Post-transplant Complications Research Articles

Graft Versus Host Disease: Management Issues in the Intensive Care Unit.

Graft versus host disease (GVHD) in acute and chronic forms is a frequent post-transplant complication and seen in 50% of patients in acute and up to 70% cases in chronic GVHD setting. Patients with multiorgan involvement and those who are steroid refractory, frequently present with complications arising from this post-transplant complication. These GVHD patients are frequently managed in the Intensive care unit for treatment of air leaks, effusions, management of hypoxemia due to lung GVHD or infections. Close coordination between hematologists and Pulmonary medicine specialists is critical for timely management of these complications to improve patient outcomes.

Long-Term Outcomes of Living Donor Liver Transplantation for Methylmalonic Acidemia.

Despite early diagnosis and medical interventions, patients with methylmalonic acidemia (MMA) suffer from multi-organ damage and recurrent metabolic decompensations. We conducted the largest retrospective multi-center cohort study so far, involving five transplant centers (NCCHD, KUH, KUHP, ATAK, and EMC), and identified all MMA patients (n = 38) undergoing LDLT in the past two decades. Our primary outcome was patient survival, and secondary outcomes included death-censored graft survival and posttransplant complications. The overall 10-year patient survival and death-censored graft survival rates were 92% and 97%, respectively. Patients who underwent LDLT within 2 years of MMA onset showed significantly higher 10-year patient survival compared to those with an interval more than 2 years (100% vs. 81%, p = 0.038), although the death-censored graft survival were not statistically different (100% vs. 93%, p = 0.22). Over the long-term follow-up, 14 patients (37%) experienced intellectual disability, while two patients developed neurological complications, three patients experienced renal dysfunction, and one patient had biliary anastomotic stricture. The MMA level significantly decreased from 2218.5 mmol/L preoperative to 307.5 mmol/L postoperative (p = 0.038). LDLT achieves favorable long-term patient and graft survival outcomes for MMA patients. While not resulting in complete cure, our findings support the consideration of early LDLT within 2 years of disease onset. This approach holds the potential to mitigate recurrent metabolic decompensations, and preserve the long-term renal function.

Cancer Screening in Renal Transplant Recipients: Real-World Data.

Multiple international guidelines have endorsed cancer screening in renal transplant patients. This study aimed to describe a series of patients with post-transplant cancer and to report physicians' adherence to cancer screening guidelines. This is a retrospective study of cancer patients who had a history of renal transplant. Charts of patients who were treated at our institution between 2012 and 2023 were reviewed, patients' clinical data were collected. Thirty-nine patients were identified. The most common types of cancer were lymphoma (n = 9, 23%), squamous cell carcinoma (SCC) of the skin (n = 8, 20.5%), and breast (n = 6, 15.4%). The median age at diagnosis was 56.5 years (range: 16.9 - 70.2), family history of malignancy was depicted in 18 (46.2%) cases. Chart review and patients' questionnaire revealed that increased risk of malignancy was discussed in seven (18%) out of 39 recipients (P < 0.001) at time of transplant, and only three (7.7%, P < 0.001) patients were on post-transplant age-matched cancer screening. The increased risk of malignancy is a serious post-transplant complication. Lymphoma and non-melanoma skin cancer were the most common cancers. Most patients were not offered routine cancer screening; it is important to raise awareness among nephrologists and caregivers regarding the risk of post-transplant malignancy.

Brief cycling intervals incrementally increase the number of hematopoietic stem and progenitor cells in human peripheral blood

