Organ Transplantation Research Articles

Increasing Positive Attitudes towards Organ Donation and Improving the Competence of Coping with Death through Organ Transplant Nursing Course: A Two-Group Quasi-Experimental Study

AimThe aim of the study was to determine the effect of an organ transplant nursing course offered to nursing students on increasing positive attitudes towards organ donation and developing competence in coping with death. BackgroundIncorporating organ donation education into undergraduate nursing curricula and promoting of coping mechanisms for coping with death, has been emphasized as a critical foundation for the preparating of the next generation of nurses. DesignTwo-groups pre- and post-intervention evaluation quasi-experimental design study. MethodsThis study was conducted between February and July 2023 with a total of 237 nursing students studying at two different universities, 116 of whom took the organ transplant course and 121 of whom did not take the course. Sociodemographic Characteristics Form, Coping with Death Scale-Short Form and Organ Donation Attitudes Scale were used for data collection. Mann-Whitney U test, Chi-Square, t-test, Pearson correlation and linear regression were used to analyze the data. ResultsThere was a statistically significant difference between the students who took organ transplant nursing courses and those who did not in terms of the mean scores of coping with death competence and positive and negative attitudes toward organ donation (p<0.05). It was found that taking an organ transplant nursing course affected nursing students' coping with death competence and their positive and negative attitudes toward organ donation (p <0.01). ConclusionTaking the organ transplant nursing course was associated with improved competence in coping with death a increased positive and decreased negative attitudes.

Fibrosing cholestatic hepatitis as a variant of the course of hepatotropic viruses’ infection

Fibrosing cholestatic hepatitis is a special variant of infectious hepatitis, with a rapid progressive deterioration of liver function, and usually results in immunosuppression. It has also been reported in patients with immunocompetent status having viral hepatitis B and C. Fibrosing cholestatic hepatitis is diagnosed based on the histological examination of the liver tissue, which reveals severe damage to hepatocytes with pronounced ballooning over a weak inflammatory reaction, pericellular and perisinusoidal fibrosis, and intracellular and tubular cholestases. Analysis of the literature confirms the authors’ assumption that pathological changes in the liver, described as fibrosing cholestatic hepatitis, can develop in different conditions under the influence of various infectious agents. Despite the availability of effective antiviral therapy for hepatitis B and C, the outcomes of fibrosing cholestatic hepatitis are often unfavorable, particularly in cases not associated with solid-organ transplantation. Currently, because of the emergence of numerous drugs that selectively act on the immune system and the development of new areas of medicine such as hematology, rheumatology, oncology, transplantology, and infectious diseases, doctors in these specialties increasingly encounter severe liver damage in patients receiving specific therapy. The authors believe that doctors who do not work at liver transplantation centers underestimate the possibility of fibrosing cholestatic hepatitis development in patients with viral hepatitis B and C, in the clinic of infectious and internal diseases.

Exercise training in solid organ transplant candidates and recipients.

Exercise training programs are an integral part of the management of solid organ transplantation (SOT) candidates and recipients. Despite this, they are not widely available and specific guidelines on exercise parameters for each type of organ are not currently provided. A review of this topic could help clinicians to prescribe appropriate exercise regimens for their patients. In this narrative review, we discuss the physical impairments of SOT candidates and recipients and how these affect their physical function and transplant outcomes. We examine recent systematic reviews, statements, and randomized controlled trials on exercise training in SOT candidates and recipients and present the current available evidence while providing some practical recommendations for clinicians based on the frequency, intensity, time, and type principle. While randomized controlled trials of better methodology quality are needed to strengthen the evidence for the effects of exercise training and for the optimal training characteristics, the available evidence points to beneficial effects of many different types of exercise. The current evidence can provide some guidance for clinicians on the prescription of exercise training for transplant candidates and recipients.

The Liver Frailty Index: a model for establishing organ-specific frailty metrics across all solid organ transplantation.

In this review, we discuss the development of the Liver Frailty Index (LFI) and how it may serve as a model for developing other organ-specific frailty indices. As the demand for solid organ transplants continues to increase, the transplantation community is enhancing its strategies for organ allocation to gain deeper insights into patient risk profiles and anticipated outcomes. Frailty has emerged as a critical concept in transplant care, offering valuable insights into adverse health outcomes. Standardizing frailty assessment across transplant programs could enhance prognostic accuracy and inform pretransplant interventions.The LFI comprises of three performance-based tests that each represents essential components of the multidimensional frailty construct. This composite metric provides insights beyond liver function and considers nonhepatic comorbid factors. Identifying common frailty principles among all transplant candidates and adopting the LFI methodology, which assesses fundamental frailty principles using liver-specific tools, could establish a foundational pool of shared core frailty principles. From this pool, organ-specific frailty indices could be derived, each equipped with the clinically relevant organ-specific tools to evaluate common core principles. Creating a standardized framework across all solid-organ transplants, with common principles and organ-specific measurements, would facilitate consistent frailty assessment, standardize the integration of the frailty construct into transplant decision-making, and enable center-level interventions to improve outcomes for patients with end-stage organ disease.

