Transplant Recipients Research Articles

Factors Influencing the Attrition Rate of a 10-Week Multimodal Rehabilitation Program in Patients After Lung Transplant: A Neural Network Analysis

Background/Objectives: Despite the effectiveness of exercise and nutritional interventions to improve aerobic capacity and quality of life in lung transplant (LT) recipients, their compliance is low. Strategies to reduce the high attrition rate (participants lost over time) is a major challenge. Artificial neural networks (ANN) may assist in the early identification of patients with high risk of attrition. The main objective of this study is to evaluate the usefulness of ANNs to identify prognostic factors for high attrition rate of a 10-week rehabilitation program after a LT. Methods: This prospective observational study included first-time LT recipients over 18 years of age. The main outcome for each patient was the attrition rate, which was estimated by the amount of missing data accumulated during the study. Clinical variables including malnutrition, sarcopenia, and their individual components were assessed at baseline. An ANN and regression analysis were used to identify the factors determining a high attrition rate. Results: Of the 41 participants, 17 (41.4%) had a high rate of attrition in the rehabilitation program. Only 23 baseline variables had no missing data and were included in the analysis, from which a low age-dependent body mass index (BMI) was the most important conditioning factor for a high attrition rate (p = 7.08 × 10−5), followed by end-stage respiratory disease requiring PT (p = 0.000111), low health-related quality-of-life (HRQoL) (p = 0.0009078), and low handgrip strength (p = 0.023). Conclusions: The prevalence of high attrition rate in LT recipients is high. The profile of patients with a high probability of attrition includes those with chronic obstructive pulmonary disease, low BMI and handgrip strength, and reduced HRQoL.

Can Novel Biomarkers Effectively Predict Acute Kidney Injury in Liver or Kidney Transplant Recipients?

Acute kidney injury (AKI) constitutes a common complication associated with liver or kidney transplantation, which may significantly impact the graft condition and perioperative mortality. Current AKI diagnostic criteria based on serum creatinine (sCr) and urine output alterations are widely utilized in routine clinical practice. However, the diagnostic value of sCr may be limited by various confounding factors, including age, sex, reduced or increased muscle mass, and pre-existing chronic kidney disease (CKD). Furthermore, sCr is rather a late indicator of AKI, as its concentration tends to increase only when the severity of the injury is enough to decrease the estimated glomerular filtration rate (eGFR). Recent expertise highlights the need for novel biomarkers in post-transplantation AKI diagnosis, prediction of event-associated mortality, or evaluation of indications for renal replacement treatment (RRT). Over the last decade, the diagnostic performance of various AKI biomarkers has been assessed, among which some showed the potential to outperform sCr in AKI diagnosis. Identifying susceptible individuals, early diagnosis, and prompt intervention are crucial for successful transplantation, undisturbed graft function in long-term follow-up, and decreased mortality. However, the research on AKI biomarkers in transplantation still needs to be explored. The field lacks consistent results, rigorous study designs, and external validation. Considering the rapidly growing prevalence of CKD and cirrhosis that are associated with the transplantation at their end-stage, as well as the existing knowledge gap, the aim of this article was to provide the most up-to-date review of the studies on novel biomarkers in the diagnosis of post-transplantation AKI.

Impact of physical activity on physical function and quality of life after liver transplantation

Introduction and aim of the study: Liver-related diseases are very common in our society, and as a result, the number of people requiring liver transplantation is likewise increasing. In our research, we intended to analyze the topic of increasing survival rates and improving comfort along with the quality of life while waiting for a transplant, as well as in the postoperative period. We determined that we would investigate the impact of physical activity on risk factors that increase hospitalizations after surgery and decrease quality of life. We summarized the effect and type of exercise on sarcopenia, frailty, and their direct relation to the pre- and post-operative period of liver transplantation. In addition, we analyzed possible obstacles and difficulties arising from the implementation of physical activity in liver transplant recipients. Materials and methods: The authors conducted an extensive review of articles available in PubMed, Google Scholar, UpToDate, Science Direct, and Cochrane databases. The keywords liver transplantation, physical activity, quality of life, sarcopenia, and frailty were the basis of the review. Studies published between 2001 and 2024 were included in the review. Results: The vast majority of the studies emphasized the positive effects of exercise, particularly aerobic and resistance training, on improving the clinical conditions and well-being of liver transplant patients. The papers with inconsistent results nevertheless underscored the need to delve further into this topic. Thus, the overall evidence supports the inclusion of physical exercise in post-transplant care as a key strategy for improving health and quality of life. Conclusion: Regular physical activity is beneficial for clinical outcomes and patients’ quality of life after liver transplantation.

