Prevention of Fractures after Solid Organ Transplantation: A Meta-Analysis

Abstract Context: Bone loss and fracture are serious sequelae of organ transplantation, particularly in the first posttransplant year. Most interventional studies have been inadequately powered to detect effects on fracture. Objective: The objective of the study was to determine whether treatment with bisphosphonates (BP) or active vitamin D analogs (vitD) during the first year after transplantation reduces fracture risk and estimate the effect of these interventions on bone loss. Data Sources: Sources included PUBMED, MEDLINE, Cochrane Library, and abstracts from scientific meetings (presented 2003–2010). Study Selection: Randomized controlled clinical trials of BP or vitD in solid organ transplant recipients were included if treatment was initiated at the time of transplantation and fracture data were collected. Data Extraction: Two investigators independently extracted data and rated study quality. Fixed effect and random-effects models were used to obtain pooled estimates. Data Synthesis: Eleven studies of 780 transplant recipients (134 fractures) were included. Treatment with BP or vitD reduced the number of subjects with fracture [odds ratio (OR) 0.50 (0.29, 0.83)] and number of vertebral fractures, [OR 0.24 (0.07, 0.78)]. An increase in bone mineral density at the lumbar spine [2.98% (1.31, 4.64)] and femoral neck [3.05% (2.16, 3.93)] was found with treatment. When BP trials (nine studies, 625 subjects) were examined separately, there was a reduction in number of subjects with fractures [OR 0.53 (0.30, 0.91)] but no significant reduction in vertebral fractures [OR 0.34 (0.09, 1.24)]. Conclusions: Treatment with BP or vitD during the first year after solid organ transplant was associated with a reduction in the number of subjects with fractures and fewer vertebral fractures.

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Cytomegalovirus in Solid Organ Transplant Recipients: Clinical Updates, Challenges and Future Directions

Current Pharmaceutical Design ◽

10.2174/1381612826666200531152901 ◽

2020 ◽

Vol 26 (28) ◽

pp. 3497-3506

Author(s):

Raymund R. Razonable

Keyword(s):

Organ Transplantation ◽

Solid Organ Transplantation ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Solid Organ ◽

Transplant Recipients ◽

Cmv Infection ◽

Future Directions ◽

Prevention And Treatment ◽

Solid Organ Transplant Recipients

Cytomegalovirus is the classic opportunistic infection after solid organ transplantation. This review will discuss updates and future directions in the diagnosis, prevention and treatment of CMV infection in solid organ transplant recipients. Antiviral prophylaxis and pre-emptive therapy are the mainstays of CMV prevention, but they should not be mutually exclusive and each strategy should be considered depending on a specific situation. The lack of a widely applicable viral load threshold for diagnosis and preemptive therapy is emphasized as a major factor that should pave the way for an individualized approach to prevention. Valganciclovir and intravenous ganciclovir remain as drugs of choice for CMV management, and strategies for managing drug-resistant CMV infection are enumerated. There is increasing use of CMV-specific cell-mediated immune assays to stratify the risk of CMV infection after solid organ transplantation, and their potential role in optimizing CMV prevention and treatment efforts is discussed.

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Neurocognitive Effects of Solid Organ Transplantation

Cognitive and Behavioral Abnormalities of Pediatric Diseases ◽

10.1093/oso/9780195342680.003.0053 ◽

2010 ◽

Author(s):

Nataliya Zelikovsky ◽

Debra S. Lefkowitz

Keyword(s):

Organ Transplantation ◽

Survival Rates ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Chronic Illnesses ◽

Solid Organ ◽

Transplant Recipients ◽

Transplant Patients ◽

Neurocognitive Outcomes ◽

Medical Advances

The first successful organ transplant was a kidney transplant performed between identical twins in 1954. Since that time, major medical advances have been made to help improve survival rates for transplant recipients. In 2008, there were 1,964 solid organ transplants performed for children under age 18 (2007 Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients [OPTN/SRTR] Annual Report 1997–2006). Currently, approximately 1,830 pediatric patients are awaiting some type of solid organ transplant (2007 OPTN/SRTR Annual Report 1997–2006). Organ transplantation in children is relatively recent compared to other treatments for children with chronic illnesses. The focus over the first few decades has been on medical advances and improving survival rates for transplant patients. In the recent years, increasing attention has been given to the developmental, neurocognitive, and psychosocial outcomes prior to transplant and in the short-term period post transplant. Most chronic illnesses and acute traumatic medical events have implications for neurocognitive outcomes. End-stage disease of the liver, kidney, heart, and lung are all believed to affect intellectual, academic, and neurocognitive functions. Gross neurodevelopmental deficits have become less common due to early medical intervention (e.g., improved nutrition, surgical intervention, reduced exposure to aluminum (Warady 2002). Organ transplantation is believed to ameliorate the deleterious long-term developmental and neurocognitive effects, but this topic has received little attention in the literature, and the available results with regard to intellectual, academic, and neurodevelopmental results have been mixed. In a combined sample of solid organ transplant patients, 40% had clinically significant cognitive delays (Brosig et al. 2006). Examining the impact of different underlying disease processes and transplantation of each solid organ separately is critical. Thus, we discuss the neurocognitive outcomes of each organ group separately in this chapter. Neurocognitive outcomes can be assessed in a variety of ways depending upon the age of the child. Among infants and toddlers, neurocognitive functioning is measured by an assessment of motor function, social and environmental interaction, and language development. Assessment of older children may involve the evaluation of intelligence, academic achievement, emotional and behavioral functioning, and adaptive skills.

