Post-transplant Patients Research Articles

Viral Infections in HSCT Recipients with Post-Transplant Lymphoproliferative Disorder: The Role of Torque Teno Virus as a Marker of Immune Functions

Monitoring immune function in post-transplant patients is crucial to reduce the risk of viral infections (e.g., cytomegalovirus [CMV] or Epstein–Barr virus [EBV]), which can lead to serious complications such as post-transplant lymphoproliferative disorder (PTLD). Recently, Torque Teno virus (TTV) has attracted interest as a marker of immune function. Thus, we studied the kinetics of common post-transplant viral infections (TTV, EBV, CMV, human herpesvirus-6 [HHV-6], and adenovirus [AdV]) and their association with clinical parameters in 23 HSCT recipients who developed PTLD (PTLD-HSCT) and 25 post-HSCT patients without PTLD (Non-PTLD-HSCT) at three different timepoints: at the time of the transplant (T0), 3 months (T1), and 6 months (T2) post-HSCT. Additionally, 25 healthy donors (HD) were used as the control. EBV, CMV, HHV-6, or AdV infections were found in a few samples, while TTV was found in all of our samples. The highest TTV levels (4.61 [T0], 6.24 [T1] and 6.70 [T2] log10 copies/mL) were seen in PTLD-HSCT patients compared to Non-PTLD-HSCT (3.39 [T0], 4.86 [T1], and 3.75 [T2] log10 copies/mL) and HD (2.25 log10 copies/mL) at all timepoints. Higher TTV levels were also seen in patients with a destructive type of PTLD and in surviving PTLD-HSCT patients compared to deceased ones. TTV kinetics in PTLD patients post-HSCT showed that TTV levels increase with the fall in the host immunocompetence and that by monitoring TTV kinetics, the immune status of the patient can be monitored.

Risk factors and clinical outcomes of cytomegalovirus infection following haploidentical hematopoietic stem cell transplantation in patients with aplastic anemia: a single-center retrospective study

BackgroundCytomegalovirus (CMV) infection remains a critical cause of mortality after allogeneic hematopoietic stem cell transplantation, despite significant advancements in CMV prevention and treatment with the introduction and widespread use of letermovir. However, in China, due to limitations in the availability and cost of medications, some patients still face challenges in accessing letermovir. For this subset of the population, exploring the risk factors for CMV infection remains significant in predicting its occurrence.MethodsTherefore, a retrospective analysis was conducted on 88 haploidentical hematopoietic stem cell transplant recipients over 4 years.ResultsOur study results indicate that chronic graft-versus-host disease (cGVHD) is an independent risk factor for CMV infection following haploidentical hematopoietic stem cell transplantation (Haplo-HSCT). Survival analysis reveals lower survival rates in the refractory CMV infection (RCI) group compared to the non-RCI group, with patients having lower viral loads demonstrating higher rates of seroconversion and improved survival under the same treatment regimen.ConclusionStrengthening the monitoring of CMV-DNA in post-transplant patients, actively promoting hematopoietic recovery, preventing the occurrence of CMV infection, and controlling the development of CMV infection can lead to better survival outcomes for patients with aplastic anemia undergoing Haplo-HSCT.

P-2297. Evaluation of a Meta-Virus Signature as a Diagnostic Tool to Predict the Severity of Respiratory Viral Infections in Hematopoietic Cell Transplant Recipients

