Post-transplant Follow-up Research Articles

Increased delay to lung transplantation for women candidates: gender-based disparity matters in the lung transplant trajectory

BackgroundLung transplantation (LT) is a highly dynamic segment of solid organ transplantation in which gender plays a central role.Our objective was to investigate the causes of outcome differences between women and men all along the LT pathway.MethodsWe used data from the COhort in Lung Transplantation (COLT) study (12 participating LT centers). Analyses were performed in three phases: baseline clinical characteristics, peri-transplantation period, and post-transplantation follow-up.ResultsOverall, 1710 participants (802 women and 908 men) were included in this study. Women were less likely than men to undergo transplantation (91.6%versus95.6%, p=0.001) and waited longer before transplantation (115versus73 days, p<0.001). Female gender and pre-transplant class I anti-HLA antibodies were identified as independent factors associated with longer waiting time duration. Female LT recipients commonly received lungs from height- and sex-matched donors, despite higher female waiting-list mortality and a higher proportion of male donors. Importantly, women with oversized lung transplantation (defined by predicted TLC ratio and weight mismatch) did not have worse survival. The overall post-transplant survival of female recipients was significantly higher than that of male recipients (65.6%versus57.3%, p<0.001), although the prevalence of specific major LT outcomes did not differ according to gender.ConclusionWomen waited longer and were less likely to undergo transplant. Women transplanted with an oversized lung did not have worse survival after transplantation, suggesting that size matching criteria based on pTLC ratio and weight mismatch may be less stringent in this context.

Predicting graft survival in paediatric kidney transplant recipients using machine learning.

Identification of factors that affect graft survival in kidney transplantation can increase graft survival and reduce mortality. Artificial intelligence modelling enables impartial evaluation of clinician bias. This study aimed to examine factors that affect the survival of grafts in paediatric kidney transplantation through the use of machine learning. A retrospective review was conducted on records of paediatric patients who underwent kidney transplantation between 1994 and 2021 and had post-transplant follow-up > 12months. The nearest neighbour method was used to impute missing fields from a total of 48 variables in the dataset. Models including Naive Bayes, logistic regression, support vector machine (SVM), multi-layer perceptron, and XGBoost were trained to predict graft survival. The study used 80% of the patients for training and the remaining 20% for testing. Modelling success was evaluated based on accuracy and F1 score metrics. The study analysed 465 kidney transplant recipients. Of these, 56.7% were male. The mean age at transplantation was 12.08 ± 5.01years. Of the kidney transplants, 73.1% (n = 339) were from living donors, 34.5% (n = 160) were pre-emptive transplants, and 2.2% (n = 10) were second-time transplants. The machine learning model identified several features associated with graft survival, including antibody-mediated rejection (+ 0.7), acute cellular rejection (+ 0.66), eGFR at 3years (+ 0.43), eGFR at 5years (+ 0.34), pre-transplant peritoneal dialysis (+ 0.2), and cadaveric donor (+ 0.2). The successes of the logistic regression and SVM models were similar. The F1 score was 91.9%, and accuracy was 96.5%. Machine learning can be used to identify factors that affect graft survival in kidney transplant recipients. By expanding similar studies, risk maps can be created prior to transplantation.

Haploidentical hematopoietic stem cell transplantation using post-transplant cyclophosphamide in patients with inborn errors of immunity: Experience in a reference center in Colombia

Inborn errors of immunity is a diverse group of rare diseases caused by over 400 genetic mutations affecting the immune system and increasing infection susceptibility, autoimmunity, and malignancy. Hematopoietic stem cell transplantation offers a curative option for some inborn errors of immunity, with haploidentical donors providing a viable alternative when identical donors are unavailable. To determine survival, usefulness of weekly chimerism monitoring, immune reconstitution, and complications in patients with inborn errors of immunity who underwent haploidentical hematopoietic stem cell transplantation at a reference center in Colombia. We conducted a retrospective and observational study of a case series of pediatric patients who underwent haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide and follow-up with weekly chimerism. Survival analysis was performed using the Kaplan-Meier method. Sixteen patients with haploidentical familial donor transplantation were included. The most frequent diagnosis was severe combined immunodeficiency (n=5). Eleven out of seventeen patients received a non-myeloablative conditioning regimen. Twelve out of sixteen patients developed acute graft-versus-host disease. Out of these, 3 corresponded to grades III-IV. Post-transplant infections affected 14 of the subjects, predominating bacterial agents. Median T-cell chimerism was greater than 80% during the follow-up. Reconstitution of B and T lymphocytes was achieved in more than 80%. Overall survival at five years was 81%. Survival at 100 days was 94%. Haploidentical hematopoietic stem cell transplantation using post-transplant cyclophosphamide is a viable alternative for inborn errors of immunity when an identical donor is unavailable. Serial chimerism monitoring is useful for graft follow-up.

