Post-transplant Complications Research Articles

Kidney transplant to vesicostomy: A safe strategy for children with end stage renal disease and lower urinary tract anomalies

Resolution of underlying urinary tract anomalies prior to kidney transplantation in patients with end stage renal disease (ESRD) secondary to uropathy, has been historically supported under the argument that this would help prevent infectious complications and graft loss. We propose to perform earlier kidney transplantation with a transient vesicostomy, deferring resolution of the uropathy to the post-transplantation period. The aim of this study was to evaluate the outcomes of kidney transplantation in children with a vesicostomy. A retrospective, multicenter study was performed including all patients under 18 years of age who underwent kidney transplantation with a vesicostomy, between January 2005 and December 2020 and had at least one year of follow up. Data related with the indication and timing of vesicostomy, time until transplantation, post-transplantation complications, urinary tract infections (UTI) and graft survival rate were collected. Of the 758 transplantations performed in the study period, 16 patients met the inclusion criteria. Mean age at transplantation was 58 months (range 20-151), and mean weight was 13.5Kg (range 8.4-20). Mean time from vesicostomy to kidney transplantation was 30 months (range 0-70). There were 2 (12.5%) ureteral complications that required reoperation. Eighteen episodes of UTI were identified in 8 patients (50%), accounting for 0.4 UTIs per patient-year of follow-up. UTIs did not lead to graft loss in any of the cases. Urinary tract reconstruction was performed in 5 patients (31.3%) at an interval of 1-91 months post-transplantation. After a mean follow-up of 44.8 months (range 13-200) from transplantation, patients with vesicostomy had a mean creatinine clearance of 86.6ml/min/1.73m2, with a mean serum creatinine level of 0.6mg/dl. Graft survival rate was 100%. Early kidney transplantation into a vesicostomy permits a resolution of the ESRD, avoiding deleterious effects related to dialysis. With a low rate of UTIs, we found no graft loss due to infectious complications. This strategy permits careful planning and better timing for the urinary tract reconstruction without delaying kidney transplantation. Kidney transplantation in pediatric patients with vesicostomy seems to be a safe and effective strategy. UTI rate was similar to that reported in the literature of patients with corrected urinary anomalies undergoing kidney transplantation without urinary diversion.

Long Survival Following Lung Transplantation: What Matters?

A retrospective review of the UNOS/OPTN Database was performed from 1 October 1987–31 December 2019. Recipients were classified as LSu (15+ years survival without GF/ReTx), normal survival (3–15 years) and short survival (<3 years). In total, 22,646 patients were identified. Groups were assessed with comparative statistics in addition to a multivariate analysis which included recipient, donor, transplant characteristics and select post-transplant complications. LSu recipients were younger, more commonly female, healthier and more commonly had cystic fibrosis, pulmonary vascular disease or bilateral lung transplantation. LSu donors were younger, healthier and lacked clinical infection. Recipients with restrictive lung disease, single lung transplant and dialysis postoperatively were less likely to be LSu. Several recipient, donor and transplant characteristics are associated with long lung transplantation survival. While some factors cannot be altered, others related to donor selection and posttransplant management can potentially be influenced. Understanding these characteristics and employing discretion in donor selection, in appropriate recipients, may optimize the longevity of transplanted lungs.

The International Consortium on Primary Graft Dysfunction: Redefining Clinical Risk Factors in the Contemporary Era of Heart Transplantation