Role of letermovir therapeutic drug monitoring for cytomegalovirus prophylaxis in allogeneic hematopoietic stem cell transplantation recipients: a prospective study.

The role of therapeutic drug monitoring (TDM) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients receiving letermovir has not yet been clarified. This study is to explore letermovir trough concentration (Cmin) correlation with its clinical efficacy and adverse events, and factors affecting its plasma concentrations. A prospective, non-interventional study was performed in allo-HSCT recipients receiving letermovir prophylaxis. Plasma concentrations were determined using high-performance liquid chromatography-tandem mass spectrometry. Data analysis was performed using logistic regression, linear regression, and classification and regression tree (CART) models. 701 trough concentrations from 71 recipients were included, uncovering pronounced intra- and inter-individual variability in letermovir Cmin. During 24-week follow-up, CMV infection incidence was 16.4%. A significant correlation was identified between letermovir Cmin and its clinical efficacy, and the CART model showed an increased risk of CMV infection when Cmin ≤ 2731 ng/mL. However, no clear correlation was found between Cmin and adverse events. Gastrointestinal graft-versus-host disease, cyclosporine Cmin, gender, and concomitant medications, including mycophenolate mofetil, ondansetron, caspofungin, and methylprednisolone, may impact letermovir Cmin. Additionally, coadministration with cyclosporine injection significantly decreased median letermovir Cmin compared with cyclosporine capsules (2311 vs. 3386 ng/mL). Moreover, with the extension of time post-transplant, trough concentrations of both cyclosporine and letermovir significantly decreased. TDM for letermovir may be beneficial in allo-HSCT recipients considering the variability in letermovir Cmin and its correlation with clinical efficacy. Moreover, drug interactions and the effects of changes in cyclosporine dosage forms or concentrations require careful monitoring for their effect on letermovir Cmin.

Mutations in human cytymegalovirus (Orthoherpesviridae: Herpesvirales: Cytomegalovirus: Cytomegalovirus humanbeta 5) UL97 gene lead to increase in viremia duration and poor antiviral response in recipients of allogeneic hematopoietic stem cells.

Human cytomegalovirus (Orthoherpesviridae: Herpesvirales: Cytomegalovirus: Cytomegalovirus humanbeta 5) (HCMV) is one of the most commonly detected viruses in recipients of allogeneic hematopoietic stem cell (allo-HSCT) transplants. However, the emergence of resistance to antiviral drugs such as ganciclovir (GCV) poses a challenge in managing these patients. This study aims to investigate the prevalence and impact of mutations in the HCMV UL97 gene associated with resistance to GCV on the course of infection among allo-HSCT patients. The study examined the association between UL97 mutations and the clinical course of HCMV infection in allo-HSCT patients. Genetic sequencing was performed to identify mutations, and their impact on viral replication and resistance to GCV was assessed. Six mutations were identified (D490A, T502A, C592G, C592F, E596G, C603W). C592G, C592F, E596G, and C603W are associated with resistance to antiviral drugs, while D490A and T502A described for the first time. When comparing patients with wild-type and those carrying the mutant variant, several parameters of peripheral blood were significantly lower in the former group. The median time to peak viral load following allo-HSCT, duration of viremia, and rate of virological response to high-dose therapy also differed significantly between the two groups. It was shown that approximately one third (4 out of 14) of allogeneic stem cell transplant recipients had mutations associated with resistance to GCV. Patients carrying the mutant variant of HCMV had longer viremia and took longer to achieve a negative virological test result after starting high-dose therapy. Performing genotyping may help make more evidence-based therapeutic decisions.