Transfusions, disease-modifying treatments, and curative therapies for sickle cell anemia in Africa: where are we now?

The mortality burden of sickle cell anemia (SCA) is centered in sub-Saharan Africa. In addition to a lack of systematic programs for early diagnosis, access to disease-modifying treatments is limited to only a few urban centers. Providing a safe and adequate blood supply is a major challenge, heightening mortality from SCA-associated complications that require urgent blood transfusion and making the delivery of regular transfusion therapy for stroke prevention nonfeasible. Hydroxyurea therapy with proven clinical benefits for pain episodes, acute chest syndrome, malaria, transfusions, hospitalizations, and stroke prevention is the most feasible treatment for SCA in Africa. Access barriers to hydroxyurea treatment include poor availability, unaffordable costs, health professionals' reluctance to prescribe, a lack of national guidelines, and exaggerated fears about drug toxicities. Strategies for the local manufacture of hydroxyurea combined with the systematic education and training of health professionals using guidelines supported by the World Health Organization can help surmount the access barriers. Hematopoietic stem cell transplantation as a curative therapy is available in only 7 countries in Africa. The few patients who have suitable sibling donors and can afford a transplant must usually travel out of the country for treatment, returning to their home countries where expertise and resources for posttransplant follow-up are lacking. The recently developed ex-vivo gene therapies are heavily dependent on technical infrastructure to deliver, a daunting challenge for Africa. Future in-vivo gene therapies that bypass myeloablation and ex-vivo processing would be more suitable. However, enthusiasm for pursuing these gene therapies should not overlook strategies to make hydroxyurea universally accessible in Africa.

Infections in Kidney Transplant Recipients: Perspectives in French Caribbean.

Few studies have focused on the infectious complications in kidney transplant recipients in tropical regions, particularly in the Caribbean. The primary objective of this study was to determine the incidence of bacterial, fungal, and parasitic infections in kidney transplant recipients in the French Caribbean and French Guiana. We included all patients who received a kidney transplant at the University Hospital of Guadeloupe between January 2014 and October 2016, with post-transplant follow-up in the French Caribbean. A total of 91 patients were included, of whom 57 developed an infectious event during follow-up. When infections were documented (94/111), bacterial infections were the most frequent (79/94), followed by fungal (11/94) and parasitic infections (4/94). Four cases of nocardiosis were identified (4/79). Phaeohyphomycosis was the most common fungal infection (7/11). In a multivariate analysis, the female gender and diabetes mellitus at the time of transplant were significantly associated with a higher risk of infection. This study is the first to describe the epidemiology of infections in kidney transplant recipients in the Caribbean and to analyze the potential risk factors. We reported a similar profile of bacterial infections to that which were observed in the European and American studies. However, we found a higher incidence of tropical infections, such as nocardiosis and phaeohyphomycosis, which highlights the need for heightened awareness among healthcare teams to ensure earlier and more appropriate treatment. Further studies focusing on these rare tropical infections are necessary to better understand their risk factors.

Early Monitoring of Donor-Derived Cell-Free DNA in Kidney Allograft Recipients Followed-Up for Two Years: Experience of One Center.