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

10.1101/19013797 ◽

2019 ◽

Author(s):

Jiawen Deng ◽

Wenteng Hou

Keyword(s):

Bone Mineral Density ◽

Systematic Review ◽

Bone Loss ◽

Bone Mineral ◽

Conflict Of Interest ◽

Meta Analysis ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Solid Organ ◽

Mineral Density

ABSTRACTPurposeSolid organ transplant (SOT) recipients can develop skeletal diseases 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 RCT data to provide the most comprehensive ranking of antiresorptive interventions according to their ability to decrease fracture incidences and increase BMD in SOT recipients.MethodsWe will search MEDLINE, EMBASE, Web of Science, CINAHL, CENTRAL and Chinese literature sources for RCTs, and we will include adult SOT recipients who took antiresorptive therapies starting at the time of transplant with relevant outcomes. We will perform title and full-text screening as well as data extraction in duplicate. We will report changes in BMD as weighted or standardized mean differences, and fracture incidences as risk ratios. We will use SUCRA scores to provide rankings of interventions, and we will examine the quality of evidence using risk of bias and CINeMA.ResultsThe results of this systematic review and network meta-analysis will be published in a peer-reviewed journal.ConclusionsTo our knowledge, this systematic review and network meta-analysis 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.CONFLICT OF INTERESTJiawen Deng, and Wenteng Hou declare that they have no conflict of interest.MINI ABSTRACTWe propose a network meta-analysis investigating the use of antiresorptive interventions to prevent bone loss and fractures in solid organ transplant (SOT) recipients. We aim to provide a comprehensive ranking of antiresorptive therapies in terms of their ability to increase bone mineral density and decrease fracture incidence in SOT recipients.

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572. Antiviral Toxicities Among Pediatric Solid Organ Transplant Recipients

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.766 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S351-S351

Author(s):

Kevin J Downes ◽

Anna Sharova ◽

Marina Mitrou ◽

Molly Hayes ◽

Despoina Galetaki ◽

...

Keyword(s):

Medication Management ◽

Organ Transplant ◽

Kidney Injury ◽

Solid Organ Transplant ◽

Incidence Rates ◽

First Year ◽

Solid Organ ◽

Transplant Recipients ◽

Cmv Disease

Abstract Background Ganciclovir (GCV) and valganciclovir (VGCV) are used for prophylaxis (PPX) and treatment for CMV in pediatric solid organ transplant (SOT) recipients, but the frequency and impact of toxicities from these medications are not well described. Methods Retrospective cohort study of children undergoing SOT at Children’s Hospital of Philadelphia from Jan 2012 - Jun 2018. EMR were reviewed to identify laboratory-based toxicities between 15 days and 1 year post-transplant; medication management within 14 days of toxicity onset was recorded. Toxicities were defined as GCV or VGCV-associated if a patient was on the antiviral at toxicity onset. We defined acute kidney injury (AKI) as ≥50% change in creatinine (Cr) from 30 days prior, leukopenia as WBC < 3500/µL, neutropenia as ANC < 1000/µL, and thrombocytopenia as < 100K/µL. Incidence rates of toxicities on PPX and treatment were compared to rates during no antiviral using univariate Poisson regression. Results 285 children received 299 SOTs: 108 liver, 91 kidney, 69 heart, 31 lung. Nearly half (46%) of toxicities during the first year after transplant occurred while on GCV or VGCV PPX or treatment, but their use accounted for only 23% of all follow-up time. Receipt of VGCV and GCV PPX and treatment were associated with significantly higher incidence rates of toxicities compared to no antiviral (Fig 1). Of 259 GCV or VGCV-associated toxicities, 44% (n=113) were leukopenia, 26% (66) neutropenia, 26% (66) AKI, and 6% (15) thrombocytopenia (Table 1). Most recipients of VGCV PPX (64%) sustained at least one toxicity while on PPX. AKI during VGCV PPX led to stopping/dose-adjusting of VGCV in 43% and of immunosuppression in 57% of cases. Neutropenia during VGCV PPX resulted in stopping/dose-adjusting of VGCV in 63%, of immunosuppression in 36%, and of TMPX/SMX PPX in 36% of cases. During VGCV PPX, 81% of AKI was stage II/III (≥100% change in Cr) and 65% of neutropenia was severe (< 500/µL); 11% of both AKI (n=6) and neutropenia (n=7) during VGCV PPX resulted in hospitalization. Figure 1. Incidence Rates of Toxicities from Day 15 through 1 Year After Transplant Table 1. Antiviral Use and Toxicity 2 Weeks to 1 Year After Transplant Conclusion GCV and VGCV use was associated with significant renal and hematological toxicities in pediatric SOT recipients. While VGCV and GCV are effective at preventing CMV disease in pediatric SOT, clinicians should consider risk of toxicity when evaluating CMV prevention strategies. Disclosures Kevin J. Downes, MD, Merck, Inc. (Grant/Research Support)