Association of Oral Tobacco-Free Nicotine Delivery Product with Acute Renal Tubular Necrosis

Usage of novel non-tobacco oral nicotine delivery products (ONDPs) has been increasing among adolescents in the United States. It is presumed that they are less toxic than their tobacco-containing counterparts, but that has not been examined in controlled studies. Most of the studies have focused on non-renal manifestations of tobacco consumption via different means. The renal manifestations of non-tobacco ONDPs are not very well known, especially in immunocompromised patients. A 19-year-old male transplant recipient presented with flank pain and a few days’ history of intake of ZYNR pouches. Immunosuppression was with tacrolimus, mycophenolate, and steroids. Baseline serum creatinine was 1.1–1.3 mg/dL. Laboratory evaluation showed elevated C-reactive protein, increased serum creatinine and blood urea nitrogen, leukocytosis, neutrophilia, and increased lactate dehydrogenase (LDH). Infectious disease work-up was negative. A kidney transplant biopsy showed severe acute tubular injury/necrosis (ATN) without evidence of rejection. Donor-specific antibodies were negative. Other etiologies of hemolysis were negative. He did not require renal replacement therapy. Kidney function and LDH improved gradually. The most recent follow-up eight months after presentation showed a serum creatinine level of 2.6 mg/dL with stable electrolytes, with eGFR of 35 mL/min/1.73 m2. Here, we describe a 19-year-old adolescent with a kidney transplant who sustained ATN leading to advanced chronic disease apparently following the usage of non-tobacco ONDP. Further larger studies are needed to study ATN as a possible renal manifestation of these next-generation products to raise awareness among the public.

Prevalence of Trypanosoma cruzi infection in Solid Organ Transplant recipients: a neglected disease in America

Abstract This study investigates the prevalence of Trypanosoma cruzi infection among solid organ transplant recipients in the United States from 2019 to 2023 before transplantation. Utilizing data from a large multicenter network, we identified a rising seroprevalence of 4.8% from 1523 Solid Organ Transplant Recipients at the time of the evaluation for transplantation, particularly among lung and heart transplant recipients. The findings highlight the need for improved screening protocols to address this neglected tropical disease in transplant populations.

Sodium-glucose co-transporter 2 inhibitors in left ventricular assist device and heart transplant recipients: a mini-review.

In recent years, sodium-glucose co-transporter 2 inhibitors (SGLT2i) emerged as promising therapeutic agents in managing heart failure (HF). They demonstrated a significant impact on reducing HF hospitalizations and related mortality in patients with reduced and preserved ejection fraction. However, evidence supporting their use in patients with left ventricular assist device (LVAD) and heart transplant (HT) recipients is still limited. We identified six key studies investigating the safety and efficacy of SGLT2i in LVAD and HT recipients. In patients with LVAD, prescription of SGLT2i was predominantly associated with improved fluid management and reduced pulmonary artery pressures. However, the results regarding their effects on body weight, hemoglobin A1c, diuretic use, and right ventricular function were contradictory. In terms of safety, SGLT2i were generally well-tolerated in the LVAD population, and the reported incidence of adverse events was low. In HT recipients, SGLT2i were associated with better glycemic control and weight reduction. No relevant adverse events were reported. Despite these encouraging results, the long-term safety and efficacy of SGLT2i in these vulnerable patient populations are yet to be investigated. Future randomized controlled trials are needed to address existing gaps in evidence and help integrate SGLT2i into clinical practice for LVAD and HT recipients.

Single-cell RNA-sequencing of BK polyomavirus replication in primary human renal proximal tubular epithelial cells identifies specific transcriptome signatures and a novel mitochondrial stress pattern.