IntroductionPeripheral blood stem cell (PBSC) donation is the primary procedure used to collect hematopoietic stem and progenitor cells (HSPCs) for hematopoietic stem cell transplantation. Single bouts of exercise transiently enrich peripheral blood with HSPCs and cytolytic natural killer cells (CD56dim), which are important in preventing post-transplant complications. To provide a rationale to investigate the utility of exercise in a PBSC donation setting (≈3 h), this study aimed to establish whether interval cycling increased peripheral blood HSPC and CD56dim concentrations to a greater degree than continuous cycling.MethodsIn a randomised crossover study design, eleven males (mean ± SD: age 25 ± 7 years) undertook bouts of moderate intensity continuous exercise [MICE, 30 min, 65%–70% maximum heart rate (HRmax)], high-volume high intensity interval exercise (HV-HIIE, 4 × 4 min, 80%–85% HRmax) and low-volume HIIE (LV-HIIE, 4 × 2 min, 90%–95% HRmax). The cumulative impact of each interval on circulating HSPC (CD34+CD45dimSSClow) and CD56dim concentrations (cells/µL), and the bone marrow homing potential of HSPCs (expression of CXCR-4 and VLA-4) were determined.ResultsThere was an increase in HSPC concentration after two intervals of LV-HIIE (Rest: 1.84 ± 1.55 vs. Interval 2: 2.94 ± 1.34, P = 0.01) and three intervals of HV-HIIE only (Rest: 2.05 ± 0.86 vs. Interval 3: 2.51 ± 1.05, P = 0.04). The concentration of all leukocyte subsets increased after each trial, with this greatest for CD56dim NK cells, and in HIIE vs. MICE (LV-HIIE: 4.77 ± 2.82, HV-HIIE: 4.65 ± 2.06, MICE: 2.44 ± 0.77, P &amp;lt; 0.0001). These patterns were observed for concentration, not frequency of CXCR-4+ and VLA-4+ HSPCs, which was unaltered. There was a marginal decrease in VLA-4, but not CXCR-4 expression on exercise-mobilised HSPCs after all trials (P &amp;lt; 0.0001).DiscussionThe results of the present study indicate that HIIE caused a more marked increase in HSPC and CD56dim NK cell concentrations than MICE, with mobilised HSPCs maintaining their bone marrow homing phenotype. LV-HIIE evoked an increase in HSPC concentration after just 2 × 2-minute intervals. The feasibility and clinical utility of interval cycling in a PBSC donation context should therefore be evaluated.

Lung Transplant for Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) carries a high burden of morbidity and mortality to patient and a high cost to health care systems. Lung transplantation is a last resort available for end-stage COPD patients interested in pursuing it and meeting the strict transplant requirements. It requires commitment from patients and their loved ones to support them through this tough process. This review will cover history of transplant, indications, candidate selection, evaluation testing, transplant listing, type of transplant (single versus bilateral), posttransplant complications, immunosuppression, and rejection. It is tailored to the COPD patient when applicable; however, many aspects of lung transplantation are shared amongst all lung diseases eligible for transplant.

Liver function maximum capacity test during normothermic regional perfusion predicts graft function after transplantation

Abstract Purpose In an effort to reduce waitlist mortality, extended criteria donor organs, including those from donation after circulatory death (DCD), are being used with increasing frequency. These donors carry an increased risk for postoperative complications, and balancing donor-recipient risks is currently based on generalized nomograms. Abdominal normothermic regional perfusion (aNRP) enables individual evaluation of DCD organs, but a gold standard to determine suitability for transplantation is lacking. This study aimed to incorporate individualized and predictive measurements of the liver maximum capacity (LiMAx) test to objectively grade liver function during aNRP and prevent post-op complications. Methods aNRP was performed to salvage 18 DCD liver grafts, otherwise discarded. Continuous variables were presented as the median with the interquartile range. Results The liver function maximum capacity (LiMAx) test was successfully performed within the aNRP circuit in 17 aNRPs (94%). Donor livers with good lactate clearance during aNRP demonstrated significantly higher LiMAx scores (396 (301–451) µg/kg/h versus those who did not 105 (70–158) µg/kg/h; P = 0.006). This was also true for manifesting stress hyperglycemia &gt; 20 mmol/l (P = 0.032). LiMAx score correlated with alanine aminotransferase (ALT; R = − 0.755) and aspartate transaminase (AST; R = − 0.800) levels during perfusion and distinguished livers that were selected for transplantation (397 (346–453) µg/kg/h) from those who were discarded (155 (87–206) µg/kg/h; P &lt; 0.001). Twelve livers were accepted for transplantation, blinded for LiMAx results, and all had LiMAx scores of &gt; 241 µg/kg/h. Postoperatively, LiMAx during aNRP displayed correlation with 24-h lactate levels. Conclusions This study shows for the first time the feasibility to assess liver function during aNRP in individual donor livers. LiMAx presents an objective tool to predict donor liver function and risk of complications in the recipient, thus enabling individualized matching of donor livers for an individual recipient. The LiMAx test may present a valuable test for the prediction of donor liver function, preventing post-transplant complication, and personalizing the selection of donor livers for individual recipients.