Background: Primary Graft Dysfunction (PGD) is the leading cause of morbidity and mortality early after heart transplant (HT). The International Consortium on PGD is a multicenter collaboration dedicated to identifying the clinical risk factors for PGD in the contemporary era of HT. The objectives of the current report were to 1) assess the incidence of severe PGD in an international cohort, 2) evaluate the performance of the most validated PGD risk tool, the RADIAL score, in a contemporary cohort, and 3) redefine clinical risk factors for severe PGD in the current era of HT. Methods: This is a retrospective, observational study of consecutive adult HT recipients between 2010 and 2020 in 10 centers in the United States, Canada, and Europe. Patients with severe PGD were compared to those without severe PGD (comprising those with no, mild and moderate PGD). The RADIAL score was calculated for each transplant recipient. The discriminatory power of the RADIAL score was evaluated using receiver operating characteristic (ROC) analysis and its calibration was assessed by plotting the percentage of PGD predicted versus observed. To identify clinical risk factors associated with severe PGD, we performed multivariable mixed-effects logistic regression modeling to account for among-center variability. Results: A total of 2,746 patients have been enrolled in the registry to date, including 2,015 (73.4%) from North America, and 731 (26.6%) from Europe. 215 participants (7.8%) met the criteria for severe PGD. There was an increase in the incidence of severe PGD over the study period (p-value for trend by difference sign test = 0.004). The Kaplan Meier estimate for 1-year survival was 75.7% [95%CI 69.4-80.9%] in patients with severe PGD as compared to 94.4% [95% CI 93.5-95.2%] in those without severe PGD (log-rank p-value <0.001). The RADIAL score performed poorly in our contemporary cohort and was not associated with severe PGD with an AUC of 0.53 (95%CI 0.48-0.58). In the multivariable regression model, acute preoperative dialysis (OR 2.41, 95% CI 1.31 – 4.43), durable LVAD support (OR 1.77, 95% CI 1.13 – 2.77), and total ischemic time (OR 1.20 for each additional hour, 95% CI 1.02 – 1.41) were associated with an increased risk of severe PGD. Conclusions: Our consortium has identified an increasing incidence of PGD in the modern transplant era. We identified contemporary risk factors for this early post-transplant complication, which confers a high mortality risk. These results may enable the identification of patients at high risk for developing severe PGD in order to inform peri-transplant donor and recipient management practices.

What Do Donor-Specific Antibody Changes Mean in Kidney Transplant Patients?

Objective: The role of immunological evaluation is significant in selecting a suitable donor to reduce post-transplant complications in kidney transplantation (KTx). It is unknown how often donor-specific antibody (DSA) positivity causes rejection or how often rejection will develop in patients who do not develop DSA positivity. We aimed to evaluate the relationship between the DSA changes and the KTx patients' biochemical parameters.&#x0D; Methods: The study was a cross-sectional study evaluating 45 KTx patients. Demographic and clinical characteristics of the patients, pre-transplant DSA values, post-transplant DSA values, and biochemical parameters were retrospectively scanned from the hospital system. The patients' data were divided into three groups according to DSA changes.&#x0D; Results: DSA was negative in 21 (46%) patients and positive in 24 (54%) before transplantation. In the post-transplant follow-up, it was observed that the DSA value became positive in 7 patients and turned negative in 9 patients. Rejection developed in 22% of 9 patients whose DSA was positive before transplantation and turned negative after transplantation, and in 28% of 7 patients turned positive from negative. Estimated glomerular filtration rate (e-GFR) and creatinine levels in the post-transplant period were associated with the change in DSA. Also, e-GFR and neutrophil values were independently associated with rejection.&#x0D; Conclusions: Although DSA change affects kidney functions, we found that DSA positivity alone cannot predict rejection, and rejection may occur in the DSA-negative group. Neutrophil count and e-GFR changes were closely related to rejection. Therefore, DSA levels should be monitored regularly, but DSA change alone is insufficient for rejection evaluation.

Normothermic ex vivo perfusion of deceased donor kidneys and its clinical potential in kidney transplantation outcomes.

In recent years, normothermic machine perfusion (NMP) has emerged in conversation surrounding organ preservation and transplantation techniques with the goal of improving patient and clinical outcomes. This is in great attempt to address the rate of non-utilization and the shortage of available organs in kidney transplantation. This focus in mind, normothermic perfusion presents itself as a potential tool to mimic physiological conditions and improve current preservation methods, such as static cold storage. This review serves to improve understanding of the observed connection between the consequences of ischemia and reperfusion injury and traditional preservation techniques as well as how renal NMP may mitigate these issues. Previous studies suggest that reducing time in static cold storage methods by promoting the normothermic perfusion model results in decreased delayed graft function and post-transplant complications. This review also aims to present the immense clinical potential NMP has on future kidney transplantation success and what this means for the fields of nephrology and transplantation. While great strides have been made to evaluate normothermic perfusion's impact on kidney graft viability and transplant success, future research into unified protocol, clinically relevant biomarkers, cost-utility analysis, and use with associated therapeutic and imaging modalities is paramount.

Prevalence, management, and new treatment modalities of EBV-DNA-emia and EBV-PTLD after allo-HCT: survey of Infectious Diseases Working Party EBMT.