(1) Background: donor-derived circulating free DNA (dd-cfDNA), an innovative biomarker with great potential for the early identification and prevention of graft damage. (2) Methods: Samples were collected prospectively and the study was performed retrospectively to analyze dd-cfDNA plasma levels in 30 kidney transplant patients during their post-transplant follow-up (15 days, 3, 6, and 9 months), to determine if the result could be of interest in the identification of possible adverse events, especially rejection. The aim was to verify whether the data on sensitivity, specificity, NPV, and PPV compare with reference values and creatinine values. (3) Results: We observed levels of dd cfDNA > 1% in six of nine patients with active rejection (ABMR or TCMR) and elevated values (>0.5%) in two other patients in this rejection group. Our results show low values of sensitivity = 50%, specificity = 61.11%, rejection NPV = 64.71%, and rejection PPV = 46.13% of the technique compared to reference values previously published. With respect to creatinine, only for TCRM, we observed better results for dd-cfDNA in these parameters than in creatinine. Also, our data suggest that dd-cfDNA could help to differentiate those patients with dnDSAs that are going to through rejection better than creatinine, specially at 15 d post transplant. In this study, this appears to have no positive predictive value for borderline rejection (BR) or TCMR IA. (4) Conclusions: plasma levels of dd-cfDNA could be considered an additional or alternative biomarker for graft rejection monitoring in early post-kidney transplant up to several months before its clinical presentation, especially for patients with suspected TCMR or ABMR.

The incidence and risk factors of post-transplant diabetes mellitus in living donor kidney transplantation patients: a retrospective study

BackgroundPost-transplant diabetes mellitus (PTDM) is a well-known complication of kidney transplantation that significantly impacts recipient morbidity and mortality. Over the recent years, the incidence of PTDM has increased considerably worldwide. Therefore, the primary purpose of this study was to evaluate the incidence and risk factors for PTDM in living donor kidney transplantation patients in Riyadh, Saudi Arabia.MethodsA retrospective cohort study was conducted at a tertiary transplant center in Riyadh, Saudi Arabia, and data were extracted between February 2016 and March 2022. Patients aged ≥ 18 years who underwent renal transplant with at least one year of post-transplant follow-up were included in the analysis, and their medical records were comprehensively reviewed. Patients < 18 years of age, history of diabetes mellitus, other organ transplants, or those who underwent transplantation outside the Kingdom of Saudi Arabia were excluded from the study.ResultsThe study included 247 living donor kidney transplant patients, with a mean age of 39.5 ± 14.6 years. 17.0% of the patients were diagnosed with PTDM. Patient age and fasting glucose levels at 6-months and 12-months after transplantation were found to be significant risk factors for the development of PTDM.ConclusionAn increased occurrence of PTDM emphasizes the importance of identifying high-risk patients prior to transplantation and implementing early interventions to prevent potential complications that could affect graft and patient survival.

Egyptian pediatric kidney transplantation: highlights on post-transplant follow-up and management of complications by the Egyptian Pediatric Clinical Practice Guidelines Committee (EPG) Nephrology Group

BackgroundPediatric kidney transplantation is unique when compared to adults. They need optimum post-transplant care to achieve longer graft and patient survival. Infections, rejection, recurrence, malignancy, bone problems, hypertension, and surgical complications are the most important challenges that require prevention, early detection, and management. Chronic allograft nephropathy needs different approaches based on its related causes, allograft pathology, graft function, and availability of re-transplantation.Aim/objectivesThis national adapted guideline aims to frame evidence-based post-transplant recommendations adopted or adapted from EB source guidelines to optimize post-transplant patient care.MethodsOur guideline is evidence based adapted from four national and international source guidelines with permissions [KDIGO 2020, RA/BTS 2022–2018, EAU 2018] that were appraised with AGREE II instrument tool. We followed the “adapted ADAPTE” CPG formal adaptation methodology that consists of 3 phases and 24 steps and tools. Virtual monthly meetings all through the year 2023 were activated for reviewing and validation of final adaptation of evidence-based guideline draft, considering all comments of external reviewers. This guideline was registered in the practice guideline registration for transparency (PREPARE), number: PREPARE-2023CN364.ResultsRecommendation statements in guidelines stand for results in articles. Discussion of important recommendations and the rationale behind selection of adopted statements and tailoring of others to suit our local facilities, expertise, and renal native disease profile was presented in the text with reasons and references.ConclusionThe provided guidelines aim to improve graft and patient outcome through prevention and early management of complications and suggest research areas lacking validated research recommendations.