Abstract Background Predicting respiratory viral infection (RVI) outcomes may lead to earlier intervention and improved prognosis in immunocompromised hosts. A microarray and RNA-Seq results meta-analysis identified a conserved gene expression host response to RVI of 396 genes called the Meta-Virus Signature (MVS). While the MVS score positively correlates to RVI severity, a 42-gene subset called the Severe-or-Mild (SoM) score distinguishes severity groups with higher accuracy (PMID 33765435). This assay has not been validated for use in immunocompromised patients with RVIs. We aim to determine if SoM scores are associated with the severity of RVIs in hematopoietic cell transplant (HCT) recipients.Table 1:Baseline characteristics and clinical outcomes following respiratory infection (n=50) Abbreviations: Allo=allogenic, BiPAP= bilevel positive airway pressure, BMI= Body mass index, CKD= chronic kidney disease, COPD= chronic obstructive pulmonary disease, CPAP=continuous positive airway pressure, ESRD= end-stage renal disease, GVHD= graft-versus-host disease, HCT= hematopoietic stem cell transplantation, HFNC= high-flow nasal cannula, HM=hematologic malignancy, ISI= immunodeficiency scoring index, IQR= interquartile range, LRI= lower respiratory tract infection, MRD= matched related donor, MUD= matched unrelated donor, PIV= parainfluenza virus, RSV= respiratory syncytial virus, RVI= respiratory virus infection, SD=standard deviation, SoM= Severe-to-mild, URI= upper respiratory tract infection. Methods We prospectively enrolled 40 HCT recipients with different RVIs (respiratory syncytial virus, influenza, parainfluenza, and SARS-CoV-2; 10 for each cohort) and 10 post-transplant patients with respiratory symptoms but negative viral respiratory panel (control cohort). Patients were followed for 30 days. Whole blood was collected in HemaSure-OMICS tubes on Day 0 and Day 5. Expression of the SoM score genes was measured by RT-PCR on the Fluidigm Biomark. Data was normalized to the Delta Ct method using the geometric mean of YWHAZ and UBC Ct values. The SoM score was calculated by taking the sum of the geometric means of previously defined modules 3 and 4 divided by the sum of the geometric means of modules 1 and 2. Infection severity was defined based on 30-day maximal oxygen requirements.Figure 1. Median Severe-or-Mild scoring according to 30-day maximal oxygen requirements (among patients with RVI, n=40).Abbreviations: BiPAP= bilevel positive airway pressure, CPAP= continuous positive airway pressure, IQR= intra quartile range, RVI= respiratory virus infection, SoM= Severe-or-Mild.*Mild infection is defined as no oxygen requirement, moderate infection is defined as the maximal O2 requirement of a nasal cannula or face mask, and severe infection as the need for high flow nasal cannula, BiPAP, CPAP, or mechanical ventilation. Results Among the 50 patients enrolled, 33 (66%) had a mild infection, 13 (26%) were moderate, and 4 (8%) experienced severe infections leading to mortality (Table 1). We observed a trend between higher SoM scores and RVI severity, with median SoM scores of 0.694, 0.860, and 1.550 in patients with mild, moderate, and severe infections, respectively (p=0.370) (Figures 1,2). The association between an elevated SoM score and severe infections was stronger for HCT recipients infected with parainfluenza (Figure 2).Figure 2. Median Severe-or-Mild scoring and severity of respiratory infection (n=50).Abbreviations: BiPAP= bilevel positive airway pressure, CPAP= continuous positive airway pressure, PIV= parainfluenza virus, RSV= respiratory syncytial virus, SoM= Severe-or-Mild.*Mild infection is defined as no oxygen requirement, moderate infection is defined as the maximal O2 requirement of a nasal cannula or face mask, and severe infection as the need for high flow nasal cannula, BiPAP, CPAP, or mechanical ventilation. Conclusion SOM score was elevated in HCT recipients with severe RVIs, although not statistically significant. Larger prospective cohort studies will be needed to identify clinically relevant applications of gene expression analysis to predict the severity of infection. Disclosures Ronnie LaCombe, PhD, Eurofins Viracor: Employee Genevieve S. Hanna, B.S. Biology, Eurofins Viracor: Employee Isabelle Ulloa, n/a, Eurofins-Viracor: Employment Rohita Sinha, PhD, Eurofins Viracor: I am a salaried employee of Eurofins Viracor Pam Morris, M.S., PMP, Eurofins Viracor: Employee Karen Howard-Shipley, M.S., PMP, Eurofins Viracor: Employment Steve Kleiboeker, PhD, Eurofins: employee|Eurofins: Stocks/Bonds (Public Company) Fareed Khawaja, MBBS, Eurofins Viracor: Grant/Research Support|Symbio: Grant/Research Support Roy F. Chemaly, MD/MPH, AiCuris: Advisor/Consultant|AiCuris: Grant/Research Support|Ansun Pharmaceuticals: Advisor/Consultant|Ansun Pharmaceuticals: Grant/Research Support|Astellas: Advisor/Consultant|Eurofins-Viracor: Grant/Research Support|InflaRX: Advisor/Consultant|Janssen: Advisor/Consultant|Karius: Advisor/Consultant|Karius: Grant/Research Support|Merck/MSD: Advisor/Consultant|Merck/MSD: Grant/Research Support|Moderna: Advisor/Consultant|Oxford Immunotec: Advisor/Consultant|Oxford Immunotec: Grant/Research Support|Roche/Genentech: Advisor/Consultant|Roche/Genentech: Grant/Research Support|Shinogi: Advisor/Consultant|Takeda: Advisor/Consultant|Takeda: Grant/Research Support|Tether: Advisor/Consultant