The aim of this study was to determine the current approach of EBV-driven post-transplant complications in context of monitoring, diagnosis, prevalence and treatment in EBMT transplant centers. Routine serology testing in patient and donor before HCT is performed in 95.5% centers. Pretransplant EBV-DNA is routinely tested in all patients in 32.7% centers. Monitoring for EBV infection is feasible in 98.2% centers: including 66.7% centers using standardized PCR. Post-HCT regular monitoring is performed in all patients in 80.5% centers. Anti-EBV prophylaxis with rituximab is used in 12.4% centers. Frequency of csEBV-DNA-emia was 7.4% (adults: 6.2%, children: 12.6%). The PCR threshold used to start preemptive treatment was differentiated among centers. Frequency of EBV-PTLD was 1.6% (adults: 1.3%; children: 3.5%). First-line therapy of EBV-driven complications was rituximab and reduction of immunosuppressive therapy. The rate of failure of first-line preemptive treatment was 12.0%. EBV-specific viral-specific T-lymphocytes were available in 46.0% centers. A number of new experimental therapies were given in 28 patients with resistant/refractory PTLD. In conclusion, the prevalence of EBV-DNA-emia and EBV-PTLD over the period 2020-2021 decreased in comparison to historical data. New trends (routine pretransplant screening for EBV-DNA, wider access to VST, new experimental therapies) are being observed in management of EBV infection after allo-HCT.

Endovascular Treatment of Venous Outflow and Portal Venous Complications After Liver Transplantation

Liver transplantation continues to rapidly evolve, and in 2020, 8906 orthotopic liver transplants were performed in the United States. As a technically complex surgery with multiple vascular anastomoses, stenosis and thrombosis of the venous anastomoses are among the recognized vascular complications. While rare, venous complications may be challenging to manage and can threaten the graft and the patient. In the last 20 years, endovascular approaches have been increasingly utilized to treat post-transplant venous complications. Herein, the evaluation and interventional treatment of post-transplant venous outflow complications, portal vein stenosis, portal vein thrombosis, and recurrent portal hypertension with transjugular intrahepatic portosystemic shunt (TIPS) are reviewed.

Incidental appendicectomy in pancreas transplantation: A single-center study.

Appendicitis in pancreatic transplant recipients can be challenging to diagnose and manage. Incidental appendicectomy (IA) during pancreas transplantation obviates the risk of appendicitis but potentially at the cost of increased operating time or early post-operative complications. This study reviewed the value of IA at a single center. This was a retrospective study of patients who underwent a pancreas transplant in our unit from January 1st, 2012 to December 31st, 2020, with end of follow-up on May 21st, 2023; recipients were grouped by whether or not an IA was performed during pancreas transplantation. Donor, recipient, operative, and graft outcomes were compared between the two groups. Post-transplant complications related to appendiceal pathology (or IA) were recorded and classified. Two hundred forty-three patients underwent a pancreas transplant; 227 (93%) patients had an appendix in situ at transplantation, and of these 53 (23%) underwent an IA and 174 (77%) did not. There were no statistically significant differences in operative time (p=.06) or hospital stay (p=.50) between the two groups. In the IA cohort, there were no Clavien-Dindo Grade III-V complications relating to the appendicectomy. In those that did not undergo an IA, two patients (1%) subsequently required appendicectomy due to appendicitis. Comparison of pancreatic graft survival showed no statistically significant difference between the groups (p=.44). This study suggests that IA is effective at reducing risks of post-transplant appendiceal complications without significantly prolonging inpatient stay or impairing graft survival. These data support the consideration of undertaking an IA for all patients undergoing a pancreas transplant.

Outcomes of kidney, liver, and simultaneous liver and kidney transplants from hepatitis c infected donors to hepatitis c naïve recipients: A large single center experience.

