Early extracorporeal photopheresis treatment is associated with better survival in patients with chronic or recurrent acute lung allograft dysfunction.

BACKGROUND: Due to development of chronic lung allograft dysfunction (CLAD), prognosis for patients undergoing lung transplantation (LTx) is still worse compared to other solid organ transplant recipients. Treatment options for slowing down CLAD progression are scarce with extracorporeal photopheresis (ECP) as an established rescue therapy. The aim of the study was to identify characteristics of responders and non-responders to ECP treatment, assess their survival, lung function development and by that define the subset of patients who should receive early ECP treatment. METHODS: We performed a retrospective study of all LTx patients receiving ECP treatment at the University Hospital Zurich between January 2010 and March 2020. Patients were followed-up for a maximum period of 5 years. Mortality and lung function development were assessed by CLAD stage and by CLAD subtype before initiation of ECP treatment. RESULTS: Overall, 105 patients received at least one ECP following LTx. A total of 57 patients (61.3%) died within the study period with a median survival of 15 months. Mortality was 57% for patients who started ECP at CLAD1, 39% for CLAD2, 93% for CLAD3, and 90% for CLAD4 (p < 0.001). Survival and lung function development was best in young patients at early CLAD stages 1 and 2. Response to ECP treatment was worst in patients with CLAD-RAS/mixed subtype (14.3%) and patients with ECP initiation in CLAD stages 3 (7.1%) and 4 (11.1%). Survival was significantly better in a subset of patients with recurrent acute allograft dysfunction and earlier start of ECP treatment (105 vs 15 months). CONCLUSION: In this retrospective analysis of a large group of CLAD patients treated with ECP after LTx, early initiation of ECP was associated with better long-term survival. Besides a subset of patients suffering of recurrent allograft dysfunction, especially a subset of patients defined as responders showed an improved response rate and survival, suggesting that ECP should be initiated in early CLAD stages and young patients. ECP might therefore prevent long-term disease progression even in patients with CLAD refractory to other treatment options and thus prevent or delay re-transplantation.

Circulating anti-human leukocyte antigen IgM antibodies as a potential early predictor of allograft rejection and a negative clinical outcome after lung transplantation.

PURPOSE: Anti-human leukocyte antigen (HLA) immunoglobulin (Ig) M production stimulated by an alloantigen is sensitive, making IgM a novel potential marker of allorejection after organ transplantation. This study examined the relationship between the serum levels of anti-HLA IgM early after clinical lung transplantation (LTx) and the post-transplant outcomes. METHODS: Thirty-one consecutive patients who underwent deceased LTx were included. Immunoreactivity against HLA was retrospectively analyzed by measuring the anti-HLA IgM levels in the serum sampled for the first 14 days after LTx. The flow panel reactive antibody technique was used. The ratio of the anti-class I IgM level at each day to baseline was obtained, and the peak IgM level was determined for each case. The correlation between the peak IgM level and subsequent development of acute rejection (AR), chronic lung allograft dysfunction (CLAD), and survival outcomes were examined. RESULTS: The peak IgM level was a significant risk factor for AR within 90 days in univariate and multivariate analyses. In the long term, the patients with positive IgM (peak level > 1.8) tended to have a poorer CLAD-free and overall survival than those with negative IgM. CONCLUSION: Elevation of anti-HLA IgM levels early after LTx may be correlated with a higher incidence of rejection and negative clinical outcomes.

Extracorporeal Membrane Oxygenation after Heart Transplantation: Impact of Type of Cannulation.

BACKGROUND: Primary graft dysfunction (PGD) is a common cause of early death after heart transplantation (htx). The use of extracorporeal life support (ECLS) after htx has increased during the last years. It is still discussed controversially whether peripheral cannulation is favorable compared to central cannulation. We aimed to compare both cannulation techniques. METHODS: Ninety patients underwent htx in our department between 2010 and 2017. Twenty-five patients were treated with ECLS due to PGD (10 central extracorporeal membrane oxygenator [cECMO] and 15 peripheral extracorporeal membrane oxygenator [pECMO] cannulation). Pre- and intraoperative parameters were comparable between both groups. RESULTS: Thirty-day mortality was comparable between the ECLS-groups (cECMO: 30%; pECMO: 40%, p = 0.691). Survival at 1 year (n = 18) was 40 and 30.8% for cECMO and pECMO, respectively. The incidence of postoperative renal failure, stroke, limb ischemia, and infection was comparable between both groups. We also did not find significant differences in duration of mechanical ventilation, intensive care unit stay, or in-hospital stay. The incidence of bleeding complications was also similar (cECMO: 60%; pECMO: 67%). Potential differences in support duration in pECMO group (10.4 ± 9.3 vs. 5.7 ± 4.7 days, p = 0.110) did not reach statistical significance. CONCLUSIONS: In patients supported for PGD, peripheral and central cannulation strategies are safe and feasible for prolonged venoarterial ECMO support. There was no increase in bleeding after central implantation. With regard to the potential complications of a pECMO, we think that aortic cannulation with tunneling of the cannula and closure of the chest could be a good option in patients with PGD after htx.

