AIMS OF THE STUDY:

The impact of coronavirus disease 2019 (COVID-19) on patients listed for solid organ transplantation has not been systematically investigated to date. Thus, we assessed occurrence and effects of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on patients on the Swiss national waiting list for solid organ transplantation.

METHODS:

Patient data were retrospectively extracted from the Swiss Organ Allocation System (SOAS). From 16 March to 31 May 2020, we included all patients listed for solid organ transplantation on the Swiss national waiting list who were tested positive for SARS-CoV-2. Severity of COVID-19 was categorised as follows: stage I, mild symptoms; stage II, moderate to severe symptoms; stage III, critical symptoms; stage IV, death. We compared the incidence rate (laboratory-confirmed cases of SARS-CoV-2), the hospital admission rate (number of admissions of SARS-CoV-2-positive individuals), and the case fatality rate (number of deaths of SARS-CoV-2-positive individuals) in our study population with the general Swiss population during the study period, calculating age-adjusted standardised incidence ratios and standardised mortality ratios, with 95% confidence intervals (CIs).

RESULTS:

A total of 1439 patients were registered on the Swiss national solid organ transplantation waiting list on 31 May 31 2020. Twenty-four (1.7%) waiting list patients were reported to test positive for SARS-CoV-2 in the study period. The median age was 56 years (interquartile range 45.3–65.8), and 14 (58%) were male. Of all patients tested positive for SARS-CoV-2, two patients were asymptomatic, 14 (58%) presented in COVID-19 stage I, 3 (13%) in stage II, and 5 (21%) in stage III. Eight patients (33%) were admitted to hospital, four (17%) required intensive care, and three (13%) mechanical ventilation. Twenty-two patients (92%) of all those infected recovered, but two male patients aged >65 years with multiple comorbidities died in hospital from respiratory failure. Comparing our study population with the general Swiss population, the age-adjusted standardised incidence ratio was 4.1 (95% CI 2.7–6.0).

CONCLUSION:

The overall rate of SARS-CoV-2 infections in candidates awaiting solid organ transplantation was four times higher than in the Swiss general population; however, the frequency of testing likely played a role. Given the small sample size of affected patients, conclusions have to be drawn cautiously and results need verification in larger cohorts.

BACKGROUND:

Donor-derived, cell-free DNA (dd-cfDNA) level correlates with allograft injury with clinical validity and utility for quiescence and active acute rejection (AR) in kidney transplant recipients. We analyzed trends in dd-cfDNA level immediately preceding and during the coronavirus disease 2019 (COVID-19) pandemic with implemented "shelter in place" and a tele-health strategy with remote home phlebotomy to limit COVID-19 exposure.

METHODS:

During COVID-19 in the United States (US), we surveyed weekly (January 6, 2020-May 25, 2020) metrics for dd-cfDNA corresponding to both a low risk for active rejection (dd-cfDNA < 0.5%) and cohorts with indeterminate levels of 0.5% to 1.0% and > 1.0%. During the study timeframe, over 11,000 patient samples (67%) from 150 kidney transplantation centers were transitioned from standard facility-based to remote phlebotomy.

RESULTS:

The proportion of dd-cfDNA samples, analyzed in 21 weekly aggregated cohorts by risk-stratification category, was unchanged during the COVID-19 escalation in the US. Linearized slopes for numbers of samples corresponding to indeterminate risk for AR cohorts of > 1.0% and 0.5% to 1.0% were -0.31 and -0.12, respectively; indicating that prevalence of these "at risk for AR cohorts" decreased during remote surveillance. Approximately 73% of samples corresponded to low risk of AR (dd-cfDNA < 0.5%), while an additional 15% of samples had dd-cfDNA level ≤ 1.0%.

CONCLUSION:

The combination of remote home phlebotomy including dd-cfDNA analysis and a tele-health program offer a new paradigm that may substantially improve patient compliance and assuage anxiety regarding the state of kidney allograft health during the COVID-19 pandemic. Further prospective multi-center studies with robust outcomes data are warranted.

Cardiovascular events are among the most common causes of late death in the transplant recipient (Tx) population. Moreover, major cardiac surgical procedures are more challenging and risky due to immunosuppression and the potential impact on the transplanted organ's functional capacity. We aimed to assess open cardiac surgery safety in abdominal solid organ transplant recipients, comparing the postoperative outcomes with those of nontransplant (N-Tx) patients. Electronic databases of PubMed, EMBASE, and SCOPUS were searched. The endpoints were: overall rate of infectious complications (wound infection, septicemia, pneumonia), cardiovascular and renal events (stroke, cardiac tamponade, acute kidney failure), 30-days, 5-years, and 10-years mortality post-cardiac surgery interventions in patients with and without prior solid organ transplantation. This meta-analysis included five studies. Higher rates of wound infection (Tx vs. N-Tx: OR: 2.03, 95% CI: 1.54 to 2.67, I2 = 0%), septicemia (OR: 3.91, 95% CI: 1.40 to 10.92, I2 = 0%), cardiac tamponade (OR: 1.83, 95% CI: 1.28 to 2.62, I2 = 0%) and kidney failure (OR: 1.70, 95 %CI: 1.44 to 2.02, I2 = 89%) in transplant recipients were reported. No significant differences in pneumonia occurrence (OR: 0.95, 95% CI: 0.71 to 1.27, I2 = 0%) stroke (OR: 0.89, 95% CI: 0.54 to 1.48, I2 = 78%) and 30-day mortality (OR: 1.92, 95% CI: 0.97 to 3.80, I2 = 0%) were observed. Surprisingly, 5-years (OR: 3.74, 95% CI: 2.54 to 5.49, I2 = 0%) and 10-years mortality rates were significantly lower in the N-Tx group (OR: 3.32, 95% CI: 2.35 to 4.69, I2 = 0%). Our study reveals that open cardiac surgery in transplant recipients is associated with worse postoperative outcomes and higher long-term mortality rates.

