Distinct clinical features of transplanted children with Parvovirus B19 infection.

BACKGROUND: The immature and suppressed immune response makes transplanted children a special susceptible group to Parvovirus B19 (PVB19). However, the clinical features of transplanted children with PVB19 infection haven't been comprehensively described. METHODS: We searched the medical records of all the transplant recipients who attended the Children's Hospital of Fudan University from 1 Oct 2020 to 31 May 2023, and reviewed the medical literature for PVB19 infection cases among transplanted children. RESULTS: A total of 10 cases of PVB19 infection were identified in 201 transplanted children at our hospital, and the medical records of each of these cases were shown. Also, we retrieved 40 cases of PVB19 infection among transplanted children from the literature, thus summarizing a total of 50 unique cases of PVB19 infection. The median time to the first positive PVB19 DNA detection was 14 weeks post-transplantation. PVB19 IgM and IgG were detected in merely 26% and 24% of the children, respectively. The incidence of graft loss/dysfunction was as high as 36%. Hematopoietic stem cell transplant (HSCT) recipients showed higher PVB19 load, lower HGB level, greater platelet damage, lower PVB19 IgM/IgG positive rates, and more graft dysfunction than solid-organ transplant (SOT) recipients, indicating a more incompetent immune system. CONCLUSIONS: Compared with the published data of transplanted adults, transplanted children displayed distinct clinical features upon PVB19 infection, including lower PVB19 IgM/IgG positive rates, more graft dysfunction, and broader damage on hematopoietic cell lines, which was even more prominent in HSCT recipients, thus should be of greater concern.

Risk assessment of organ transplant operation: A fuzzy hybrid MCDM approach based on fuzzy FMEA.

Nowadays, most fatal diseases are attributed to the malfunction of bodily. Sometimes organ transplantation is the only possible therapy, for instance for patients with end-stage liver diseases, and the preferred treatment, for instance for patients with end-stage renal diseases. However, this surgical procedure comes with inherent risks and effectively managing these risks to minimize the likelihood of complications arising from organ transplantation (maximizing life years from transplant and quality-adjusted life years) is crucial. To facilitate this process, risk ranking is used to identify and promptly address potential risks. Over recent years, considerable efforts have been made, and various approaches have been proposed to enhance Failure Modes and Effects Analysis (FMEA). In this study, taking into account the uncertainty in linguistic variables (F-FMEA), we introduce an approach based on Fuzzy Multi Criteria Decision Making (F-MCDM) for effectively evaluating scenarios and initial failure hazards. Nevertheless, the results of ranking failure modes generated by different MCDM methods may vary. This study is a retrospective study that suggests a comprehensive unified risk assessment model, integrating multiple techniques to produce a more inclusive ranking of failure modes. Exploring a broad spectrum of risks associated with organ transplant operations, we identified 20 principal hazards with the assistance of literature and experts. We developed a questionnaire to examine the impact of various critical factors on the survival of transplanted organs, such as irregularities in immunosuppressive drug consumption, inappropriate dietary habits, psychological disorders, engaging in strenuous activities post-transplant, neglecting quarantine regulations, and other design-related factors. Subsequently, we analyzed the severity of their effects on the durability of transplanted organs. Utilizing the Mamdani algorithm as a fuzzy inference engine and the Center of Gravity algorithm for tooling, we expressed the probability and severity of each risk. Finally, the failure mode ranking obtained from the F-FMEA method, three fuzzy MCDM methods, and the proposed combined method were identified. Additionally, the results obtained from various methods were evaluated by an expert team, demonstrating that the highest consistency and effectiveness among different methods are attributed to the proposed method, as it achieved a 91.67% agreement with expert opinions.

Bone Loss after Solid Organ Transplantation: A Review of Organ-Specific Considerations.

This review article investigates solid organ transplantation-induced osteoporosis, a critical yet often overlooked issue, emphasizing its significance in post-transplant care. The initial sections provide a comprehensive understanding of the prevalence and multifactorial pathogenesis of transplantation osteoporosis, including factors such as deteriorating post-transplantation health, hormonal changes, and the impact of immunosuppressive medications. Furthermore, the review is dedicated to organ-specific considerations in transplantation osteoporosis, with separate analyses for kidney, liver, heart, and lung transplantations. Each section elucidates the unique challenges and management strategies pertinent to transplantation osteoporosis in relation to each organ type, highlighting the necessity of an organ-specific approach to fully understand the diverse manifestations and implications of transplantation osteoporosis. This review underscores the importance of this topic in transplant medicine, aiming to enhance awareness and knowledge among clinicians and researchers. By comprehensively examining transplantation osteoporosis, this study contributes to the development of improved management and care strategies, ultimately leading to improved patient outcomes in this vulnerable group. This detailed review serves as an essential resource for those involved in the complex multidisciplinary care of transplant recipients.