Importance of the preoperative prognostic nutritional index score as a predictor of chronic lung allograft dysfunction after lung transplantation: a Japanese single-institution study.

PURPOSES: Numerous indicators have been discussed as predictive markers for the incidence of chronic allograft dysfunction (CLAD) after lung transplantation (LTX). The aim of this study was to evaluate whether or not the preoperative prognostic nutrition index (PNI) correlated with the development of CLAD. METHOD: This study is a single-center and retrospective cohort study. Forty-six patients underwent cadaveric lung transplantation between 2000 and 2016 at our institution. The primary endpoint of this study was the CLAD-free survival of the patients. RESULT: CLAD was diagnosed in 11 patients (23%) during the follow-up period. Potential risk factors included recipient factors, donor factors, number of HLA mismatches, operation-related factors, and preoperative blood test results, including the preoperative PNI. The patients with a higher PNI showed a longer CLAD-free survival after LTX than those with lower values according to univariate and multivariate analyses (p = 0.01, 0.04, respectively). The 5-year CLAD-free survival rates in the higher-PNI patients and lower-PNI patients were 94% and 62%, respectively. CONCLUSION: We found that a lower preoperative PNI of the recipient was significantly associated with a higher incidence rate of CLAD. The preoperative PNI may, therefore, be useful as a predictor of the development of CLAD.

A case series: the outcomes, support duration, and graft function recovery after VA-ECMO use in primary graft dysfunction after heart transplantation.

Primary graft dysfunction (PGD) is a rare complication associated with high mortality after heart transplantation, which may require veno-arterial extra-corporeal membrane oxygenation (VA-ECMO) support. A standardized definition for PGD was developed by the International Society of Heart and Lung Transplantation in 2014. Due to limited reports using this definition, the detailed outcomes after VA-ECMO support remain unclear. Therefore, we retrospectively analyzed our single-center outcomes of PGD following VA-ECMO support. Between September 2014 and August 2018, 160 patients underwent heart transplantation in our single center. Nine PGD patients required VA-ECMO support, with an incidence of 5.6%. Pre-operative recipient/donor demographics, intra-operative variables, timing of VA-ECMO initiation and support duration, graft function recovery during 30 days after heart transplant, VA-ECMO complications, and survival were analyzed. The indication for VA-ECMO support was biventricular failure for all nine patients. Six patients had severe PGD requiring intra-operative VA-ECMO, while two patients had moderate PGD and one patient had mild PGD requiring post-operative VA-ECMO. All cohorts were successfully decannulated in a median of 10 days. Survival to discharge rate was 88.9%. One-year survival rate was 85.7%. Left ventricular ejection fraction recovered to normal within 30 days in all PGD patients. Our study showed VA-ECMO support led to high survival and timely graft function recovery in all cohorts. Further larger research can clarify the detailed effects of VA-ECMO support which may lead to standardized indication of VA-ECMO support for PGD patients.

Expanding the horizons: Uncontrolled donors after circulatory death for lung transplantation-First comparison with brain death donors.