372. Impact of Updated 2020 Public Health Service Guidelines on Deceased Organ Donors and Transplant Recipients

Abstract Background New guidelines for assessing solid organ donors and recipients for Human Immunodeficiency Virus (HIV), Hepatitis B (HBV), and Hepatitis C (HCV) infection were published by the US Public Health Service (PHS) in 2020 and implemented into Organ Procurement and Transplantation Network (OPTN) policy on 3/1/21. Changes included a shorter risk criteria inclusionary timeframe and the removal of 4 risk criteria. Methods We analyzed OPTN deceased donor and transplant data 2 years pre-(3/1/19-2/28/21) and post-(3/1/21-3/1/23) implementation of the updated guidelines. For Kaplan-Meier survival analyses, the post- cohort included recipients transplanted before 1/1/23 to ensure recipients had at least 1 year follow-up plus a 3-month data lag. Utilization rates, defined as number of organs transplanted divided by number of available organs from donors with at least 1 organ recovered for the purpose of transplant, are shown for thoracic organs. Non-use rates, defined as number of organs recovered for the purpose of transplant but not transplanted divided by the total number of organs recovered for the purpose of transplant, are shown for abdominal organs. Results The proportion of donors considered to have PHS risk factors decreased by approximately 10% post-policy, both overall and by organ type (Fig. 1). There were no major differences pre- to post- in reported donor HIV, HCV or HBV NAT test results (Fig2. ). Post-policy, utilization rates for heart and lung for donors with risk factors were 34.9% and 17.5% respectively, compared to 34.3% and 20.0% pre-policy; while kidney and liver non-use rates for donors with risk factors were 20.3% and 8.2% respectively, compared to 17.2% and 7.9% pre-policy. There was no significant change in 1-year post-transplant patient survival for recipients who received organs from donors with PHS risk factors (Fig. 3). Conclusion Less restrictive PHS guidelines led to fewer donors being classified as having risk factors for disease transmission. Updated guidelines did not significantly affect donor infectious disease test results or post-transplant survival for recipients. Changes in donor organ utilization and non-use may be due to donor pool changes and/or overlapping policy implementations, and further investigation is warranted. Disclosures Lara A. Danziger-Isakov, MD, MPH, Aicuris: clinical research contract, paid to institutio|Ansun BioPharma: clinical research contract, paid to institution|Astellas: Advisor/Consultant|Astellas: clinical research contract, paid to institutio|Merck: clinical research contract, paid to institutio|Pfizer: Grant/Research Support|Takeda: clinical research contract, paid to institutio

Friend or Foe? Safety and Efficacy of Hepatitis B Viremic Solid Organ Allograft into Seronegative Recipients.

Long-term outcomes of HBV nucleic acid test (NAT)-positive (+) allograft use in seronegative liver transplant (LT) and kidney transplant (KT) recipients remains unknown despite being incorporated into practice by select centers. This study compares long-term outcomes between HBV NAT+ and NAT-negative (-) allografts in seronegative recipients. All recipients of an HBV core antibody-positive (HBcAb+) LT or KT were prospectively evaluated at a single transplant center from 6/2015-3/2023 and compared by NAT status. Study endpoints were post-transplant viremia, patient, and graft survival. 144 HBcAb+ LT and 220 HBcAb+ KT were performed including 57 (39.6%) NAT+ LT's and 123 (55.9%) NAT+ KT's with a median follow-up of 36 months. 14.8% of NAT+ and 3.5% of NAT- LTs experienced post-transplant viremia (p=0.004). At the time of last follow-up, 100% of NAT+ and 98.9% of NAT- LT recipients had undetectable HBV DNA (p=0.31). 4.1% of NAT+ and 6.2% of NAT- KTs experienced post-transplant viremia (p=0.12). At the time of last follow-up, 100% of NAT+ and 96.9% of NAT- KT recipients had undetectable HBV DNA (p=0.85). LT and KT patient and graft survival were not different between groups (p>0.05). With close surveillance, HBV seronegative recipients transplanted with NAT+ allografts can develop viremia which can be cleared with antiviral therapy. This is the first and largest single-center study reporting longer-term experience with HBV NAT+ allografts in seronegative recipients demonstrating the safe expansion of the donor pool.

