PGD Grade Research Articles

Frequency of Unplanned Readmissions Following Lung Transplantation During the SAR-COV-2 Pandemic When Hospital Resources Were Strained

Despite the concerted efforts by lung transplant recipients (LTR) and their medical teams, hospital readmissions are common in the first year following transplantation. Reasons for unplanned readmissions include allograft rejection, infections, and respiratory failure before the SARS-COV-2 pandemic. Clinical predictors of readmissions have changed over time with the higher risk factors of acceptable criteria for recipients and donors. We aimed to assess more recent readmission rates based on group classifications to better understand specific groups that are at risk for various readmissions during the SARS-COV-2 pandemic when hospital resources were strained. A retrospective analysis for LTR at UCSD was performed from 1/1/2018 to 6/30/2022. We recorded the baseline demographics; LAS at the time of lung transplant; mechanical ventilation prior to lung transplant; the need for VV-or VA-ECMO prior to or after lung transplantation; categories for UNOS listing (groups A, B, C, D); PGD grade 3 based on the ISHLT definition; and acquisition of serious donor-derived infections. We recorded the primary reason for all the readmissions and the duration of admission. Descriptive statistics were used for the analysis of this 4.5-year patient cohort. 149 LT were performed. 29 were single LTR while 120 were bilateral LTR. Median age of 57 years, 63 patients (42%) were female. Indications for transplantation included 28 (19%) group A, 19 (13%) group B, 12 (8%) group C, and 90 (60%) group D. The median length of follow-up following lung transplant was 1.7 years. Collectively, there were 73 patients (49%) that required readmissions. On average, there are 2.5 readmissions per patient for our cohort. Most common reasons for unplanned readmission included infections, transplant-related (transplant rejection, other complications of transplant, etc.), and GI Related. This was primarily seen in the group D cohort. The median hospital LOS at readmission was 3.8 days (4 hours to 34.6 days). Despite infection being the leading cause of readmission, only 11 cases were related to COVID-19 infection. No death occurred with a readmission. Groups B and D appear to be at a higher risk for readmission, irrespective of the pre-LT LAS and need for mech vent or VV-ECMO.

Long-Term Survival Following Primary Graft Dysfunction Development in Lung Transplantation

IntroductionPrimary graft dysfunction (PGD) is a known risk factor for early mortality following lung transplant (LT). However, the outcomes of patients who achieve long-term survival following index hospitalization are unknown. We aimed to determine the long-term association of PGD grade 3 (PGD3) in patients without in-hospital mortality. MethodsLT recipients were identified from the United Network for Organ Sharing Database. Patients were stratified based on the grade of PGD at 72 h (No PGD, Grade 1/2 or Grade 3). Groups were assessed with comparative statistics. Long-term survival was evaluated using Kaplan–Meier methods and a multivariable shared frailty model including recipient, donor, and transplant characteristics. ResultsThe PGD3 group had significantly increased length of stay, dialysis, and treated rejection post-transplant (P < 0.001). Unadjusted survival analysis revealed a significant difference in long-term survival (P < 0.001) between groups; however, following adjustment, PGD3 was not independently associated with long-term survival (hazard ratio: 0.972; 95% confidence interval: 0.862-1.096). Increased mortality was significantly associated with increased recipient age and treated rejection. Decreased mortality was significantly associated with no donor diabetes, bilateral LT as compared to single LT, transplant in 2015-2016 and 2017-2018, and no post-transplant dialysis. ConclusionsWhile PGD3 remains a challenge post LT, PGD3 at 72 h is not independently associated with decreased long-term survival, while complications such as dialysis and rejection are, in patients who survive index hospitalization. Transplant providers should be aggressive in preventing further complications in recipients with severe PGD to minimize the negative association on long-term survival.

