Primary Graft Dysfunction Grade Research Articles

Early serum biomarkers to characterise different phenotypes of primary graft dysfunction after lung transplantation: a systematic scoping review

BackgroundLung transplantation (LUTX) often is complicated by primary graft dysfunction (PGD). Plasma biomarkers hold potential for PGD phenotyping and targeted therapy. This scoping review aims to collect the available literature in search of serum biomarkers for PGD phenotyping.MethodsFollowing JBI and PRISMA guidelines, we conducted a systematic review searching MEDLINE, Web of Science, EMBASE, and The Cochrane Library for papers reporting the association between serum biomarkers measured within 72 h of reperfusion and PGD, following ISHLT guidelines. We extracted study details, patient demographics, PGD definition and timing, biomarker concentration, and their performance in identifying PGD cases.ResultsAmong the 1050 papers screened, 25 prospective observational studies were included, with only 9 conducted in the last decade. These papers included 1793 unique adult patients (1195 double LUTX, median study size 100 (IQR 44–119). Most (n=21) compared PGD grade 3 to less severe PGD, but only 4 adhered to 2016 PGD definitions. Enzyme-linked immunosorbent assays and the multiplex bead array technique were utilised in 23 and 2 papers, respectively. In total, 26 candidate biomarkers were identified, comprising 13 inflammatory, 3 endothelial activation, 3 epithelial injury, 3 cellular damage, 2 coagulation dysregulation markers. Only 5 biomarkers (sRAGE, ICAM-1, PAI-1, SP-D, FSTL-1) underwent AUROCC analysis, yielding a median value of 0.58 (0.51, 0.78) in 406 patients (276 double LUTX).ConclusionsSeveral biomarkers exhibit promise for future studies aimed at PGD phenotyping after LUTX. To uncover the significant existing knowledge gaps, further international prospective studies incorporating updated diagnostic criteria, modern platforms, and advanced statistical approaches are essential.

Donor Lung Preservation at 10 °C: Clinical and Logistical Impact

IntroductionCold static donor lung preservation at 10°C appears to be a promising method to safely extend the cold ischemic time (CIT) and improve lung transplant (LTx) logistics. MethodsLTx from November 2021 to February 2023 were included in this single institution, prospective, non-randomized study comparing prolonged preservation at 10°C versus standard preservation on ice. The inclusion criteria for 10°C preservation were suitable grafts for LTx without any donor retrieval concerns. Primary endpoint: primary graft dysfunction (PGD) grade-3 at 72-h. Secondary endpoints: clinical outcomes, cytokine profile and logistical impact. ResultsThirty-three out of fifty-seven cases were preserved at 10°C. Donor and recipient characteristics were similar across the groups. Total preservation times (h:min) were longer (p<0.001) in the 10°C group [1st lung: median 12:09 (IQR 9:23–13:29); 2nd: 14:24 (12:00–16:20)] vs. standard group [1st lung: median 5:47 (IQR 5:18–6:40); 2nd: 7:15 (6:33–7:40)]. PGD grade-3 at 72-h was 9.4% in 10°C group vs. 12.5% in standard group (p=0.440). Length of mechanical ventilation (MV), ICU and hospital stays were similar in both groups. Thirty and ninety-day mortality rates were 0% in 10°C group (vs. 4.2% in standard group). IL-8 concentration was significantly higher 6-h post-LTx in the standard group (p=0.025) and IL-10 concentration was increased 72-h post-LTx in the 10°C group (p=0.045). ConclusionsPreservation at 10°C may represent a safe and feasible strategy to intentionally prolong the CIT. In our center, extending the CIT at 10°C may allow for semi-elective LTx and improve logistics with similar outcomes compared to the current standard preservation on ice.

Extended ischemic time (>15 hours) using controlled hypothermic storage in lung transplantation: A multicenter experience

Static ice storage has long been the standard-of-care for lung preservation, although freezing injury limits ischemic time (IT). Controlled hypothermic storage (CHS) at elevated temperature could safely extend IT. This retrospective analysis assesses feasibility and safety of CHS with IT>15h. Three lung transplant (LuTx) centers (April-October 2023) included demographics, storage details, IT and short-term outcome from 13 LuTx recipients (8 male, 59 years old). Donor lungs were preserved in a portable CHS-device at 7(5-9.3)°C. Indication was overnight bridging and/or long-distance transport. IT of second-implanted lung was 17.3(15.1-22)h. LuTx were successful, 4/13 exhibited primary graft dysfunction grade 3 within 72h and 0/13 at 72h. Post-LuTx mechanical ventilation was 29(7-442)h. Intensive care unit stay was 9(5-28) and hospital stay 30(16-90) days. Four patients needed post-operative extracorporeal membrane oxygenation (ECMO). One patient died (day seven) following malpositioning of an ECMO cannula. This multi-center experience demonstrates the possibility of safely extending IT>15h by CHS.