Real-world analysis of the underdiagnosis, clinical outcomes and associated burden of hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) in the United States

BackgroundThrombotic microangiopathy (TMA) associated with hematopoietic stem cell transplantation (HSCT-TMA) is a serious post-transplant complication. Diagnosis is difficult due to overlapping symptoms with other conditions and a lack of universally adopted diagnostic criteria.MethodsThis retrospective, observational study investigated HSCT-TMA incidence between July 2009–August 2020 using the TriNetX US Electronic Medical Record database. Patients who underwent autologous or allogeneic HSCT procedures and had conditioning agents were stratified as follows: confirmed TMA (≥1 hemolytic uremic syndrome (HUS)/TMA diagnosis code), suspected TMA [no HUS/TMA code but met modified published Cho (adult) or Jodele (pediatric) diagnostic criteria (further information in main text), and non-TMA (met neither criteria). Baseline demographics, clinical characteristics and outcomes, and all-cause unadjusted healthcare resource utilization (HCRU) within 12-months of HSCT, were assessed. Statistical comparisons were against the non-TMA cohort (p&amp;lt;0.05).ResultsThe study included 16,809 adults and 901 pediatrics. Of these, 125 adults (0.7%) and 30 pediatrics (3.3%) had confirmed TMA, 3029 (18.0%) adults and 94 (10.4%) pediatrics had suspected TMA; 13,655 (81.2%) adults and 777 (86.2%) pediatrics met non-TMA criteria. Confirmed and suspected TMA incidences were higher after allogeneic HSCT in adults. In pediatrics, confirmed TMA incidence was higher following autologous transplantation, and suspected TMA higher after allogeneic transplantation. Confirmed and suspected TMA patients had significantly higher Charlson Comorbidity Indexes pre-HSCT and more post-HSCT complications. In adults with confirmed and suspected TMA, mortality estimates within 12-months of HSCT were significantly higher compared to non-TMA patients, and numerically higher in pediatrics. All confirmed and suspected TMA patients had significantly more ER visits, inpatient stays and ICU admissions. HCRU within 12-months of HSCT was higher in all confirmed TMA patients; ≤0.1% of patients with suspected TMA, and 25.6–50.0% of patients with confirmed TMA, received complement inhibitors.ConclusionsOur results demonstrate that incidence of HSCT-TMA in the real world, as per billing codes, is low compared with historical literature. However, a proportion of suspected TMA cases, based on diagnosis criteria, share similarly poor outcomes and HCRU. HSCT-TMA is likely underdiagnosed, or under-coded, in real world practice. Our study highlights the need for greater vigilance to this severe complication.

Prediction of portal venous pressure in living donor liver transplantation: A retrospective study.

Liver transplantation is the definitive treatment for advanced liver cirrhosis with portal hypertension. In Japan, the scarcity of deceased donors leads to reliance on living donors, often resulting in smaller grafts. Managing portal venous pressure (PVP) is critical to prevent fatal posttransplant complications. This study explored the possibility of predicting intraoperative PVP. We analyzed 475 living donor liver transplant cases from 2006 to 2023, excluding those with acute liver failure or prior splenectomy or splenic artery embolization. Patients were divided into a training group (n=425) and a test group (n=50). We evaluated the correlation between preoperative factors and PVP at laparotomy, to predict PVP at laparotomy and closure. The predictive model was validated with the test group data. PVP at laparotomy could be predicted using correlated preoperative factors: prothrombin time (p<0.001), predicted splenic volume (p<0.001), and presence of a portosystemic shunt (p=0.002), as follows: Predicted PVP at laparotomy (mmHg)=25.818 - 0.077×[prothrombin time (%)]+0.004×[predicted splenic volume (ml)] - 2.067×[1: with a portosystemic shunt] (p<0.001; R=0.346). Additionally, PVP at closure could be predicted using correlated operative factors, including measured PVP at laparotomy, as follows: predicted PVP at closure (mmHg)=14.268+0.149×[measured PVP at laparotomy (mmHg)] - 0.040×[GV/SLV (%)] - 0.862×[1: splenectomy (if yes)] - 3.511×[1: splenic artery ligation without splenectomy (if yes)] (p<0.001; R=0.339).This study demonstrated the feasibility of predicting intraoperative PVP using preoperative factors in liver transplant patients with decompensated cirrhosis. This predictive approach could refine surgical planning, potentially improving patient outcomes.