Immunosuppression at ICU admission is not associated with a higher incidence of ICU-acquired bacterial bloodstream infections: the COCONUT study

BackgroundImmunosuppression at intensive care unit (ICU) admission has been associated with a higher incidence of ICU-acquired infections, some of them related to opportunistic pathogens. However, the association of immunosuppression with the incidence, microbiology and outcomes of ICU-acquired bacterial bloodstream infections (BSI) has not been thoroughly investigated.MethodsRetrospective single-centered cohort study in France. All adult patients hospitalized in the ICU of Lille University-affiliated hospital for > 48 h between January 1st and December 31st, 2020, were included, regardless of their immune status. Immunosuppression was defined as active cancer or hematologic malignancy, neutropenia, hematopoietic stem cell and solid organ transplants, use of steroids or immunosuppressive drugs, human immunodeficiency virus infection and genetic immune deficiency. The primary objective was to compare the 28-day cumulative incidence of ICU-acquired bacterial BSI between immunocompromised and non-immunocompromised patients. Secondary objectives were to assess the microbiology and outcomes of ICU-acquired bacterial BSI in the two groups.ResultsA total of 1313 patients (66.9% males, median age 62 years) were included. Among them, 271 (20.6%) were immunocompromised at ICU admission. Severity scores at admission, the use of invasive devices and antibiotic exposure during ICU stay were comparable between groups. Both prior to and after adjustment for pre‐specified baseline confounders, the 28-day cumulative incidence of ICU-acquired bacterial BSI was not statistically different between immunocompromised and non-immunocompromised patients. The distribution of bacteria was comparable between groups, with a majority of Gram-negative bacilli (~ 64.1%). The proportion of multidrug-resistant bacteria was also similar between groups. Occurrence of ICU-acquired bacterial BSI was associated with a longer ICU length-of-stay and a longer duration of invasive mechanical ventilation, with no significant association with mortality. Immune status did not modify the association between occurrence of ICU-acquired bacterial BSI and these outcomes.ConclusionThe 28-day cumulative incidence of ICU-acquired bacterial BSI was not statistically different between patients with and without immunosuppression at ICU admission.

Changes in post-transplant serum testosterone levels in men undergoing lung transplantation: a pilot study using the TriNetX Research Network.

Hypogonadism is understudied in men requiring solid organ transplants, particularly among lung transplant recipients. Improvement in serum testosterone levels has been reported in kidney and liver transplantation. Using the TriNetX Research Network, we performed a retrospective cohort study to evaluate the incidence of peri-transplant hypogonadism and the natural course of serum testosterone following successful lung transplantation. Men aged ≥ 18 with a lung transplant and total testosterone drawn within one year pre- and post-transplant were included. Men with receipt of testosterone therapy were excluded. A low testosterone (<300 ng/dL) and normal testosterone (≥300 ng/dL) cohort was created before employing descriptive and analytic statistics to investigate the incidence of peri-transplant hypogonadism and the change in serum testosterone levels following lung transplantation. In our entire cohort, lung transplantation was not associated with a significant increase in post-transplant serum testosterone (329.86 ± 162.56 ng/dL pre-transplant and 355.13 ± 216.11 ng/dL post-transplant, p = 0.483). The number of men with low testosterone decreased by 9.8% following lung transplantation but was not significant, p = 0.404. In this pilot study, no significant change in the number of hypogonadal men nor serum testosterone levels was observed among men undergoing lung transplantation.