Plasma concentrations of histidine-rich glycoprotein in primary graft dysfunction after lung transplantation.

Histidine-rich glycoprotein has been reported as an anti-inflammatory glycoprotein that inhibits acute lung injury in mice with sepsis and as a prognostic biomarker in patients with sepsis. We investigated the relationship between plasma concentrations of histidine-rich glycoprotein and the risk of occurrence of primary graft dysfunction. According to the primary graft dysfunction grade at post-transplant 72 h, patients who underwent lung transplantation were divided into three groups: non-primary graft dysfunction group (grade 0-1), moderate primary graft dysfunction group (grade 2), and severe primary graft dysfunction group (grade 3). The plasma concentrations of histidine-rich glycoprotein measured daily during the first post-transplant 7 days were compared among the three groups. Appropriate cutoff values of the concentrations were set for survival analyses after lung transplantation. A total of 68 patients were included. The plasma histidine-rich glycoprotein concentration at post-transplant 72 h was significantly lower in the severe primary graft dysfunction group (n = 7) than in the other two groups [non-primary graft dysfunction group (n = 43), P = 0.042; moderate primary graft dysfunction group (n = 18), P = 0.040]. Patients with plasma histidine-rich glycoprotein concentration ≥34.4 µg/ml at post-transplant 72 h had significantly better chronic lung allograft dysfunction-free survival (P = 0.012) and overall survival (P = 0.037) than those with the concentration <34.4 µg/ml. Plasma histidine-rich glycoprotein concentrations at post-transplant 72 h might be associated with the risk of development of primary graft dysfunction.

Lung Transplantation in Pulmonary Arterial Hypertension: The Portuguese Experience

In patients with pulmonary arterial hypertension (PAH), refractory to medical therapy, lung transplantation emerges as an option. This study describes the outcomes of 8 PAH patients who underwent lung transplantation. A retrospective, single-center study was conducted among patients with PAH who underwent lung transplantation in our center. Patients had a median age of 46 years, with female sex predominance (75%). Causes of HAP were pulmonary veno-occlusive disease (n = 5, 62.5%), idiopathic PAH (n = 2, 25%), and heritable PAH (n = 1, 12.5%). Pre-transplant hemodynamics revealed a median mean pulmonary artery pressure of 58.5 mm Hg (48-86). All patients received bilateral lung transplants with extracorporeal membrane oxygenation support, displaying immediate post-transplant hemodynamic improvement. Primary graft dysfunction grade 3 (PGD 3) was observed in 75% of patients. Five patients (62.5%) died, with a 72.9% survival at 12 months and 29.2% at 24 months post-transplantation. Our study reveals the complexity and challenges of lung transplants in patients with PAH. Despite notable immediate hemodynamic improvements, high rates of PGD 3 and the survival rate remain a concern. Further research to define optimal peri and post-transplant management to improve survival is required.

National utilization, trends, and lung transplant outcomes of static versus portable ex vivo lung perfusion platforms

BackgroundThis study compared utilization and outcomes of the 2 widely utilized ex vivo lung perfusion (EVLP) platforms in the United States: a static platform and a portable platform. MethodsAdult (age 18 years or older) bilateral lung-only transplants utilizing EVLP between February 28, 2018, and December 31, 2022, in the United Network for Organ Sharing database were included. Predischarge acute rejection, intubation at 72 hours posttransplant, extracorporeal membrane oxygenation at 72 hours posttransplant, primary graft dysfunction grade 3 at 72 hours posttransplant, 30-day mortality, and 1-year mortality were evaluated using multivariable regressions. ResultsOverall, 607 (6.3%) lung transplants during the study period used EVLP (51.2% static, 48.8% portable). Static EVLP was primarily utilized in the eastern United States, whereas portable EVLP was primarily utilized in the western United States. Static EVLP donors were more likely to be donation after circulatory death (33.4% vs 26.0%; P = .005), have a >20 pack-year smoking history (13.5% vs 6.5%; P = .005), and be extended criteria donors (92.3% vs 85.0%; P = .013), whereas portable EVLP donors were more likely to be older than age 55 years (14.2% vs 8.0%; P = .02). Transplants utilizing the static and portable platforms had similar risk of acute rejection, intubation at 72 hours, extracorporeal membrane oxygenation at 72 hours, primary graft dysfunction grade 3 at 72 hours, and posttransplant mortality at 30 days and 1 year (all P values > .05). ConclusionsThe static and portable platforms had significant differences in donor characteristics and geographic distributions of utilization. Despite this, posttransplant survival was similar between the 2 EVLP platforms.