Malignancy following solid organ transplantation: Current techniques for determination of donor versus recipient origin.

Among the post-transplantation complications that patients may encounter, the transmission of a donor-derived malignant neoplasm is uncommon but potentially life threatening. The determination of donor versus recipient origin is essential particularly in the setting of multiple transplant recipients from the donor. Advances in molecular biology now allow accurate discrimination utilizing routine tissue samples in a timely and cost-effective manner. The techniques are routinely performed in hospital molecular biology laboratories and are also available in commercial labs. The current methodologies are discussed and future possibilities are presented for clinicians caring for solid organ recipients.

Outcomes of pediatric heart transplantation in children with selected genetic syndromes

ObjectiveGenetic syndromes (GSs) are often linked to congenital heart disease (CHD) and cardiomyopathy (CM). The effect of GSs on survival following pediatric heart transplant (HT) has not been well described. We aimed to compare outcomes following HT between children with a GS and those without a GS. MethodsThe United Network for Organ Sharing (UNOS) transplantation database was merged with the Pediatric Health Information System (PHIS) administrative database to identify children with GS who underwent HT between 2009 and 2019. Characteristics and outcomes were compared between children with a GS (GS group) and those without a GS (no GS group). ResultsGSs were present in 225 of 2429 HT recipients (9%). The most common GSs were DiGeorge syndrome (n = 28), muscular dystrophy (n = 27), Down syndrome (n = 26), and Turner syndrome (n = 14). The incidence of CHD was higher in the GS group compared to the no GS group (54% vs 38%; P < .1); however, patient demographics, hemodynamics, renal and hepatic dysfunction, and requirements for dialysis, mechanical ventilation, extracorporeal membrane oxygenation, and mechanical circulatory support were not different between the 2 groups. Time on the waitlist was not significantly different between the GS and no GS groups (55 days vs 53 days; P = .4). There also was no between-group difference in the incidence of post-transplantation complications, including dialysis (8% vs 5%; P = .38), stroke (3% vs 4%; P = .34), primary graft dysfunction (2% vs 2%; P = .75), need for pacemaker (1% vs 1%; P = .84) and rejection (3.4% vs 3.4%; P = .96). Survival at 10 years post-HT was 75% for the no GS group and 72% for the GS group (P = .59). The survival curves also did not differ between patients with CM and those with CHD. ConclusionsChildren with certain GSs and end-stage heart failure can be expected to have similar post-transplantation outcomes to those without a GS. Although early and late post-transplantation care is individualized to each patient, the presence of a GS should not influence the decision to list for HT.

Primary cilia as a targetable node between biliary injury, senescence and regeneration in liver transplantation

Biliary complications are a major cause of morbidity and mortality in liver transplantation. Up to 25% of patients that develop biliary complications require additional surgical procedures, re-transplantation or die in the absence of a suitable regraft. Here, we investigate the role of the primary cilium, a highly-specialised sensory organelle, in biliary injury leading to post-transplant biliary complications. Human biopsies were used to study the structure and function of primary cilia in liver transplant recipients that develop biliary complications (N=7) in comparison with recipients without biliary complications (N=12). To study the biological effects of the primary cilia during transplantation, we generated murine models that recapitulate liver procurement and cold storage, and assessed the elimination of the primary cilia in biliary epithelial cells in the K19CreERTKif3aflox/flox mouse model. To explore the molecular mechanisms responsible for the observed phenotypes we used in vitro models of ischemia, cellular senescence and primary cilia ablation. Finally, we used pharmacological and genetic approaches to target cellular senescence and the primary cilia, both in mouse models and discarded human donor livers. Prolonged ischemic periods before transplantation result in ciliary shortening and cellular senescence, an irreversible cell cycle arrest that blocks regeneration. Our results indicate that primary cilia damage results in biliary injury and a loss of regenerative potential. Senescence negatively impacts primary cilia structure and triggers a negative feedback loop that further impairs regeneration. Finally, we explore how targeted interventions for cellular senescence and/or the stabilisation of the primary cilia improve biliary regeneration following ischemic injury. Primary cilia play an essential role in biliary regeneration and we demonstrate that senolytics and cilia-stabilising treatments provide a potential therapeutic opportunity to reduce the rate of biliary complications and improve clinical outcomes in liver transplantation. Up to 25% of liver transplants result in biliary complications, leading to additional surgery, retransplants, or death. We found that the incidence of biliary complications is increased by damage to the primary cilium, an antenna that protrudes from the cell and is key to regeneration. Here, we show that treatments that preserve the primary cilia during the transplant process provide a potential solution to reduce the rates of biliary complications.