Oversizing lung allografts deteriorates outcomes in patients with pulmonary fibrosis

BackgroundLung transplantation is the only curative treatment for patients with end-stage pulmonary fibrosis. Due to the shortage of donor organs most lung allografts are either oversized or undersized. It is still under debate whether over- or undersizing is preferably performed regarding the postoperative outcome. We therefore analysed our data using predicted total lung capacity to compare size-mismatches. MethodsPatient records were retrospectively reviewed. Three groups were formed, one including patients with a donor-recipients pTLC-ratio (DRPR) of <1.0 (undersized group), the second with a DRPR of ≥1.0 and <1.1 (size matched group) and the third group with a DRPR of ≥1.1 (oversized group). Outcomes were evaluated using Chi-Square test and Kruskall-Wallis test as well as Kaplan-Meier analysis, competing risk analysis and multivariable analysis, respectively. ResultsBetween January 2010 and May 2023, among the 1501 patients transplanted at our institution, 422 (28%) patients were included, 26 (2%) patients forming the oversized group (median DRPR: 1.14), 101 (7%) patients forming the size matched group (median DRPR: 1.03) and 296 (20%) patients forming the undersized group (median DRPR: 0.92). Patients from the oversized group had a higher PGD grade 3 rate at 24 (p<0.001), 48 (p<0.001) and 72 (p=0.039) hours after transplantation as well as a higher in-hospital mortality compared to the undersized group (p=0.033). The long-term survival was also better in the undersized group compared to the oversized group (p=0.011) and to the size matched group (p=0.01). ConclusionOversizing lung allografts more than 10% deteriorated early postoperative outcomes and long-term survival in patients with pulmonary fibrosis.

Intraoperative Extracorporeal Support during Lung Transplantation: Not Just for the High-Risk Patient.

The use of intraoperative mechanical support during lung transplantation has traditionally been a controversial topic. Trends for intraoperative mechanical support strategies swing like a pendulum. Historically, cardiopulmonary bypass (CPB) was the modality of choice during transplantation. It provides full hemodynamic support including oxygenation and decarboxylation. Surgical exposure is improved by permitting the drainage of the heart and provides more permissive retraction. CPBs contain drainage reservoirs with hand-held pump suction catheters promoting blood conservation through collection and re-circulation. But CPB has its disadvantages. It is known to cause systemic inflammation and coagulopathy. CPB requires high doses of heparinization, which increases bleeding risks. As transplantation progressed, off-pump transplantation began to trend as a preferable option. ECMO, however, has many of the benefits of CPB with less of the risk. Outcomes were improved with ECMO compared to CPB. CPB has a higher blood transfusion requirement, a higher need for post-operative ECMO support, a higher re-intubation rate, high rates of kidney injury and need for hemodialysis, longer ICU stays, higher incidences of PGD grade 3, as well as overall in-hospital mortality when compared with ECMO use. The focus now shifts to using intraoperative mechanical support to protect the graft, helping to reduce ischemia-reperfusion injury and allowing for lung protective ventilator settings. Studies show that the routine use of ECMO during transplantation decreases the rate of primary graft dysfunction and many adverse outcomes including ventilator time, need for tracheostomy, renal failure, post-operative ECMO requirements, and others. As intraoperative planned ECMO is considered a safe and effective approach, with improved survival and better overall outcomes compared to both unplanned ECMO implementation and off-pump transplantation, its routine use should be taken into consideration as standard protocol.

Effect of targeted coagulopathy management and 5% albumin as volume replacement therapy during lung transplantation on allograft function: a secondary analysis of a randomized clinical trial

BackgroundPrimary graft dysfunction (PGD) after lung transplantation (LuTx) contributes substantially to early postoperative morbidity. Both intraoperative transfusion of a large amount of blood products during the surgery and ischemia–reperfusion injury after allograft implantation play an important role in subsequent PGD development.MethodsWe have previously reported a randomized clinical trial of 67 patients where point of care (POC) targeted coagulopathy management and intraoperative administration of 5% albumin led to significant reduction of blood loss and blood product consumption during the lung transplantation surgery. A secondary analysis of the randomized clinical trial evaluating the effect of targeted coagulopathy management and intraoperative administration of 5% albumin on early lung allograft function after LuTx and 1-year survival was performed.ResultsCompared to the patients in the control (non-POC) group, those in study (POC) group showed significantly superior graft function, represented by the Horowitz index (at 72 h after transplantation 402.87 vs 308.03 with p < 0.001, difference between means: 94.84, 95% CI: 60.18–129.51). Furthermore, the maximum doses of norepinephrine administered during first 24 h were significantly lower in the POC group (0.193 vs 0.379 with p < 0.001, difference between the means: 0.186, 95% CI: 0.105–0.267). After dichotomization of PGD (0–1 vs 2–3), significant difference between the non-POC and POC group occurred only at time point 72, when PGD grade 2–3 developed in 25% (n = 9) and 3.2% (n = 1), respectively (p = 0.003). The difference in 1-year survival was not statistically significant (10 patients died in non-POC group vs. 4 patients died in POC group; p = 0.17).ConclusionsUtilization of a POC targeted coagulopathy management combined with Albumin 5% as primary resuscitative fluid may improve early lung allograft function, provide better circulatory stability during the early post-operative period, and have potential to decrease the incidence of PGD without negative effect on 1-year survival.Trial registrationThis clinical trial was registered at ClinicalTrials.gov (NCT03598907).