The impact of immunosuppression on the mortality and hospitalization of Monkeypox: a systematic review and meta-analysis of the 2022 outbreak

BackgroundLimited data is available regarding the severity and mortality of Mpox in individuals with immunocompromised conditions. Therefore, we performed this meta-analysis to understand the impact of HIV- or non-HIV-associated immunosuppression on the severity of Mpox requiring hospitalization and mortality.MethodsA thorough literature search was performed from 2022 up to January 2024. The results were presented as odds ratios (ORs). We only included patients who required hospitalization for severity rather than isolation.ResultsA total of 34 studies were included in this analysis. Our analysis did not find a significant difference in the hospitalization risk between HIV-positive individuals and those who were HIV-negative (OR = 1.03; P = 0.85; 7 studies; CD4 count of fewer than 200 cells/µL was less than 0.5% across all studies). Patients with a CD4 count lower than 200 cells/µL or an unsuppressed RNA viral load (> 200 copies/ml) had a significantly higher hospitalization risk (OR = 5.3, P < 0.001) and (OR = 3, P < 0.001), respectively. Most of the reported deaths were reported in patients with HIV with CD4 counts below 200 cells/µL, with some fatal cases occurring in non-HIV immunosuppressed patients, particularly organ transplant recipients. Based on the autopsy findings, Mpox was confirmed in multiple organs, particularly the digestive tract, lung, and testes. Furthermore, some studies documented cases of death that were suspected to be related to hemophagocytic lymphohistiocytosis (HLH) and immune reconstitution inflammatory syndrome (IRIS). Most of the death reports showed concomitant non-Mpox infections at the time of hospitalization and deathConclusionsOur finding shows that Mpox acts as an opportunistic pathogen in immunocompromised individuals. These individuals should be prioritized for early care and closely monitored for signs of deteriorating clinical conditions. Clinical manifestations and autopsy findings strongly suggest Mpox dissemination to multiple organs, particularly the digestive tract, and lungs. However, the presence of concomitant non-Mpox infections complicates the assessment of the attribution of Mpox to death. Caution should be exercised when interpreting data suggesting poorer outcomes in individuals with non-HIV immunosuppression, as current evidence is scarce and further research is needed.

Burden and frequency of viral testing of kidney and non-kidney transplant recipients.

Transplant patients are at risk of infections due to long-term immunosuppression contributing to morbidity and mortality in this population. Post-transplant testing guidelines were established to monitor and guide therapeutic interventions in transplant recipients. We hypothesize that there are gaps in adherence to the recommended frequency of laboratory testing in post-transplant patients. We analyzed national reference laboratory data to compare viral post-transplant infection (PTI) testing frequency with their respective published guidelines to understand patient uptake and compliance. We evaluated the ordering patterns, positivity rates, and frequency of molecular infectious disease tests (MIDTs). We included 345 patients with International Classification of Diseases (ICD)-10 codes for transplant (Z940-Z942, Z944, Z9481, Z9483, Z9484) with at least two tests (within 7 days) in January 2019 and at least one test in December 2020 to find patients in the post-transplant period. We analyzed two cohorts: kidney transplant recipients (KTRs; 40%) and non-KTR (60%) then followed them longitudinally for the study period. In KTR cohort, high-to-low proportion of ordered MIDT was blood BK virus (bBKV) followed by cytomegalovirus (CMV); in non-KTR cohort, CMV was followed by Epstein-Barr virus (EBV). KTR cohort positivity was highest for urine BK virus (uBKV; 58%) followed by EBV (46%), bBKV (40%), and CMV (31%). Non-KTR cohort positivity was highest for uBKV (64%), EBV (51%), CMV (30%), bBKV (8%), and adenovirus (7%). All patients were tested at progressively longer intervals from the date of the first post-transplant ICD-10-coded test. More than 40% of the KTR cohort were tested less frequently for EBV and bBKV, and more than 20% of the non-KTR cohort were tested for EBV less frequently than published guidelines 4 months after transplant. Despite regular testing, the results of MIDT testing for KTR and non-KTR patients in the post-transplant period are not aligned with published guidelines.IMPORTANCEGuidance for post-transplant infectious disease testing is established, however, for certain infections it allows for clinician discretion. This leads to transplant center policies developing their own testing/surveillance strategies based on their specific transplant patient population (kidney, stem cell, etc.). The Organ Procurement and Transplant Network (OPTN) has developed a strategic plan to improve and standardize the transplant process in the US to improve outcomes of living donors and recipients. Publishing national reference lab data on the testing frequency and its alignment with the recommended guidelines for post-transplant infectious diseases can inform patient uptake and compliance for these strategic OPTN efforts.

A local drug delivery system prolongs graft survival by dampening T cell infiltration and neutrophil extracellular trap formation in vascularized composite allografts.