Harnessing deep learning to detect bronchiolitis obliterans syndrome from chest CT

BackgroundBronchiolitis Obliterans Syndrome (BOS), a fibrotic airway disease that may develop after lung transplantation, conventionally relies on pulmonary function tests (PFTs) for diagnosis due to limitations of CT imaging. Deep neural networks (DNNs) have not previously been used for BOS detection. This study aims to train a DNN to detect BOS in CT scans using an approach tailored for low-data scenarios.MethodsWe trained a DNN to detect BOS in CT scans using a co-training method designed to enhance performance in low-data environments. Our method employs an auxiliary task that makes the DNN more sensitive to disease manifestations and less sensitive to the patient’s anatomical features. The DNN was tasked with predicting the sequence of two CT scans taken from the same BOS patient at least six months apart. We evaluated this approach on CT scans from 75 post-transplant patients, including 26 with BOS, and used a ROC-AUC metric to assess performance.ResultsWe show that our DNN method achieves a ROC-AUC of 0.90 (95% CI: 0.840–0.953) in distinguishing BOS from non-BOS in CT scans. Performance correlates with BOS progression, with ROC-AUC values of 0.88 for stage I, 0.91 for stage II, and 0.94 for stage III BOS. Notably, the DNN shows comparable performance on standard- and high-resolution CT scans. It also demonstrates the ability to predict BOS in at-risk patients (FEV1 between 80% and 90% of best FEV1) with a ROC-AUC of 0.87 (95% CI: 0.735–0.974). Using visual interpretation techniques for DNNs, we reveal sensitivity to hyperlucent/hypoattenuated areas indicative of air-trapping or bronchiectasis.ConclusionsOur approach shows potential for improving BOS diagnosis by enabling early detection and management. The ability to detect BOS from standard-resolution scans at any stage of respiration makes this method more accessible than previous approaches. Additionally, our findings highlight that techniques to limit overfitting are crucial for unlocking the potential of DNNs in low-data settings, which could assist clinicians in BOS studies with limited patient data.

Comparing mental health and substance use disorders in patients receiving durable VADs versus transplants: A TriNetX database analysis.

Ventricular assist device (VAD) and cardiac transplant patients experience significant strain on their physical and mental wellbeing postoperatively. Mental health and substance use disorders (MHDs and SUDs) have substantial effects on the quality of life and compliance of transplant and VAD patients. In this study, we compare and characterize MHDs and SUDs between VAD and cardiac allograft patients and transplant list patients with and without VADs. This study compares the incidence of MHDs and SUDs between VAD and cardiac transplant patients. Cohorts were defined using ICD-10 codes in TriNetX, a large public database. Patient characteristics were matched by using propensity score matching. Incidence was analyzed using the log-rank test. Statistical significance was set at p < 0.05. Survival analysis showed a statistically significant impact of adjustment disorder, nicotine dependence, and mood disorder in VAD patients as compared to cardiac allograft recipients. Depression and opioid use disorder had a significantly higher incidence in post-transplant patients compared to their VAD counterparts. Survival analysis showed that PTSD and mood disorder had a statistically significant effect on the patients waiting on transplant wait list without VADs as compared to those with VADs. MHDs and SUDs have profound implications on quality of life, survival, and medication compliance. The incidence of MHDs and SUDs differed between VAD versus cardiac transplant patients as well as the patients on the transplant waitlist with and without VADs. Mental health resources should be tailored to address risk factors that may be unique to each group of patients.

Tacrolimus- and Mycophenolate-Mediated Toxicity: Clinical Considerations and Options in Management of Post-Transplant Patients.

Tacrolimus and mycophenolate are important immunosuppressive agents used to prevent organ rejection in post-transplant patients. While highly effective, their use is associated with significant toxicity, requiring careful management. Tacrolimus, a calcineurin inhibitor, is linked to nephrotoxicity, neurotoxicity, metabolic disturbances such as diabetes mellitus and dyslipidemia, and cardiovascular complications such as hypertension and arrhythmias. Mycophenolate, a reversible inhibitor of inosine monophosphate dehydrogenase, frequently causes gastrointestinal disturbances, including diarrhea and colitis, as well as hematologic side effects like anemia and leukopenia, which increase infection risk. Therapeutic drug monitoring (TDM) and pharmacogenomics have emerged as essential strategies for mitigating these toxicities. TDM ensures tacrolimus trough levels are maintained within a therapeutic range, minimizing the risks of nephrotoxicity and rejection. Pharmacogenomic insights, such as CYP3A5 polymorphisms, allow for personalized tacrolimus dosing based on individual metabolic profiles. For mycophenolate, monitoring inosine monophosphate dehydrogenase activity provides a pharmacodynamic approach to dose optimization, reducing gastrointestinal and hematologic toxicities. Emerging tools, including dried blood spot sampling and pharmacokinetic modeling, offer innovative methods to simplify monitoring and enhance precision in outpatient settings. Despite their utility, the toxicity profiles of these drugs, including those of early immunosuppressants such as cyclosporine and azathioprine, necessitate further consideration of alternative immunosuppressants like sirolimus, everolimus, and belatacept. Although promising, these newer agents require careful patient selection and further research. Future directions in immunosuppressive therapy include integrating individual pharmacogenetic data to refine dosing, minimize side effects, and improve long-term graft outcomes. This narrative review underscores the importance of personalized medicine and advanced monitoring in optimizing post-transplant care.

