analysis of pre-transplant patients (n = 34) found a median pre-transplant CTSQ of 2 (IQR 1-6), suggesting that PTSS are onset before transplant and persist afterward. CONCLUSIONS: PTSS are highly prevalent in the SOT population. Risk factors include recent adverse medical experiences and complexity, whereas family stability may be protective. Additional research is needed to improve early ascertainment and support for patients at high risk of developing PTSS throughout their transplant journey.

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Importance: Median organ waiting times published by transplant organizations may be biased when not appropriately accounting for censoring, death, and competing events. This can lead to overly optimistic waiting times for all transplant programs and, consequently, may deceive patients on the waiting list, transplant physicians, and health care policymakers. Objective: To apply competing-risk multistate models to calculate probabilities for transplantation and adverse outcomes on the Swiss national transplant waiting list. Design, Setting, and Participants: The WAIT (Waitlist Analysis in Transplantation) study was a retrospective cohort study of all transplant candidates in Switzerland listed from January 1, 2018, or later and observed until December 31, 2023. Transplant candidates were listed in 1 of the 6 transplant centers (Basel, Bern, Geneva, Lausanne, St Gallen, and Zurich) for heart, liver, lungs, kidney, or pancreas and/or islet transplant. A total of 4352 candidates were listed during the study period, of whom 709 (16.3%) were excluded due to living-donor transplant (691 in the kidney program and 18 in the liver program). Exposure: Waiting for organ transplant. Main Outcomes and Measures: Time to transplantation, death, or delisting. Competing-risk multistate models were used to analyze time-to-event data from the national organ waiting list with the Aalen-Johansen estimator to compute probabilities for both transplant and adverse outcomes. Results were compared with the sample median among only those undergoing transplant and the Kaplan-Meier method with censoring of competing events. Results: Data from 3643 transplant candidates (2428 [66.6%] male; median age, 56 [range, 0-79] years) were included in the analysis. The median time to transplantation (MTT) was 0.91 (95% CI, 0.83-1.07) years for heart, 3.10 (95% CI, 2.57-3.77) years for kidney, 1.32 (95% CI, 0.76-1.55) years for liver, 0.80 (95% CI, 0.37-1.12) years for lung, and 1.62 (95% CI, 0.91-2.17) years for pancreas and/or islet programs. Alternative estimation methods introduced bias to varying degrees: the sample median among only persons undergoing transplantation underestimated the waiting time by 38% to 61% and the Kaplan-Meier method by 2% to 12% compared with the MTT. Conclusions and Relevance: In this cohort study of transplant candidates in Switzerland, the MTT, the duration at which the transplant probability is 0.50, was used as a measure of average waiting time. Suboptimal methods led to biased and overly optimistic waiting time estimations; thus, applying appropriate competing-risk methods to address censoring and competing events is crucial.

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Cytomegalovirus (CMV) infection is arguably the most important infectious complication that negatively affects the outcome of solid organ transplantation. For decades, CMV management after transplantation has relied on antiviral drugs that inhibit viral DNA polymerase (ganciclovir, foscarnet, and cidofovir). However, their use has been complicated by myelosuppression, nephrotoxicity, and selection of drug-resistant viruses. During the past few years, the therapeutic armamentarium for the management of CMV in solid organ transplant recipients has expanded with the approval of letermovir for CMV prophylaxis in high-risk CMV D+/R- kidney recipients, and maribavir for the treatment of refractory and resistant CMV infection. Both drugs offer significant improvement when compared to standard anti-CMV therapies; letermovir was as efficacious for CMV prevention, whereas maribavir was more effective in treating refractory and resistant CMV infections. Both letermovir and maribavir have favorable safety profiles compared to CMV DNA polymerase inhibitors, without the risk of neutropenia and leukopenia associated with ganciclovir and renal toxicities associated with foscarnet and cidofovir. Moreover, letermovir and maribavir are orally bioavailable, which allows convenient outpatient treatment. However, letermovir and maribavir have a significant drug interaction potential in solid organ transplant recipients, resulting in higher levels of calcineurin inhibitors (cyclosporine and tacrolimus) and mTOR inhibitors (sirolimus and everolimus). Both letermovir and maribavir are CMV-specific and do not have clinical efficacy against other herpes viruses. Thus, there is a need for additional antiviral drugs to prevent herpes simplex and other herpes viruses when clinically indicated. This article provides a comprehensive review of the clinical data supporting the use of letermovir and maribavir in clinical practice. The author provides perspectives on the role of these newly approved drugs in the current management landscape of CMV infection in solid organ transplantation.