Evaluation of Pre-Transplant Antifibrotic Agents on Post-Transplant Outcomes

<h3>Purpose</h3> Antifibrotic therapy, i.e. pirfenidone or nintedanib, is commonly used for idiopathic pulmonary fibrosis (IPF) patients awaiting lung transplantation. However, they are inferred to cause increased wound healing complications post-transplant. This study compares post-transplant outcomes in IPF patients on the basis of pre-transplant antifibrotic treatment. <h3>Methods</h3> IPF patients transplanted after January 2015 were included in a cohort study with three groups: no antifibrotic, pirfenidone, and nintedanib. Pre-specified outcomes of interest included: PGD grades immediately after transplant (T0) and on post-operative day 3 (T72), duration of mechanical ventilation, wound dehiscence, anastomosis complications, time to CLAD development, and overall survival. <h3>Results</h3> Of the 85 eligible patients, 26 received no pre-transplant antifibrotic medication, 31 received pirfenidone, and 28 received nintedanib. Fewer female patients received antifibrotic therapy, but the groups were otherwise similar with regards demographics and clinical variables (Table). There were no differences between groups in PGD status at T0 or T72, but patients who received antifibrotics pre-transplant were more likely resolve PGD between T0 and T72 than patients who did not (mean change in PGD grade: nintedanib -0.3±0.9 vs. pirfenidone -0.5±1.3 vs. no antifibrotic +0.3±1.5, p=0.026). There was a trend toward decreased time on mechanical ventilation in the patients receiving antifibrotic treatment (no-antifibrotic vs. any antifibrotic medication p=0.025, between all group p=0.07). Anastomosis stenosis was less common in the antifibrotic groups (p=0.020). No differences were observed for wound dehiscence, incidence of CLAD, or mortality. <h3>Conclusion</h3> Receiving any pre-transplant antifibrotic therapy is associated with increased resolution of PGD, shorter duration of mechanical ventilation, and decreased incidence of anastomosis stenosis.

Small Anastomotic Dehiscence Identified Late After Lung Transplant

<h3>Introduction</h3> Anastomotic airway complications, such as necrosis with dehiscence of the anastomotic site, may cause morbidity after lung transplant (LT). In rare cases, sloughing and necrosis of the anastomotic site can mask partial, asymptomatic dehiscence. <h3>Case Report</h3> We present the case of a masked, partial anastomotic dehiscence in a 71-year-old man after bilateral LT (06/2021) for COPD. His postoperative course was complicated by PGD grade 1 and positive crossmatch with the donor, requiring plasma exchange and IVIG. During the transplant stay, he also required frequent bronchoscopies given thick secretions in the bilateral anastomotic sites. We initiated inhaled antibiotics with tobramycin and amphotericin; donor cultures were positive for MRSA, for which the recipient was also adequately covered. Chest CT showed small, bilateral pneumothoraces, more pronounced on the right (<b>Figure 1A</b>), but no evidence of dehiscence (<b>Figure 1B</b>). At 2 weeks posttransplant, secretions were slowing, but a fifth bronchoscopy showed continued sloughing (<b>Figure 1C</b>) with need for forceps to remove the necrotic debris. He was ultimately discharged in stable condition, without bronchoscopic findings of dehiscence. Two months later, surveillance bronchoscopy showed resolution of sloughing. However, a small hole near the anastomotic site was seen, suspicious for partial dehiscence. Because there was no evidence of allograft dysfunction or pneumothorax, we lowered his steroid dose and monitored healing with frequent bronchoscopies. Alongside aggressive antibiotic therapy and airway clearance, a repeat bronchoscopy performed 10 days later showed pseudomembrane formation and healed dehiscence (<b>Figure 1D</b>). Fortunately, the patient had no issues with initial chest tube removal after transplant. <h3>Summary</h3> Partial, asymptomatic anastomotic dehiscence can be masked in the immediate posttransplant period. Careful inspection of the bilateral anastomosis with repeat bronchoscopies may be necessary to rule out dehiscence with certainty.