Evaluation and Management of Urological Complications Following Pediatric Kidney Transplantation: Experience from a Single Tertiary Center.

Background/Objectives: Kidney transplantation is the treatment of choice for children with end-stage renal disease (ESRD), but its outcome can be affected by urological complications, with incidence rates of 2.5-25%. The aim of this study was to evaluate the occurrence of urological complications and their management in a cohort of pediatric kidney transplant recipients. Materials and Methods: A retrospective analysis on 178 patients who received a renal transplant at our Pediatric Kidney Transplant Center between 2011 and 2023 was conducted. Demographic and clinical data were analyzed. Urological complications were categorized as early, intermediate, or late based on their onset time. Results: Out of 178 patients, 28 (15.7%) experienced urological complications. Most patients (61%) had a pre-existing uropathy. Early complications (7-30 days) were all obstructive, namely, ureterovesical junction obstruction and perirenal collections. Intermediate complications (1-3 months) comprised ureteral stenosis, symptomatic vesicoureteral reflux (VUR), and obstructive lymphocele. Late complications (>3 months) included symptomatic VUR and ureteral stenosis, with one case leading to ureteral rupture. Early complications were often detected due to acute graft dysfunction, while late ones were mainly identified during routine clinical, laboratory, or ultrasound follow-up. Urological complications requiring surgical or endoscopic therapy were 13.4%. Most ureteral stenoses were treated with initial endoscopic stents, followed by definitive surgery. VUR was treated with endoscopic correction with a high success rate (75%), while open surgery was reserved for cases where initial treatments failed or complications recurred. No clear correlations were found between patient characteristics and risk of urological complication. Urological complications required multiple diagnostic procedures and therapeutic interventions (+2.5 admissions in mean and approximately +EUR 24,000) compared to an uncomplicated post-transplant course. However, they did not significantly impact transplant outcomes, with a graft survival rate comparable to that of the control group. Conclusions: Regular post-transplant follow-up is crucial, especially for patients with known risk factors, to allow for timely detection and treatment of urological complications, avoiding detrimental effects on graft function and improving transplantation outcomes.

'Between Inner Strength and Fighting Prejudice': Psycho-Social Processes Implemented by Women with Leukemia Along the Illness Trajectory: A Grounded Theory Study.

Disease trajectories in leukemia are often unpredictable and recurrent, and patients' experiences can impact their quality of life. Studies in the literature often do not explore gender-related illness experiences from an intersectional approach and throughout the illness trajectory. This comprehensive study aims to explore the full spectrum of experiences lived by women with leukemia throughout the disease trajectory, from diagnosis to treatments and post-stem cell transplant follow-up. A grounded theory approach was meticulously developed to analyze semi-structured interviews with 13 women with leukemia in the post-transplant follow-up phase at a hospital in Northern Italy. The data analysis was an iterative process, conducted concurrently using a constant comparative method. Data collection concluded when data saturation was reached. The core category identified is women's inner strength during the disease trajectory, which was identified for its recurrence and cross-cutting nature, according to the women. This core category interconnects with five main categories: 1. Facing the disease: Between resistance and surrender. 2. Living for today and moving forward. 3. Unexpected elements in relationships. 4. Changes that shape women. 5. Demystifying the body and embracing 'diminished beauty'. An explanatory model of the disease trajectory of women with leukemia was defined as: 'Women with leukemia, between inner strength and fighting prejudice'. An in-depth analysis of the disease experiences revealed aspects that are not easily understood through a purely biological perspective of gender differences, often overlooking the psycho-social and relational peculiarities of women.

