Solid organ transplant recipients may be at a high risk for SARS‐CoV‐2 infection and poor associated outcomes. We herein report our initial experience with solid organ transplant recipients with ...SARS‐CoV‐2 infection at two centers during the first 3 weeks of the outbreak in New York City. Baseline characteristics, clinical presentation, antiviral and immunosuppressive management were compared between patients with mild/moderate and severe disease (defined as ICU admission, intubation or death). Ninety patients were analyzed with a median age of 57 years. Forty‐six were kidney recipients, 17 lung, 13 liver, 9 heart, and 5 dual‐organ transplants. The most common presenting symptoms were fever (70%), cough (59%), and dyspnea (43%). Twenty‐two (24%) had mild, 41 (46%) moderate, and 27 (30%) severe disease. Among the 68 hospitalized patients, 12% required non‐rebreather and 35% required intubation. 91% received hydroxychloroquine, 66% azithromycin, 3% remdesivir, 21% tocilizumab, and 24% bolus steroids. Sixteen patients died (18% overall, 24% of hospitalized, 52% of ICU) and 37 (54%) were discharged. In this initial cohort, transplant recipients with COVID‐19 appear to have more severe outcomes, although testing limitations likely led to undercounting of mild/asymptomatic cases. As this outbreak unfolds, COVID‐19 has the potential to severely impact solid organ transplant recipients.
In this multicenter study of 90 solid organ transplant recipients diagnosed with COVID‐19 during the first three weeks of the outbreak in New York City, the authors report on the clinical presentation, laboratory abnormalities, risk factors, disease severity, and outcomes.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The safety and efficacy of tocilizumab for the treatment of severe respiratory symptoms due to COVID‐19 remain uncertain, in particular among solid organ transplant (SOT) recipients. Thus, we ...evaluated the clinical characteristics and outcomes of 29 hospitalized SOT recipients who received tocilizumab for severe COVID‐19, compared to a matched control group who did not. Among a total of 117 total SOT recipients hospitalized with COVID‐19, 29 (24.8%) received tocilizumab. The 90‐day mortality was significantly higher among patients who received tocilizumab (41%) compared to those who did not (20%, P = .03). When compared to control patients matched by age, hypertension, chronic kidney disease, and administration of high dose corticosteroids, there was no significant difference in mortality (41% vs 28%, P = .27), hospital discharge (52% vs 72%, P = .26), or secondary infections (34% vs 24%, P = .55). Among patients who received tocilizumab, there was also no difference in mortality based on the level of oxygen support (intubated vs not intubated) at the time of tocilizumab initiation. In this matched cohort study, tocilizumab appeared to be safe but was not associated with decreased 90‐day mortality. Larger randomized studies are needed to identify whether there are subsets of SOT recipients who may benefit from tocilizumab for treatment of COVID‐19.
Solid organ transplant recipients who receive off‐label tocilizumab for severe COVID‐19 have no difference in mortality, hospital discharge, or secondary infections when compared to a matched cohort of nontransplant recipients.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Tens of thousands of patients with advanced lung diseases may be eligible to be considered as potential candidates for lung transplant around the world each year. The timing of referral, evaluation, ...determination of candidacy, and listing of candidates continues to pose challenges and even ethical dilemmas. To address these challenges, the International Society for Heart and Lung Transplantation appointed an international group of members to review the literature, to consider recent advances in the management of advanced lung diseases, and to update prior consensus documents on the selection of lung transplant candidates. The purpose of this updated consensus document is to assist providers throughout the world who are caring for patients with pulmonary disease to identify potential candidates for lung transplant, to optimize the timing of the referral of these patients to lung transplant centers, and to provide transplant centers with a framework for evaluating and selecting candidates. In addition to addressing general considerations and providing disease specific recommendations for referral and listing, this updated consensus document includes an ethical framework, a recognition of the variability in acceptance of risk between transplant centers, and establishes a system to account for how a combination of risk factors may be taken into consideration in candidate selection for lung transplantation.
Duodeno-gastroesophageal reflux aspiration is associated with chronic lung allograft dysfunction (CLAD). Reflux aspirate can contain bile acids (BA), functional molecules in the gastro-intestinal ...tract with emulsifying properties. We sought to determine and quantify the various BA species in airways of the lung transplant recipients to better understand the various effects of aspirated BA that contribute to post-transplantation outcomes.
Bronchial washings (BW) were prospectively collected from lung transplant recipients and subsequently assayed by liquid chromatography-mass spectrometry for 13 BA and 25 lipid families. Patients were monitored for CLAD, rejection, inflammation and airway infections.