The standard treatment for preventing rejection in vascularized composite allotransplantation (VCA) currently relies on systemic immunosuppression, which exposes the host to well-known side effects. Locally administered immunosuppression strategies have shown promising results to bypass this hurdle. Nevertheless, their progress has been slow, partially attributed to a limited understanding of the essential mechanisms underlying graft rejection. Recent discoveries highlight the crucial involvement of innate immune components, such as neutrophil extracellular traps (NETs), in organ transplantation. Here we aimed to prolong graft survival through a tacrolimus-based drug delivery system and to understand the role of NETs in VCA graft rejection. To prevent off-target toxicity and promote graft survival, we tested a locally administered tacrolimus-loaded on-demand drug delivery system (TGMS-TAC) in a multiple MHC-mismatched porcine VCA model. Off-target toxicity was assessed in tissue and blood. Graft rejection was evaluated macroscopically while the complement system, T cells, neutrophils and NETs were analyzed in graft tissues by immunofluorescence and/or western blot. Plasmatic levels of inflammatory cytokines were measured using a Luminex magnetic-bead porcine panel, and NETs were measured in plasma and tissue using DNA-MPO ELISA. Lastly, to evaluate the effect of tacrolimus on NET formation, NETs were induced in-vitro in porcine and human peripheral neutrophils following incubation with tacrolimus. Repeated intra-graft administrations of TGMS-TAC minimized systemic toxicity and prolonged graft survival. Nevertheless, signs of rejection were observed at endpoint. Systemically, there were no increases in cytokine levels, complement anaphylatoxins, T-cell subpopulations, or neutrophils during rejection. Yet, tissue analysis showed local infiltration of T cells and neutrophils, together with neutrophil extracellular traps (NETs) in rejected grafts. Interestingly, intra-graft administration of tacrolimus contributed to a reduction in both T-cellular infiltration and NETs. In fact, in-vitro NETosis assessment showed a 62-84% reduction in NETs after stimulated neutrophils were treated with tacrolimus. Our data indicate that the proposed local delivery of immunosuppression avoids off-target toxicity while prolonging graft survival in a multiple MHC-mismatch VCA model. Furthermore, NETs are found to play a role in graft rejection and could therefore be a potential innovative therapeutic target.

Cardiac magnetic resonance imaging characterization of acute rejection in a porcine heterotopic heart transplantation model.

Preclinical disease models are important for the advancement of therapeutics towards human clinical trials. One of the difficult tasks of developing a well-characterized model is having a reliable modality with which to trend the progression of disease. Acute rejection is one of the most devastating complications that can occur following organ transplantation. Specifically in cardiac transplantation, approximately 12% of patients will experience at least one episode of moderate or severe acute rejection in the first year. Currently, the gold standard for monitoring rejection in the clinical setting is to perform serial endomyocardial biopsies for direct histological assessment. However, this is difficult to reproduce in a porcine model of acute rejection in cardiac transplantation where the heart is heterotopically transplanted in an abdominal position. Cardiac magnetic resonance imaging is arising as an alternative for serial screening for acute rejection in cardiac transplantation. This is an exploratory study to create and define a standardized cardiac magnetic resonance screening protocol for characterizing changes associated with the presence of acute rejection in this preclinical model of disease. Results demonstrate that increases in T1 mapping, T2 mapping, left ventricular mass, and in late gadolinium enhancement are significantly correlated with presence of acute rejection.

Blockade of CD80/CD86-CD28 co-stimulation augments the inhibitory function of peptide antigen-specific regulatory T cells.

Mixed lymphocyte culture under the blockade of CD80/CD86-CD28 co-stimulation induces anergic (completely hyporesponsive) T cells with immune suppressive function (inducible suppressing T cells: iTS cells). Previously, iTS cell therapy has demonstrated outstanding benefits in clinical trials for organ transplantation. Here, we examined whether peptide antigen-specific iTS cells are inducible. DO 11.10 iTS cells were obtained from splenocytes of BALB/c DO 11.10 mice by stimulation with OVA peptide and antagonistic anti-CD80/CD86 mAbs. When DO 11.10 iTS or Foxp3- DO 11.10 iTS cells were stimulated with OVA, these cells produced IL-13, but not IL-4. DO 11.10 iTS cells decreased IL-4 and increased IL-13 production from OVA-stimulated naïve DO 11.10 splenocytes. When Foxp3+ DO 11.10 iTS cells were prepared, these cells significantly inhibited the production of IL-4 and IL-13 compared with freshly isolated Foxp3+ DO 11.10 T cells. Moreover, an increase in the population expressing OX40, ICOS, and 4-1BB suggested activation of Foxp3+ DO 11.10 iTS cells. Thus, blockade of CD80/CD86-CD28 co-stimulation during peptide antigen stimulation augments the inhibitory function of Foxp3+ regulatory T cells, and does not induce anergic Foxp3- conventional T cells. Peptide-specific Foxp3+ regulatory iTS cells could be useful for the treatment of allergic and autoimmune diseases without adverse effects.