Bronchiectasis After Solid-Organ Transplant: A Retrospective Single Center Study.

OBJECTIVES: Bronchiectasis is characterized by abnormal, persistent, and irreversible enlargement of the bronchi. Many etiological factors have been described, but there are limited data on the development of bronchiectasis after organ transplantation. Our study is the first to study evaluate the frequency of bronchiectasis in heart and liver transplants as well as kidney transplants. Our aim is to analyze the frequency of bronchiectasis development after solid-organ transplant and the characteristics of the cases and to evaluate potential relationships. MATERIALS AND METHODS: We retrospectively analyzed data of patients who underwent solid-organ transplant at the Baskent University Faculty of Medicine Hospital through the hospital electronic information system. Demographic, clinical, and laboratory data and thoracic computed tomography scans were evaluated. RESULTS: The study included 468 patients (151 females/317 males). Kidney transplant was performed in 61.5% (n = 207), heart transplant in 20.3% (n = 95), and liver transplant in 18.2% (n = 85) of patients. Development of bronchiectasis was detected in only 13 patients (2.7%). We determined a 13.64-fold risk of developing bronchiectasis in patients with chronic obstructive pulmonary disease and 10.08-fold risk in patients with pneumonia by multivariate regression analyzes, in which all possible risk factors for the development of bronchiectasis after transplant were evaluated. CONCLUSIONS: The pathophysiology of transplantassociated bronchiectasis has not yet been clarified. Underlying diseases, recurrent pulmonary infections, and potential effects from immunosuppressive drugs may contribute to the pathogenesis of bronchiectasis. Further prospective studies are needed to include long-term health outcomes in transplant patients with and without bronchiectasis.

Association between oral nutrition and inflammation after intestinal transplantation.

Intestinal transplantation (Itx) can be a life-saving treatment for certain patient populations, including those patients with intestinal failure (IF) who develop life-threatening complications due to the use of parenteral nutrition (PN). Most patients who have undergone Itx are eventually able to tolerate a full oral diet. However, little guidance or consensus exists regarding optimizing the specific components of an oral diet for Itx patients, including macronutrients, micronutrients and dietary patterns. While oral dietary prescriptions have moved to the forefront of primary and preventive care, this movement has yet to occur across the field of organ transplantation. Evidence to date points to the role of systemic chronic inflammation (SCI) in a wide variety of chronic diseases as well as post-transplant graft dysfunction. This review will discuss current trends in oral nutrition for Itx patients and also offer novel insights into nutritional management techniques that may help to decrease SCI and chronic disease risk as well as optimize graft function.

Comparative analysis of tabelecleucel and current treatment in patients with Epstein-Barr virus-positive post-transplant lymphoproliferative disease following hematopoietic cell transplant or solid organ transplant.

AIMS: With recent European Union marketing authorization, tabelecleucel is the first off-the-shelf, allogeneic Epstein-Barr virus (EBV)-specific T-cell immunotherapy approved for the treatment of relapsed/refractory EBV-positive post-transplant lymphoproliferative disease (EBV+ PTLD). In the absence of a control arm, real-world evidence can provide a comparative benchmark for single-arm studies in ultra-rare populations. This study assessed the treatment effect of tabelecleucel in the single-arm phase 3 ALLELE study (NCT03394365) versus a treatment group from a multinational, multicenter retrospective chart review study (RS002) of patients with EBV+ PTLD. METHODS: In ALLELE, patients had disease relapsed/refractory to rituximab ± chemotherapy and received tabelecleucel 2x106 cells/kg on days 1, 8, and 15 in 35-day cycles. Patients in RS002 had disease relapsed/refractory to rituximab ± chemotherapy and received next line of systemic therapy between January 2000 and December 2018. Propensity score-based standardized mortality/morbidity ratio weighting was used to achieve balance between treatment and comparator arms. Kaplan-Meier estimators and Cox regression models were used to compare overall survival (OS) in the re-weighted sample. RESULTS: 30 patients (n = 14 hematopoietic cell transplant [HCT], n = 16 solid organ transplant [SOT]) from ALLELE (data cutoff: November 2021) and 84 patients (n = 36 HCT, n = 48 SOT) from RS002 (data lock: January 2021) were included. Median time from diagnosis to first tabelecleucel dose (ALLELE) or start date of next line of systemic therapy (RS002) was 3.6 months. Tabelecleucel was associated with a substantial OS benefit compared with current treatment, with an unadjusted HR of 0.47 (95% confidence interval [CI] 0.25-0.88) and adjusted HR of 0.37 (95% CI 0.20-0.71) when using the start date of the next line of therapy as the index date. Sensitivity analyses yielded consistent results. CONCLUSIONS: In this study of real-world data, tabelecleucel was associated with an OS benefit among patients with R/R EBV+ PTLD for whom there is high unmet need.