Artemis deficiency: A large cohort including a novel variant with increased radiosensitivity.

Artemis deficiency is an autosomal recessive disorder characterized by a combined immunodeficiency with increased cellular radiosensitivity. In this review, the clinical and genetic characteristics of 15 patients with DCLRE1C variants are presented. The demographic, clinical, immunologic, and genetic characteristics of patients with confirmed DCLRE1C variants diagnosed between 2013 and 2023 were collected retrospectively. Three patients were evaluated for radiosensitivity by the Comet assay, compared with age- and sex-matched healthy control. Seven patients who had severe infections in the first 6 months of life were diagnosed with T-B-NK+ SCID (severe combined immunodeficiency). Among them, four individuals underwent transplantation, and one of those died due to post-transplant complications in early life. Eight patients had hypomorphic variants. Half of them were awaiting a suitable donor, while the other half had already undergone transplantation. The majority of patients were born into a consanguineous family (93.3%). Most patients had recurrent sinopulmonary infections (73.3%), and one patient had no other infection than an acute respiratory infection before diagnosis. Two patients (13.3%) had autoimmunity in the form of autoimmune hemolytic anemia. Growth retardation was observed in only one patient (6.6%), and no malignancy was detected in the surviving 11 patients during the median (IQR) of 21.5 (12-45) months of follow-up. Three patients who had novel variants exhibited increased radiosensitivity and compromised DNA repair, providing a potential vulnerability to malignant transformation. Early diagnosis, radiation avoidance, and careful preparation for transplantation contribute to minimizing complications, enhancing life expectancy, and improving the patient's quality of life.

Outcomes of heart transplantation in children with heterotaxy syndrome.

End-stage congenital heart disease in children with heterotaxy syndrome might necessitate heart transplantation. Heart transplantation in heterotaxy patients can be associated with several technical (e.g. redo, systemic/pulmonary-venous/situs anomalies, pulmonary artery reconstruction), and extra-cardiac (e.g. ciliary dyskinesia, infections, gastrointestinal) challenges. We aim to examine if heterotaxy syndrome is associated with increased early or late transplantation risks. The United Network for Organ Sharing transplantation database was merged with the Paediatric Health Information System administrative database to identify children with heterotaxy who received heart transplantation. Characteristics and outcomes were compared between children with heterotaxy and contemporaneous non-heterotaxy congenital and non-congenital cardiomyopathy control groups. After merger, our cohort of 1122 patients was divided to three groups: group heterotaxy (n = 143), group non-heterotaxy congenital (n = 428) and group cardiomyopathy (n = 551). There were differences in the characteristics between the 3 groups, with heterotaxy being comparable to non-heterotaxy congenital group. The waitlist duration was longer for heterotaxy than non-heterotaxy congenital and cardiomyopathy groups (91 vs 63 vs 56 days, p < 0.001). Early post-transplant complications were similar for all groups except for operative mortality that was 1% for cardiomyopathy and 4% for heterotaxy and non-heterotaxy congenital, p < 0.001. Post-transplant stay was shorter for cardiomyopathy (57) compared to non-heterotaxy congenital (99) and heterotaxy (89) days, p < 0.001. While rejection prior to discharge was comparable between heterotaxy and CHD groups, it was higher at 1-year for heterotaxy (22%), than non-heterotaxy congenital (19%) and cardiomyopathy (13%), p < 0.001. Survival at 5 years was superior for cardiomyopathy (87%) compared to heterotaxy (69%) and non-heterotaxy congenital (78%), p < 0.001. For the heterotaxy group, no risk factors affecting survival were identified on multivariable analysis. Despite complexity, heart transplantation in selected children with heterotaxy is associated with good mid-term outcomes. Despite early results that are comparable to other patients with congenital heart disease, the increasing rejection rate at one year and the relatively accelerated attrition at mid-term warrant further follow-up. Due to database limitations in defining morphologic and surgical details, further work is warranted to delineate anatomic and surgical variables that could affect survival.