Uncontrolled donation after cardiac death is an appealing source of organs for lung transplantation. We compare early and long-term outcomes of lung transplantation with these donors with a cohort of transplants from brain death donors at our institution. Retrospective analysis of all lung transplantations was performed from 2002 to 2012. We collected variables regarding recipients, donors, recover and transplant procedures, early and late complications, and survival. We included 292 lung transplants from brain death donors and 38 from uncontrolled donors after cardiac death. Both groups were comparable except for sex mismatch (male recipient-female donor was more frequent in the brain death cohort, 17.8% vs 0%, P 0.002), total ischemic time (longer for donors after cardiac death, 657 minutes for the first lung and 822 minutes for the second vs 309 and 425 minutes, P < 0.001), and ex vivo evaluation (more frequent in cardiac death donors, 21.1% vs 1.4%, P < 0.001). Early and late outcomes were not different (ICU stay [9 vs 10.5 days], hospital stay [33.5 vs 35 days], primary graft dysfunction G3 [24 vs 34.2%], and chronic graft dysfunction HR 1.19 [0.61-2.32]), but overall survival was significantly lower for patients transplanted from cardiac death donors [HR 1.67 (1.06-2.64)]. Lung transplantation after uncontrolled cardiac death offers poorer results in terms of survival compared to brain death donation. Refinement of current strategies for graft preservation and evaluation is essential to improve outcomes with this source of grafts.

Does donor-recipient age difference matter in outcome of heart transplantation?

OBJECTIVE: Potential interactions between donor-recipient age difference and outcomes after heart transplantation are not well known. We thus aimed to study the impact of donor-recipient age difference on heart transplantation outcomes. METHODS: Between 1995 and 2017, we assessed 234 heart transplantation patients. Based on donor-recipient age difference histogram, we stratified these patients into three groups: older donors (donor-recipient difference > 0; n = 48), younger donors (donor-recipient difference 0 to -20 years; n = 82), and much younger donors (donor-recipient difference <-20 years; n = 104). RESULTS: The baseline metabolic risk profile of the recipients was significantly higher for the much younger donor group compared with the younger and older groups, including hypertension (52% vs 33% vs 25%, P = 0.002), dyslipidemia (51% vs 51% vs 29%, P = 0.027), diabetes (30% vs 16% vs 17%, P = 0.044), and smoking history (53% vs 46% vs 29%, P = 0.024), respectively. There were no significant differences between the groups in long-term survival, cardiac allograft vasculopathy, or rejection-free survival in unadjusted and adjusted analyses. In the much younger donor group, gender matching was associated with a lower incidence of primary graft dysfunction (37% vs 58% P = 0.05). CONCLUSIONS: Donor-recipient age difference does not significantly impact long-term heart transplantation outcomes.

The association of post-lung transplant acute kidney injury with mortality is independent of primary graft dysfunction: A cohort study.

BACKGROUND: Prior studies of post-lung transplant acute kidney injury (AKI) have not accounted for confounding effects of primary graft dysfunction (PGD). We sought to test the impact of PGD on AKI risk factors and on the association of AKI with mortality. METHODS: We included patients transplanted at the University of Pennsylvania from 2005-12, defined AKI using consensus criteria during transplant hospitalization, and defined PGD as grade 3 at 48-72 hours. We used multivariable logistic regression to test the impact of PGD on AKI risk factors and Cox models to test association of AKI with one-year mortality adjusting for PGD and other confounders. RESULTS: Of 299 patients, 188 (62.9%) developed AKI with 142 (75%) cases occurring by postoperative day 4. In multivariable models, PGD was strongly associated with AKI (OR 3.76, 95% CI 1.72-8.19, P = .001) but minimally changed associations of other risk factors with AKI. Both AKI (HR 3.64, 95% CI 1.68-7.88, P = .001) and PGD (HR 2.55, 95% CI 1.40-4.64, P = .002) were independently associated with one-year mortality. CONCLUSIONS: Post-lung transplant AKI risk factors and association of AKI with mortality were independent of PGD. AKI may therefore be a target for improving lung transplant mortality rather than simply an epiphenomenon of PGD.

Moderate-severe primary graft dysfunction after pediatric heart transplantation.