Pancreas transplantation: indications, surgical technique, and clinical significance

Pancreas transplantation (PT) is a vital therapeutic option for patients with diabetes mellitus (DM)|, particularly those with end-stage renal disease (ESRD) or severe metabolic complications. Over the past several decades, advancements in surgical techniques, organ preservation and procurement methods, and immunosuppression therapies have significantly enhanced post-transplant patient survival, graft survival, and quality of life. The primary goals of PT are to achieve effective and stable glycemic control, often leading to insulin independence, improve the patient's quality of life, and reduce secondary complications associated with DM. PT encompasses a variety of procedures, including PT alone from a living donor, whole PT, pancreas with kidney transplantation, and pancreatic islet cell transplantation. PT is most commonly performed in conjunction with kidney transplantation for selected patients with DM and ESRD. Over the past decade, unadjusted patient survival rates have exceeded 96% at 1-year post-transplant and &gt; 80% at 5 years.

Influence of gut flora on diabetes management after kidney transplantation.

Post-transplant diabetes mellitus (PTDM) is a common complication following renal transplantation, and its incidence has been gradually increasing in recent years, posing a significant public health challenge. Managing PTDM is complex, as studies suggest that it involves changes in the microbial flora across multiple organs. Recent research highlights the critical role of gut flora metabolism in the development of diabetes among post-renal transplant patients. This paper reviews the alterations in gut flora observed in PTDM patients and explores how gut flora influences PTDM. These findings may offer new perspectives on targeting gut flora metabolites for the prevention and treatment of PTDM.

Combination Therapy for Cryptosporidiosis in Immunocompromised Patients: A Systematic Review

Cryptosporidium sp. is a pathogen that causes gastroenteritis and may increase mortality and morbidity in immunocompromised patients. Cryptosporidium became widely recognized as a human pathogen. Diarrhea is a common problem in AIDS patients and about 30%–60% of patients in developed countries and 90% in developing countries experience diarrhea. This study was conducted using a systematic review design. Two articles with cohort design and two with case report design were selected based on the eligibility criteria. Three of these studies used a combination of nitazoxanide with azithromycin as an intervention, one in cohort design and two in case report design. One cohort study used a nitazoxanide and fluoroquinolone combination as an intervention. 54 samples participated in this study were post kidney transplantation patients and one sample was with acute lymphoblastic leukemia (ALL). Nitazoxanide and fluoroquinolone combination is a better therapy for cryptosporidiosis in immunocompromised patients compared to nitazoxanide and azithromycin combination. The(OR) for stool clearance was significantly lower with nitazoxanide alone compared to that of nitazoxanide and fluoroquinolone (OR: 0.65, 95% CI: 0.34, 0.92, P= 0.01), and the OR for diarrhea stopped was significantly lower with nitazoxanide alone compared to that of nitazoxanide and fluoroquinolone (OR: 0.45, 95% CI: 0.21, 0.81, P= 0.004). The OR for stool clearance was lower with nitazoxanide and azithromycin than monotherapy (OR 0.27, 95% CI: 0.01, 5.77), but P=0.24, which means not statistically significant.

Epithelioid angiosarcoma at a non-functioning arteriovenous fistula site in a renal transplant patient.