Voriconazole metabolism is associated with the number of skin cancers per patient.

Voriconazole exposure is associated with skin cancer, but it is unknown how the full spectrum of its metabolizer phenotypes impacts this association. We conducted a retrospective cohort study to determine how variation in metabolism of voriconazole as measured by metabolizer status of CYP2C19 is associated with the total number of skin cancers a patient develops and the rate of development of the first skin cancer after treatment. There were 1,739 organ transplant recipients with data on CYP2C19 phenotype. Of these, 134 were exposed to voriconazole. There was a significant difference in the number of skin cancers after transplant based on exposure to voriconazole, metabolizer phenotype, and the interaction of these two (p < 0.01 for all three). This increase was driven primarily by number of squamous cell carcinomas among rapid metabolizes with voriconazole exposure (p < 0.01 for both). Patients exposed to voriconazole developed skin cancers more rapidly than those without exposure (Fine-Grey hazard ratio 1.78, 95% confidence interval 1.19-2.66). This association was similarly driven by development of SCC (Fine-Grey hazard ratio 1.83, 95% confidence interval 1.14-2.94). Differences in voriconazoles metabolism are associated with an increase in the number of skin cancers developed after transplant, particularly SCC.

Can the pan-immune-inflammation value predict gram negative bloodstream infection-related 30-day mortality in solid organ transplant patients?

BACKGROUND: The recently used pan-immune-inflammation value (PIV) has not been adequately studied as a predictive marker for mortality in immunosuppressed patients. The aim of this study was to evaluate the usefulness of baseline PIV level as a predictor of 30-day mortality in solid organ transplant (SOT) recipients with gram negative bloodstream infections (GN-BSI). METHODS: This retrospective, cross-sectional study was conducted between January 1, 2019, and December 31, 2022, in 1104 SOT recipients. During the study period, 118 GN-BSI were recorded in 113 patients. Clinical, epidemiological, and laboratory data were collected, and mortality rates (30-day and all-cause) were recorded. RESULTS: The 113 recipients had a median age of 50 years [interquartile range (IQR) 37.5-61.5 years] with a male predominance (n = 72, 63.7%). The three most common microorganisms were as follows: 46 isolates (38.9%) of Escherichia coli, 41 (34.7%) of Klebsiella pneumoniae, and 12 (10.2%) of Acinetobacter baumannii. In 44.9% and 35.6% of the isolates, production of extended-spectrum beta-lactamases and carbapenem resistance were detected, respectively. The incidence of carbapenem-resistant GN-BSI was higher in liver recipients than in renal recipients (n = 27, 69.2% vs n = 13, 17.6%, p < 0.001). All-cause and 30-day mortality rates after GN-BSI were 26.5% (n = 30), and 16.8% (n = 19), respectively. In the group with GN-BSI-related 30-day mortality, the median PIV level was significantly lower (327.3, IQR 64.8-795.4 vs. 1049.6, IQR 338.6-2177.1; p = 0.002). The binary logistic regression analysis identified low PIV level [hazard ratio (HR) = 0.93, 95% confidence interval (CI) 0.86-0.99; p = 0.04], and increased age (HR = 1.05, 95% CI 1.01-1.09; p = 0.002) as factors associated with 30-day mortality. The receiver operating characteristic analysis revealed that PIV could determine the GN-BSI-related 30-day mortality with area under curve (AUC): 0.723, 95% CI 0.597-0.848, p = 0.0005. CONCLUSIONS: PIV is a simple and inexpensive biomarker that can be used to estimate mortality in immunosuppressed patients, but the results need to be interpreted carefully.

Donation after Brain Death and Circulatory Death in Turkey: Current Status.