Pulmonary Function in Pediatric Stem Cell Transplantation

BackgroundPediatric hematopoietic stem cell transplantation often results in pulmonary complications, yet limited data exist on pulmonary function in Thailand. This study aims to assess pulmonary function, investigating associated complications and identifying clinical factors linked to pre- and post-transplant pulmonary function defects. MethodsIn this retrospective cohort study, we focused on children aged 6-18 years who underwent hematopoietic stem cell transplantation between 1999 and 2020, ensuring accessible pulmonary function tests results. ResultsAmong 48 patients, abnormal pulmonary function pre- and post-transplant (2-8 years) included a diffusion defect in 16.7% and 18.8%, a restrictive defect in 20.8% and 8.3%, and an obstructive defect in 4.2% and 10.4%, respectively. Pulmonary complications occurred in 16 patients (33.3%), including 15 infections and 1 case of bronchiolitis obliterans. While pretransplant pulmonary function defects were not significantly associated with specific characteristics, post-transplant pulmonary complications correlated with post-transplant pulmonary function defects (aOR = 4.11, 95% CI = 1.23-13.64, P = .02). Among the 6 patients with pre- and post-transplant follow-up, those with pulmonary complications showed a discernible decline in pulmonary function over time, while those without pulmonary complications remained stable or improved. However, the differences between these groups did not reach statistical significance (P = .13-.76). ConclusionsPrevalent pulmonary function defects and complications in pediatric hematopoietic stem cell transplantation highlight the importance of close pulmonary function monitoring. Post-transplant pulmonary complications are associated with defects, suggesting a potential trend of a subsequent decline in lung function, warranting further prospective validation.

Donor-derived Cell-free DNA Evaluation in Pediatric Heart Transplant Recipients: A Single-center 12-mo Experience.

Endomyocardial biopsy (EMB) is considered the gold-standard method to diagnose rejection after heart transplantation. However, the many disadvantages and potential complications of this test restrict its routine application, particularly in pediatric patients. Donor-derived cell-free DNA (dd-cfDNA), released by the transplanted heart as result of cellular injury, is emerging as a biomarker of tissue damage involved in ischemia/reperfusion injury and posttransplant rejection. In the present study, we systematically evaluated dd-cfDNA levels in pediatric heart transplant patients coming for follow-up visits to our clinic for 12 mo, with the aim of determining whether dd-cfDNA monitoring could be efficiently applied and integrated into the posttransplant management of rejection in pediatric recipients. Twenty-nine patients were enrolled, and cfDNA was obtained from 158 blood samples collected during posttransplant follow-up. dd-cfDNA% was determined with a droplet-digital polymerase chain reaction assay. EMB scores, donor-specific antibody measurements, and distress marker quantification were correlated with dd-cfDNA, together with echocardiogram information. The percentage of dd-cfDNA increased when EMBs scored positive for rejection (P = 0.0002) and donor-specific antibodies were present (P = 0.0010). N-terminal pro-B-type natriuretic peptide and high-sensitive troponin I elevation were significantly associated with dd-cfDNA release (P = 0.02 and P < 0.0001, respectively), as were reduced isovolumetric relaxation time (P = 0.0031), signs of heart failure (P = 0.0018), and treatment for rejection (P = 0.0017). By determining a positive threshold for rejection at 0.55%, the test had a negative predictive value maximized at 100%. Collectively, results indicate that dd-cfDNA monitoring has a high negative prognostic value, suggesting that in heart transplanted children with dd-cfDNA levels of <0.55% threshold, protocol EMBs may be postponed.

Report on post-transplantation cancer in southeast Asia from the Thai kidney transplantation cohort

Post-transplantation cancer is a significant cause of mortality among kidney transplant recipients (KTR). The incidence of post-transplantation cancer varies based on geographic region and ethnicity. However, data on KTR from South East Asia, where characteristics differ from other parts of Asia, is lacking. We conducted a retrospective cohort study at a transplant center in Thailand to investigate the incidence of post-transplantation cancer and mortality rates. Factors associated with post-transplantation cancer and patient outcomes were analyzed using competing-risks regression. The study included 1156 KTR with a post-transplant follow-up duration of 5.1 (2.7–9.4) years. The age- and sex-adjusted incidence rate of post-transplant cancer was highest for urothelial cancer (6.9 per 1000 person-years), which also resulted in the highest standardized incidence ratio (SIR) of 42.5 when compared to the general population. Kidney cancer had the second-highest SIR of 24.4. Increasing age was the factor associated with an increased risk of post-transplant cancer (SHR 1.03; 95% CI 1.01–1.05). Human leukocyte antigen (HLA) DR mismatch was associated with a decreased risk of post-transplant cancer (SHR 0.72; 95% CI 0.52–0.98). Post-transplantation cancer was significantly associated with patient mortality (HR 3.16; 95% CI 2.21–4.52). Cancer significantly contributes to KTR mortality, and the risk profile for cancer development in Thai KTRs differs from that of Western and most Asian counterparts. Further research is essential to explore appropriate screening protocols for countries with high rates of urothelial and kidney cancer, including Thailand.