We present a case of biopsy-proven epithelioid angiosarcoma in an arteriovenous fistula (AVF). Angiosarcomas developing in non-functioning AVF in renal transplant recipients are rare clinical entities with poor prognosis. A 59-year-old male adequately immunosuppressed kidney transplant patient presented with pain and swelling at the site of a previously asymptomatic fistula. A duplex scan confirmed the presence of thrombosis present along the length of the AVF; however, in light of worsening pain and skin changes, an MRI scan was requested. This demonstrated a thrombosed brachiocephalic AVF and a more sinister appearing irregular segment infiltrating the underlying anterior compartment musculature with associated muscle oedema and internal irregular enhancement. A staging CT thorax showed indeterminate lymphadenopathy in the left axilla with no pulmonary lesions. Core needle biopsy of the primary lesion at the fistula site and subsequent biopsy of the axillary lymph nodes revealed metastatic angiosarcoma. A multidisciplinary decision was made to perform radical surgery with above-elbow amputation and simultaneous left axillary lymph node clearance. We focus on relevant imaging findings to facilitate early recognition of angiosarcoma, in particular, the importance of requesting urgent imaging of vascular access sites (functioning or not) in post-transplant patients presenting with swelling. Although rare, angiosarcoma is an important entity that should be considered in the differential diagnosis of soft tissue masses arising from a vascular access, especially in immunocompromised patients.

Association of transplant recipient status with clinical and financial outcomes among patients undergoing major surgery

BackgroundTransplant recipients undergoing surgery may represent a vulnerable population because of transplant-related comorbidities as well as reliance on immunosuppressive medications. We sought to characterize the association of prior transplant status on postoperative outcomes among patients undergoing major non–transplant-related surgical procedures. MethodsData on patients who underwent a major surgical procedure (pneumonectomy, coronary artery bypass graft, abdominal aortic aneurysm repair, Whipple, colectomy) between 2016 and 2020 were obtained from the Nationwide Readmission Database. After balancing the 2 cohorts using entropy balancing, multivariable regression models were used to assess the relationship between post-transplant status and patient outcomes. ResultsAmong 1,818,973 patients, 0.45% (n = 8,212) had a history of solid organ transplantation (liver: n = 1,773, 21.6%; heart/lung: n = 1,087, 13.2%; kidney/pancreas: n = 4,891, 59.6%; and multiple: n = 461, 5.6%). In the unmatched cohort, patients who had a history of organ transplant were more likely to be male (64.1% vs 57.7%) and have Medicare insurance (71.7% vs 59.3%) (both P < .001). On multivariable analysis, prior transplant recipient status was associated with higher odds of postoperative complications (odds ratio 1.30, 95% confidence interval 1.22–1.38), 30-day readmission (odds ratio 1.42, 95% confidence interval 1.31–1.54), and in-hospital mortality (odds ratio 1.20, 95% confidence interval 1.03–1.40) (all P < .05). Moreover, organ transplantation was associated with higher index hospitalization costs (14.4% difference, 95% confidence interval 14.1%–14.6%) and 30-day postdischarge costs (16.2% difference, 95% confidence interval 15.3%–17.0%) (both P < .001). ConclusionsPrior transplant recipient status was associated with adverse clinical and financial outcomes following subsequent major surgery. Prior history of transplant may be an important factor to incorporate into risk stratification of patients undergoing subsequent major surgical procedures.

Acute metabolic decompensation after liver transplant in a patient with maple syrup urine disease.

Maple syrup urine disease (MSUD) is an inborn error of metabolism characterized by the accumulation of branched-chain amino acids (leucine, isoleucine, and valine) caused by a defect in the branched-chain alpha-keto acid dehydrogenase complex. Liver transplant is an effective therapy for MSUD, and patients can usually tolerate a regular diet after transplant without symptomatic metabolic decompensation. Most post-transplant patients do not follow a sick-day diet. We report a case of a 7-year-old male with MSUD Type IA, status post-liver transplant at 2 years of age, who presented with profound encephalopathy following poor oral intake and vomiting for 3 days. Broad laboratory workup was significant for hyperleucinosis and an unrevealing infectious workup. We conducted a review of eight post-liver transplant MSUD patients followed at Washington University in St. Louis. The review revealed that plasma amino acids were generally not checked during intercurrent illnesses in this patient cohort. While most of our patients have not had documented encephalopathy, one of the patients with epilepsy had a seizure during a gastrointestinal illness. Based on the review of the literature and from our center's experience, acute metabolic decompensation with intercurrent illnesses in MSUD patients after liver transplant appears to be rare. This case report raises awareness that patients with MSUD are still at risk of developing metabolic crisis post-liver transplant and provides additional insight into the risk factors associated with metabolic decompensation in this patient cohort.

Skeletal Muscle 31P MR Spectroscopy Surpasses CT in Predicting Patient Survival After Liver Transplantation.