With the introduction of direct-acting antiviral therapies (DAAs), the non-use rate of hepatitis C virus (HCV)-positive donor organs (D+) has decreased significantly. We present the donor, recipient, and transplant allograft characteristics, along with recipient outcomes, in one of the largest cohorts of HCV-D+ transplants into HCV-naïve recipients (R-). Charts of HCV D+/R- kidney (KT), liver (LT), and simultaneous liver-kidney (SLKT) transplant recipients between January 2019 and July 2022 were reviewed. Primary outcomes of interest included waitlist times and 1-year graft failure. Secondary outcomes included hospital and intensive care unit length of stay, post-transplant complications, effectiveness of DAA therapy, and characteristics of patients who relapsed from initial DAA therapy. Fifty-five HCV D+/R- transplants at our center [42 KT (26 nucleic acid testing positive [NAT+], 16 NAT-), 12 LT (eight NAT+, four NAT-), and one SLKT (NAT+)] had a median waitlist time of 69days for KT, 87days for LT, and 15days for SLKT. There were no graft failures at 1year. All viremic recipients were treated with a 12-week course of DAAs, of which 100% achieved end of treatment response (EOTR)-85.7% (n=30) achieved sustained virologic response (SVR) and 14.3% relapsed (n=5; four KT, one LT). All relapsed recipients were retreated and achieved SVR. The most common post-transplantation complications include BK virus infection (n=9) for KT and non-allograft infections (n=4) for LT. Our study has demonstrated no graft failures or recipient deaths at 1year, and despite a 14.3% relapse rate, we achieved 100% SVR. Complications rates of D+/R- appeared comparable to national D-/R- complication rates. Further studies comparing D+/R- to D-/R- outcomes are needed.

Significance of HLA-E and its two NKG2 receptors in development of complications after allogeneic transplantation of hematopoietic stem cells.

Transplantation of hematopoietic stem cells (HSCT) is a procedure commonly used in treatment of various haematological disorders which is associated with significantly improved survival rates. However, one of its drawbacks is the possibility of development of post-transplant complications, including acute and chronic graft-versus-host disease (GvHD) or CMV infection. Various studies suggested that NK cells and their receptors may affect the transplant outcome. In the present study, patients and donors were found to significantly differ in the distribution of the NKG2A rs7301582 genetic variants - recipients carried the C allele more often than their donors (0.975 vs 0.865, p<0.0001). Increased soluble HLA-E (sHLA-E) levels detected in recipients' serum 30 days after transplantation seemed to play a prognostic and protective role. It was observed that recipients with higher sHLA-E levels were less prone to chronic GvHD (11.65 vs 6.33 pg/mL, p=0.033) or more severe acute GvHD grades II-IV (11.07 vs 8.04 pg/mL, p=0.081). Our results also showed an unfavourable role of HLA-E donor-recipient genetic incompatibility in CMV infection development after transplantation (OR=5.92, p=0.014). Frequencies of NK cells (both CD56dim and CD56bright) expressing NKG2C were elevated in recipients who developed CMV, especially 30 and 90 days post-transplantation (p<0.03). Percentages of NKG2C+ NK cells lacking NKG2A expression were also increased in these patients. Moreover, recipients carrying a NKG2C deletion characterized with decreased frequency of NKG2C+ NK cells (p<0.05). Our study confirms the importance of NK cells in the development of post-transplant complications and highlights the effect of HLA-E and NKG2C genetic variants, sHLA-E serum concentration, as well as NKG2C surface expression on transplant outcome.

Assessing the role of phosphorylated S6 ribosomal protein in the pathological diagnosis of pulmonary antibody-mediated rejection

BackgroundPulmonary antibody-mediated rejection is still a challenging diagnosis as C4d has poor sensitivity. Previous studies have indicated that the phosphorylated S6 ribosomal protein, a component of the mammalian target of rapamycin (mTOR) pathway, is correlated with de novo donor-specific antibodies in lung transplantation. The objective of this study was to evaluate the phosphorylation of S6 ribosomal protein as a surrogate for AMR diagnosis in lung transplant patients. MethodsThis multicentre retrospective study analyzed transbronchial biopsies from 216 lung transplanted patients, 114 with antibody-mediated rejection and 102 without (19 with acute cellular rejection, 17 with ischemia/reperfusion injury, 18 with infection, and 48 without post-transplant complications). Immunohistochemistry was used to quantify phosphorylated S6 ribosomal protein expression in macrophages, endothelium, epithelium, and inter-pathologist agreement was assessed. ResultsMedian phosphorylated S6 ribosomal protein expression values were higher in antibody-mediated rejection cases than in controls for all cell components, with the highest sensitivity in macrophages (0.9) and the highest specificity in endothelial expression (0.8). The difference was mainly significant in macrophages compared to other post-lung transplantation complications. Inter-pathologist agreement was moderate for macrophages and endothelium, with higher agreement when phosphorylated S6 ribosomal protein expression was dichotomized into positive/negative. The inclusion of phosphorylated S6 ribosomal protein in the diagnostic algorithm could have increased antibody-mediated rejection certainty levels by 25%. ConclusionsThe study supports the role of the mTOR pathway in antibody-mediated rejection-related graft injury and suggests that tissue phosphorylation of S6 ribosomal protein could be a useful surrogate for a more accurate pathological diagnosis of lung antibody-mediated rejection.