BACKGROUND: PGD is a complication after heart transplantation (OHT) and a significant cause of mortality, particularly in infant recipients. Lack of standardized definition of PGD in the pediatric population makes the prevalence and magnitude of impact unclear. METHODS: ISHLT PGD consensus guidelines, which include inotrope scores and need for MCS, were applied retrospectively to 208 pediatric OHT recipients from a single institution from 1/2005-5/2016. PGD was defined as: moderate PGD-inotrope score >10 on postoperative day 1 (24-48 hours), and severe PGD-MCS within 24 hours (in the absence of detectable rejection). RESULTS: PGD occurred in 34 patients (16.3%); 14 of which had severe PGD (6.7%). Multivariate risk factors for PGD included CPB time (OR 10.3/10 min, 95% 10.05, 10.2, P = 0.03), Fontan palliation (OR 1.9, 95% 1.2, 3.97), and PCM (OR 5.65, 95% 1.52, 22.4); but not age, weight, ischemic time, or donor characteristics. Upon sub-analysis excluding patients with PCM, increased CPB was a significant multivariate risk factor (OR 10.09, 95% 9.89, 10.12, P = 0.003). Patients with PGD had decreased discharge survival compared to those without PGD (85% vs 96%, P < 0.01). Severe PGD was associated with the poorest 1-year survival (57% vs 91% without PGD, P = 0.04). CONCLUSION: Patients with prolonged CPB are potentially at risk for developing PGD. Neither infant recipients nor donor characteristics were associated with an increased risk of PGD in the current era.

Quantitative Evidence for Revising the Definition of Primary Graft Dysfunction after Lung Transplant.

RATIONALE: Primary graft dysfunction (PGD) is a form of acute lung injury that occurs after lung transplantation. The definition of PGD was standardized in 2005. Since that time, clinical practice has evolved, and this definition is increasingly used as a primary endpoint for clinical trials; therefore, validation is warranted. OBJECTIVES: We sought to determine whether refinements to the 2005 consensus definition could further improve construct validity. METHODS: Data from the Lung Transplant Outcomes Group multicenter cohort were used to compare variations on the PGD definition, including alternate oxygenation thresholds, inclusion of additional severity groups, and effects of procedure type and mechanical ventilation. Convergent and divergent validity were compared for mortality prediction and concurrent lung injury biomarker discrimination. MEASUREMENTS AND MAIN RESULTS: A total of 1,179 subjects from 10 centers were enrolled from 2007 to 2012. Median length of follow-up was 4 years (interquartile range = 2.4-5.9). No mortality differences were noted between no PGD (grade 0) and mild PGD (grade 1). Significantly better mortality discrimination was evident for all definitions using later time points (48, 72, or 48-72 hours; P < 0.001). Biomarker divergent discrimination was superior when collapsing grades 0 and 1. Additional severity grades, use of mechanical ventilation, and transplant procedure type had minimal or no effect on mortality or biomarker discrimination. CONCLUSIONS: The PGD consensus definition can be simplified by combining lower PGD grades. Construct validity of grading was present regardless of transplant procedure type or use of mechanical ventilation. Additional severity categories had minimal impact on mortality or biomarker discrimination.

Primary graft dysfunction after heart transplantation: Outcomes and resource utilization.

BACKGROUND: A unified definition of primary graft dysfunction (PGD) after heart transplantation was adopted in 2014, with moderate and severe PGD defined as a need for mechanical circulatory support. While risk factors for PGD are well identified, outcomes and resource utilization have not been well-studied. We examined the resource utilization and associated costs with PGD. METHODS: All adult heart transplantations (2001-2016) from a statewide Society of Thoracic Surgery database were analyzed by dividing them into two groups-with PGD (requiring mechanical circulatory support) and without PGD. RESULTS: Of the 718 heart transplants, 110 (15.3%) patients developed PGD. Prevalence of PGD for the study duration ranged from 3.7% to 22.7% with no significant trend. The most frequently used mechanical circulatory support device was intra-aortic balloon pump (88%), followed by extracorporeal membrane oxygenation (17%), and catheter-based circulatory support devices (3%). There were no significant differences in demographics or preoperative variables between the two groups. Resource utilization such as total intensive care unit hours, ventilation hours, reoperation for bleeding, blood product transfusions, and length of stay were significantly higher in the PGD group. Postoperative complications were also higher in PGD group including operative mortality (31.8% vs 3.8%, P < .0001). The median cost of heart transplantation was significantly higher in the PGD group $229 482 ($126 044-$388 889) vs $101 788 ($72 638-$181 180) P < .0001. CONCLUSION: Primary graft dysfunction following heart transplantation developed in 15% of patients. Patients with PGD had significantly higher complications, resource utilization, and mortality. Preventive measures to address the development of PGD would reduce resource utilization and improve outcomes.

Impact of chronic lung allograft dysfunction, especially restrictive allograft syndrome, on the survival after living-donor lobar lung transplantation compared with cadaveric lung transplantation in adults: a single-center experience.

