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Monitoring specific underlying causes of death in solid organ transplant (SOT) recipients is important in order to identify emerging trends and health challenges. This retrospective cohort study includes all SOT recipients transplanted at Rigshospitalet between January 1st, 2010 and December 31st, 2019. The underlying cause of death was determined using the newly developed Classification of Death Causes after Transplantation (CLASS) method. Cox regression analyses assessed risk factors for all-cause and cause-specific mortality. Of the 1774 SOT recipients included, 299 patients died during a total of 7511 person-years of follow-up (PYFU) with cancer (N = 57, 19%), graft rejection (N = 55, 18%) and infections (N = 52, 17%) being the most frequent causes of death. We observed a lower risk of all-cause death with increasing transplant calendar year (HR 0.91, 95% CI 0.86-0.96 per 1-year increase), alongside death from graft rejection (HR 0.84 per year, 95% CI 0.74-0.95) and death from infections (HR 0.86 per year, 95% CI 0.77-0.97). Further, there was a trend towards lower cumulative incidence of death from cardiovascular disease, graft failure and cancer in more recent years, while death from other organ specific and non-organ specific causes did not decrease. All-cause mortality among SOT recipients has decreased over the past decade, mainly due to a decrease in graft rejection- and infection-related deaths. Conversely, deaths from a broad range of other causes have remained unchanged, suggesting that cause of death among SOT recipients is increasingly diverse and warrants a multidisciplinary effort and attention in the future., Competing Interests: The authors have declared that no competing interests exist.

Post-transplant diabetes mellitus (PTDM) is associated with a higher risk of adverse outcomes. We aimed to describe the proportion of patients with diabetes prior to solid organ transplantation (SOT) and post-transplant diabetes mellitus (PTDM) in three time periods (early-likely PTDM: 0-45 days; 46-365 days and >365 days) post-transplant and to estimate possible risk factors associated with PTDM in each time-period. Additionally, we compared the risk of death and causes of death in patients with diabetes prior to transplant, PTDM, and non-diabetes patients. A total of 959 SOT recipients (heart, lung, liver, and kidney) transplanted at University Hospital of Copenhagen between 2010 and 2015 were included. The highest PTDM incidence was observed at 46-365 days after transplant in all SOT recipients. Age and the Charlson Comorbidity Index (CCI Score) in all time periods were the two most important risk factors for PTDM. Compared to non-diabetes patients, SOT recipients with pre-transplant diabetes and PTDM patients had a higher risk of all-cause mortality death (aHR: 1.77, 95% CI: 1.16-2.69 and aHR: 1.89, 95% CI: 1.17-3.06 respectively). Pre-transplant diabetes and PTDM patients had a higher risk of death due to cardiovascular diseases and cancer, respectively, when compared to non-diabetes patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dos Santos, Hornum, Terrones-Campos, Crone, Wareham, Soeborg, Rasmussen, Gustafsson, Perch, Soerensen, Lundgren, Feldt-Rasmussen and Reekie.)

Background: Mumps, measles, rubella, and varicella zoster (MMRV) viruses may cause severe infections in seronegative adult solid organ transplant (SOT) recipients, but can be prevented by vaccination. We aimed to determine MMRV serostatus in adult SOT recipients before and 1 year after transplantation as well as evidence of MMRV infections in a large, prospective cohort of SOT recipients., Methods: This was a prospective study of 1182 adult SOT recipients included in the Management of Posttransplant Infections in Collaborating Hospitals (MATCH) cohort from 2011 to 2017 with a 1-year follow-up. Systematic monitoring of MMRV serology was performed prior to transplantation and 1 year posttransplantation. Polymerase chain reaction (PCR) was used to confirm viral replication in SOT recipients presenting with clinical evidence of infection., Results: Among 1182 adult SOT recipients, 28 (2.4%), 77 (6.5%), 65 (5.5%), and 22 (1.9%) were seronegative for measles, mumps, rubella, and varicella zoster virus (VZV), respectively, and 165 (14%) were seronegative for at least 1 of the MMRV viruses. One year posttransplantation, 29 of 823 (3.5%) of seropositive SOT recipients had seroreverted, and 63 of 111 (57%) of seronegative SOT recipients seroconverted for at least 1 MMRV virus. No evidence of measles, mumps, or rubella infection was found, but 8 (0.7%) SOT recipients developed symptoms and had a positive VZV PCR., Conclusions: A large proportion of SOT recipients were seronegative for at least 1 of the MMRV viruses. MMRV infections in SOT recipients may disseminate and become fatal, and although only a few cases of VZV infection were detected, results from this study suggest increase attention toward vaccination of patients waiting for SOT., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Routine monitoring of parvovirus B19 (B19V) the first 6 months posttransplantation was performed in 241 seronegative solid organ transplant (SOT) recipients. Incidence rates during the first month and the second to sixth months posttransplantation were 1.2 (95% confidence interval [CI], .33-3.2) and 0.21 (95% CI, .06-.57) per 100 recipients per month, respectively. Of the 6 SOT recipients with positive B19V polymerase chain reaction, 3 (50%) were admitted to hospital and 2 (33%) were treated with intravenous immunoglobulin. Thus, routine monitoring of B19V in seronegative SOT recipients may not be necessary. Targeted screening 1 month posttransplantation and screening upon clinical suspicion could be an alternative strategy., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Infectious complications after solid organ transplantation (SOT) are often more severe and remain a diagnostic challenge due to vague and atypical clinical presentations. Diagnostic performance of conventional diagnostic tools is frequently inadequate which may lead to delayed diagnosis with the risk of poorer outcomes. This literature review aimed to investigate the current evidence on the use of 18 F-fluoro-deoxy-glucose (FDG) Positron Emission Tomography (PET)/computer tomography (CT) in infectious complications after SOT. Based on search in PubMed, Medline, and Cochrane databases, 13 articles and 46 case reports were included. For inclusion, articles were to include data on patients with infectious complications after SOT, and where FDG PET/CT was part of the work-up. Final searches were conducted on 02 September 2020. Overall, in the absence of initial diagnostic clues, FDG PET/CT should be considered as the imaging technique of choice as it may guide further investigations and eventually reveal the diagnosis in most of the patients. However, the available literature of the role of FDG PET/CT in SOT recipients with infectious complications is scarce and well-designed prospective studies including control groups are warranted to establish the role of FDG PET/C/ in SOT recipients. The main drawback of FDG PET/CT is the lack of ability to differentiate between cancer and infectious diseases which are both highly prevalent in this patient group. Accordingly, the main reasons for "false" results of FDG PET/CT is the misdiagnosis of cancer in benign inflammatory or infectious processes, information which nonetheless can be useful., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Cytomegalovirus (CMV) infection is common among solid organ transplant (SOT) recipients and may cause CMV disease. To optimize the implementation of existing prevention strategies, the Management of Post-transplant Infections in Collaborating Hospitals (MATCH) program was developed. Two key performances of MATCH (diagnosing CMV infection at low viral load (VL) and before the onset of CMV disease) were assessed prior to, during and after the implementation of MATCH., Methods: The MATCH program included a personalized surveillance plan, prophylaxis and preemptive therapy determined by the recipient's risk of CMV infection. The plan was composed through predefined algorithms and implemented through harvesting of real-time data from medical records. Risk of CMV disease was compared for recipients transplanted during and after vs prior to the implementation of MATCH. Lung and non-lung transplants were analyzed separately., Results: A total of 593, 349, 520, and 360 SOT recipients were transplanted before (2007-2010), during (2011-2012), early after (2013-2015), and late after (2016-2017) implementation of MATCH with an observed reduction of diagnostic VL (P < .001) over time. Risk of CMV disease was reduced among non-lung transplant recipients transplanted during (adjusted hazard ratios [95% CI] 0.15 [0.04-0.54], P = .003), early after (aHR 0.27 [0.11-0.63], P = .003), and late after (aHR 0.17 [0.06-0.52], P = .002) compared with prior to MATCH. No significant change was observed among lung transplants., Conclusion: Implementation of CMV preventive strategies through MATCH was associated with a reduced risk of CMV disease among non-lung transplant recipients. Furthermore, the limitations of VL as a sole indicator for CMV disease in lung transplants were emphasized., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Solid organ (SOT) and allogeneic haematopoietic stem cell (HSCT) transplant recipients have elevated risks of de novo or secondary cancer. We explored risk factors hereof., Methods: Among SOT and HSCT between January 2004 and December 2014, standardised incidence ratio (SIR) of de novo/secondary cancer compared with the Danish population was determined and risk factors were identified using Poisson regression., Results: During a median of 3.4 (IQR 1.3-6.4) and 2.6 (0.8-5.4) person-years (PY) after SOT and HSCT, a total of 212/1656 (13%) and 75/992 (8%) persons developed cancer; SIR 3.61 (3.0-4.3) and 2.2 (1.6-3.0), resp.). SIR correlated with younger age and was highest for skin and haematological cancers for both types of transplantation. Within the cohort, cancer was associated with older age (adjusted incidence rate ratio > 50 vs ≤ 19 years, among SOT and HSCT: 9.4 (3.4-25.7) and 25.4 (5.1-126.0), resp.) and current elevated C-reactive protein (CRP) (≥ 10 vs < 10 mg/L: 2.5 (1.8-3.4) and 2.3 (1.4-3.9), resp.), but neither with prior cancer nor type of immunosuppressants., Conclusion: Rates of de novo or secondary cancers are elevated in both SOT and HSCT compared with the general population and mainly for skin and haematological cancers. Among transplant recipients, older age and current elevated CRP are risk factors.