Characteristics and Outcomes of Lung Transplants Performed with Ex-Vivo Lung Perfusion

<h3>Purpose</h3> Ex-vivo lung perfusion (EVLP) can be used to assess and rehabilitate donor lungs to expand the donor pool. However, the frequency of EVLP utilization and its outcomes are not well-studied. The goal of this study was to describe the characteristics and outcomes of lungs transplants performed with EVLP in the US. <h3>Methods</h3> We conducted retrospective review of the UNOS registry of all primary adult lung transplant recipients from Feb 28, 2018 to June 30, 2021, excluding recipients with prior transplants, multiorgan transplants, and those waitlisted for other organs. Lung transplants were dichotomized as those that were performed with EVLP versus no EVLP. Baseline characteristics and short-term outcomes were compared. One-year survival was assessed by the Kaplan Meier method and multivariable Cox proportional hazards regression. <h3>Results</h3> Of 8,204 lung transplants performed during our study period, 426(5.2%) were performed with EVLP. Perfusion was performed by the OPO in 29(7%), transplant center in 291(68%), and external perfusion center in 106(25%) of cases. EVLP donors were older (39±13 vs 36±14 yrs, p<0.01), more likely DCD (31% vs 5%, p<0.01), and had lower P:F ratio(415±124 vs 442±130, p<0.01). Recipients had lower LAS scores[39(35-53) vs 41 (35-57), p<0.01)]. EVLP lungs traveled further[232(122-489) vs 169 (71-270) nautical miles, p<0.01], had longer ischemic times(11.5±4.1 vs 5.5±1.6 hrs, p<0.01), and were more likely double lung transplants(85% vs 76%, p<0.01). At 72 hours, recipients of EVLP lungs were more likely to remain intubated(47% vs 30%, p<0.01), be on ECMO(16% vs 8%, p<0.01), and experience PGD grade III (24% vs 17%, p<0.01). They also had higher total length of stay[21(13-39) vs 18(13-30) days, p<0.01). EVLP was associated with worse one-year survival on univariable(84% vs 88%, HR 1.41, 95% CI 1.07-1.85, p=0.02) but not multivariable analysis(aHR 1.18, 95% CI 0.88-1.59, p=0.26), particularly after adjusting for DCD donation(aHR 1.46, 95% CI 1.11-1.91) <h3>Conclusion</h3> EVLP technology is used in a minority of donor lungs in the United States. A majority of the EVLP procedures are performed by the transplant centers with a higher proportion of DCD donors. The short-term outcomes and one-year survival of recipients of EVLP lungs appear worse than those not managed with EVLP. The role of this technology in the broad filed of lung transplantation remains to be defined.

Outcomes After Transplantation of Lungs Subjected to Prolonged Cold Ischaemic Time Following Ex-Vivo Lung Perfusion

<h3>Purpose</h3> Ex vivo lung perfusion (EVLP) rewarms donor lungs to normothermia following a period of cold static preservation (CIT1) and returns the lungs to a state of cold static preservation following EVLP (CIT2). We hypothesize that EVLP interrupts cold ischemic injury and allows for safe additional cold ischemic time after EVLP. <h3>Methods</h3> We performed a retrospective review of data from the Toronto Lung Transplant Program Database. Adult patients who underwent bilateral lung transplant following EVLP assessment between January 2008 and December 2020 were included. CIT1, EVLP, and CIT2 times were collected and outcomes including PGD grade 3 at 72 hours and 30-day and 12-month mortality were assessed. <h3>Results</h3> A total of 1186 bilateral lung transplants were performed over the study period of which 315 were performed following EVLP assessment. Mean[SD] CIT1 of the lungs was 4.7h[1.6]. Mean[SD] EVLP time was 4.5h[1.5]. The first lung had a mean[SD] CIT2 of 3.8h[2.1] and the second had a mean[SD] CIT2 of 6.0h[2.2]. Survival was similar when comparing CIT2<6 hours versus CIT2>6 hours of the second lung (p=0.53) (Figure). PGD3 rate was also similar between those groups (18.1% vs 17.2%, p=1). <h3>Conclusion</h3> Prolonged (>6h) ischemic time following EVLP assessment (CIT2) did not affect short- and long-term mortality in our patients. Therefore we feel that using a period of CIT after EVLP assessment is acceptable, and it provides us flexibility in terms of logistics, widening geographical reach of our program, and allows us to make lung transplantation a semi-elective procedure.