Is Donation after Circulatory Determination of Death in Japan Uncontrolled or Controlled?

Using donation after circulatory determination of death (DCD) donors has been shown to be a potential means of increasing the number of donors for organ transplantation. The purpose of this study was to examine the published practice of DCD in Japan to properly define their practice as controlled or uncontrolled. Through the Web of Science database, we systematically searched articles describing uncontrolled DCD, controlled DCD or Maastricht classification. A total of 12 articles (ten articles related to kidney, one to pancreas, another to islet transplantation), which were published between 1999 and 2023 from Japanese institutes, were eligible for our study. Systematic review revealed that most DCD in Japan occurs when a terminally ill patient undergoes an expected cardiac arrest without rapid discontinuation from a ventilator, and in some cases with premortem interventions such as cannulation to the femoral vessels. Surprisingly, these DCD donors in Japan have been categorized as uncontrolled DCD. This categorization confuses the donation and transplantation community globally because the international consensus is that uncontrolled DCD occurs after an unexpected cardiac arrest. Further clear definition of terminology would be required within Japan as well as other countries practicing uncontrolled DCD.

An Ethics Committee's Evaluation of Normothermic Regional Perfusion (NRP) in 2018-Unsatisfactory Answers Then-and Now.

An adult university hospital ethics committee evaluated a proposed TA-NRP protocol in the fall of 2018. The protocol raised ethical concerns about violation of the Uniform Determination of Death Act and the prohibition known as the Dead Donor Rule, with potential resultant legal consequences. An additional concern was the potential for increased mistrust by the community of organ donation and transplantation. The ethics committee evaluated the responses to these concerns as unable to surmount the ethical and legal boundaries and the ethics committee declined to endorse the procedure. These concerns endure.

Tacrolimus and Cyclosporin Pharmacotherapy, Detection Methods, Cytochrome P450 Enzymes after Heart Transplantation.

Advances in organ transplantation were made after the discovery of the pure form of cyclosporine by Dr Jean Borel in the 1970s. In fact, in clinical practice achieving a delicate balance in circulating immunosuppressive necessitate focus on the difficult task of post-transplant therapeutic drug monitoring. The purpose of this study was to determine the pharmacologic properties of cyclosporine-tacrolimus, detection methods, and the effects on the activity of cytochrome P450 enzymes when prescribing the most efficient treatments in forms of polypharmacy for the recipients of heart transplantation. Scientific literature on the interactions of tacrolimus and cyclosporine with human cytochrome P450 enzymes was searched using PUBMED.Gov (https://pubmed.ncbi.nlm.nih.gov/), Web of Science, and Scopus. Prescription immunosuppressive drugs based on polypharmacy accompanied by induction agents could result in hidden neurotoxicity and nephrotoxicity. A literature search shows that cyclosporine prescription with antihypertensives drugs needs close monitoring. Co-administration of tacrolimus and diltiazem or verapamil needs a decrease in the tacrolimus dose by 20-50%. Vigilant attention to the lowest possible statin dose is needed when coadministered with fluvastatin or pravastatin. Polypharmacy based on ticlopidine, clopidogrel, and cyclosporine or tacrolimus needs monitoring of immunosuppressive drug levels for several months. A prescription with clotrimazole or fluconazole needs close monitoring, and itraconazole or ketoconazole needs to reduce the initial dose by 50%. Combination with nefazodone needs to be avoided, and alternative drugs such as sertraline or citalopram could be prescribed in addition to further monitoring consideration. In prescription with phenytoin, the bound and free phenytoin levels need close monitoring. Polypharmacy based on tacrolimus or cyclosporine needs vigilant therapeutic drug monitoring due to the cytochrome P450 enzymes associated with biochemical variables in metabolic pathways. Further attention to polypharmacy should be given to circulate drugs that could hide pharmacokinetics interactions associated with infections, malignancies, chronic kidney disease, and rejection after organ transplantation.

Comparative risk of obesity-related cancer with glucagon-like protein-1 receptor agonists vs. bariatric surgery in patients with BMI ≥ 35.