Activation of NLRP3 inflammasome in patients with renal transplantation: relation to allograft dysfunction, inflammation, and renal fibrosis

ABSTRACT Background Chronic allograft dysfunction (CAD) represents a complex process of inflammatory response, fibrosis, and tissue restoration, mediated by a myriad of proinflammatory cytokines, enzymes, and growth factors. NOD-like receptor protein3 (NLRP3) inflammasome is one of the NLR protein families. It drives proteolysis of proinflammatory caspases which induces maturation of pro-interleukin (IL)-1β and pro-IL-18. The aim of this work is to study NLRP3 inflammasome activation in patients with renal transplantation in relation to allograft function, inflammation, and renal fibrosis. Methods Thirty renal transplant recipients (RTR): 15 patients with stable renal function (Group I), 15 patients with CAD (Group II), and 15 healthy subjects (Group III) were included. Serum and urinary NLRP3, caspase-1, and interleukin-1β were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Serum high sensitivity C-reactive protein (hs-CRP) level was measured, and neutrophil-lymphocyte ratio (NLR) was calculated. Renal function was evaluated by serum creatinine (S.Cr) and estimated glomerular filtration rate (eGFR). Resistive index (RI) was calculated with Doppler ultrasonography. In patients with CAD, renal interstitial fibrosis (RIF) was graded in renal biopsies. Results Serum NLRP3, caspase-1, serum and urinary IL-1β, and hs-CRP showed a statistically significant increase in RTR, particularly in those with CAD compared to the controls with a positive correlation with each other, their urinary level, S. Cr, hs-CRP, NLR, RI, and RIF (p < 0.001). The receiver operating characteristic curve showed high diagnostic accuracy of serum NLRP3, caspase-1, and IL-1β in discriminating patients with CAD from patients with stable renal function. Conclusion The NLRP3-caspase1-IL-1β cascade is activated and upregulated in renal transplant recipients, particularly those with advanced renal impairment, and thus may play a role in developing CAD and renal fibrosis. They could be potential biomarkers for post-transplant outcome, follow-up, and early diagnosis. Moreover, their cascade could be a target for future anti-inflammatory therapeutic strategies for allograft dysfunction.

Dynamic Relapse Prediction by Peripheral Blood WT1mRNA after Allogeneic Hematopoietic Cell Transplantation for Myeloid Neoplasms

Although various relapse prediction models based on pretransplant information have been reported, they cannot update the predictive probability considering post-transplant patient status. Therefore, these models are not appropriate for deciding on treatment adjustment and preemptive intervention during post-transplant follow-up. A dynamic prediction model can update the predictive probability by considering the information obtained during follow-up. This study aimed to develop and assess a dynamic relapse prediction model after allogeneic hematopoietic cell transplantation (allo-HCT) for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) using peripheral blood Wilms' tumor 1 messenger RNA (WT1mRNA). We retrospectively analyzed patients with AML or MDS who underwent allo-HCT at our institution. To develop dynamic models, we employed the landmarking supermodel approach, using age, refined disease risk index, conditioning intensity, and number of transplantations as pretransplant covariates and both pre- and post-transplant peripheral blood WT1mRNA levels as time-dependent covariates. Finally, we compared the predictive performances of the conventional and dynamic models by area under the time-dependent receiver operating characteristic curves. A total of 238 allo-HCT cases were included in this study. The dynamic model that considered all pretransplant WT1mRNA levels and their kinetics showed superior predictive performance compared to models that considered only pretransplant covariates or factored in both pretransplant covariates and post-transplant WT1mRNA levels without their kinetics; their time-dependent areas under the curve were 0.89, 0.73, and 0.87, respectively. The predictive probability of relapse increased gradually from approximately 90 days before relapse. Furthermore, we developed a web application to make our model user-friendly. This model facilitates real-time, highly accurate, and personalized relapse prediction at any time point after allo-HCT. This will aid decision-making during post-transplant follow-up by offering objective relapse forecasts for physicians.