INTRODUCTION:

Heart transplantation is the gold standard treatment for selected patients with end-stage heart failure. Although this procedure can improve quality and prolong life expectancy, several of these patients persist with decreased exercise tolerance. Evidence suggests that exercise training can bring multifactorial benefits to heart transplant (HTx) recipients. However, it is unclear that exercise modality should be preferred. Therefore, the aim of this systematic review and network meta-analysis is to compare the efficacy and safety of different training modalities in HTx recipients.

METHODS AND ANALYSIS:

We will perform a comprehensive literature search in PubMed/MEDLINE, Embase, The Cochrane Library, CINAHL, Scopus, SportDISCUS, Web of Science Core Collection and PEDro from inception until November 2020. Two registries (ClinicalTrials.gov and REBEC) will also be searched for potential results in unpublished studies. There will be no restriction on language, date of publication, publication status or sample size. We will include randomised controlled trials enrolling adult HTx recipients with the presence of at least one exercise training group, which might be compared with another training modality and/or a non-exercise control group for a minimum of 4 weeks of intervention. The primary outcomes will be peak oxygen consumption and occurrence of adverse events. As secondary outcomes, the interaction between pulmonary ventilation, pulmonary perfusion and cardiac output, oxygen uptake efficiency slope, heart rate response, oxygen pulse, peak blood pressure and peak subjective perception of effort. In addition, we will evaluate the 6 min walking distance, health-related quality of life, endothelial function, muscle strength, body fat percentage and lean mass. Risk of bias will be assessed using the Cochrane RoB V.2.0 tool, and we plan to use the Confidence in Network Meta-Analysis tool to assess confidence in the results. All materials (raw data, processed data, statistical code and outputs) will be shared in a public repository.

ETHICS AND DISSEMINATION:

Given the nature of this study, no ethical approval will be required. We believe that the findings of this study may show which is the most efficacious and safe physical training modality for HTx recipients. The completed systematic review and network meta-analysis will be submitted to a peer-reviewed journal.

PROSPERO REGISTRATION NUMBER:

CRD42020191192.

PURPOSE:

Cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) is a treatment for post-transplant lymphoproliferative disease (PTLD) following solid organ transplant (SOT) after failing rituximab, an aggressive and potentially fatal lymphoma. This study explores the humanistic and economic burden of CHOP-associated adverse events (AEs) in PTLD patients. Since PTLD is rare, searches included lymphoproliferative disease with lymphoma patients.

DESIGN:

This comprehensive literature review used the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) protocol, pre-specifying the search strategy and criteria. CHOP-associated short-term AEs with an incidence of >4% were sourced from published literature and cancer websites to inform the search strategy. PubMed and EMBASE searches were used to identify humanistic and economic burden studies.

RESULTS:

PubMed and EMBASE searches identified 3946 citations with 27 lymphoma studies included. Studies were methodologically heterogeneous. Febrile neutropenia (FN) was the AE most encountered, followed by chemotherapy-induced (CI) anemia (A), infection, CI-nausea and vomiting, thrombocytopenia, and CI-peripheral neuropathy (PN). FN and infections were associated with significant disutility, increased hospitalization, and extended length of stay (LOS). Infections and CIPN significantly impacted the utility of patients and CIA-related fatigue showed reductions in quality of life (QoL). Many patients continue to have QoL deficits continued even after AEs were treated. Management costs varied greatly, ranging from nominal (CIPN) to over $100,000 in the USA for infections, EUR 10,290 in Europe for infections, or CAN$1012 in Canada for FN. Cost of outpatient care varied but had a lower economic impact compared to hospitalizations.

CONCLUSIONS:

Short-term AEs from CHOP in the lymphoma population were associated with substantial humanistic and economic burden.

BACKGROUND:

The impact of de novo anti-HLA donor-specific alloantibodies (DSA) which develop after long-term liver transplantation (LT) remains controversial and unclear. The aim of this study was to investigate the role of de novo DSAs on the outcome in LT.

METHODS:

We did a systematic review and meta-analysis of observational studies published until Dec 31, 2019, that reported de novo DSA outcome data (≥1 year of follow-up) after liver transplant. A literature search in the MEDLINE/PubMed, EMBASE, Cochrane Library, Scopus and Web of Science Core Collection databases was performed.