10508 Background: Bariatric surgery is suggested to reduce the risk of obesity-related cancers, prompting us to explore whether glucagon-like peptide-1 receptor agonist (GLP-1 RA) offers a similar association. Methods: We queried TriNetX, a global healthcare database to identify patients with BMI of ≥ 35. Three pair-wise propensity score-matched (PSM) comparisons were created: 1) GLP-1 RA vs. Bariatric Surgery, 2) GLP-1 RA vs. No Intervention, 3) Bariatric Surgery vs. No Intervention. Cohorts were exclusive and no intervention was defined as an ambulatory visit. Patients required a minimum of 1 year of continuous GLP-1 RA therapy or follow-up, extended to 3 and 5 years in sensitivity analyses. Exclusions included a history of cancer or in situ neoplasms, as well as factors that significantly impact cancer risk and/or mortality including alcohol use disorder, organ transplantation, HIV, decompensated cirrhosis, peptic ulcer disease, dialysis dependency, left ventricular ejection fraction ≤ 20%, or other weight loss medication exposure. PSM utilized obesity therapy indications, Elixhauser and Charlson Comorbidity indices, prior follow-up, and demographics. Follow-up extended to 15 years, assessing 13 obesity-related cancers after intervention using Kaplan Meier (KM) and Cox-proportional Hazards Models (HR). Secondary outcomes included the risk of all-cause mortality and precancerous lesions. Results: After PSM, we identified 20,009, 3,229, and 11,104 patients in Comparison 1, 2, and 3, respectively. For Comparison 1, at 15 years, 273 (KM event rate 8.75%) patients on GLP-1 RA therapy and 397 (6.58%) with bariatric surgery developed an obesity-associated cancer, respectively (HR 0.99; 95% CI 0.87 - 1.13). Patients who received GLP-1 RA (HR 0.61; 95% CI 0.46 - 0.81) and bariatric surgery (HR 0.78; 95% CI 0.67 - 0.91) had a reduced risk of obesity-related cancer compared to no intervention. Among 20,009 patients, 40 (0.353%) and 61 (0.876%) of patients developed thyroid cancer in the GLP-1 RA and bariatric surgery groups, respectively (HR: 0.837; CI: 0.558 - 1.254). Patients lost significantly more weight after bariatric surgery as compared to GLP-1 RA at 1-2 years (BMI change -5.31 ± 6.05 vs. -1.57 ± 5.12 kg/m2; p &lt; 0.0001). GLP-1 RA initiation was associated with lower all-cause mortality compared to control (HR 0.5; 95% CI 0.40 - 0.62) and bariatric surgery (HR 0.859; 95% CI 0.77 - 0.96). Neither GLP-1 RA nor bariatric surgery was associated with precancerous lesions compared to control. Sensitivity analyses supported the above outcomes. Conclusions: GLP-1 RA was associated with a lower risk of obesity-related cancer comparable to bariatric surgery in patients with BMI ≥ 35. GLP-1 RA has superior all-cause mortality benefits despite inferior weight loss compared to bariatric surgery.

T cell-mediated rejection and cancer risk in 579,905 organ transplant recipients.

10552 Background: Prolonged immunosuppression following organ transplant raises post-transplant malignancy (PTM) risk without affecting chronic rejection graft failure (CRGF) rates. Our study investigated if T cell responses during rejection could protect against cancer, whereas T cell suppression in PTM might prevent rejection. Methods: Data from 1987 to 2023 on adult first-time single-organ transplant recipients were collected from the UNOS-OPTN database, excluding those with a history of malignancy. Time-dependent Cox regression and landmark analyses (at 1, 2, 3, 5, 10, 15, and 20 years) were used to explore the link between rejection-induced graft failure (RGF) and PTM. Results: The study included 579,905 recipients (kidney 386,878, liver 108,390, heart 45,046, lung 37,643, pancreas 1,948), with a mean follow-up of 7.3 years. RGF occurred in 9.5% of recipients (kidney 12.1%, liver 1.8%, heart 3.9%, lung 12.0%, pancreas 10.2%; p&lt;0.001), with 2.1% experiencing acute rejection graft failure (ARGF) and 7.4%, CRGF. PTM occurred in 12.0% of recipients (kidney 9.9%, liver 12.4%. heart 20.9%, lung 22.6%, pancreas 11.3%; p&lt;0.001), including breast (0.5%), digestive (1.2%), genitourinary (1.7%), gynecologic (0.1%), head and neck (0.3%), hematologic (1.4%), musculoskeletal (0.1%), neurologic (0.0%), respiratory (1.1%), and skin/Kaposi sarcoma (6.4%). In recipients with RGF, PTM risk significantly decreased (HR 0.21 [0.19-0.24]; p&lt;0.001), with consistent trends observed across seven time landmarks (HR 0.20-0.07; p&lt;0.001). Both ARGF and CRGF were associated with lower PTM risk (HR 0.23 [0.18-0.29], 0.21 [0.19-0.24]; p&lt;0.001). In organ-specific analyses, kidney transplants showed similar outcomes for RGF, ARGF, and CRGF (HR 0.21-0.22; p&lt;0.001). Lung transplants exhibited significant risk reductions with RGF (HR 0.44 [0.22-0.89]; p=0.02) and CRGF (HR 0.47 [0.24-0.94]; p=0.03), with no significant results in other organs. All findings remained consistent even after excluding re-transplantations and deaths due to rejection. Excluding PTM-related deaths from PTM cases significantly lowered RGF risk (HR 0.69 [0.65-0.73]; p&lt;0.001), a trend that was consistent across all time landmarks (HR 0.51-0.80; p&lt;0.001). This inverse pattern was seen in kidney, liver, heart, and lung transplants (HR 0.90 [0.84-0.95], 0.21 [0.11-0.38], 0.21 [0.14-0.31], 0.18 [0.14-0.23]; p&lt;0.001) but not in pancreas transplants (HR 1.62 [0.69-3.77]; p=0.27). Conclusions: This study shows that rejection lowers cancer risk in kidney and lung transplants and that PTM reduces rejection risk in kidney, liver, heart, and lung transplants. Implementing enhanced cancer screening for those who have not experienced rejection may be considered. Further research is needed to elucidate the underlying T cell biology specific to each type of transplant.