Adoption of Telehealth as a Strategy for Pre-Transplant Evaluation and Post-Transplant Follow-up

Adoption of Telehealth as a Strategy for Pre-Transplant Evaluation and Post-Transplant Follow-up

Impact of COVID-19 Infection in Kidney Transplant Patients: A Review

Managing COVID-19 in kidney transplant patients is complex due to limited data on its severity, treatment, and management. Conflicting information from studies necessitates case-by-case treatment decisions. Atypical symptoms can lead to misdiagnosis, so a thorough evaluation is crucial. Immunosuppressants and comorbidities can worsen the disease, leading to the controversial approach of discontinuing or reducing immunosuppressive drugs. Kidney transplantation is challenging due to the surgical procedure’s sensitivity and high risk of transmission. While vaccines offer protection, their efficacy may be altered by immunosuppressive drugs in these patients. This review summarizes the management of COVID-19 in kidney transplant patients, addressing these complexities. Kidney transplant patients face unique COVID-19 challenges due to weakened immunity. They are at higher risk for severe illness and complications from both the virus and immunosuppressant medications. Early identification and intervention are crucial, including antiviral treatment like remdesivir in severe cases. Managing immunosuppressants is critical to balancing the risk of transplant rejection with COVID-19 severity. Drug interactions with COVID-19 treatments require careful consideration, potentially necessitating dose adjustments or alternative medications. The pandemic has disrupted transplant services, highlighting the need for prioritized vaccination and safe access to care. Telemedicine can help minimize virus exposure during post-transplant follow-up. While immunosuppression may impact vaccine responses, vaccination remains crucial to reducing the severe COVID-19 risk. Booster doses and continued precautions are important. Mental health support is essential to address pandemic-related anxiety, depression, and social isolation. More data is needed on the safety and effectiveness of COVID-19 treatments and vaccines in this population. A multidisciplinary approach, including close monitoring, careful medication management, vaccination, and psychosocial support is needed to optimize management and improve outcomes.

Kidney transplantation in patients with ANCA-associated vasculitis is associated with a high incidence of post-transplant cancer

BackgroundAntineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare disease with limited data on outcomes after transplantation.MethodsIn this single-center retrospective cohort study, we describe the outcomes of kidney transplant patients with AAV transplanted at our institute from February 2006 to January 2022.ResultsWe identified 9 patients among 1026 with a pre-transplant diagnosis of AAV; all patients had received previous treatment with cyclophosphamide. Maintenance immunosuppression after transplantation was tacrolimus-based in 89% of the patients. At the end of a mean follow-up of 132 ± 61.1 months after transplantation, only one case of extrarenal vasculitis relapse was observed. The relapse rate was 0.01 per patient per year, which is comparable to that reported in the literature. However, seven patients were diagnosed with cancer after a mean follow-up of 81.4 months after transplantation; six had skin cancer and three had renal cell carcinoma (RCC) of the native kidneys (cumulative incidence of 78%). One patient died from metastatic squamous cell carcinoma.ConclusionIn this study, we found a noticeable decrease in disease relapse (1 relapse in the present cohort vs 7 relapses in 19 patients in the previous cohort) in kidney transplant patients with AAV compared with previous data from our group (December 1987–January 2006). Conversely, we found a high incidence of post-transplant cancer. This result could be attributed to reduced immunosurveillance due to immunosuppression therapy before and after transplantation. Therefore, constant cancer early diagnosis and prevention is mandatory during the post-transplant follow-up of AAV patients.Graphical abstract

Double lung transplantation in patients with metastatic lung-limited non-small cell lung carcinoma (NSCLC): A case series.