Evaluation of CHROMagar™ B. cepacia agar for the detection of Burkholderia cepacia complex species from sputum samples of patients with cystic fibrosis

IntroductionBurkholderia cepacia complex (BCC) are non-fermenting Gram-negative bacteria that can chronically colonize the lungs of people with cystic fibrosis (pwCF), causing a severe and progressive respiratory failure, post-transplant complications and epidemic outbreaks. Therefore, rapid and accurate identification of these bacteria is relevant for pwCF, in order to facilitate early eradication and prevent chronic colonization. However, BCCs are often quite difficult to detect on culture media as they have a slow growth rate and can be hidden by other fast-growing microorganisms, including Pseudomonas aeruginosa and filamentous fungi.Material and methodsWe evaluated the sensitivity of CHROMagar™ B. cepacia agar using 11 isolates from a well-characterized BCC collection, using BCA agar (Oxoid, UK) as a gold standard. We also studied 180 clinical sputum samples to calculate positive (PPV) and negative (NPV) predictive values. Furthermore, we used three of the well-characterized BCC isolates to determine the limit of detection (LOD).ResultsEleven isolates grew on CHROMagar™ B. cepacia at 37ºC after 48 h. The NPV and PPV of CHROMagar™ B. cepacia were 100% and 87.5%, respectively. The LOD of CHROMagar™ B. cepacia was around 1 × 103 CFU/ml, requiring a ten-fold dilution lower bacterial load than BCA for BCC detection.ConclusionCHROMagar™ B. cepacia agar proved to have a very good sensitivity and specificity for the detection of clinical BCCs. Moreover, the chromogenic nature of the medium allowed us to clearly differentiate BCC from other Gram-negative species, filamentous fungi and yeasts, thereby facilitating the identification of contaminants.

Robotic-Assisted Management of Ureteral Complications in Post-Renal Transplant Patients: A Case Series and Literature Review.

Introduction: Urologic complications are thought to be the most common surgical complication of renal transplantation. Ureteral pathology, including stenosis, urine leak, and vesicoureteral reflux, predominates. Although endourologic and interventional radiological management may be utilized, failure rates remain relatively high and surgical reconstruction remains the definitive management. Robotic ureteral reconstruction has been demonstrated to provide patient benefit in nontransplant populations, but the literature on transplant reconstruction is very limited. This study reports an additional series of patients with a focus on surgical technique, as well as reviews the available evidence for robotic reconstruction for post-transplant ureteral complications. Methods: All institutional patients undergoing robotic-assisted reconstruction for post-transplant ureteral complications for the years 2019-2022 were included. Intra- and postoperative variables, patient demographics, and follow-up data were obtained retrospectively from parsing of patient records. Statistics were tabulated descriptively. Results: Eleven patients underwent ureteral reconstruction. Of the 11, 9 (81%) were male with a mean age of 51.9 years (16-70) and BMI of 33.8 (24.3-49.1). The most common (10/11) indication for reconstruction was stricture; the most common (10/11) technique used was Lich-Gregoir reimplantation. Mean operative time was 288 minutes (143-500). There were no intra- or immediate postoperative complications. Median length of stay was 2 days (1-22). There were two incidences of mortality at 2 and 5 months postoperatively unrelated to surgery. There were four readmissions within 30 days, three for urinary tract infection (UTI) and one for a pelvic abscess which required washout. The remainder of the cohort has been followed for a mean of 14.6 months (6-41) without any incidences of graft loss or recurrence of ureteral pathology. Conclusions: Robotic-assisted ureteral reconstruction is a technically challenging but highly feasible technique that may provide the benefits of minimally invasive surgery while still allowing definitive reconstruction. Centers with extensive robotic capabilities should consider the technique.