Temporal correlation between postreperfusion complement deposition and severe primary graft dysfunction in lung allografts

Growing evidence implicates complement in the pathogenesis of primary graft dysfunction (PGD). We hypothesized that early complement activation postreperfusion could predispose to severe PGD grade 3 (PGD-3) at 72 hours, which is associated with worst posttransplant outcomes. Consecutive lung transplant patients (n = 253) from January 2018 through June 2023 underwent timed open allograft biopsies at the end of cold ischemia (internal control) and 30 minutes postreperfusion. PGD-3 at 72 hours occurred in 14% (35/253) of patients; 17% (44/253) revealed positive C4d staining on postreperfusion allograft biopsy, and no biopsy-related complications were encountered. Significantly more patients with PGD-3 at 72 hours had positive C4d staining at 30 minutes postreperfusion compared with those without (51% vs 12%, P < .001). Conversely, patients with positive C4d staining were significantly more likely to develop PGD-3 at 72 hours (41% vs 8%, P < .001) and experienced worse long-term outcomes. In multivariate logistic regression, positive C4d staining remained highly predictive of PGD-3 (odds ratio 7.92, 95% confidence interval 2.97-21.1, P < .001). Hence, early complement deposition in allografts is highly predictive of PGD-3 at 72 hours. Our data support future studies to evaluate the role of complement inhibition in patients with early postreperfusion complement activation to mitigate PGD and improve transplant outcomes.

The role of lung microbiota in primary graft dysfunction in lung transplant recipients.

Recent studies have shown that the lung microbiota is altered in critically ill patients and predicts clinical outcomes. Primary graft dysfunction (PGD) is a common complication and a leading cause of death within 1 month of lung transplantation, but the clinical significance of changes in the lung bacterial community during PGD is unclear. The aim of this study was to determine the contribution of the lung microbiota to the development and course of severe PGD. We conducted a retrospective study to characterize the lung microbiota of 32 lung transplant patients with combined PGD using next-generation sequencing of bronchoalveolar lavage samples. The relationship between lung flora dysbiosis and lung immunity in PGD was assessed by quantification of alveolar cytokines. The contribution of microbiota characteristics to patient outcomes was assessed by estimating overall survival. Patients diagnosed with PGD grade 3 showed a reduction in alpha diversity, driven by a significant increase in the abundance of the genera Modestobacter, Scardovia and Selenomonas, and a reduction in the proportion of the genera Klebsiella and Oribacterium. Alpha diversity of the lung microbiota in PGD3 patients was negatively correlated with BALF interleukin (IL)-2 (r=-.752, p<.05). In addition, bacterial diversity in the lung microbiota of non-survivors was lower than that of survivors (p=.041). There is variation in the lung microbiota of PGD grade 3 patients and dysbiosis of the lung microbiota is associated with lung immunity. The lung microbiota has potential in the diagnosis and treatment of PGD grade 3.

Initial experience and outcomes with a hybrid extracorporeal membrane oxygenation and cardiopulmonary bypass circuit for lung transplantation

