Lung transplant patients are a vulnerable group of immunosuppressed patients that are prone to frequent respiratory infections. We studied 60 episodes of respiratory symptoms in 71 lung transplant ...patients. Almost half of these episodes were of unknown infectious etiology despite extensive routine diagnostic testing.
We re-analyzed respiratory samples of all episodes with undetermined etiology in order to detect potential viral pathogens missed/not accounted for in routine diagnostics. Respiratory samples were enriched for viruses by filtration and nuclease digestion, whole nucleic acids extracted and randomly amplified before high throughput metagenomic virus sequencing. Viruses were identified by a bioinformatic pipeline and confirmed and quantified using specific real-time PCR.
In completion of routine diagnostics, we identified and confirmed a viral etiology of infection by our metagenomic approach in four patients (three Rhinovirus A, one Rhinovirus B infection) despite initial negative results in specific multiplex PCR. Notably, the majority of samples were also positive for Torque teno virus (TTV) and Human Herpesvirus 7 (HHV-7). While TTV viral loads increased with immunosuppression in both throat swabs and blood samples, HHV-7 remained at low levels throughout the observation period and was restricted to the respiratory tract.
This study highlights the potential of metagenomic sequencing for virus diagnostics in cases with previously unknown etiology of infection and in complex diagnostic situations such as in immunocompromised hosts.
Organ donation after circulatory death (DCD) was reintroduced in Switzerland in 2011 and accounts for a third of deceased organ donors today. Controversy persists if DCD transplants are of similar ...quality to transplants following donation after brain death (DBD), mainly due to warm ischaemia time DCD organs are exposed to. We compared DCD with DBD in Switzerland.
Data on deceased adults who were referred to and approved for organ donation from 1 September 2011 to 31 December 2019 were retrospectively analysed (217 DCD, 840 DBD donors). We compared DCD and DBD donor/organ characteristics, transplant rates of lungs, liver, kidneys, and pancreas, and early liver and kidney graft function in the recipient. The effect of DCD/DBD on transplant rates (organ transplanted or not) and 72-hour recipient graft function (moderate/good vs delayed graft function / organ loss) was analysed using multivariable logistic regression. Among utilised DCD donors, we analysed the effect of functional warm ischaemia time (FWIT) and donor age on 72-hour post-transplant liver and kidney graft function, also using multivariable logistic regression.
DCD donors were more often male (64.5% vs 56.8% p = 0.039), presented with heart disease (36.4% vs 25.5%, p <0.001), were resuscitated before hospital admission (41.9% vs 30.7%, p = 0.006), and died from anoxia (41.9% vs 23.9%). Kidney function before transplantation was comparable, lung, liver and pancreas function were poorer in DCD than DBD. Eighty-one and 91% of approved DCD and DBD donors were utilised (p <0.001). Median FWIT in DCD was 29 minutes (interquartile range 25-35). DCD transplant rates ranged from 4% (pancreas) to 73% (left kidney) and were all lower compared with DBD. Seventy-two-hour liver graft function was comparable between DCD and DBD (94.2% vs 96.6% moderate/good, p = 0.199). DCD kidney transplants showed increased risk of delayed graft function or early organ loss (odds ratios 8.32 and 5.05; 95% confidence intervals CI 5.28-13.28 and 3.22-7.95; both p <0.001, for left and right kidney transplants, respectively). No negative effect of prolonged FWIT or higher donor age was detected.
Despite less favourable donor/organ characteristics compared with donation after brain death, donation after circulatory death donors are increasingly referred and today provide an important source for scarce transplants in Switzerland. We identified a higher risk for delayed graft function or early organ loss for DCD kidney transplants, but not for DCD liver transplants. When carefully selected and allowed for other risk factors in organ allocation, prolonged functional warm ischaemia time or higher age in donation after circulatory death does not seem to be associated with impaired graft function early after transplantation.
Chronic lung allograft dysfunction (CLAD) is the main factor limiting long-term survival after lung transplantation. Besides bronchiolitis obliterans syndrome, a restrictive phenotype of CLAD (rCLAD) ...exists, which is associated with poor prognosis after diagnosis. However, survival determinants for rCLAD remain to be elucidated. Our aim in this study was to establish parameters predicting survival in patients with rCLAD.
All patients diagnosed with rCLAD in 2 lung transplant centers were assessed in a retrospective manner. Various clinical parameters demography, pulmonary function, bronchoalveolar lavage (BAL), histopathology, radiology and blood differentials at rCLAD diagnosis were correlated with graft survival using unadjusted and adjusted analysis.
A total of 53 patients with rCLAD were included with a median graft survival after diagnosis of 1.1 years. Univariate analysis demonstrated that lower-lobe-dominant or diffuse infiltrates on chest computed tomography, presence of an identifiable trigger before rCLAD onset, lymphocytic bronchiolitis, increased BAL neutrophilia, increased BAL eosinophilia and increased blood eosinophils were associated with inferior graft survival after rCLAD diagnosis. Multivariate analysis confirmed the association of location of infiltrates and blood eosinophilia on graft survival.
In this study we have identified parameters associated with graft survival after rCLAD diagnosis that may be useful to predict prognosis.
Purpose: Utilization of donation after circulatory death (DCD) donors has the potential to decrease donor shortage in lung transplantation (LTx). This study reviews the long-term outcome of LTx from ...DCD donors.Methods: We included all consecutive DCD (Maastricht Category III) and all donations after brain death (DBD) donor lung transplants at our Center performed between January 2012 and February 2017. Data were analyzed comparing the two groups in regard of survival after LTx as primary outcome.Results: Median withdrawal to cardiac arrest time was 17 min (interquartile range IQR: 11.5–20.5). Median cardiac arrest to cold perfusion was 32 min (IQR: 24.5–36.5). Primary graft dysfunction (PGD) grade 3 at T72 occurred in three recipients. Chronic lung allograft dysfunction (CLAD) led to death in two cases. In DCD group, there was no 90-day mortality. In DCD, group 1- and 3-year survival rates were 100% and 80%. In DBD group, 1- and 3-year survival rates were 85% and 69% (p = 0.4).Conclusions: Our report confirmed the comparable outcome from DCD donors compared with DBD donors. Utility of DCD donors is a safe option to overcome donor shortage.
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.
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).
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).
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.
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