PURPOSE: The differences in chronic lung allograft dysfunction (CLAD) between living-donor lobar lung transplantation (LDLLT) and cadaveric lung transplantation (CLT) remain unclear. We conducted this study to compare the impact of CLAD on the outcomes after LDLLT vs. CLT. METHODS: We conducted a retrospective review of the data of 97 recipients of bilateral lung transplantation, including 51 recipients of LDLLT and 46 recipients of CLT. RESULTS: The CLAD-free survival and overall survival after LDLLT were similar to those after CLT. CLAD and restrictive allograft syndrome (RAS), but not bronchiolitis obliterans syndrome (BOS), developed significantly later after LDLLT than after CLT (p = 0.015 and p = 0.035). Consequently, patients with CLAD and RAS, but not those with BOS, after LDLLT had a significantly better overall survival than those after CLT (p = 0.037 and p = 0.0006). Furthermore, after the diagnosis of CLAD, the survival of patients with RAS after LDLLT tended to be better than that after CLT (p = 0.083). CONCLUSION: CLAD, especially RAS, appears to develop later after LDLLT than after CLT and seems to have a lower impact on the overall survival after LDLLT than that after CLT.

Aquaporin 4 blockade improves survival of murine heart allografts subjected to prolonged cold ischemia.

Prolonged cold ischemia storage (CIS) is a leading risk factor for poor transplant outcome. Existing strategies strive to minimize ischemia-reperfusion injury in transplanted organs, yet there is a need for novel approaches to improve outcomes of marginal allografts and expand the pool of donor organs suitable for transplantation. Aquaporins (AQPs) are a family of water channels that facilitate homeostasis, tissue injury, and inflammation. We tested whether inhibition of AQP4 improves the survival of fully MHC-mismatched murine cardiac allografts subjected to 8 hours of CIS. Administration of a small molecule AQP4 inhibitor during donor heart collection and storage and for a short-time posttransplantation improves the viability of donor graft cells, diminishes donor-reactive T cell responses, and extends allograft survival in the absence of other immunosuppression. Furthermore, AQP4 inhibition is synergistic with cytotoxic T lymphocyte-associated antigen 4-Ig in prolonging survival of 8-hour CIS heart allografts. AQP4 blockade markedly reduced T cell proliferation and cytokine production in vitro, suggesting that the improved graft survival is at least in part mediated through direct effects on donor-reactive T cells. These results identify AQPs as a promising target for diminishing donor-specific alloreactivity and improving the survival of high-risk organ transplants.

Donor liver apoptosis is associated with early allograft dysfunction and decreased short-term graft survival after liver transplantation.

BACKGROUND: The clinical significance of apoptosis in assessing the quality of donor liver grafts remains unknown. AIMS: This study aimed to determine whether apoptosis in a donor liver is predictive of early allograft dysfunction (EAD) and graft survival after liver transplantation (LT). METHODS: Donor liver specimens were analyzed for apoptosis using TUNEL assays. The prognostic factors for EAD were identified through logistic regression analyses, and a nomogram was developed. RESULTS: The apoptosis index of donor livers in EAD patients was significantly higher than that of donors livers in non-EAD patients (median 5.3; interquartile range [IQR] 3.4 vs 3.5; 3.6, P < 0.001). Multivariate analyses identified the apoptosis index of the donor liver (HR = 6.927, P < 0.001) and five other characteristics as independent predictors of EAD. A nomogram built on these predictive variables showed good calibration and discriminatory abilities, with a c-index value of 0.847. The 30-day graft survival rates in the high apoptosis index (apoptosis index >4.4%) group were significantly lower than those in the low apoptosis index (apoptosis index ≤4.4%) group (84.4% vs 97.6%, P = 0.004). CONCLUSIONS: Donor liver apoptosis plays a significant role in predicting EAD after LT. Furthermore, a high apoptosis index in the donor liver was associated with inferior graft survival in the short-term.

Quantitative chest CT for subtyping chronic lung allograft dysfunction and its association with survival.