Tissue and organ transplantation is the best treatment option for end-stage organ failure. However, organ shortage still remains to be the greatest challenge facing the field of organ transplantation. Millions of people die and are buried with healthy organs, which could save the lives of many patients who continue to wait on transplant lists. Countries must aim to work towards a system of matching organs as much as possible with the deceased donation to meet the growing demand for organs. This action will not only result in the reduction of organ trafficking activities but shall also make an enormous difference to those patients awaiting transplants where living organ donors are not an option. Donation after circulator death (DCD) has gained much attention over the last decade as one of the accepted practices in order to expand the donor pool. DCD donation takes place after declaration of death using cardio-respiratory criteria in contrast to donation after brain death (DBD) where neurological criteria are used. Although DCD remains a focus of interest and contributes to donor numbers in many countries, it also poses many challenges medically, ethically and legally.

Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients.

BACKGROUND: The risk of cytomegalovirus (CMV) infection in solid organ transplant recipients has resulted in the frequent use of prophylaxis to prevent the clinical syndrome associated with CMV infection. This is an update of a review first published in 2005 and updated in 2008 and 2013. OBJECTIVES: To determine the benefits and harms of antiviral medications to prevent CMV disease and all-cause death in solid organ transplant recipients. SEARCH METHODS: We contacted the information specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 5 February 2024 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing antiviral medications with placebo or no treatment, comparing different antiviral medications or different regimens of the same antiviral medications for CMV prophylaxis in recipients of any solid organ transplant. Studies examining pre-emptive therapy for CMV infection are studied in a separate review and were excluded from this review. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study eligibility, risk of bias and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: This 2024 update found four new studies, bringing the total number of included studies to 41 (5054 participants). The risk of bias was high or unclear across most studies, with a low risk of bias for sequence generation (12), allocation concealment (12), blinding (11) and selective outcome reporting (9) in fewer studies. There is high-certainty evidence that prophylaxis with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment is more effective in preventing CMV disease (19 studies: RR 0.42, 95% CI 0.34 to 0.52), all-cause death (17 studies: RR 0.63, 95% CI 0.43 to 0.92), and CMV infection (17 studies: RR 0.61, 95% CI 0.48 to 0.77). There is moderate-certainty evidence that prophylaxis probably reduces death from CMV disease (7 studies: RR 0.26, 95% CI 0.08 to 0.78). Prophylaxis reduces the risk of herpes simplex and herpes zoster disease, bacterial and protozoal infections but probably makes little to no difference to fungal infection, acute rejection or graft loss. No apparent differences in adverse events with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment were found. There is high certainty evidence that ganciclovir, when compared with aciclovir, is more effective in preventing CMV disease (7 studies: RR 0.37, 95% CI 0.23 to 0.60). There may be little to no difference in any outcome between valganciclovir and IV ganciclovir compared with oral ganciclovir (low certainty evidence). The efficacy and adverse effects of valganciclovir or ganciclovir were probably no different to valaciclovir in three studies (moderate certainty evidence). There is moderate certainty evidence that extended duration prophylaxis probably reduces the risk of CMV disease compared with three months of therapy (2 studies: RR 0.20, 95% CI 0.12 to 0.35), with probably little to no difference in rates of adverse events. Low certainty evidence suggests that 450 mg/day valganciclovir compared with 900 mg/day valganciclovir results in little to no difference in all-cause death, CMV infection, acute rejection, and graft loss (no information on adverse events). Maribavir may increase CMV infection compared with ganciclovir (1 study: RR 1.34, 95% CI: 1.10 to 1.65; moderate certainty evidence); however, little to no difference between the two treatments were found for CMV disease, all-cause death, acute rejection, and adverse events at six months (low certainty evidence). AUTHORS' CONCLUSIONS: Prophylaxis with antiviral medications reduces CMV disease and CMV-associated death, compared with placebo or no treatment, in solid organ transplant recipients. These data support the continued routine use of antiviral prophylaxis in CMV-positive recipients and CMV-negative recipients of CMV-positive organ transplants.

Cardiovascular outcomes in solid organ transplant recipients undergoing cardiac surgery: A matched pair analysis.