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Solid organ transplant recipients (SOTRs) are at high risk of cutaneous squamous cell carcinoma (cSCC) metastasis. Despite prior studies identifying risk factors, mortality remains high. Understanding additional risk factors may aid in reducing mortality in this population. This study aimed to investigate risk factors and predictive variables for metastatic cSCC in SOTRs. The primary goal was to accurately identify transplant patients at increased risk of metastatic cSCC. A retrospective case-control study in a single institution of 3576 cases of organ transplants were identified from January 1991 to July 2022. A cohort of metastatic cancer patients and two randomly generated age and organ matched control cohorts were identified. 16 SOTR patients developed metastatic cSCC. The majority were male, with high-risk tumor sites. Tumor depth varied and half exhibited perineural invasion. Cylex® (p = 0.05) and white blood cell counts (p = 0.04) were significantly lower in these patients compared to control. Lung transplants were at highest risk relative to other solid organ transplants. Voriconazole exposure was also associated with increased metastatic risk (p = 0.04). Small sample size at a single institution. Close monitoring of SOTR, especially those with lung transplants given their increased risk, reducing immunosuppression, and limiting exposure to voriconazole can improve outcomes in SOTRs with metastatic cSCC.

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Background: Observational studies have suggested that herpes virus infections increase the risk of allograft dysfunction after tissue and organ transplantation, but it is still unclear whether this association is causal. The aim of this study was to assess the causal relationship between four herpes virus infections and allograft dysfunction. Methods: We used two-sample bidirectional Mendelian randomization (MR) to investigate the causality between four herpes virus infections - cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV) and varicella zoster virus (VZV) - and allograft dysfunction after tissue and organ transplantation. Based on summary data extracted from genome-wide association studies (GWAS), we chose eligible single nucleotide polymorphisms (SNPs) as instrumental variables. The Inverse variance weighted (IVW) method was used as the main analysis method, supplemented by Weighted median and MR-Egger analyses. The MR-PRESSO test, MR-Egger intercept test, heterogeneity test, leave-one-out analysis and funnel plot were used to analyze the sensitivity of MR results. Results: We found EBV early antigen-D (EA-D) antibody levels and shingles were the only two variables associated with an increased risk of allograft dysfunction. No evidence of allograft dysfunction increasing the risk of the four herpes virus infections was observed. Sensitivity analyses confirmed the robustness of our results. Conclusions: Our results suggest that EBV and VZV are involved in graft rejection or dysfunction. However, the relationship between CMV and HSV infections and allograft dysfunction remains unclear and requires further clarification.

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Ehrlichiosis and anaplasmosis are rising tickborne infections posing significant risks to solid-organ transplant (SOT) patients. We present three cases highlighting clinical presentations, diagnostic challenges, and the benefits of microbial cell-free DNA (mcfDNA) sequencing. Emphasizing early diagnosis and preventive measures, we advocate for advanced diagnostic modalities to improve outcomes in this vulnerable population.

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PURPOSE OF REVIEW: Prehabilitation, defined as preparing the body physically and psychologically for upcoming surgery is of increasing prominence in presurgical care. The aim of this review is to discuss the evidence base around prehabilitation in solid organ transplantation, the use of digital health as a tool to deliver these interventions, and consider future directions. RECENT FINDINGS: Prehabilitation is of increasing interest as an adjunct to pretransplant care for individuals working up for solid organ transplantation. To date, research has shown that prehabilitation is acceptable and feasible; however, the literature base remains small. The majority of research has been delivered using in-person rehabilitation programmes, and the evidence base utilizing digital health as a means to deliver prehabilitation is limited. SUMMARY: To date, the research evidence base in prehabilitation for solid organ transplantation is limited. Evidence in other surgical populations has demonstrated promising results, particularly in aerobic capacity, physical function and postoperative complications. Further high-quality randomized controlled clinical trials are required to strengthen the evidence base, understand how digital health can be harnessed and utilized to deliver multimodal prehabilitation with an aim to see how this may form part of routine care in the solid organ transplantation pathway.