BK polyomavirus (BKPyV) contributes to premature renal failure in 10%-20% of kidney transplant recipients. Current treatment relies on reducing immunosuppression to regain BKPyV-specific immune control. Subsequently, declining allograft function may result from persisting viral cytopathology, BKPyV-specific immune reconstitution, or alloimmunity/rejection, all being poorly distinguishable by current histological or molecular approaches. To reduce the complexity encountered in BKPyV-replicating kidneys, we analyzed differentially expressed genes (DEGs) in primary human renal proximal tubular epithelial cells at 24 and 48 h post-infection (hpi) using single-cell RNA-sequencing (10x-Genomics-3´ kit). At 24 hpi, viral transcript reads predominantly mapped to the early viral gene region (EVGR) and shifted to >100-fold higher late viral gene region (LVGR) levels at 48 hpi, matching the sequential bi-directional viral protein expression from the circular double-stranded BKPyV-DNA genome. Besides expected coverage "hills" at viral 3´-poly-A sites, unexpected "spike" and "pulse" reads resulted from off-target TSO priming. "Spike" and "pulse" patterns were rare for the mostly unidirectional reads mapping to the circular mitochondrial genome. Bioinformatic curation removed "spikes" and "pulses" and reclassified 10% of DEGs in renal proximal tubular epithelial cells (RPTECs). Up-regulated gene ontologies included S and G2/M phase, double-stranded DNA repair, proximal tubulopathy, and renal tubular dysfunction, whereas allograft rejection, antigen presentation, innate immunity, translation, and autophagy were down-regulated. BKPyV-LVGR expression induced a novel mitochondrial cell stress pattern consisting of discordant up-regulation and down-regulation of mitochondria-encoded and nucleus-encoded mitochondrial genes, respectively. We explored which top-scoring gene sets of late-phase BKPyV-replicating RPTECs can identify BKPyV-associated nephropathy in kidney transplant biopsies. The results should facilitate distinguishing BKPyV-associated pathology from other entities in kidney transplant biopsies.IMPORTANCEBK polyomavirus (BKPyV) infects more than 90% of the general population and then persists in the reno-urinary tract. Subsequently, low-level urinary shedding is seen in 10% of healthy BKPyV-seropositive persons, indicating that BKPyV replication occurs despite the presence of virus-specific cellular and humoral immunity. Notably, transplantation of donor kidneys with low-level BKPyV replication is a risk factor for progression to high-level BKPyV viruria, new-onset BKPyV-DNAemia and biopsy-proven BKPyV nephropathy. Here, we identify a short list of robust up- and down-regulated nucleus-encoded differentially expressed genes potentially allowing to discriminate viral from allograft immune damage. By carefully curating viral and mitochondrial transcriptomes, we identify a novel virus-associated mitochondrial stress pattern of up-regulated mitochondria-encoded and down-regulated nucleus-encoded mitochondrial transcripts which heralds the BKPyV-agnoprotein-mediated immune escape by breakdown of the mitochondrial membrane potential and network and mitophagy. The results may prove useful when assessing the role of BKPyV replication in kidney transplant patients with suspected acute rejection and/or BKPyV nephropathy.

Hypothalamic-Pituitary-Adrenal Axis Activity and Metabolic Disorders in Kidney Transplant Recipients on Long-Term Glucocorticoid Therapy

Background/Objectives: Glucocorticoids are commonly used for maintenance immunosuppressive therapy in kidney transplant recipients (KTRs). We aimed to investigate the prevalence of hypothalamic-pituitary-adrenal (HPA) axis suppression and its association with metabolic disorders in stable KTRs on low-dose glucocorticoids. Methods: This cross-sectional study included adult KTRs on low-dose glucocorticoids. HPA axis suppression was defined as baseline morning cortisol < 5 μg/dL. Adrenocorticotropic hormone (ACTH), dehydroepiandrosterone-sulphate (DHEAS) and 24 h urinary free cortisol (UFC) levels were also assessed. Examined metabolic disorders included hypertension, dyslipidemia, central obesity and post-transplant diabetes mellitus (PTDM). Results: Eighty adult KTRs with a median 57 months (IQR 24–102) since transplantation were included in the study. The mean prednisolone dose was 5.0 ± 1.3 mg/day. Baseline cortisol < 5.0 μg/dL was observed in 27.5% of the KTRs. Participants with baseline cortisol < 5.0 μg/dL were older (55.1 vs. 47.4 years, p = 0.023) and had had a transplant for a longer time (101.4 vs. 67.0 months, p = 0.043), compared with the rest of the cohort. Baseline cortisol correlated positively with ACTH (rho = 0.544, p < 0.001), DHEAS (rho:0.459, p < 0.001) and UFC (rho: 0.377, p = 0.002). The area under the receiver-operating characteristic curve for ACTH as a predictor of baseline cortisol > 5.0 μg/dL was 0.79 [95% confidence interval (CI): 0.68–0.89]. After adjustment for covariates, HPA axis suppression was not associated with the examined metabolic disorders. Conclusions: Our study showed that stable KTRs on chronic low-dose glucocorticoids exhibited an increased prevalence of HPA axis suppression. ACTH may serve as a surrogate biomarker for HPA axis activity in this population. Further research could evaluate the association of glucocorticoid-induced HPA axis inhibition with metabolic disorders.