INTRODUCTION: This study aimed to compare postoperative outcomes after cardiac surgery in solid-organ transplant recipients and nontransplant patients. METHODS: We performed a retrospective analysis of 78 consecutive transplant recipients who underwent cardiac surgery at Asan Medical Center between 2000 and 2022 and were matched with 312 nontransplant patients who underwent cardiac surgery at a 1:4 ratio. The outcomes included 30-day mortality, all-cause death, cardiac death, readmission, and cardiac readmission. RESULTS: There was no significant difference in baseline characteristics between the two groups. The most common type of cardiac surgery performed in solid organ transplant recipients was isolated valve surgery, followed by isolated CABG. The 30-day mortality was not significantly different between transplant recipients and nontransplant patients (3.9% vs. 3.5%; P > .99). Solid organ transplant recipients showed a higher all-cause mortality compared to nontransplant patients (29.1% vs. 14.3% at 5 years; P = .001); however, there was no significant difference in cardiac death between the two groups (2.6% vs. 3.2% at 5 years; P = .80). In addition, the readmission and cardiac readmission rates showed comparable findings to that of mortality. CONCLUSION: Cardiac surgery can be performed safely in solid organ transplant recipients, with postoperative cardiovascular outcomes comparable to those observed in nontransplant patients.

Updates in Skin Cancer in Transplant Recipients and Immunosuppressed Patients: Review of the 2022-2023 Scientific Symposium of the International Immunosuppression and Transplant Skin Cancer Collaborative.

The International Immunosuppression and Transplant Skin Cancer Collaborative (ITSCC) and its European counterpart, Skin Care in Organ Transplant Patients-Europe (SCOPE) are comprised of physicians, surgeons, and scientist who perform integrative collaborative research focused on cutaneous malignancies that arise in solid organ transplant recipients (SOTR) and patients with other forms of long-term immunosuppression. In October 2022, ITSCC held its biennial 4-day scientific symposium in Essex, Massachusetts. This meeting was attended by members of both ITSCC and SCOPE and consisted of specialists including Mohs micrographic and dermatologic oncology surgeons, medical dermatologists, transplant dermatologists, transplant surgeons, and transplant physicians. During this symposium scientific workshop groups focusing on consensus standards for case reporting of retrospective series for invasive squamous cell carcinoma (SCC), defining immunosuppressed patient status for cohort reporting, development of multi-institutional registry for reporting rare tumors, and development of a KERACON clinical trial of interventions after a SOTRs' first cutaneous SCC were developed. The majority of the symposium focused on presentation of the most up to date research in cutaneous malignancy in SOTR and immunosuppressed patients with specific focus on chemoprevention, immunosuppression regimens, immunotherapy in SOTRs, spatial transcriptomics, and the development of cutaneous tumor registries. Here, we present a summary of the most impactful scientific updates presented at the 2022 ITSCC symposium.

Safety of Biologics and Small Molecules for Inflammatory Bowel Diseases in Organ Transplant Recipients.

PURPOSE: This study aimed to evaluate the safety of biologics and small molecules for the treatment of inflammatory bowel diseases (IBD) in patients receiving antirejection therapies after organ transplants. MATERIALS AND METHODS: We reviewed the medical records of patients with IBD who received organ transplants at the Asan Medical Center between January 1989 and December 2021. We compared the parameters of patients receiving biologics or small molecules to those of patients without those therapies. RESULTS: This study included a total of 53 patients (ulcerative colitis, 41; Crohn's disease, 6; and gastrointestinal Behçet's disease, 6). Among them, 15 patients were receiving biologics or small molecules and 38 were not. During a mean follow-up of 119 months, the proportion of patients experiencing severe infections was significantly higher in those treated with biologics or small molecules than in those not treated. However, other safety outcomes (e.g., malignancies, adverse events, including organizing pneumonia or hepatic failure, and death) were not different between the two groups. Kaplan-Meier curve analysis revealed no significant difference in the safety outcome rate related to the use of biologics or small molecules. During follow-up, eight patients underwent bowel resections for IBD. The rate of bowel resection was not different between the two groups. CONCLUSION: The use of biologics or small molecules for patients with IBD who received organ transplants did not show a significant difference in safety outcomes. However, the possibility of severe infections must be considered.

Genetic and Epigenetic Associations with Post-Transplant Diabetes Mellitus.