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Human cytomegalovirus (HCMV) infection remains a major complication for solid organ transplant recipients (SOTRs). The aim of this study was to evaluate the role of HCMV-specific T cell immunity measured at the time of the HCMV-DNA peak in predicting the spontaneous clearance of infection. The performance of cytokine flow cytometry using infected dendritic cells (CFC-iDC), infected cell lysate (CFC-iCL) and pp65 peptide pool (CFC-pp65 pool) as stimuli, as well as ELISPOT assays using infected cell lysate (ELISPOT-iCL) and the pp65 peptide pool (ELISPOT-pp65 pool), was analysed. Among the 40 SOTRs enrolled, 16 patients (40%) required antiviral treatment for an HCMV infection (Non-Controllers), while the others spontaneously cleared the infection (Controllers). At the HCMV-DNA peak, the number of HCMV-specific CD4+ T cells detected by the CFC-iDC, CFC-iCL and CFC-pp65 pool assays in Controllers was higher than that detected in Non-Controllers, while no difference was observed in terms of HCMV-specific CD8+ T cell response. The same trend was observed when the HCMV-specific T cell response was measured by ELISPOT-iCL and ELISPOT-pp65 pool. We observed that the CD4+ CFC-pp65 pool assay was the best predictor of self-resolving HCMV infection at the time of the HCVM-DNA peak. The CFC-pp65 pool assay is able to discriminate between CD4+ and CD8+ T cell responses and could be used in daily clinical practice.

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BACKGROUND: Patients listed for solid organ transplants (LSOTP) are at high risk for severe COVID-19 outcomes. Despite national guidelines recommending COVID-19 vaccination for LSOTP, vaccine hesitancy and underuse are reported in this population; however, reasons for this finding have not been examined thoroughly. METHODS: This single-center retrospective survey analysis aimed to characterize reasons for COVID-19 vaccine hesitancy among 110 heart, liver, and kidney patients LSOTP who had not received all the recommended vaccine doses at the time of the study. Survey questions also investigated experiences with influenza vaccination. RESULTS: Fifty-four patients (49.1%) responded to the telephone survey. The most common reasons for vaccine hesitancy were perceived lack of research in vaccine development (31%), fear of vaccine-related side effects (22%), and belief that the vaccine was unnecessary (20%). Of the respondents, 35% reported changing their vaccine perception after being listed for a transplant, most commonly attributing this to a perception that the COVID-19 vaccine is not safe for transplant recipients (32%). Gender differences in hesitancy reasons were observed, with males more likely to delay vaccination until after transplantation, although this difference was not significant (P = .07). Despite these findings, 54% of all respondents reported receiving annual influenza vaccines consistently. CONCLUSION: Despite their risk, patients LSOTP show significant hesitancy toward COVID-19 vaccines owing to perceived safety and necessity issues. The results of this study can inform targeted educational efforts to address and rectify misconceptions and concerns about COVID-19 vaccination among patients LSOTP. Future studies focused on larger, more diverse cohorts are needed to expand our understanding of and address vaccination hesitancy among this vulnerable patient population.

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BACKGROUND: Solid organ transplant recipients experience a period of unique vulnerability during adolescence, when normative developmental changes intersect with health-related variables to influence psychological health. METHODS: This article builds on previous reviews of psychological health in solid organ transplant recipients and proposes opportunities for clinical intervention during adolescence. RESULTS: Transplant recipients often experience neurocognitive changes, particularly with respect to executive functions, that impact health management tasks and autonomous care. Recipients should be monitored for the development of anxiety, depression, and posttraumatic stress symptoms during adolescence, which in turn can negatively impact adherence to immunosuppression. Recent research in posttraumatic growth and resiliency factors may represent a promising avenue of intervention, leveraging normative developmental processes during this time period. CONCLUSIONS: As pediatric transplant providers, adolescence represents a developmental period for targeted interventions to foster adjustment and adherence and promote a successful transition to adult care.

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In recent years, the Middle East has witnessed a significant rise in commercial transplantation activities. This practice is driven by a multitude of factors including economic disparities, inadequate healthcare infrastructure, and cultural attitudes towards organ donation. In this article, we try to explore the complex landscape of commercial transplantation within the Middle East, shedding light on the ethical, legal, and socio-economic dimensions of this contentious issue.

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