BackgroundThe utilization of extracorporeal life support (ECLS) for intraoperative support during lung transplantation has increased over the past decade. Although veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has recently emerged as the preferred modality over cardiopulmonary bypass (CPB), many centers continue to use both forms of ECLS during lung transplantation. Our novel hybrid VA-ECMO/CPB circuit allows for seamless transition from VA-ECMO to CPB at a significant cost savings compared to a standalone VA-ECMO circuit. This study describes our initial experience and outcomes in the first 100 bilateral lung transplantations using this novel hybrid VA-ECMO/CPB circuit. MethodsMedical records from September 2017 to May 2021 of the first 100 consecutive patients undergoing bilateral lung transplantation with intraoperative hybrid VA-ECMO support were examined retrospectively. We excluded patients with single lung transplants, retransplantations, preoperative ECLS bridging, and veno-venous (VV) ECMO and those supported with CPB only. Perioperative recipient, anesthetic, perfusion variables, and outcomes were assessed. ResultsOf the 100 patients supported with VA-ECMO, 19 were converted intraoperatively to CPB. Right ventricular dysfunction was seen in 37% of patients, and the median mean pulmonary artery pressure was 28 mm Hg. No oxygenator clotting was observed with a median heparin dose of 13,000 units in the VA-ECMO group. Primary graft dysfunction grade 3 at 72 hours was observed in 10.1% of all patients and observed 1-year mortality was 4%. ConclusionsThe use of a hybrid VA-ECMO/CPB circuit in our institution allows for rapid conversion to CPB with acceptable outcomes across a diverse recipient group at a significantly reduced cost compared to standalone VA-ECMO circuits.

Hemodynamic failure and graft dysfunction after lung transplant: A possible clinical continuum with immediate and long-term consequences.

The postoperative hemodynamic management after lung transplant (LUTX) is guided by limited evidence. We aimed to describe and evaluate risk factors and outcomes of postoperative vasoactive support of LUTX recipients. In a single-center retrospective analysis of consecutive adult LUTX, two cohorts were identified: (1) patients needing prolonged vasoactive support (>12h from ICU admission) (VASO+); (2) or not (VASO-). Postoperative hemodynamic characteristics were thoroughly analyzed. Risk factors and outcomes of VASO+ versus VASO- cohorts were assessed by multivariate logistic regression and propensity score matching. One hundred and thirty-eight patients were included (86 (62%) VASO+ versus 52 (38%) VASO-). Vasopressors (epinephrine, norepinephrine, dopamine) were used in the first postoperative days (vasoactive inotropic score at 12h: 6 [4-12]), while inodilators (dobutamine, levosimendan) later. Length of vasoactive support was 3 [2-4] days. Independent predictors of vasoactive use were: LUTX indication different from cystic fibrosis (p=.003), higher Oto score (p=.020), longer cold ischemia time (p=.031), but not preoperative cardiac catheterization. VASO+ patients showed concomitant hemodynamic and graft impairment, with longer mechanical ventilation (p=.010), higher primary graft dysfunction (PGD) grade at 72h (PGD grade>0 65% vs. 31%, p=.004, OR 4.2 [1.54-11.2]), longer ICU (p<.001) and hospital stay (p=.013). Levosimendan as a second-line inodilator appeared safe. Vasoactive support is frequently necessary after LUTX, especially in recipients of grafts of lesser quality. Postoperative hemodynamic dysfunction requiring vasopressor support and graft dysfunction may represent a clinical continuum with immediate and long-term consequences. Further studies may elucidate if this represents a possible treatable condition.

Short airway telomeres are associated with primary graft dysfunction and chronic lung allograft dysfunction

Primary graft dysfunction (PGD) is a major risk factor for chronic lung allograft dysfunction (CLAD) following lung transplantation, but the mechanisms linking these pathologies are poorly understood. We hypothesized that the replicative stress induced by PGD would lead to erosion of telomeres, and that this telomere dysfunction could potentiate CLAD. In a longitudinal cohort of 72 lung transplant recipients with >6years median follow-up time, we assessed tissue telomere length, PGD grade, and freedom from CLAD. Epithelial telomere length and fibrosis-associated gene expression were assessed on endobronchial biopsies taken at 2 to 4weeks post-transplant by TeloFISH assay and nanoString digital RNA counting. Negative-binomial mixed-effects and Cox-proportional hazards models accounted for TeloFISH staining batch effects and subject characteristics including donor age. Increasing grade of PGD severity was associated with shorter airway epithelial telomere lengths (p=0.01). Transcriptomic analysis of fibrosis-associated genes showed alteration in fibrotic pathways in airway tissue recovering from PGD, while telomere dysfunction was associated with inflammation and impaired remodeling. Shorter tissue telomere length was in turn associated with increased CLAD risk, with a hazard ratio of 1.89 (95% CI 1.16-3.06) per standard deviation decrease in airway telomere length, after adjusting for subject characteristics. PGD may accelerate telomere dysfunction, potentiating immune responses and dysregulated repair. Epithelial cell telomere dysfunction may represent one of several mechanisms linking PGD to CLAD.