Systemic Sclerosis as a Challenge for Heart Transplantation: A Case Report

AimAssessment of the principles of qualification and the range of organ transplantation in a patient with diagnosis of system sclerosis with pulmonary manifestation and severe myocardial insufficiency. Methodswe present a 43-year-old patient with confirmed systemic sclerosis with pulmonary manifestation and biventricular heart insufficiency, after disease exacerbation and sudden cardiac arrest in the PEA mechanism with effective resuscitation, with the growing of shortness of breath and the need to use inotropes and levosimendan infusion without significantly improvement in general state. Due to the diagnosis of a systemic disease with no option of pharmacological or any other treatment of the heart failure he was re-evaluated and put on an urgent waiting list for isolated heart transplantation. After 7 days the patient was transplanted. Because of the risk of progression of the disease and possible lung transplantation in the future the pleural cavities remained untouched. The standard protocol of immunosuppression was induced with the induction of the therapy with rabbit anti-thymocyte globulin. ResultsPatient was extubated 24 hours after heart transplantation. The results of endomyocardial biopsy during the hospital stay and 6 months follow-up were negative. Patient was discharged home after 22 days of uneventful hospital stay. ConclusionsScleroderma as an autoimmunological disease still remains a challenge for transplant team as a possible progressive multiorgan insufficiency requiring organ transplantation qualification. The course of the disease varies depending on the form of systemic sclerosis. Careful assessment, qualification and determination of appropriate pre- and post-procedure immunosuppressive treatment determines the uncomplicated course of treatment.

Surging Liver Transplantation for Nonalcoholic Steatohepatitis from 2000-2022: A National Database Study.

Our aim was to provide an up-to-date, large-scale overview of the trends and clinicodemographics for NASH LTs performed in the United States compared with all other LT indications between 2000 and 2022. We also examined the demographic factors that will predict future demand for NASH LT. Our analysis of NASH LT from the Organ Procurement & Transplantation Network database spanning 2000-2022 consisted primarily of descriptive statistics and hypothesis testing with corrections for multiple testing when necessary. Trend lines and linear correlations were also explored. NASH LTs have experienced a remarkable surge, escalating from 0.12% of all LTs in 2000 to a substantial 14.7% in 2022, marking a 100-fold increase. Examining demographic trends, a significant proportion of NASH LTs recipients fall within the 50- to 64-year-old age group. Moreover, 52% of these recipients concurrently exhibit type 2 diabetes mellitus, a notably higher percentage than the 19% observed in all LT recipients. Type 2 diabetes mellitus emerges as a prominent risk factor for NASH progressing to end-stage liver disease. The phenomenon of repeat transplantation is noteworthy; although 6% of all LTs necessitate repeat procedures, this figure dramatically drops to 0.6% for NASH LTs. Ethnic disparities are apparent, with African Americans representing a mere 2% of NASH LT recipients, significantly lower than their representation in the overall population. Regionally, the East Coast has a higher proportion of NASH LT recipients compared with waitlist additions. This trend holds true across demographics. Our findings underscore the need for increased resources, particularly for minority, uninsured, or noncitizen individuals requiring LT for NASH. This analysis provides valuable insights into the dynamic landscape of LTs in the context of NASH, shaping the trajectory of medical interventions in the 21st century.