Purpose: Emerging EBV DNAemia in plasma is considered an early sign of post-transplant lymphoproliferative disorder (PTLD). The aim of this study was to quantify the extent of benefit from screening for EBV DNAemia to detect emerging PTLD among solid organ (SOT) or hematopoietic stem cell transplant recipients (HSCT)., Methods: We used receiver operating characteristic (ROC) curves for assessing ability of models to predict PTLD. Among 2642 recipients transplanted between January 2004 and December 2014, 79 (3%) developed PTLD., Results: EBV DNAemia was observed in 331/1784 recipients (18.6%, 95% CI 16.8-20.4) with measured EBV DNA. The area under the curve (AUC) of the ROC of EBV DNAemia to identify persons with subsequent PTLD was 72% (95% CI, 64-79%) among SOT and 59% (51-68%) among HSCT. Including clinical predictors such as age, gender, transplant year and type, high-risk EBV serostatus, and routine biochemistry in addition to EBV DNAemia increased AUC to 83% (75-90%) among SOT and 84% (79-89%) among HSCT. Among HSCT, including additional factors such as T-cell-depleting treatment, acute graft vs. host disease and donor match increased AUC to 85% (78-91%)., Conclusions: We constructed a model to better predict PTLD compared to EBV DNA screening alone which could have clinical implications.

Purpose: Solid organ transplant (SOT) recipients are at high risk of developing infections and malignancies. 18 F-FDG PET/CT may enable timely detection of these diseases and help to ensure early intervention. We aimed to describe the clinical utility of FDG PET/CT in consecutive, diagnostic unresolved SOT recipients transplanted from January 2004 to May 2015., Methods: Recipients with a post-transplant FDG PET/CT performed as part of diagnostic work-up were included. Detailed chart reviews were done to extract relevant clinical information and determine the final diagnosis related to the FDG PET/CT. Based on á priori defined criteria and the final diagnosis, results from each scan were classified as true or false, and diagnostic values determined., Results: Among the 1,814 recipients in the cohort, 145 had an FDG PET/CT performed; 122 under the indication of diagnostically unresolved symptoms with a suspicion of malignancy or infection. The remaining (N = 23) had an FDG PET/CT to follow-up on a known disease or to stage a known malignancy. The 122 recipients underwent a total of 133 FDG PET/CT scans performed for a suspected malignancy (66 %) or an infection (34 %). Sensitivity, specificity, and positive and negative predictive values of the FDG PET/CT in diagnosing these conditions were 97, 84, 87, and 96 %, respectively., Conclusion: FDG PET/CT is an accurate diagnostic tool for the work-up of diagnostic unresolved SOT recipients suspected of malignancy or infection. The high sensitivity and NPV underlines the potential usefulness of PET/CT for excluding malignancy or focal infections in this often complex clinical situation., Competing Interests: Compliance with Ethical Standards Funding This study was supported by funding from Centre of Health and Infectious Disease Research (CHIP) at Rigshospitalet, Copenhagen, as well as the Danish National Research Foundation [grant number DNRF126]. Conflict of interest None. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required. Informed consent Approval for patient chart review was obtained from the Danish Health and Medicines Authorities according to Danish legislation on retrospective studies.