Detectable BA were present in 45/50 patients (90%) at 3 months after transplant. Elevated BA and predominance of conjugated species were independent predictors of CLAD (hazard ratio 7.9; 95% confidence interval 2.7-23.6; p < 0.001 and 7.3; 2.4-22; p < 0.001, respectively) and mortality (hazard ratio 4.4; 1.5-12.7; p = 0.007 and 4.8; 1.4-15.8; p = 0.01, respectively). High BA associated with increased positive bacterial cultures (60% vs 25%, p = 0.02). Primary conjugated species independently correlated with the rate of bacterial cultures during the first-year post-transplant (Beta coefficient: 0.77; 0.28-1.26; p = 0.003) and changes in airway lipidome and cytokines.
Higher BA levels and predominance of conjugated BA are independent predictors of chronic lung allograft dysfunction, mortality and bacterial infections. Primary conjugated BA are related to distinct changes in airway lipidome and inflammatory cytokines. This elucidates novel evidence into the mechanism following BA aspiration and proposes novel markers for prediction of adverse post-transplant outcomes.
Ex-vivo lung perfusion (EVLP) sustains and allows advanced assessment of potentially useable donor lungs prior to transplantation, potentially relieving resource constraints.
We sought to ...characterize the effect of EVLP on organ utilization and patient outcomes.
We performed a retrospective, before-after cohort study using linked institutional data sources of adults wait-listed for lung transplant and donor organs transplanted in Ontario, Canada between 2005-2019. We regressed the annual number of transplants against year, EVLP use, and organ characteristics. Time-to-transplant, waitlist mortality, primary graft dysfunction, tracheostomy insertion, in-hospital mortality, and chronic lung allograft dysfunction (CLAD) were evaluated using propensity score-weighted regression.
EVLP availability (P=0.01 for interaction) and EVLP use (P<0.001 for interaction) were both associated with steeper increases in transplantation than expected by historical trends. EVLP was associated with more donation after circulatory death (DCD) and extended-criteria donors transplanted, while the numbers of standard-criteria donors remained relatively stable. Significantly faster time-to-transplant was observed after EVLP was available (hazard ratio HR 1.64 1.41-1.92; P<0.001). Fewer patients died on the waitlist after EVLP was available, but no difference in the hazard of waitlist mortality was observed (HR 1.19 0.81-1.74; P=0.176). We observed no difference in the likelihood of CLAD before versus after EVLP was available.
We observed a significant increase in organ transplantation since EVLP was introduced into practice, predominantly from increased acceptance of DCD and extended-criteria lungs. Our findings suggest that EVLP-associated increases in organ availability meaningfully alleviated some barriers to transplant.
CT measurement of body composition may improve lung transplant candidate selection. We assessed whether skeletal muscle adipose deposition on abdominal and thigh CT scans was associated with 6 min ...walk distance (6MWD) and wait-list survival in lung transplant candidates. Each ½-SD decrease in abdominal muscle attenuation (indicating greater lipid content) was associated with 14 m decrease in 6MWD (95% CI -20 to -8) and 20% increased risk of death or delisting (95% CI 10% to 40%). Each ½-standard deviation decrease in thigh muscle attenuation was associated with 15 m decrease in 6MWD (95% CI -21 to -10). CT imaging may improve candidate risk stratification.
Background
The incidence and impact of de novo fungal airway colonization and infection in lung transplant recipients (LTRs) with known chronic lung allograft dysfunction (CLAD) has not been ...established. We aimed to determine the 1‐year cumulative incidence and risk factors of de novo fungal colonization or infection in LTRs with CLAD and assess the impact of colonization or infection on post‐CLAD survival.
Methods
Prospectively collected Toronto Lung Transplant Program database and chart review were used for double‐LTRs who were diagnosed with CLAD from January 1, 2016 to January 1, 2020 and who were free of airway fungi within 1 year prior to CLAD onset. International Society for Heart and Lung Transplantation definitions were used to define clinical syndromes. Cox‐Proportional Hazards Models were used for risk‐factor analysis. Survival analysis could not be completed secondary to low number of fungal events; therefore, descriptive statistics were employed for survival outcomes.
Results
We found 186 LTRs diagnosed with CLAD meeting our inclusion criteria. The 1‐year cumulative incidence for any fungal event was 11.8% (7.0% for infection and 4.8% for colonization). Aspergillus fumigatus was a causative pathogen in eight of 13 (61.5%) patients with infection and six of nine (66.7%) patients with colonization. No patients with fungal colonization post‐CLAD developed fungal infection. Peri‐CLAD diagnosis (3 months prior or 1 month after) methylprednisolone bolus (hazards ratio: 8.84, p = .001) increased the risk of fungal events. Most patients diagnosed with fungal infections (53.8%) died within 1‐year of CLAD onset.