THU298 Effect Of SGLT2 Inhibition On Metabolic, Cardiac And Renal Outcomes In Heart Transplant Recipients (EMPA-HTx study): Protocol And Study Design

Abstract Disclosure: L.M. Raven: None. C.A. Muir: None. C. Kessler Iglesias: None. E. Kotlyar: None. K. Muthiah: None. N.K. Bart: Advisory Board Member; Self; Bristol-Myers Squibb. Grant Recipient; Self; Pfizer, Inc. Speaker; Self; Pfizer, Inc. P.S. Macdonald: Speaker; Self; Boehringer Ingelheim, AstraZeneca. C.S. Hayward: None. A. Jabbour: None. J.R. Greenfield: Speaker; Self; Boehringer Ingelheim, AstraZeneca. Background: Heart transplantation (HTx) is standard of care for treatment of end-stage heart failure. Immunosuppression medication, required to prevent rejection, can result in adverse metabolic and renal effects. Clinically significant post-transplant complications include metabolic (diabetes, weight gain), renal impairment and cardiac disease, such as allograft vasculopathy and myocardial fibrosis. Sodium glucose co-transporter 2 inhibitors (SGLT2i) may have positive effects on all of these post-transplant complications. SGLT2i have been observed to improve metabolic parameters in patients with type 2 diabetes following cardiac and renal transplantation, but their benefit and safety in HTx has not been evaluated in randomised prospective studies. Aims: The overall aim of this project is to study the safety and efficacy of empagliflozin in HTx recipients. The primary end point will be improvement in glycaemic control assessed by change in glycosylated hemoglobin (HbA1c) and/or fructosamine, with secondary endpoints of cardiac fibrosis assessed by cardiac magnetic resonance, and renal function assessed by serum creatinine. Methods: Randomised, placebo-controlled trial of empagliflozin 10 mg daily versus placebo in recent HTx recipients. One hundred participants will be randomised 1:1. They will commence the study medication within 6-8 weeks of transplantation. Follow up will be 12 months after transplantation. Results from routine pre-HTx assessment will be reviewed to assess for pre-HTx diagnosis of diabetes. Routine laboratory tests, including full blood count, biochemistry, glucose, lipids and liver function as well as HbA1c, fructosamine, beta-hydroxybutyrate and urine albumin creatinine ratio, will be measured at baseline prior to receipt of study drug or placebo. Patients will be reviewed monthly during the study until 12 months post-HTx and data will be collected for each patient at each study visit. Cardiovascular magnetic resonance will be measured at baseline and 12 months after HTx. This study has been approved by St Vincent’s Hospital Human Research Ethics Committee (2021/ETH12184). Trial registration: ACTRN12622000978763. Discussion: This study will, for the first time, determine the efficacy and safety of SGLT2i in HTx recipients. Presentation: Thursday, June 15, 2023

Impact of Previous Conventional Cardiac Surgery on the Clinical Outcomes After Heart Transplantation.

The impact of the type, purpose, and timing of prior surgery on heart transplantation (HT) remains unclear. This study investigated the influence of conventional cardiac surgery (PCCS) on HT outcomes. This study analyzed HTs performed between 1999 and 2019 at a single institution. Patients were categorized into two groups: those with and without PCCS. Short-term outcomes, including post-transplant complications and mortality rates, were evaluated. Cox proportional and Kaplan-Meier survival analyses were used to identify risk factors for mortality and assess long-term survival, respectively. Of 368 patients, 29% had PCCS. Patients with PCCS had a higher incidence of post-transplant complications. The in-hospital and 1year mortality rates were higher in the PCCS group. PCCS and cardiopulmonary bypass time were significant risk factors for 1year mortality (hazard ratios = 2.485 and 1.005, respectively). The long-term survival rates were lower in the PCCS group, particularly in the first year. In sub-analysis, patients with ischemic cardiomyopathy and PCCS had the poorest outcomes. The era of surgery and timing of PCCS in relation to HT did not significantly impact outcomes. In conclusion, PCCS worsen the HT outcomes, especially in patients with ischemic etiology. However, the timing of PCCS and era of HT did not significantly affect this concern.