Comparative effectiveness of the bivalent COVID-19 mRNA vaccines, mRNA1273-222 and BNT162b2, in immunocompromised adults in the US.

e23057 Background: Despite the decline in COVID-19–related hospitalizations and mortality during the period of omicron predominance, immunocompromised individuals, including those with cancer, remain at an increased risk for severe COVID-19 outcomes. A subanalysis of a retrospective observational cohort study assessed the relative vaccine effectiveness (rVE) of 2 previously approved bivalent vaccines targeting the ancestral SARS-CoV-2 and the omicron BA.4/BA.5 variant, mRNA-1273.222 (Moderna, Inc., Cambridge, MA, USA) and BNT162b2 bivalent (Pfizer Inc., New York, NY, USA; BioNTech GmbH, Mainz, Germany), in immunocompromised adults in the United States. Methods: The study used a US electronic health record dataset (Veradigm) linked with medical and pharmacy claims data of adults aged ≥18 years with at least 1 underlying medical condition associated with increased risk of severe COVID-19 who received a dose of mRNA-1273.222 or BNT162b2 bivalent vaccines between August 31, 2022, and February 28, 2023. A subgroup analysis was conducted among an immunocompromised population, encompassing cancer patients, organ or stem cell transplant recipients, individuals with primary immunodeficiency, individuals with HIV, and individuals receiving immunosuppressing medications. Comorbid conditions were based on prior medical encounters in the 365 days before vaccination. The outcomes measured were rVE of the two bivalent mRNA vaccines against COVID-19-related hospitalizations (primary outcome) and outpatient visits (secondary outcome). Follow-up started 7 days after vaccination until May 31, 2023 (end of available claims data). Propensity score weighting was used to adjust for baseline differences between groups. Results: The subanalysis included 427,260 immunocompromised individuals, of which 250,573 (58.6%) were identified as having cancer. In the overall weighted immunocompromised population, 169,509 individuals received mRNA-1273.222, and 257,751 received BNT162b2 bivalent. The adjusted rVEs of mRNA-1273.222 versus BNT162b2 bivalent vaccine against COVID-19–related hospitalizations and outpatient visits were 15.0% (95% CI, 7.2%-22.0%; P&lt; 0.001) and 4.8% (95% CI, 1.8%-7.7%; P= 0.002), respectively. Conclusions: In this study, the mRNA-1273.222 vaccine offered greater protection against COVID-19–related hospitalization compared with the BNT162b2 bivalent vaccine among immunocompromised individuals. This study emphasizes the importance of assessing COVID-19 vaccine formulations and optimizing protection, especially in immunocompromised adults, including those with cancer.

Early extracorporeal photopheresis treatment is associated with better survival in patients with chronic or recurrent acute lung allograft dysfunction.

Due to development of chronic lung allograft dysfunction (CLAD), prognosis for patients undergoing lung transplantation (LTx) is still worse compared to other solid organ transplant recipients. Treatment options for slowing down CLAD progression are scarce with extracorporeal photopheresis (ECP) as an established rescue therapy. The aim of the study was to identify characteristics of responders and non-responders to ECP treatment, assess their survival, lung function development and by that define the subset of patients who should receive early ECP treatment. We performed a retrospective study of all LTx patients receiving ECP treatment at the University Hospital Zurich between January 2010 and March 2020. Patients were followed-up for a maximum period of 5 years. Mortality and lung function development were assessed by CLAD stage and by CLAD subtype before initiation of ECP treatment. Overall, 105 patients received at least one ECP following LTx. A total of 57 patients (61.3%) died within the study period with a median survival of 15 months. Mortality was 57% for patients who started ECP at CLAD1, 39% for CLAD2, 93% for CLAD3, and 90% for CLAD4 (p < 0.001). Survival and lung function development was best in young patients at early CLAD stages 1 and 2. Response to ECP treatment was worst in patients with CLAD-RAS/mixed subtype (14.3%) and patients with ECP initiation in CLAD stages 3 (7.1%) and 4 (11.1%). Survival was significantly better in a subset of patients with recurrent acute allograft dysfunction and earlier start of ECP treatment (105 vs 15 months). In this retrospective analysis of a large group of CLAD patients treated with ECP after LTx, early initiation of ECP was associated with better long-term survival. Besides a subset of patients suffering of recurrent allograft dysfunction, especially a subset of patients defined as responders showed an improved response rate and survival, suggesting that ECP should be initiated in early CLAD stages and young patients. ECP might therefore prevent long-term disease progression even in patients with CLAD refractory to other treatment options and thus prevent or delay re-transplantation.