8643 Background: Despite technological advances and expanded indications in lung transplantation, lung cancer constituted less than 0.1% of the lung transplantation over the past two decades. Double lung transplantation (DLT) may offer curative treatment for metastatic lung-limited NSCLC patients without extrapulmonary disease. We present a case series of consecutive NSCLC patients who underwent DLT. Methods: Patients treated with DLT were identified between 09/2021 and 02/2024 at Canning Thoracic Institute of Northwestern University. All patients had enrolled in the DLT registry aimed for lung-limited malignancies (DREAM) study cohort A (NCT05671887). Exclusion criteria includes presence of extrapulmonary disease. Results: Six patients with stage IVA NSCLC who underwent lung transplantation were included. Five (83.3%) patients underwent double lung, and one (16.7%) patient single lung transplantation. Four (66.7%) patients had invasive mucinous, and two (33.3%) had invasive non-mucinous adenocarcinoma histology. One of the two invasive non-mucinous patients had acinar, and the other had mixed lepidic, papillary, and acinar histology. Patients were aged 56-71; one (16.7%) was Asian, five (83.3%) were White, four (66.7%) were male, and three (50%) had a history of smoking. One (16.7%) patient had a past medical history of interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD). The median pretransplant treatment lines were 2 (1-5). All patients had high oxygen requirements before DLT due to cancer progression. Pre-transplant endobronchial ultrasound and evaluation of bilateral pneumonectomy lungs found no lymph node involvement (pN0). One patient had an epidermal growth factor receptor (EGFR) mutated cancer but had failed relevant targeted therapy prior to transplant. All patients had disease progression on standard of care treatments with/without clinical trials. The indication for DLT was respiratory failure or refractory cancer for all patients. After DLT, one patient had a recurrence of the disease at 18 months with a 1cm solid nodule and was treated with stereotactic body radiotherapy (SBRT). Both original and recurrent tumors had invasive mucinous adenocarcinoma histology, negative PD-L1 expression, and the same JAK3 c.2174C &gt; T, P725L mutated clone. It suggests that the recurrence likely arose from the original cancer. Transplant rejection did not occur in any of the cases. Following the transplant, there was no requirement for oxygen therapy for any patient. All patients are alive with 28, 18, 8, 8, 5, and 4-month posttransplant follow-up. Conclusions: Six patients underwent DLT successfully without significant complications. All patients were alive and in good health. Ongoing DREAM study will continue to investigate the role of DLT in metastatic lung-limited NSCLC patients (especially in pN0). Clinical trial information: NCT05671887 .

Double lung transplantation in patients with recent history of malignancy.

e20614 Background: Recent history of malignancy has been considered as a contraindication for double lung transplantation (DLT) due to concerns for risk of cancer recurrence and worse outcomes. However, the relationship between the recent malignancy history and lung transplantation mortality remains unclear. Methods: Among patients treated with DLT between 09/2021 and 02/2024 in single institution, patients with a recent history of other cancers were included in this study. All patients had enrolled in cohort C of the DLT registry aimed for lung-limited malignancies (DREAM) study (NCT05671887). Exclusion criteria include extrapulmonary metastatic disease and medical ineligibility for DLT. All patients were followed up with computed tomography every 12 weeks. Results: Four patients were included; three (75%) patients with a histology of NSCLC (squamous cell, stage Ib-IIIb), and one (25%) with prostate adenocarcinoma (stage IIc). The median no-evidence-of-disease (NED) time was 19.5 months (0-41). Patients were aged 57-68, three (75%) were male. The indication for DLT was chronic obstructive pulmonary disease (1/4, 25%), interstitial lung disease (2/4, 50%), and idiopathic pulmonary fibrosis (1/4, 25%). All patients had high oxygen requirements before DLT. The median duration of the waitlist for DLT was sixteen days (3-61). There was no in-hospital mortality and the median hospital stay was 20.5 days (16-32). During a median follow-up of 2.5 months (range 0-9), rejection and post-transplant malignancy did not occur in any of the cases (Table 1). Conclusions: Four patients with history of cancers underwent DLT without significant complications. The median post-transplant follow-up was 2.5 months (0-9). Ongoing DREAM study cohort C will continue to investigate the role of DLT in patients with a recent history of malignancy. Clinical trial information: NCT05671887 . [Table: see text]