Histiocytic sarcoma in renal transplant patients: a literature review

BackgroundHistiocytic sarcoma (HS) is defined as neoplasm resembling morphological and immunophenotypic characteristics of mature histiocytes. It is a rare form of lymphoid neoplasms. Despite advances in treatment and diagnosis of histiocytic sarcoma, majority of cases had poor prognosis due to progressive nature of the disease. In the following article, all reported cases of histiocytic sarcoma in renal transplant patients are reviewed.MethodsIn our literature review, all relevant reports were collected electronically by entering the necessary keywords. A Boolean approach using Medical Subject Heading (MeSH) keywords was implemented. After establishing the inclusion/exclusion criteria, article titles and abstracts were evaluated by Systematic Reviews and Meta-Analyses (PRISMA) standards for 2020. All cases of histiocytic sarcoma in renal transplant patients were included.ResultBased on our inclusion and exclusion criteria 4 case reports were yielded in this review. Two were males and 2 were females with the mean age of 42.25 years. Fever was the most common symptom. Although tumor originated from the native kidney on one patient, the site of the primary tumor was thorax, oropharynx, and transplanted kidney in the rest. Metastasis was detected in all cases. Prednisone was used for all cases. EBV was positive in 2 cases and negative in one of them. Histology was diagnostic and similar in all cases. Immunohistochemistry was done for 3 cases. Although chemotherapy was done for 3 patients, all 4 cases ended in mortality.ConclusionDespite the fact that neoplasms are post renal transplant complications, histiocytic sarcoma is a scarce and fatal entity in such patients. Histological and immunohistochemistry tests are the corner stone in diagnosis of histiocytic sarcoma.

Targeted delivery of galunisertib using machine perfusion reduces fibrogenesis in an integrated ex vivo renal transplant and fibrogenesis model.

Fibrosis in kidney allografts is a major post-transplant complication that contributes to graft failure. Lately, multiple potent inhibitors of fibrosis-related pathways have been developed such as galunisertib, an inhibitor of the transforming growth factor-beta (TGF-β/TGFβ1) signalling pathway. This drug, however, poses risks for adverse effects when administered systemically. Therefore, we devised a new repurposing strategy in which galunisertib is administered ex vivo. We combined machine perfusion and tissue slices to explore the antifibrotic effects of galunisertib in renal grafts. Porcine kidneys were subjected to 30 min of warm ischaemia, 24 h of oxygenated hypothermic machine perfusion and 6 h of normothermic machine perfusion with various treatments (i.e. untreated control, TGFβ1, galunisertib or TGFβ1 + galunisertib; n = 8 kidneys per group). To determine whether effects persisted upon ceasing treatment, kidney slices were prepared from respective kidneys and incubated for 48 h. Galunisertib treatment improved general viability without negatively affecting renal function or elevating levels of injury markers or by-products of oxidative stress during perfusion. Galunisertib also reduced inflammation and, more importantly, reduced the onset of fibrosis after 48 h of incubation. Our findings demonstrate the value of using machine perfusion for administering antifibrotic drugs such as galunisertib, proving it to be an effective example of repurposing.

LUNG TRANSPLANT: NAVIGATING CHALLENGES AND ADVANCEMENTS IN PULMONARY MEDICINE

Lung transplantation, a complex and lifealtering medical intervention, serves as a beacon of hope for individuals grappling with end-stage pulmonary diseases. This research embarks on a comprehensive exploration of the dynamic landscape of lung transplantation, unraveling the challenges faced by both medical practitioners and recipients while spotlighting recent advancements that have reshaped the field. The introduction sets the stage by delineating the critical importance of lung transplantation in the context of organ transplants. The unique challenges inherent in lung transplantation, distinct from other organ transplants, are highlighted. The literature review critically examines existing studies, revealing gaps and limitations that this research seeks to address, adding depth to our understanding of this intricate medical procedure. Methodologically, a meticulous approach is adopted, encompassing a retrospective analysis of diverse lung transplant cases. The research design, selection criteria, and ethical considerations are transparently outlined, ensuring the robustness and reliability of the study. This section serves as the groundwork for unraveling the nuances of lung transplantation. Results are presented with clarity, offering insights into post-transplant complications, patient outcomes, and factors influencing long-term success. Visual aids, including graphs and tables, complement the narrative, providing a comprehensive visual representation of the data. This section aims to contribute valuable empirical evidence to the growing body of knowledge in lung transplantation. The discussion section delves into the implications of the findings, addressing challenges in post-transplant care such as rejection episodes and infectious complications. Simultaneously, it explores the impact of technological advancements and evolving immunosuppressive strategies in mitigating these challenges. This dynamic analysis underscores the adaptability of pulmonary medicine in the face of an ever-evolving medical landscape. In conclusion, this research synthesizes key findings, emphasizing their implications for the future of lung transplantation. By bridging gaps in the current literature, it contributes to the ongoing dialogue in pulmonary medicine, offering a nuanced perspective that combines empirical evidence with a deep understanding of the challenges and advancements in lung transplantation. The abstract invites readers on a journey through the intricacies of lung transplantation, providing a comprehensive overview that balances challenges with the potential for medical advancements. As the demand for lung transplantation continues to rise, this research endeavors to inform and guide future practices, fostering a more effective and personalized approach to enhance the success and sustainability of this life-saving procedure.