Post-transplant diabetes mellitus (PTDM) is a common complication of solid organ transplantation. PTDM prevalence varies due to different diabetes definitions. Consensus guidelines for the diagnosis of PTDM have been published based on random blood glucose levels, glycated hemoglobin (HbA1c), and oral glucose tolerance test (OGTT). The task of diagnosing PTDM continues to pose challenges, given the potential for diabetes to manifest at different time points after transplantation, thus demanding constant clinical vigilance and repeated testing. Interpreting HbA1c levels can be challenging after renal transplantation. Pre-transplant risk factors for PTDM include obesity, sedentary lifestyle, family history of diabetes, ethnicity (e.g., African-Caribbean or South Asian ancestry), and genetic risk factors. Risk factors for PTDM include immunosuppressive drugs, weight gain, hepatitis C, and cytomegalovirus infection. There is also emerging evidence that genetic and epigenetic variation in the organ transplant recipient may influence the risk of developing PTDM. This review outlines many known risk factors for PTDM and details some of the pathways, genetic variants, and epigenetic features associated with PTDM. Improved understanding of established and emerging risk factors may help identify people at risk of developing PTDM and may reduce the risk of developing PTDM or improve the management of this complication of organ transplantation.

Immune modulation in transplant medicine: a comprehensive review of cell therapy applications and future directions.

Balancing the immune response after solid organ transplantation (SOT) and vascularized composite allotransplantation (VCA) remains an ongoing clinical challenge. While immunosuppressants can effectively reduce acute rejection rates following transplant surgery, some patients still experience recurrent acute rejection episodes, which in turn may progress to chronic rejection. Furthermore, these immunosuppressive regimens are associated with an increased risk of malignancies and metabolic disorders. Despite significant advancements in the field, these IS related side effects persist as clinical hurdles, emphasizing the need for innovative therapeutic strategies to improve transplant survival and longevity. Cellular therapy, a novel therapeutic approach, has emerged as a potential pathway to promote immune tolerance while minimizing systemic side-effects of standard IS regiments. Various cell types, including chimeric antigen receptor T cells (CAR-T), mesenchymal stromal cells (MSCs), regulatory myeloid cells (RMCs) and regulatory T cells (Tregs), offer unique immunomodulatory properties that may help achieve improved outcomes in transplant patients. This review aims to elucidate the role of cellular therapies, particularly MSCs, T cells, Tregs, RMCs, macrophages, and dendritic cells in SOT and VCA. We explore the immunological features of each cell type, their capacity for immune regulation, and the prospective advantages and obstacles linked to their application in transplant patients. An in-depth outline of the current state of the technology may help SOT and VCA providers refine their perioperative treatment strategies while laying the foundation for further trials that investigate cellular therapeutics in transplantation surgery.

Pharmacological prevention of bone loss and fractures following solid organ transplantations: Protocol for a systematic review and network meta-analysis.

INTRODUCTION: Solid organ transplant (SOT) recipients can experience bone loss caused by underlying conditions and the use of immunosuppressants. As a result, SOT recipients are at risk for decreased bone mineral density (BMD) and increased fracture incidences. We propose a network meta-analysis (NMA) that incorporates all available randomized control trial (RCT) data to provide the most comprehensive ranking of anti-osteoporotic interventions according to their ability to decrease fracture incidences and increase BMD in SOT recipients. METHODS: We will search MEDLINE, EMBASE, Web of Science, CINAHL, CENTRAL and CNKI for relevant RCTs that enrolled adult SOT recipients, assessed anti-osteoporotic therapies, and reported relevant outcomes. Title and full-text screening as well as data extraction will be performed in-duplicate. We will report changes in BMD as weighted or standardized mean differences, and fracture incidences as risk ratios. SUCRA scores will be used to provide rankings of interventions, and quality of evidence will be examined using RoB2 and CINeMA. DISCUSSIONS: To our knowledge, this systematic review and NMA will be the most comprehensive quantitative analysis regarding the management of bone loss and fractures in SOT recipients. Our analysis should be able to provide physicians and patients with an up-to-date recommendation for pharmacotherapies in reducing incidences of bone loss and fractures associated with SOT. The findings of the NMA will be disseminated in a peer-reviewed journal.

Adult and late adolescent complications of pediatric solid organ transplantation.

BACKGROUND: There have been over 51 000 pediatric solid organ transplants since 1988 in the United States alone, leading to a growing population of long-term survivors who face complications of childhood organ failure and long-term immunosuppression. AIMS: This is an educational review of existing literature. RESULTS: Pediatric solid organ transplant recipients are at increased risk for risk for cardiovascular and kidney disease, skin cancers, and growth problems, though the severity of impact may vary by organ type. Pediatric recipients often are able to complete schooling, maintain a job, and form family and social networks in adulthood, though at somewhat lower rates than the general population, but face additional challenges related to neurocognitive deficits, mental health disorders, and discrimination. CONCLUSIONS: Transplant centers and research programs should expand their focus to include long-term well-being. Increased collaboration between pediatric and adult transplant specialists will be necessary to better understand and manage long-term complications.