Febrile Immunocompromised Renal Transplant Recipient with Allograft Dysfunction: Detection of an Undiagnosed Prostate Abscess by [18F]FDG-PET/CT along with Treatment Response Monitoring

AbstractThe purpose of this report is to provide a comprehensive description of a post-transplant febrile patient's clinical course, complications, surgical procedure, and long-term management including evaluation by 18F-fluorodeoxyglucose [(18F)FDG] positron-emission tomography combined with computed tomography (PET/CT). A 35-year-old male, a postrenal transplant patient, developed chronic allograft dysfunction and presented with fever with chills, with suspicion of acute-on-chronic graft dysfunction, but no infective focus localization on chest X-ray, ultrasonography (USG) whole abdomen, or blood culture. Urine microscopy showed 8 to 10 pus cells/high-power field (hpf) and culture showed Klebsiella pneumoniae and Pseudomonas aeruginosa with low colony count. Culture-sensitive antibiotics were prescribed for 2 weeks, and after 3 weeks febrile episodes relapsed, symptoms progressed, and required emergency hospitalization due to acute painful urinary retention. Proteinuria and no growth were noted in urine analysis, serum creatinine was 5.36 mg/dL, and C-reactive protein was 15.7mg/dL, and remaining parameters were unremarkable. [18F]FDG-PET/CT was considered in order to resolve diagnosis, which revealed abnormal heterogeneous tracer uptake in the enlarged prostate with hypodense areas within, suggesting prostatitis with abscess formation and pyelonephritis in the upper pole of the transplant kidney. USG kidney urinary bladder (KUB) correlation confirmed prostatic abscess and transurethral drainage done, and pus culture revealed Burkholderia pseudomallei. Culture-sensitive intravenous meropenem treatment was given for 3 weeks. At 5 weeks, follow-up [18F]FDG-PET/CT showed low metabolic residual prostate uptake, suggesting a good response with residual infection. Thus, intravenous antibiotics was changed to oral antibiotics for another 6 weeks. His symptoms completely resolved at the end of treatment; however, his graft function worsened, with serum creatinine reaching 6 to 7 mg/dL, and eventually, after 8 months he became dialysis dependent.

Extreme elevations of donor-derived cell-free DNA increases the risk of chronic lung allograft dysfunction and death, even without clinical manifestations of disease

Lung transplant recipients are traditionally monitored with pulmonary function testing (PFT) and lung biopsy to detect post-transplant complications and guide treatment. Plasma donor-derived cell free DNA (dd-cfDNA) is a novel molecular approach of assessing allograft injury, including subclinical allograft dysfunction. The aim of this study was to determine if episodes of extreme molecular injury (EMI) in lung transplant recipients increases the risk of CLAD or death. This multicenter prospective cohort study included 238 lung transplant recipients. Serial plasma samples were collected for dd-cfDNA measurement by shotgun sequencing. EMI was defined as a dd-cfDNA above the third quartile of levels observed for acute rejection (dd-cfDNA level of ≥ 5% occurring after 45 days post-transplant). EMI was categorized as Secondary if associated with co-existing acute rejection, infection or PFT decline; or Primary if not associated to these conditions. EMI developed in 16% of patients at a median 343.5 (IQR: 177.3-535.5) days post-transplant. Over 50% of EMI episodes were classified as Primary. EMI was associated with an increased risk of severe CLAD or death (HR: 2.52, 95% CI: 1.10 - 3.82, p= 0.024). The risk remained consistent for Primary EMI (HR: 2.34, 95% CI 1.18-4.85, p=0.015). Time to first EMI episode was a significant predictor of the likelihood of developing CLAD or death (AUC=0.856, 95% CI =.805-908, p<.001). Episodes of EMI in lung transplant recipients are often isolated and not detectable with traditional clinical monitoring approaches. EMI is associated with an increased risk of severe CLAD or death, independent of concomitant transplant complications.

Hepatitis C viremic lung transplantation to aviremic recipients: Comprehensive outcomes and post-transplant viremia.