Impact of ILD-Specific Therapies on Perioperative Course in Patients with Progressive Interstitial Lung Disease Undergoing Lung Transplantation.

Immunosuppressants and antifibrotics are currently used to treat patients with various interstitial lung diseases, which may undergo lung transplantation (LTx). The retrospective study aimed to evaluate the potential effects of therapeutic regimen on the perioperative course in patients with idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF) undergoing LTx. All patients with IPF and PPF undergoing LTx between January 2014 and December 2021 were included. We retrospectively screened for previous use of immunosuppressants and antifibrotic therapy. We analyzed perioperative courses, short-term outcomes, and safety retrospectively. In total, 286 patients with diagnosis of IPF or PPF were analyzed. According to the treatment regimen before LTx, the study cohort was divided into four groups and compared. No differences between antifibrotic monotherapy, combined antifibrotic and immunosuppressive therapy with regard to postoperative complications were observed. Length of mechanical ventilation was shorter in patients with antifibrotics prior to LTx. Pretreatment with antifibrotic monotherapy and a combination of antifibrotic drugs with immunosuppressive therapy, lower body mass index (BMI) and lower blood loss, were independently associated with primary graft dysfunction grades 0-3 72 hours after LTx (p < 0.001). Finally, patients with antifibrotic monotherapy developed significantly less de novo donor-specific antibodies (DSA) (p = 0.009). Higher intraoperative blood loss, etiology of interstitial lung disease (ILD) and older age were independently associated with shorter survival after LTx. Use of antifibrotic monotherapy and a combination of antifibrotic drugs with immunosuppressive therapy in IPF/PPF patients undergoing LTx, proved to be safe and might lead to beneficial effects after LTx.

The Procalcitonin Combined with C-Reactive Protein/Albumin Ratio as a Predictor of Mortality in Patients After Lung Transplantation

BackgroundThe Procalcitonin (PCT) and C-reactive protein (CRP)/albumin ratio have recently been used to predict early prognosis for intensive care unit (ICU) patients and patients undergoing major surgery. But there were few clinical studies in patients after lung transplantation (LTX).Aim/PurposeThe purpose of this study was to identify the association between PCT combined with CRP/albumin ratio and 30-day mortality and predict the accuracy of PCT combined with CRP/albumin ratio for 30-day mortality in patients after LTX.MethodFrom January 1, 2016 to December 1, 2020, the clinical data of 77 patients undergoing LTX who died within 30 days were retrospectively collected, we randomly collected 87 patients survived more than 30 days after LTX. ROC curve was used to evaluate the prognostic value of PCT combined with CRP/albumin in predicting mortality at 30 days after ICU admission, Cox proportional hazard model analysis was used to identify risk factors, subgroup analyses was conducted.ResultsPostoperative PCT, CRP, albumin, CRP/albumin ratio, atrial fibrillation, primary graft dysfunction (PGD) grade, the hours of postoperative mechanical ventilation (MV) and length of ICU stay between survivor and non-survivor had a significant difference. On Cox proportional hazard regression analysis, both PCT [HR 1.02 (1.00–1.05), P = 0.037] and CRP/albumin ratio [HR 1.438 (1.26–1.65), P < 0.001] were independent predictors of 30-day mortality. In all patients after LTX, the area under the curve (AUC) of PCT combined with CRP/albumin ratio for predicting 30-day mortality was 0.76 (95% CI 0.69–0.83). In subgroup analysis, the AUC of PCT combined with CRP/albumin ratio for predicting 30-day mortality was 0.83 (95% CI 0.75–0.91) in patients undergoing LTX for interstitial pulmonary fibrosis (IPF).ConclusionThe PCT combined with CRP/albumin ratio could be a predictor of the outcomes in patients undergoing LTX. The predictive efficacy was better in patients undergoing LTX for IPF.

Developing machine learning models to predict primary graft dysfunction after lung transplantation

Primary graft dysfunction (PGD) is the leading cause of morbidity and mortality in the first 30 days after lung transplantation. Risk factors for the development of PGD include donor and recipient characteristics, but how multiple variables interact to impact the development of PGD and how clinicians should consider these in making decisions about donor acceptance remain unclear. This was a single-center retrospective cohort study to develop and evaluate machine learning pipelines to predict the development of PGD grade 3 within the first 72 hours of transplantation using donor and recipient variables that are known at the time of donor offer acceptance. Among 576 bilateral lung recipients, 173 (30%) developed PGD grade 3. The cohort underwent a 75% to 25% train-test split, and lasso regression was used to identify 11 variables for model development. A K-nearest neighbor’s model showing the best calibration and performance with relatively small confidence intervals was selected as the final predictive model with an area under the receiver operating characteristics curve of 0.65. Machine learning models can predict the risk for development of PGD grade 3 based on data available at the time of donor offer acceptance. This may improve donor-recipient matching and donor utilization in the future.