Early Outcomes Of Living Donor Liver Transplant Recipients In A University Teaching Hospital Of Nepal

Introduction: The burden of chronic liver disease (CLD) is on the rise and liver transplantation remains the best treatment modality for the end stage liver disease (ESLD). Tribhuvan University Teaching Hospital has started doing living donor liver transplantation (LDLT) and we aim to report our experience and early postoperative outcomes of the first 10 living donor liver transplants performed in our institute. Methods: This is a retrospective review and included all patients who were operated for LDLT from the year 2019 to 2023 for various indications. Demographic data, Model for End-Stage Liver Disease score, Child score, etiology of CLD, liver graft type, graft-to-recipient weight ratio, operative time, blood transfusion and complications were analysed. Results: From 2019 to 2023, in total, 10 patients underwent LDLT, including one paediatric transplant. The most common etiology was alcohol (50%) and right lobe was the preferred graft. The average operative time was 7.9 ± 2.56 hours. There were no re exploration or re transplantation. The mean duration of hospital stay was around 21.37 ± 6.43 days. All patients were followed for one to five years. Four recipients had Clavien Dindo Grade II and above complications, including bile leak and post-operative bleeding. One mortality occurred on 27th post-operative day due to covid infection. Conclusions: Living donor liver transplantation is a feasible option for patients with end stage liver disease and is safe to be performed in low volume centre with the help of expertise and good team work.

Editorial Comment on "Herpes zoster development in living kidney transplant recipients receiving low-dose rituximab".

Editorial Comment on "Herpes zoster development in living kidney transplant recipients receiving low-dose rituximab".

Ceftazidime-avibactam treatment dilemma of blaKPC−2-containing Klebsiella pneumoniae due to the development of co-existence of mixed strains carrying blaKPC−2 or blaKPC−33 in lung transplant recipients

BackgroundCarbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant threat to immunocompromised populations, including lung transplant recipients. This study investigates mixed CRKP strains carrying either blaKPC−2 or blaKPC−33 following ceftazidime-avibactam (CAZ/AVI) exposure, particularly in the context of lung transplantation. Mixed CRKP strains with shifting resistance phenotypes were frequently identified in patients exposed to CAZ/AVI. We aimed to elucidate the transitional state of blaKPC variants by selecting CAZ/AVI-sensitive and -resistant CRKP strains from a lung transplantation patient.MethodsThe blaKPC-variant-carrying CRKP strains were collected from lung transplant recipients exposed to CAZ/AVI in less than two years. Antibiotic susceptibility testing (AST) was conducted using microbroth dilution, and whole-genome sequencing (WGS) was used to identify genotypes and resistance mechanisms. Limiting dilution, drop-plate, and in vitro induction experiments determined blaKPC-variant changes during CAZ/AVI administration. qPCR primers/probes were designed to identify blaKPC−2 mutations.ResultsAmong 104 lung transplant recipients infected by blaKPC-harboring CRKP strains and receiving CAZ/AVI, 10 (9.6%) experienced changing resistance phenotypes. The limiting dilution method found that Patient 10’s CRKP strains carried either blaKPC−2 or blaKPC−33. The drop-plate experiment showed differing growth patterns on CAZ/AVI mediums. The in vitro induction experiment demonstrated shifting from blaKPC−2 to blaKPC−33.ConclusionsThe study identified a “transitional state” of the mixed CRKP strains carrying either blaKPC−2 or blaKPC−33 in CAZ/AVI-exposed patients. Molecular diagnostics are crucial for identifying mixed strains and the transitional state of blaKPC variants, guiding treatment decisions in this complex landscape.

Valacyclovir versus valganciclovir for cytomegalovirus prophylaxis in kidney transplant recipients: a systematic review and comparative meta-analysis.

Valganciclovir (ValG) is the most widely used drug for cytomegalovirus (CMV) prophylaxis in kidney transplant recipients (KTRs). However, it is associated with dose-limiting side effects and considerable costs. Some centers have identified valacyclovir (ValA) as an economically attractive alternative with a lower risk of bone marrow suppression. The comparative effectiveness of these two drugs is not well-established. This study aims to compare the efficacy and safety of ValA and ValG for CMV prophylaxis in KTRs. Searches were conducted of the Medline, Cochrane, Web of Science, Embase, and Ovid databases. Endpoints encompassed the incidence of CMV disease, CMV viremia, acute rejection, leukopenia/neutropenia, and other infections, including BK polyomavirus and non-CMV herpesviruses (HVs). Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Six studies, comprising 888 patients (438 receiving ValA), were included. The groups were comparable in CMV viremia incidence (RR, 0.70; 95% CI, 0.31-1.57; P=0.4) and the development of CMV disease (RR, 0.74; 95% CI, 0.09-5.97; P=0.8). No significant differences in acute rejection rates were observed (RR, 0.97; 95% CI, 0.50-1.91; P=0.8). However, the rate of leukopenia/neutropenia was significantly lower in the ValA group (RR, 0.57; 95% CI, 0.42-0.77; P<0.01). No significant differences were noted for BK viremia (RR, 0.67; 95% CI, 0.24-1.87; P=0.4) or other HV infections (RR, 1.43; 95% CI, 0.61-3.38; P=0.4). The drugs demonstrate comparable efficacy in preventing CMV infection following kidney transplantation. However, ValA may have a lower impact on bone marrow suppression.