Computed tomography–based machine learning for donor lung screening before transplantation

Assessment and selection of donor lungs remain largely subjective and experience based. Criteria to accept or decline lungs are poorly standardized and are not compliant with the current donor pool. Using ex vivo computed tomography (CT) images, we investigated the use of a CT-based machine learning algorithm for screening donor lungs before transplantation. Clinical measures and ex situ CT scans were collected from 100 cases as part of a prospective clinical trial. Following procurement, donor lungs were inflated, placed on ice according to routine clinical practice, and imaged using a clinical CT scanner before transplantation while stored in the icebox. We trained and tested a supervised machine learning method called dictionary learning, which uses CT scans and learns specific image patterns and features pertaining to each class for a classification task. The results were evaluated with donor and recipient clinical measures. Of the 100 lung pairs donated, 70 were considered acceptable for transplantation (based on standard clinical assessment) before CT screening and were consequently implanted. The remaining 30 pairs were screened but not transplanted. Our machine learning algorithm was able to detect pulmonary abnormalities on the CT scans. Among the patients who received donor lungs, our algorithm identified recipients who had extended stays in the intensive care unit and were at 19 times higher risk of developing chronic lung allograft dysfunction within 2years posttransplant. We have created a strategy to ex vivo screen donor lungs using a CT-based machine learning algorithm. As the use of suboptimal donor lungs rises, it is important to have in place objective techniques that will assist physicians in accurately screening donor lungs to identify recipients most at risk of posttransplant complications.

Prognostic factors and predictive scores for 6-months mortality of hematopoietic stem cell transplantation recipients admitted to the pediatric intensive care unit.

Despite advances in hematopoietic stem cell transplantation (HSCT), a considerable number of pediatric HSCT patients develops post-transplant complications requiring admission to the pediatric intensive care unit (PICU). The objective of this study was to evaluate clinical findings, PICU supportive therapy and outcome as well as predictive factors for 6-months survival after discharge of HSCT patients from PICU. This retrospective single-center analysis investigated patient characteristics, microbiological findings, reasons for admission and death of 54 cases accounting for 94 admissions to the PICU of the University Children's Hospital Tuebingen from 2002 to 2017. We compared clinical characteristics between children with and without 6-months survival after discharge from PICU following HSCT. Finally, we assessed the potential prognostic value of the oncological Pediatric Risk of Mortality Score (O-PRISM), the Pediatric Sequential Organ Failure Assessment Score (pSOFA) and the pRIFLE Criteria for Acute Kidney Injury for 6-months survival using Generalized Estimating Equations (GEE) and Receiver Operating Characteristic curves. Respiratory insufficiency, gastroenterological problems and sepsis were the most common reasons for PICU admission. Out of 54 patients, 38 (70%) died during or after their last PICU admission, 30% survived for at least six months. When considering only first PICU admissions, we could not determine prognostic factors for 6-months mortality. In contrast, under consideration of all PICU admissions in the GEE model, ventilation (p=0.03) and dialysis (p=0.007) were prognostic factors for 6-months mortality. Furthermore, pSOFA (p=0.04) and O-PRISM (p=0.02) were independent risk factors for 6-months mortality considering all PICU admissions. Admission of HSCT patients to PICU is still associated with poor outcome and 69% of patients died within 6 months. Need for respiratory support and dialysis are associated with poor outcome. Prediction of 6-months survival is difficult, especially during a first PICU admission. However, on subsequent PICU admissions pSOFA and O-PRISM scores might be useful to predict mortality. These scores should be prospectively evaluated in further studies to verify whether they can identify pediatric HSCT recipients profiting most from transferal to the PICU.