Chronic lung allograft dysfunction (CLAD) is a major cause of mortality in lung transplant recipients. CLAD can be sub-divided into at least 2 subtypes with distinct mortality risk characteristics: restrictive allograft syndrome (RAS), which demonstrates increased overall computed tomography (CT) lung density in contrast with bronchiolitis obliterans syndrome (BOS), which demonstrates reduced overall CT lung density. This study aimed to evaluate a reader-independent quantitative density metric (QDM) derived from CT histograms to associate with CLAD survival. A retrospective study evaluated CT scans corresponding to CLAD onset using pulmonary function tests in 74 patients (23 RAS, 51 BOS). Two different QDM values (QDM1 and QDM2) were calculated using CT lung density histograms. Calculation of QDM1 includes the extreme edges of the histogram. Calculation of QDM2 includes the central region of the histogram. Kaplan-Meier analysis and Cox regression analysis were used for CLAD prognosis. Higher QDM values were significantly associated with decreased survival. The hazard ratio for death was 3.2 times higher at the 75th percentile compared to the 25th percentile using QDM1 in a univariate model. QDM may associate with CLAD patient prognosis.

Primary Graft Dysfunction (PGD) Following Lung Transplantation.

Primary graft dysfunction (PGD) is a form of acute lung injury that results from ischemia reperfusion injury (IRI) and is the major cause of early posttransplant morbidity and mortality. Patients who survive PGD have decreased quality of life, an increased risk of chronic lung allograft dysfunction, specifically bronchiolitis obliterans syndrome, and a significantly increased risk of death. In 2017, the International Society for Heart and Lung Transplantation released updated consensus statements on the PGD definition, most up-to-date PGD risk factors, mechanisms of PGD development, and the state-of-the-art for PGD therapeutics. Risk factor identification has led to the development of PGD predictive algorithms, although their clinical utility remains limited. Ongoing areas of controversy and discussion include further refinements to the PGD grading scheme to account for technologic advances such as extracorporeal membrane oxygenation and the increased utilization of high flow nasal cannula, the use of PGD as an outcome measure in clinical trials of ex vivo lung perfusion, enhancement of predictive algorithms incorporating biochemical risk factors, and the need for development of therapies targeted at improving PGD outcomes.

Lung volumes predict survival in patients with chronic lung allograft dysfunction.

Identification of disease phenotypes might improve the understanding of patients with chronic lung allograft dysfunction (CLAD). The aim of the study was to assess the impact of pulmonary restriction and air trapping by lung volume measurements at the onset of CLAD.A total of 396 bilateral lung transplant recipients were analysed. At onset, CLAD was further categorised based on plethysmography. A restrictive CLAD (R-CLAD) was defined as a loss of total lung capacity from baseline. CLAD with air trapping (AT-CLAD) was defined as an increased ratio of residual volume to total lung capacity. Outcome was survival after CLAD onset. Patients with insufficient clinical information were excluded (n=95).Of 301 lung transplant recipients, 94 (31.2%) developed CLAD. Patients with R-CLAD (n=20) and AT-CLAD (n=21), respectively, had a significantly worse survival (p<0.001) than patients with non-R/AT-CLAD. Both R-CLAD and AT-CLAD were associated with increased mortality when controlling for multiple confounding variables (hazard ratio (HR) 3.57, 95% CI 1.39-9.18; p=0.008; and HR 2.65, 95% CI 1.05-6.68; p=0.039). Furthermore, measurement of lung volumes was useful to identify patients with combined phenotypes.Measurement of lung volumes in the long-term follow-up of lung transplant recipients allows the identification of patients who are at risk for worse outcome and warrant special consideration.

Role of the postoperative cholesterol in early allograft dysfunction and survival after living donor liver transplantation.