Time to extubation for lung transplant recipients represents a pragmatic end-point to guide the development of prognostic tests

The field of transplantation would benefit from the integration of advanced precision medicine techniques. Although predictive tests for lung transplantation require a well-defined clinical end-point, there exists no consensus regarding which outcomes are optimal end-points for these purposes. While many possible candidate end-points exist, we propose that time-to-extubation is an optimal end-point for prognostic tests because of its: clinical relevance; objectiveness; stability over time; and association with healthcare expenditure. Herein, we describe the rationale for this selection and present the limitations of alternative outcomes for this purpose. Using a 72-hour cut-off, time to extubation correlated well with Primary Graft Dysfunction Grade 3, intensive care unit and hospital length of stay, and a greater than 2-fold increase in healthcare cost ratios. Given that time-to-extubation is an objective measure that is readily measured by all lung transplant centers, this metric represents a preferred primary end-point for prognostic tests developed for lung transplantation.

Primary graft dysfunction grade correlates with acute kidney injury stage after lung transplantation.

Primary graft dysfunction (PGD) and acute kidney injury (AKI) are major early complications of lung transplantation and are associated with increased mortality. Lung injury after PGD can contribute to renal dysfunction; however, the association between PGD and AKI severity has not been thoroughly investigated. We analyzed the association between PGD grading and AKI staging, and the impact of AKI on subsequent changes to chronic kidney disease (CKD), including glomerular filtration rate (GFR), over time. This was a retrospective review of a single-center lung transplantation database between January 2018 and June 2022. AKI and GFR categories were classified according to the Kidney Disease: Improving Global Outcomes criteria. Spearman's and Kaplan-Meier tests were used to compare disease severity and assess survival. In a total of 206 patients: 119 (57.8%), 25 (12.1%), 34 (16.5%), and 28 (13.6%) had PGD grades 0, 1, 2, and 3, respectively; 96 (46.6%), 47 (22.8%), 27 (13.1%), and 36 (17.5%) had AKI stages 0, 1, 2, and 3, respectively. Twenty-one of the 28 patients (75.0%) with PGD grade 3 had AKI stage 3. There was a significant correlation between PGD grade and AKI stage (P<0.001). There was also a significant correlation between AKI stage and GFR category of CKD at 3, 6, 9, and 12 months after lung transplantation (all P<0.001). For all AKI stages, GFR categories worsened with postoperative time. PGD grade was significantly correlated with AKI stage, and AKI stage was correlated with GFR categories of CKD.

The SHELTER Trial of Transplanting Hepatitis C Virus-Infected Lungs Into Uninfected Recipients.

This study is a single-arm trial of 10 lung transplants at a single center. Patients were included who were between 18 and 67 y of age and waitlisted for lung-only transplant. Patients were excluded who had evidence of liver disease. Primary outcome was HCV cure (sustained virologic response 12 wk after completing antiviral therapy). Recipients longitudinally reported QOL using the validated RAND-36 instrument. We also applied advanced methods to match HCV-RNA+ lung recipients to HCV-negative lung recipients in a 1:3 ratio at the same center. Between November 2018 and November 2020, 18 patients were consented and opted-in for HCV-RNA+ lung offers in the allocation system. After a median of 37 d (interquartile range [IQR], 6-373) from opt-in, 10 participants received double lung transplants. The median recipient age was 57 y (IQR, 44-67), and 7 recipients (70%) had chronic obstructive pulmonary disease. The median lung allocation score at transplant was 34.3 (IQR, 32.7-86.9). Posttransplant, 5 recipients developed primary graft dysfunction grade 3 on day 2 or 3, although none required extracorporeal membrane oxygenation. Nine patients received elbasvir/grazoprevir, whereas 1 patient received sofosbuvir/velpatasvir. All 10 patients were cured of HCV and survived to 1 y (versus 83% 1-y survival among matched comparators). No serious adverse events were found to be related to HCV or treatment. RAND-36 scores showed substantial improvement in physical QOL and some improvement in mental QOL. We also examined forced expiratory volume in 1 s-the most important lung function parameter after transplantation. We detected no clinically important differences in forced expiratory volume in 1 s between the HCV-RNA+ lung recipients versus matched comparators. SHELTER adds important evidence regarding the safety of transplanting HCV-RNA+ lungs into uninfected recipients and suggests QOL benefits.