Narrative Review: Advancing Dysbiosis Treatment in Onco-Hematology with Microbiome-Based Therapeutic Approach

This review explores the complex relationship between gut dysbiosis and hematological malignancies, focusing on graft-versus-host disease (GvHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. We discuss how alterations in microbial diversity and composition can influence disease development, progression, and treatment outcomes in blood cancers. The mechanisms by which the gut microbiota impacts these conditions are examined, including modulation of immune responses, production of metabolites, and effects on intestinal barrier function. Recent advances in microbiome-based therapies for treating and preventing GvHD are highlighted, with emphasis on full ecosystem standardized donor-derived products. Overall, this review underscores the growing importance of microbiome research in hematology–oncology and its potential to complement existing treatments and improve outcomes for thousands of patients worldwide.

Variations in Adverse Events Typology Following E-Cigarette Use: The Role of Preexisting Medical Conditions

Background Electronic cigarettes (e-cigarettes) are often marketed as safer alternatives to traditional smoking, yet evidence suggests potential health risks, especially among vulnerable populations. This study examines the immediate adverse events following e-cigarette use in individuals with preexisting health conditions to better understand these risks. Methods We conducted a STROBE-compliant observational study to identify specific preexisting medical conditions that may increase the risk of adverse events following e-cigarette use. A cross-sectional survey was deployed from January 3rd to March 3rd, 2023. A total of 4695 current and former e-cigarette users completed the survey. Logistic regression models were utilized to examine associations between 23 distinct preexisting conditions and 48 adverse events, adjusting for age, sex, race/ethnicity, education level, and income. Results The analysis encompassed 4,421 respondents, demonstrating that individuals with solid organ transplants faced notably pronounced risks, with odds ratios indicating a seven-fold increase in mouth/tongue blisters (OR = 7.05), nearly five-fold for heart palpitations (OR = 4.92), and heartburn (OR = 4.79). Stem cell transplantation recipients also showed significantly heightened risks for similar adverse events, including mouth/tongue blisters (OR = 5.53) and heart palpitations (OR = 4.65). Metabolic diseases were linked to substantially increased odds of mouth/tongue blisters (OR = 5.63), hair loss (OR = 4.09), and migraine (OR = 3.50), highlighting a specific vulnerability to e-cigarette aerosol exposure among these groups. Conclusion The findings highlight the acute health risks associated with e-cigarette use in individuals with certain preexisting conditions. These results challenge the notion that e-cigarette use poses limited harm to human health and highlight the need for tailored public health strategies to protect vulnerable populations.

Efficacy of a Standardized Regimen of Therapeutic Plasma Exchange and IVIG for Treatment of Antibody-Mediated Rejection in Lung Transplant Recipients.

Antibody-mediated rejection (AMR) in lung transplantation has been associated with poor long-term clinical course and is a risk factor for chronic lung allograft dysfunction and graft loss. Appropriate management of AMR is necessary to improve graft survival in lung transplant recipients. There is currently no standardized approach to the treatment of lung AMR, and practices vary by institution. We sought to examine the efficacy of a standardized protocol of plasma exchange (PLEX) and IVIG in decreasing donor-specific antibodies (DSAs) and improving AMR in lung transplant recipients. A retrospective chart review was conducted on all lung transplant recipients who completed a course of PLEX per UT Southwestern AMR protocol between January 2012 and December 2019 for diagnosis of AMR. Data were collected on the patient clinical course, treatment regimen, pre-PLEX DSA, post-PLEX DSA, follow-up (> 1-month post-PLEX) DSA, and pre-and post-PLEX biopsy, when available. Of 527 patients who underwent lung transplantation during the study period, 56 (11%) received an acute course of PLEX every other day per protocol for AMR of lung transplant. Forty (71%) of 56 patients had one episode of AMR requiring PLEX; 16 patients (29%) had repeat episodes of AMR within 6 weeks to 47 months of the first episode. Most patients showed improvement in AMR on biopsy (69%) and a decline in DSA (68%). Our data suggest that treatment with combined PLEX and IVIG protocol appears effective for treating lung AMR.