BACKGROUND: Many studies have confirmed that serum total cholesterol (sTC) concentrations were associated with underlying liver damage and the synthesis capacity of liver. However, the role of postoperative sTC level on evaluating graft function and predicting survival of recipients who underwent liver transplantation has not been discussed. METHODS: Clinical data of 231 living donor liver transplantation recipients from May 2003 to January 2015 were retrospectively collected. Patients were stratified into the low sTC group (sTC <1.42 mmol/L, 57 recipients) and high sTC group (sTC =1.42 mmol/L, 174 recipients) according the sTC level on postoperative day 3 based on receiver-operating characteristic curve analysis. The clinical characteristics and postoperative short- and long-term outcomes were compared between the two groups. RESULTS: Recipients with sTC <1.42 mmol/L experienced more severe preoperative disease conditions, a higher incidence of postoperative early allograft dysfunction (38.6% vs 10.3%, P<0.001), 90-day mortality (28.1% vs 10.9%, P=0.002) and severe complications (29.8% vs 17.2%, P=0.041) compared to recipients with sTC =1.42 mmol/L. The multivariate analysis demonstrated that sTC <1.42 mmol/L had a 4.08-fold (95% CI: 1.83-9.11, P=0.001) and 2.72-fold (95% CI: 1.23-6.00, P=0.013) greater risk of developing allograft dysfunction and 90-day mortality, and patients with sTC <1.42 mmol/L had poorer overall recipient and graft survival rates at 1-, 3-, and 5-year than those with sTC =1.42 mmol/L (67%, 61% and 61% vs 83%, 71% and 69%, P=0.025; 65%, 59% and 59% vs 81%, 68% and 66%, P=0.026, respectively). Cox multivariate analysis showed that sTC <1.42 mmol/L was an independent predicting factor for total recipient survival (HR=2.043; 95% CI: 1.173-3.560; P=0.012) and graft survival (HR=1.905; 95% CI: 1.115-3.255; P=0.018). CONCLUSIONS: sTC <1.42 mmol/L on postoperative day 3 was an independent risk factor of postoperative early allograft dysfunction, 90-day mortality, recipient and graft survival, which can be used as a marker for predicting postoperative short- and long-term outcomes.

Primary Graft Dysfunction and Mortality Following Lung Transplantation: A Role for Proadrenomedullin Plasma Levels.

Primary graft dysfunction (PGD) after lung transplantation (LT) is a heterogeneous syndrome that comprises clinical presentations with diverse grades of severity. Proadrenomedullin (proADM) levels may be associated with PGD and may enhance its relationship with outcomes. We prospectively included 100 LT recipients. Plasma levels of proADM were measured at 24, 48 and 72 h after admission to the intensive care unit (ICU). We assessed their relationship with PGD grade and ICU mortality. Fifty patients (50%) presented grade 3 PGD at ICU admission. Twenty-two patients (22%) developed grade 3 PGD at 72 h, the only grade associated with higher mortality (odds ratio 6.84, 95% confidence interval [CI] 1.47-38.44). ProADM levels measured at 24 h (3.25 vs. 1.61 nmol/L; p = 0.016) and 72 h (2.17 vs. 1.35 nmol/L; p = 0.011) were higher in these patients than the rest of the population. When we added the individual predictive utility of grade 3 PGD at 72 h for ICU mortality (area under the curve [AUC] 0.72, 95% CI 0.53-0.90) to that of ProADM at 72 h, the predictive value of the model improved (AUC 0.81, 95% CI 0.65-0.97). Higher levels of proADM measured following LT are associated with grade 3 PGD at 72 h. ProADM enhances the association of this entity with mortality.

Early allograft dysfunction after liver transplantation: an intermediate outcome measure for targeted improvements.

BACKGROUND: The term early allograft dysfunction (EAD) identifies liver transplant (LT) allografts with initial poor function and portends poor allograft and patient survival. Aims of this study are to use EAD as an intermediate outcome measure in a large single center cohort and identify donor, recipient and peri-operative risk factors. MATERIAL AND METHODS: In 1950 consecutive primary LT, donor, recipient and peri-operative data were collected. EAD was defined by the presence of one or more of the following: total bilirubin ≥ 10 mg/dL (171 µmol/L) or, INR ≥ 1.6 on day 7, and ALT/AST > 2,000 IU/L within the first 7 days. RESULTS: The incidence of EAD was 26.5%. 1-, 3-, and 5-year allograft and patient survival for patients who developed EAD were significantly inferior to those who did not (P < 0.01 at all time points). Multivariate analysis demonstrated associations in the development of EAD with recipient pre-operative ventilator status, donation after cardiac death allografts, donor age, allograft size, degree of steatosis, operative time and intra-operative transfusion requirements (all P < 0.01). Patients with EAD had a significantly longer hospitalization at 20.9 ± 38.9 days (median: 9; range: 4-446) compared with 10.7 ± 13.5 days (median: 7; range: 3-231) in patients with no EAD (P < 0.01). CONCLUSIONS: This is the largest single center experience demonstrating incidence of EAD and identifying factors associated with development of EAD. EAD is a useful intermediate outcome measure for allograft and patient survival. Balancing recipient pretransplant conditions, donor risk factors and intra-operative conditions are necessary for avoiding EAD.