Nothing but NETs: Cytokine adsorption correlates with lower circulating nucleosomes and is associated with decreased primary graft dysfunction

Elevated levels of neutrophil extracellular traps (NETs) have been reported in primary graft dysfunction, making methods to reduce or remove them highly valuable. The mechanisms behind primary graft dysfunction (PGD) remain rudimentarily understood but its relation to higher rates of acute and chronic rejection necessitates the development of preventative treatments. This case series explores the use of a cytokine adsorber during lung transplantation with the focus of reducing circulating nucleosome levels as a measure of NETs. Treated patients showed reduced levels of circulating nucleosomes and remained free from PGD and histopathological signs of acute rejection at 1- and 3-month post-transplant. In contrast, patients without the adsorber experienced higher levels of circulating nucleosomes, PGD grades 1 and 3, and histopathological signs of acute rejection. Using a cytokine adsorber during transplantation may provide a reduced systemic inflammatory state with lower levels of NETs and consequently support graft acceptance.

S100A8/A9 as a prognostic biomarker in lung transplantation.

S100A8/A9 is a damage-associated molecule that augments systemic inflammation. However, its role in the acute phase after lung transplantation (LTx) remains elusive. This study aimed to determine S100A8/A9 levels after lung transplantation (LTx) and evaluate their impact on overall survival (OS) and chronic lung allograft dysfunction (CLAD)-free survival. Sixty patients were enrolled in this study, and their plasma S100A8/A9 levels were measured on days 0, 1, 2, and 3 after LTx. The association of S100A8/A9 levels with OS and CLAD-free survival was assessed using univariate and multivariate Cox regression analyses. S100A8/A9 levels were elevated in a time-dependent manner until 3days after LTx. Ischemic time was significantly longer in the high S100A8/9 group than in the low S100A8/A9 group (p=.017). Patients with high S100A8/A9 levels (>2844ng/mL) had worse prognosis (p=.031) and shorter CLAD-free survival (p=.045) in the Kaplan-Meier survival analysis than those with low levels. Furthermore, multivariate Cox regression analysis showed that high S100A8/A9 levels were a determinant of poor OS (hazard ratio [HR]: 3.7; 95% confidence interval [CI]: 1.2-12; p=.028) and poor CLAD-free survival (HR: 4.1; 95% CI: 1.1-15; p=.03). In patients with a low primary graft dysfunction grade (0-2), a high level of S100A8/A9 was also a poor prognostic factor. Our study provided novel insights into the role of S100A8/A9 as a prognostic biomarker and a potential therapeutic target for LTx.

Outcomes of lung and liver transplantation after simultaneous recovery using abdominal normothermic regional perfusion in donors after the circulatory determination of death versus donors after brain death

Normothermic regional perfusion (NRP) in controlled donation after the circulatory determination of death (cDCD) is a growing preservation technique for abdominal organs that coexists with the rapid recovery of lungs. We aimed to describe the outcomes of lung transplantation (LuTx) and liver transplantation (LiTx) when both grafts are simultaneously recovered from cDCD donors using NRP and compare them with grafts recovered from donation after brain death (DBD) donors. All LuTx and LiTx meeting these criteria during January 2015 to December 2020 in Spain were included in the study. Simultaneous recovery of lungs and livers was undertaken in 227 (17%) donors after cDCD with NRP and 1879 (21%) DBD donors (P < .001). Primary graft dysfunction grade-3 within the first 72 hours was similar in both LuTx groups (14.7% cDCD vs. 10.5% DBD; P = .139). LuTx survival at 1 and 3 years was 79.9% and 66.4% in cDCD vs. 81.9% and 69.7% in DBD (P = .403). The incidence of primary nonfunction and ischemic cholangiopathy was similar in both LiTx groups. Graft survival at 1 and 3 years was 89.7% and 80.8% in cDCD vs. 88.2% and 82.1% in DBD LiTx (P = .669). In conclusion, the simultaneous rapid recovery of lungs and preservation of abdominal organs with NRP in cDCD donors is feasible and offers similar outcomes in both LuTx and LiTx recipients to transplants using DBD grafts.