Skeletal muscle alterations are associated with higher mortality and morbidity in patients with liver cirrhosis. Assessing these changes seems to be a promising method for identifying patients at a high risk of poor outcomes following liver transplantation (LT). This is particularly important given the current global shortage of organ donors. However, evidence of the impact of these alterations on the prognosis of patients undergoing LT is inconclusive. The aim of our prospective study was to evaluate the impact of skeletal muscle changes, reflected in sarcopenia, myosteatosis and metabolic changes in the calf muscles, on perioperative outcomes and long-term survival after LT. We also sought to determine the posttransplant evolution of the resting muscle metabolism. We examined 134 adult LT candidates. Of these, 105 underwent LT. Sarcopenia and myosteatosis were diagnosed by measuring the skeletal muscle index and mean psoas muscle radiation attenuation, respectively, which were obtained from computed tomography (CT) scans taken during pretransplant assessment. Additionally, patients underwent 31P MR spectroscopy (MRS) of the calf muscles at rest before LT and 6, 12 and 24 months thereafter. The median follow-up was 6 years. Patients with abnormal 31P MRS results and CT-diagnosed myosteatosis prior to LT had significantly worse long-term survival after LT (hazard ratio (HR), 3.36; 95% confidence interval (CI), 1.48-7.60; p = 0.0021 and HR, 2.58; 95% CI, 1.06-6.29; p = 0.03, respectively). Multivariable analysis showed that abnormal 31P MR spectra (HR, 3.40; 95% CI, 1.50-7.71; p = 0.003) were a better predictor of worse long-term survival after LT than myosteatosis (HR, 2.78; 95% CI, 1.14-6.78; p = 0.025). Patients with abnormal 31P MR spectra had higher blood loss during LT (p = 0.038), required a higher number of red blood cell transfusions (p = 0.006) and stayed longer in ICU (p = 0.041) and hospital (p = 0.007). Myosteatosis was associated with more revision surgeries following LT (p = 0.038) and a higher number of received red blood cell transfusion units (p = 0.002). Sarcopenia had no significant effect on posttransplant patient survival. An improvement in the resting metabolism of the calf muscles was observed at 12 and 24 months after LT. Abnormal 31P MRS results of calf muscles were superior to CT-based diagnosis of myosteatosis and sarcopenia in predicting perioperative complications and long-term survival after LT. Resting muscle metabolism normalized 1 year after LT in most recipients.

The role of daratumumab in complications post-allogeneic hematopoietic stem cell transplantation: a single-center prospective study on PRCA and AIHA.

Pure red cell aplasia (PRCA) and autoimmune hemolytic anemia (AIHA) post-hematopoietic stem cell transplantation (HSCT) are an unmet medical need with no established standard of care, significantly affecting the patient quality of life and posing a challenge for clinicians. The anti-CD38 IgG-kappa Daratumumab appears to be a safe and efficace treatment compared to prior drugs. Our study is a prospective monocentric investigation assessing the use of daratumumab in these complications following allo-HSCT. Here we describe our experience on six patients with a median age of 65 years. All treated patients, except one, who died because of sepsis during GVHD exacerbation, reached transfusion independence with erythropoietin suspension. Poor graft function remains a management challenge for clinicians and has a significant impact on the patient's quality of life. Currently, therapeutic options for PRCA and for the least common AIHA, appear ineffective, making it difficult to address the diverse needs of post-transplant patients. Although our data and those previously reported in the literature are preliminary, daratumumab prompts further reflection on its use in this setting of patients.

Outcomes of A2/A2B to B Deceased Donor Kidney Transplantation: A Retrospective Study.

Background A2/A2B to B kidney transplantation has the potential to increase transplant access for traditionally disadvantaged blood group B minority candidates. Despite prior reports of positive post-transplant safety and clinical success, A2/A2B to B kidney transplantation remains underutilized in the United States. This study aims to investigate the post-transplant outcomes of A2/A2B to B kidney transplants performed at our center. Methods A retrospective study of all A2/A2B to B deceased donor kidney transplants (DDKTs) at our center from 2017 through 2023 was performed. Recipient and donor demographics, recipient medical history, time to transplant from listing, and post-transplant clinical outcomes were assessed, including one-year graft and patient survival. Results Of the 54 A2/A2B to B DDKTs performed during this period, 36 recipients were male, and 18 were female.The mean recipient age was 53.2 years. There were 22 (40.7%) African American recipients, 12 (22.2%) Hispanic recipients, 11 (20.3%) Caucasian recipients, eight (14.8%) Asian recipients, and one (1.8%) recipient of "other" race. The mean estimated post-transplant survival score was 46.5%. The mean donor age was 40.2 years, and the mean kidney donor profile index score was 44%. The mean time from waitlisting to transplant was 216 days. Delayed graft function was observed in five (9.2%) patients. Three (5.5%) patients had biopsy-proven acute rejection in the first year after transplant. The mean serum creatinine at one-year post-transplant was 1.4 mg/dL. At one-year post-transplant, graft survival was 96.2%, and patient survival was 98.1%. Conclusions Our study demonstrated excellent one-year post-transplant graft and patient survival rates with A2/A2B to B DDKT, with minority candidates predominantly benefiting from this.