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Post-Transplant Lymphoproliferative Disorder after Solid Organ Transplant in the Pediatric Population: A Systematic Review

Blood ◽

10.1182/blood-2020-143453 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 7-8

Author(s):

Mobeen Zaka Haider ◽

Zarlakhta Zamani ◽

Muhammad Taqi ◽

Hafsa Shahid ◽

Zahoor Ahmed ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Organ Transplantation ◽

Median Duration ◽

Induction Therapy ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Cochrane Library ◽

Solid Organ ◽

Organ Transplants ◽

Post Transplant

Background: Post-transplant lymphoproliferative disease (PTLD), is one of the major complications after organ transplantation. The aim of this study is to study the incidence, risk factors especially EBV status, histopathological types, management, and outcomes of PTLD in the pediatric groups. Methods: Following the PRISMA guideline, we performed a comprehensive literature search on PubMed, Cochrane Library, Embase, and clinicaltrials.gov from the past ten years on May 04, 2020. We used the MeSH terms of organ transplantation and lymphoproliferative disorders. The initial search revealed 1741 articles. We excluded all case reports, case series, pre-clinical trials, review articles, and meta-analysis. We found twenty-eight studies. We extracted the data for baseline characteristics, recipient & donor EBV status, immunosuppression used, type & stage of PTLD, organ system involved, duration between transplant and PTLD diagnosis, treatment, and mortality. Results: We included 32 studies with a total (n) of 15597 pediatric patients after a solid organ transplant. 1210 (7.75%) patients developed PTLD, out of which 609 (50.33%) were male participants, 453 (37.4%) female, and 148 (12.23%) the gender was unknown. (Table 1) Data from 19 studies showed that among PTLD patients, 115 recipients & 76 donors tested positive for Epstein-Barr Virus (EBV), 187 recipients were seronegative and the rest were unknown at the time of transplant. Immunosuppressive drugs used after organ transplantation included; cyclosporine, tacrolimus, sirolimus, azathioprine, mycophenolate, prednisone, mTOR inhibitors, induction therapy with OKT3, IL-2 inhibitors (basiliximab, daclizumab) and anti-thymocyte/anti-lymphocyte globulin. In two studies, antiviral prophylaxis with ganciclovir/valganciclovir was achieved. Data from nine studies showed the median age at PTLD diagnosis was 6.8 years. L'Huillier et al. stated that the median duration for EBV positive recipients to develop PTLD was 1.92 years (0.35-3.09 years), compared to EBV negative recipients, which was 0.95 years (2.48-2.92 years). Overall, the median duration from organ transplant to the diagnosis of PTLD among 15 studies was 29.1 months, ranging from 0.9 months to 186 months. The histopathology of PTLD was confirmed via biopsy specimen showing predominance in monomorphic type, i.e; 265/1210 (21.9%), followed by polymorphic type with 140/1210 (11.5%), an early lesion with 46/1210 (3.80%), Non-Hodgkin lymphoma 28/1210 (2.3%), Hodgkin lymphoma 33/1210 (2.72%) and mixed type (polymorphic & monomorphic) 4/1210 (0.33%). Histopathological data for 694 patients were not available. Treatment of PTLD was achieved with reduction or complete cessation of immunosuppressive therapy, anti-CD20 antibody (rituximab), antiviral treatment with ganciclovir/valganciclovir, lymphoma treatment with chemotherapeutic agents, radiotherapy, and surgical resection. Gajarski et al. concluded that patients who received induction therapy [OKT3, IL-2 antagonists (basiliximab, daclizumab) and anti-thymocyte globulin] had significantly less PTLD development as compared to those who did not receive induction therapy, i.e., (2.9% vs. 4.9%) among 2374 total patients. According to Hayes Jr. et al., recipient EBV seronegativity continued to be associated with lower mortality hazard (HR 0.715; 95 % CI 0.547, 0.935; p = 0.014). Data from 19 studies showed the mortality rate among 494 PTLD diagnosed patients was 22.7% (112) with an overall survival of 84.2% respectively from three studies. Data from five studies showed that direct PTLD related mortality accounted for 63% (17/27) of deaths in PTLD diagnosed patients. Conclusion: Our analysis shows that post-transplant EBV positive recipients who undergo multiorgan transplants are more likely to develop PTLD compared to EBV positive recipients with single organ transplantation. The median duration from organ transplants to the diagnosis of PTLD ranged from months to years, however, this duration was reported to be less in EBV negative recipients compared to EBV positive recipients with organ transplants. The most common histological type of PTLD among pediatric groups was monomorphic and the least common was Classic Hodgkin lymphoma. Rituximab use in the treatment of PTLD was associated with a decreased use of alkylating agents and as a result, the side effects associated with these agents were reduced. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

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