RESULTS:

Of 5,325 studies identified, 15 fulfilled our inclusion criteria. The studies which reported 2016 liver transplant recipients with de novo DSAs showed an increased complication risk, i.e. graft loss and chronic rejection (OR 3.61; 95% CI 1.94-6.71, P < 0.001; I2 58.19%), and allograft rejection alone (OR 6.43; 95% CI: 3.17-13.04; P < 0.001; I2 49.77%); they were compared to patients without de novo DSAs. The association between de novo DSAs and overall outcome failure was consistent across all subgroups and sensitivity analysis.

CONCLUSIONS:

Our study suggested that de novo DSAs had a significant deleterious impact on the liver transplant risk of rejection. The routine detection of de novo DSAs may be beneficial as noninvasive biomarker-guided risk stratification.

This meta-analysis aims to compare enhanced recovery after surgery (ERAS) vs. standard perioperative practice in the management of living kidney donors. Primary endpoints included mortality, complications, length of stay (LOS) and quality of life after living donor nephrectomy. Medline, Embase, Scopus, Cochrane and Web of Science databases were searched. In total, 3029 records were identified. We then screened 114 full texts. Finally, 11 studies were included in the systematic review corresponding to 813 living donors. Of these, four randomized controlled trials were included in the meta-analysis. ERAS resulted in shorter LOS (95CI: -1.144, -0.078, I2 = 87.622%) and lower incidence of post-operative complications (95CI: 0.158, 0.582, I2 = 0%). This referred to Clavien-Dindo I-II complications (95CI: 0.158, 0.582, I2 = 0%). There was no difference in Clavien-Dindo III-V complications (95CI: 0.061,16.173, I2 = 0%). ERAS donors consumed decreased amounts of narcotics during their hospital stay (95CI: -27.694, -8.605, I2 = 0%). They had less bodily pain (95CI:6.735, 17.07, I2 = 0%) and improved emotional status (95CI: 6.593,13.319, I2 = 75.682%) one month postoperatively. ERAS protocols incorporating multimodal pain control interventions resulted in a mean reduction of 1 day in donors' LOS (95CI: -1.374, -0.763, I2 = 0%). Our results suggest that ERAS protocols result in reduced perioperative morbidity, shorter length of hospital stay and improved quality of life after living donor nephrectomy.

BACKGROUND:

Fabry disease (FD) is a rare X-linked lysosomal storage disorder with progressive systemic deposition of globotriaosylceramide, leading to life-threatening cardiac, central nervous system, and kidney disease. Current therapy involves symptomatic medical management, enzyme replacement therapy (ERT), dialysis, kidney transplantation, and, more recently, gene therapy. The aim of this systematic review was to assess outcomes of kidney transplantation among patients with FD.

METHODS:

A comprehensive literature review was conducted utilizing MEDLINE, EMBASE, and Cochrane Database, from inception through to 28 February 2020, to identify studies that evaluate outcomes of kidney transplantation including patient and allograft survival among kidney transplant patients with FD. Effect estimates from each study were extracted and combined using the random-effects generic inverse variance method of DerSimonian and Laird.

RESULTS:

In total, 11 studies, including 424 kidney transplant recipients with FD, were enrolled. The post-transplant median follow-up time ranged from 3 to 11.5 years. Overall, the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 32.5% (95%CI: 23.9%-42.5%), 14.5% (95%CI: 8.4%-23.7%), and 20.2% (95%CI: 15.4%-25.9%), respectively. In the sensitivity analysis, limited only to the recent studies (year 2001 or newer when ERT became available), the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 28.1% (95%CI: 20.5%-37.3%), 11.7% (95%CI: 8.4%-16.0%), and 20.2% (95%CI: 15.5%-26.0%), respectively. The pooled estimated rate of biopsy proven FD recurrence was 11.1% (95%CI: 3.6%-29.4%), respectively. There are no significant differences in the risks of all-cause graft failure (p = 0.10) or mortality (0.48) among recipients with vs. without FD.

CONCLUSIONS:

Despite possible FD recurrence after transplantation of 11.1%, allograft and patient survival are comparable among kidney transplant recipients with vs. without FD.

BACKGROUND:

Vitamin D may protect against respiratory virus infections, but any association with herpesviruses is unclear.

METHODS:

We undertook a systematic review of vitamin D deficiency or supplementation and the risk of 8 human herpesviruses. Six databases and 4 gray literature databases were searched for relevant cohort studies, case-control studies, and clinical trials.

RESULTS:

Ten studies were included, all conducted among immunosuppressed patients. There was no evidence that vitamin D deficiency is associated with cytomegalovirus (CMV) disease (pooled risk ratio, 1.06; 95% CI, 0.66-1.7), herpes zoster after transplantation (1 study), or HHV-8 among HIV patients (1 study). Vitamin D supplementation may decrease herpes zoster among hemodialysis patients (1 study) or CMV disease after renal transplantation (1 study), but supplementation was not associated with reduced EBV viral load among multiple sclerosis patients (1 study).

CONCLUSIONS:

Any association between vitamin D and herpesviruses remains inconclusive. Further studies in the general population are needed.