Direct-acting antiviral (DAA) therapy has revolutionized solid organ transplantation by providing an opportunity to utilize organs from HCV-viremic donors. Though transplantation of HCV-viremic donor organs into aviremic recipients is safe in the short term, midterm data on survival and post-transplant complications is lacking. We provide a midterm assessment of complications of lung transplantation (LT) up to 2 years post-transplant, including patient and graft survival between HCV-viremic transplantation (D+) and HCV-aviremic transplantation (D-). This is a retrospective cohort study including 500 patients from 2018 to 2022 who underwent LT at our quaternary care institution. Outcomes of patients receiving D+ grafts were compared to those receiving D- grafts. Recipients of HCV antibody+ but PCR- grafts were treated as D- recipients. We identified 470 D- and 30 D+ patients meeting inclusion criteria. Crude mortality did not differ between groups (p=.43). Patient survival at years 1 and 2 did not differ between D+ and D- patients (p=.89, p=.87, respectively), and graft survival at years 1 and 2 did not differ between the two groups (p=.90, p=.88, respectively). No extrahepatic manifestations or fibrosing cholestatic hepatitis (FCH) occurred among D+ recipients. D+ and D- patients had similar rates of post-transplant chronic lung allograft rejection (CLAD) (p=6.7%vs. 12.8%, p=.3), acute cellular rejection (60.0%vs. 58.0%, p=.8) and antibody-mediated rejection (16.7%vs. 14.2%, p=.7). There is no difference in midterm patient or graft survival between D+ and D-LT. No extrahepatic manifestations of HCV occurred. No differences in any type of rejection including CLAD were observed, though follow-up for CLAD was limited. These results provide additional support for the use of HCV-viremic organs in selected recipients in LT.

Surgical complications and technical failure of simultaneous pancreas-kidney transplantation: A 22-year experience from a single center.

Simultaneous pancreas-kidney transplantation (SPKT) is the best treatment for selected individuals with type 1 diabetes mellitus and end-stage renal disease. Despite advances in surgical techniques, donor and recipient selection, and immunosuppressive therapies, SPKT remains a complex procedure with associated surgical complications and adverse consequences. We conducted a retrospective study that included 263 SPKT procedures performed between May 2000, and December 2022. A total of 65 patients (25%) required at least one relaparotomy, resulting in an all-cause relaparotomy rate of 2.04 events per 100 in-hospital days. Lower donor body mass index was identified as an independent factor associated with reoperation (OR.815; 95% CI: .725-.917, p=.001). Technical failure (TF) occurred in 9.9% of cases, primarily attributed to pancreas graft thrombosis, intra-abdominal infections, bleeding, and anastomotic leaks. Independent predictors of TF at 90 days included donor age above 36 years (HR 2.513; 95% CI 1.162-5.434), previous peritoneal dialysis (HR 2.503; 95% CI 1.149-5.451), and specific pancreas graft reinterventions. The findings highlight the importance of carefully considering donor and recipient factors in SPKT. The incidence of TF in our study population aligns with the recent series. Continuous efforts should focus on identifying and mitigating potential risk factors to enhance SPKT outcomes, thereby reducing post-transplant complications.

The nature of chronic rejection after lung transplantation: a murine orthotopic lung transplant study.

Chronic rejection is a major complication post-transplantation. Within lung transplantation, chronic rejection was considered as airway centred. Chronic Lung Allograft Dysfunction (CLAD), defined to cover all late chronic complications, makes it more difficult to understand chronic rejection from an immunological perspective. This study investigated the true nature, timing and location of chronic rejection as a whole, within mouse lung transplantation. 40 mice underwent an orthotopic left lung transplantation, were sacrificed at day 70 and evaluated by histology and in vivo µCT. For timing and location of rejection, extra grafts were sacrificed at day 7, 35, 56 and investigated by ex vivo µCT or single cell RNA (scRNA) profiling. Chronic rejection originated as innate inflammation around small arteries evolving toward adaptive organization with subsequent end-arterial fibrosis and obliterans. Subsequently, venous and pleural infiltration appeared, followed by airway related bronchiolar folding and rarely bronchiolitis obliterans was observed. Ex vivo µCT and scRNA profiling validated the time, location and sequence of events with endothelial destruction and activation as primary onset. Against the current belief, chronic rejection in lung transplantation may start as an arterial response, followed by responses in venules, pleura, and, only in the late stage, bronchioles, as may be seen in some but not all patients with CLAD.