Conclusion
De novo IFIs and fungal colonization following CLAD onset were not common. Fungal colonization did not lead to fungal infection. Methylprednisolone bolus was a significant risk factors for post‐CLAD fungal events.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
BACKGROUND We conducted a retrospective cohort study using United Network of Organ Sharing (UNOS) data to determine the effect of the calculated panel reactive antibody (cPRA) value on waitlist ...outcomes for lung transplant candidates. MATERIAL AND METHODS We divided lung transplant candidates into groups based on their cPRA value at the time of waitlist activation (0-25%, 25.1-50%, 50.1-75%, and 75.1-100%) and compared each group's waitlist outcomes to the lowest quartile ("minimally sensitized") group. The primary outcome was lung transplantation and the secondary outcome was waitlist mortality (a composite of death on the waitlist/delisting for clinical deterioration). RESULTS Compared to the minimally sensitized group, candidates with a cPRA value of 25.1-50% did not have a significantly different likelihood of undergoing lung transplant or waitlist mortality, candidates with a cPRA value of 50.1-75% were 25% less likely to undergo lung transplant and 44% more likely to die on the waitlist, and candidates with a cPRA value of 75.1-100% were 52% less likely to undergo lung transplant and 92% more likely to die on the waitlist. CONCLUSIONS CPRA values of greater than 50% are associated with significantly lower rates of transplantation and higher waitlist mortality.
Gastroesophageal reflux disease (GERD) and aspiration of enteric contents are associated with worse outcomes after lung transplantation. The purpose of this study was to elucidate populations of ...patients who benefit the most from fundoplication after lung transplantation.
Lung transplantations from 2001 to 2019 (n = 971) were retrospectively reviewed and stratified by fundoplication before (n = 128) or after (n = 24) chronic lung allograft dysfunction (CLAD) development vs patients who did not undergo fundoplication. Patients with a fundoplication before CLAD were propensity matched to patients without a fundoplication. The primary outcome of interest was posttransplant survival. Time-to-event rates were calculated using a multivariable Cox proportional hazards model and Kaplan-Meier functions.
Fundoplication before CLAD improved posttransplant survival before and after propensity matching, and it remained a significant predictor after adjusting for baseline characteristics (hazard ratio HR,0.57; 95 % confidence interval CI, 0.4 to 0.8; P = .001). Transplant recipients with a restrictive disorder (HR, 0.46; 95 % CI, 0.3 to 0.73; P = .001), age younger than 65 years (HR, 0.48; 95 % CI, 0.32 to 0.71; P < ;0.001), and with both single (HR, 0.47; 95 % CI, 0.28 to 0.79; P = .005) and double (HR, 0.55; 95 % CI, 0.32 to 0.93; P = .027) lung transplants had a significant decrease in mortality after fundoplication. The effect was present after excluding early deaths and CLAD diagnoses. Gastroesophageal reflux disease diagnosed by pH, impedance, or esophagogastroduodenoscopy was not associated with worse outcomes. Among patients with CLAD, a fundoplication was an independent predictor of post-CLAD survival (HR, 0.27; 95 % CI; 0.12 to 0.61; P = .002).
Fundoplication before or after CLAD development is an independent predictor of survival. Younger patients with restrictive disease, independent of the type of transplant, have a survival benefit. Gastroesophageal reflux disease diagnosed by conventional methods was not associated with worse survival.
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Background
Morbidity and mortality in lung transplant recipients are often triggered by recurrent aspiration events, potentiated by oesophageal and gastric disorders. Previous small studies have ...shown conflicting associations between oesophageal function and the development of chronic lung allograft dysfunction (CLAD). Herein, we sought to investigate the relationship between oesophageal motility disorders and long-term outcomes in a large retrospective cohort of lung transplant recipients.
Methods
All lung transplant recipients at the Toronto Lung Transplant Program from 2012 to 2018 with available oesophageal manometry testing within the first 7 months post-transplant were included in this study. Patients were categorised according to the Chicago Classification of oesophageal disorders (v3.0). Associations between oesophageal motility disorders with the development of CLAD and allograft failure (defined as death or re-transplantation) were assessed.
Results
Of 487 patients, 57 (12%) had oesophagogastric junction outflow obstruction (OGJOO) and 47 (10%) had a disorder of peristalsis (eight major, 39 minor). In a multivariable analysis, OGJOO was associated with an increased risk of CLAD (HR 1.71, 95% CI 1.15–2.55, p=0.008) and allograft failure (HR 1.69, 95% CI 1.13–2.53, p=0.01). Major disorders of peristalsis were associated with an increased risk of CLAD (HR 1.55, 95% CI 1.01–2.37, p=0.04) and allograft failure (HR 3.33, 95% CI 1.53–7.25, p=0.002). Minor disorders of peristalsis were not significantly associated with CLAD or allograft failure.
Conclusion
Lung transplant recipients with oesophageal stasis characterised by OGJOO or major disorders of peristalsis were at an increased risk of adverse long-term outcomes. These findings will help with risk stratification of lung transplant recipients and personalisation of treatment for aspiration prevention.
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