Advance Care Planning and Palliative Care Consultation in Kidney Transplantation

Because of the high risk of waitlist mortality and posttransplant complications, kidney transplant (KT) patients may benefit from advance care planning (ACP) and palliative care consultation (PCC). We quantified the prevalence and racial disparities in ACP and PCC among KT candidates and recipients. Prospective cohort study. 2,575 adult KT candidates and 1,233 adult recipients (2008-2020). Race and ethnicity. All reports of ACP and PCC were abstracted from chart review. ACP was defined as patient self-report of an advance directive, presence of an advance directive in the medical record, or a documented goals-of-care conversation with a provider. PCC was defined as an ordered referral or a documented palliative care note in the medical record. Racial/ethnic disparities in ACP/PCC were estimated using adjusted logistic regression. 21.4% of KT candidates and 34.9% of recipients engaged in ACP. There were racial/ethnic disparities in ACP among KT candidates (White, 24.4%; Black, 19.1%; Hispanic, 15%; other race and ethnicity, 21.1%; P=0.008) and recipients (White, 39.5%; Black, 31.2%; Hispanic, 26.3%; other race and ethnicity, 26.6%; P=0.007). After adjustment, Black KT recipients had a 29% lower likelihood of engaging in ACP (OR, 0.71; 95% CI, 0.55-0.91) than White KT recipients. Among older (aged≥65 years) recipients, those who were Black had a lower likelihood of engaging in ACP, but there was no racial disparity among younger recipients (P=0.020 for interaction). 4.2% of KT candidates and 5.1% of KT recipients engaged in PCC; there were no racial disparities in PCC among KT candidates (White, 5.3%; Black, 3.6%; Hispanic, 2.5%; other race and ethnicity, 2.1%; P=0.13) or recipients (White, 5.5%; Black, 5.6%; Hispanic, 0.0%; other race and ethnicity, 1.3%; P= 0.21). Generalizability may be limited to academic transplant centers. ACP is not common among KT patients, and minoritized transplant patients are least likely to engage in ACP; PCC is less common. Future efforts should aim to integrate ACP and PCC into the KT process. Kidney transplant (KT) candidates and recipients are at elevated risk of morbidity and mortality. They may benefit from completing a document or conversation with their palliative care provider that outlines their future health care wishes, known as advance care planning (ACP), which is a component of palliative care consultation (PCC). We wanted to determine how many KT candidates and recipients have engaged in ACP or PCC and identify potential racial disparities. We found that 21.4% of candidates and 34.9% of recipients engaged in ACP. After adjustment, Black recipients had a 29% lower likelihood of engaging in ACP. We found that 4.2% of KT candidates and 5.1% of KT recipients engaged in PCC, with no racial disparities found in PCC.

Neurologic Status of Patients with Purine Nucleoside Phosphorylase Deficiency Before and After Hematopoetic Stem Cell Transplantation.

Purine nucleoside phosphorylase (PNP) deficiency is a rare autosomal recessive combined immunodeficiency. The phenotype is profound T cell deficiency with variable B and NK cell functions and results in recurrent and persistent infections that typically begin in the first year of life. Neurologic findings occur in approximately two-thirds of patients. The mechanism of neurologic abnormalities is unclear. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for PNP deficiency. We report here six patients from five unrelated families with PNP deficiency treated in two centers in Turkey. We evaluated the neurological status of patients and compared to post-transplantation period if available. Then, we performed PubMed, Google Scholar, and Researchgate searches using the terms "PNP" and "hematopoietic stem cell transplantation" to find all reported cases of PNP transplantation and compared to our cohort. Six patients were treated in two centers in Turkey. One patient died from post-transplant complications. The other four patients underwent successful HSCT with good immune reconstitution after transplantation (follow-up 21-48months) and good neurological outcomes. The other patient with a new mutation is still waiting for a matching HLA donor. In PNP deficiency, clinical manifestations are variable, and this disease should be considered in the presence of many different clinical findings. Despite the comorbidities that occurred before transplantation, HSCT currently appears to be the only treatment option for this disease. HSCT not only cures immunologic disorders, but probably also improves or at least stabilizes the neurologic status of patients.