Elevated Plasma High Sensitive C-Reactive Protein and Triglyceride/High-Density Lipoprotein Cholesterol Ratio are Risks Factors of Diabetes Progression in Prediabetes Patients After Kidney Transplant: A 3-Year Single-Center Study in Vietnam.

Determination the rate of developing post-transplant diabetes mellitus (PTDM) in prediabetic patients and the relationship with plasma hs-CRP levels and TG/HDL-C ratio in patients after kidney transplantation from living donors followed for 3 years. A total of 206 post-transplant patients diagnosed with prediabetes by oral glucose tolerance test (OGTT) were included in the study. At the time of diagnosis of prediabetes, all patients were clinically examined, paraclinical tests were performed, plasma hs-CRP was quantified, and the TG/HDL-C ratio was determined. Patients are individualized and given a reasonable diet and exercise regimen. Patients had their fasting blood glucose measured monthly or had an OGTT every 3 months. Patients meeting the criteria for diagnosis of PTDM according to the American Diabetes Association (ADA)-2018 were collected during 3 years of follow-up. The study group had an average age of 39.46 ± 10.26 years old, including 74.8% males and 25.2% females. The rate of patients who had a development of PTDM from prediabetes was 29.6% (61/206 patients). BMI, plasma TG, HDL-C, hs-CRP, and TG/HDL-C ratio at the time of prediabetes diagnosis were factors related to the progression of PTDM, in which hs-CRP and TG/HDL-C ratio were good predictors (with AUC = 0.85 and 0.874, respectively; p < 0.001). After 3 years of follow-up, nearly one-third of prediabetic patients developed PTDM post-living donor kidney transplantation. BMI, plasma TG, HDL-C, hs-CRP, and the TG/HDL-C ratio were linked to DM progression, with hs-CRP and TG/HDL-C being the strongest predictors.

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 of serum levels of sCD40, sCD40L and s4-1BB in advanced heart failure and after heart transplant

Abstract Heart failure is one of the most important problems in public health. Although big advances had been reached in treatment, the prognosis of advanced heart failure is still reserved and the heart transplant is the main therapy for this stage of disease. Allograft rejection is responsible for mortality in transplantation patients and the diagnosis of this complication is made through an invasive diagnostic method – the cardiac biopsy. The inflammatory response has been described in cardiovascular disease and in allograft rejection process. The objective of this study is to evaluate levels of sCD40, sCD40L and s4-1BB (inflammatory biomarkers) in advanced heart failure and post heart transplant with allograft rejection comparing to normal individuals and post heart transplant patients with no allograft rejection. The study population comprised 38 patients undergoing heart transplant in our center. Fifteen patients had biomarkers dosed before heart transplant and twenty three patients had dosed just after procedure. In this group, six patients were enrolled in the study for clinical suspicion of rejection. Nineteen health persons composed the control group with age between 18 and 49 years. Plasma dosage of sCD40, sCD40L e s4-1BB was made by enzyme linked immunosorbentassay (ELISA). Mann-Whitney test, Wilcoxon and t test were used to analyse dates. Statistical analysis used GraphPad®Prism6 and the value p&amp;lt; 0,05 was considered statistical significant. Allograft rejection occurred in 6,26% of studied patients. There was no statistical difference in age, sex, comorbities as hypertension, diabetes or etiology of cardiomyopathy. Serum levels of sCD40, sCD40L e s4-1BB were higher in patients with advanced heart failure comparing to controls (p&amp;lt; 0,0001). There was no difference in these levels of sCD40 (p = 0,74) e sCD40L (p = 0,44) between groups with and without rejection. Levels of s4-1BB were significantly lower in patients with allograft rejection (p= 0,02). The sCD40/PCR and s4-1BB/PCR indexs were significantly higher in the group of patients with allograft rejection (p =0,02 e p= 0,0001). We concluded that sCD40, sCD40L e s4-1BB are biomarkers of severe heart failure. The serum level of s4-1BB could be a potential biomarker of allograft rejection and the association of sCD40 and s4-1BB with PCR could be a better strategy to this.