Examining Whole Blood, Total and Free Plasma Tacrolimus in Elderly Kidney Transplant Recipients.

Therapeutic monitoring is routinely performed to ensure tacrolimus whole-blood concentrations fall within a predefined target. Despite this, patients still experience inefficacy and toxicity that could be related to variability in free (unbound) tacrolimus exposure. Therefore, the aim of this study was to compare tacrolimus-free plasma (Cu), total plasma (Cp), and whole-blood (Cwb) concentrations in adult kidney transplant recipients and to characterize tacrolimus disposition across different matrices. Twelve-hour concentration-time profiling was performed in 15 recipients, allowing simultaneous measurement of Cu, Cp, and Cwb. Pharmacokinetic parameters were estimated using noncompartmental analysis. The relationship between Cwb and Cp were examined using a capacity-limited binding model, incorporating the hematocrit fraction (fHCT) to estimate maximum binding concentration (Bmax) and dissociation constant (Kd). The relationship between Cp and Cu was evaluated using a linear binding model to estimate the nonspecific binding parameter (Nplasma). Nonlinear regression analysis was used to obtain estimates of Bmax, Kd, and Nplasma. A total of 195 paired Cwb, Cp, and Cu values were collected. The median ratios of Cwb:Cp, Cp:Cu, and Cwb:Cu were 9:1, 20:1, and 138:1, respectively. Variability in free plasma exposure was large; free trough values ranged from 8 to 51 ng/L and free area-under-the-concentration-time-curve values ranged from 424 to 7160 ng·h/L. Median (range) estimates of Bmax, Kd, and Nplasma were 90.4 µg/L (22.4-752.5 µg/L), 2.36 µg/L (0-69.2 µg/L), and 0.05 (0.035-0.085), respectively. The interindividual variability (CV%) in binding parameters was considerable (Bmax 117.2%; Nplasma 32.5%). Large variability was observed in tacrolimus-free plasma exposure and binding parameters. Future research to characterize the relationship between tacrolimus Cu and patient outcomes may be of benefit.

Association of COVID-19 With Risk of Posttransplant Diabetes Mellitus.

Posttransplant diabetes mellitus (PTDM) is an important complication for solid organ transplant recipients (SOTRs). COVID-19 has been associated with an increased risk of incident diabetes in the general population. However, the association between COVID-19 and new-onset PTDM has not been explored. Using the National COVID Cohort Collaborative Enclave, we conducted a cohort study of adults without diabetes receiving a solid organ transplant (heart, lung, kidney, or liver) in the United States between April 1, 2020, and March 31, 2023, with and without a first diagnosis of COVID-19 (COVID+ versus COVID-) within 180 d of SOT. We propensity score matched a single COVID+ SOTR with a COVID- SOTR who was diabetes free at the same point posttransplant. Within this matched cohort, we used multivariable Cox proportional hazards models to examine the adjusted risk of PTDM associated with COVID+. Among 1342 COVID+ SOTRs matched to 1342 COVID- SOTRs, the crude rate of newly diagnosed PTDM in the 2 y post-COVID was 17% in those with versus 13% in those without COVID-19 (P = 0.007). COVID-19 was significantly associated with new PTDM (adjusted hazard ratio, 1.37; 95% confidence interval, 1.12-1.68 at 2 y). Similar to other viral infections, COVID-19 is associated with an increased risk of PTDM in SOTRs.

Progress in prevention and treatment of cytomegalovirus infection in patients with allogeneic hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains an effective treatment for hematological malignancies. Cytomegalovirus (CMV) infection is one of the common Infection complications after hematopoietic stem cell transplantation, and also the main cause of death of transplant recipients, which has a significant impact on the prognosis and survival of transplant recipients. It is particularly important to take timely and effective prevention and treatment for CMV infected transplant patients. This article discusses the latest prevention and treatment of CMV infection after transplantation,and reviews the recent progress in the prevention and drug treatment of CMV infection in allo-HSCT patients by searching the relevant literature through Pubmed.