Impact of Cold Ischemic Time on Morbidity and Mortality after Lung Transplantation. An Updated Analysis of the International Multicenter Extracorporeal Life Support in Lung Transplantation Registry

Purpose Cold ischemic time (CIT) may adversely affect clinical outcomes after lung transplantation (LTx). Most centers restrict CIT to less than 6-8 hours. However, to improve donor utilization, centers are increasingly pushing the envelope of CIT. To clarify the effect of CIT on graft function and clinical outcomes, we analyzed the international multicenter ECLS in LTx registry. Methods the ECLS registry collects LTx data from 6 US and 2 European centers between January 2016 and March 2020. Single LTx, ex vivo lung perfusion, and multiple organ transplants were excluded. CIT was analyzed as a continuous variable and divided in balanced tertiles. The reperfusion of the second lung was considered the end of the CIT. Models were adjusted by 11 clinical factors. Our endpoints were PGD at T0, T24, T48 and T72 hours according to the 2016 ISHLT consensus. Length of stay, death within 90 days and at one year of follow-up was investigated. A univariate and multivariate analysis was performed. Pearson correlation analysis was used to assess effect of CIT on length of stay (LOS). Results The inclusion criteria were met by 798 patients. The mean and median CIT was 418 and 397 min, respectively. Adjusted analysis suggests that total CIT was not associated with PGD grade 3 at 48 and 72 hours (OR1.24, 0.87-1.75). However, CIT was associated with several other markers of graft dysfunction and resource utilization including PGD3 T0 (OR1.5, 1.06-2.13), tracheostomy (OR1.93, 1.3-2.87), post-op ECMO (OR3.47, 2.21-5.45), renal failure requiring dialysis (OR1.8, 1.13-2.86), death within 90 days (2.41, 1.42-4.09), death in hospital (OR2.53, 1.47-4.35), and death within one year (OR 2.37, 1.43-3.94). Total ischemic time was also independently associated with LOS (P Conclusion In a multicenter international registry, increasing CIT was associated with increased PGD at T0, higher postoperative morbidity and worse first year survival. Although patients can be transplanted with extended cold ischemic times when absolutely needed, this practice is associated with greater resource utilization and likely impact on survival.

Real-Time Lung Weight Measurement during Ex Vivo Lung Perfusion: Clinical Importance of Early Weight Gain

<h3>Purpose</h3> Lung weight gain during ex vivo lung perfusion (EVLP) can reduce lung transplant suitability. Therefore, real-time weight measurement can enhance donor lung evaluation. We sought to 1) develop/validate a real-time EVLP weight measurement system, and 2) define the time course of lung weight change during EVLP. <h3>Methods</h3> In our clinical acellular EVLP system, from 6/2019-9/2020, real-time lung weight was measured in 36 cases. Weights were recorded with a scale under the organ chamber, and back table static weights measured after EVLP. Lungs were classified as unfavorable (n = 13) if declined after EVLP (n = 8) or PGD grade ≥ 2 at 72 hrs if transplanted (n = 5). Favorable group lungs were transplanted, with PGD ≤ 1 at 72 hrs (n = 23). <h3>Results</h3> Real-time lung weights correlated well with static/back table weights (r = 0.69, p < 0.01, Figure A). Unfavorable group lungs gained significantly more weight (mean 38 g, range -59 to 135 g) during the 1^st hour of EVLP vs. favorable group lungs (mean -51 g, range -155 to +53 g) (p < 0.01, Figure B). In fact, this effect was most pronounced in the first 10 minutes of EVLP (Figure C), and correlated with an increased pulmonary artery (PA) pressures (7.0 ± 2.2 vs 5.4 ± 1.3 mmHg, p = 0.03). In contrast, lung weight gain was similar between groups during EVLP hours 2 and 3. For the 28 lungs suitable for transplant, 30-day recipient survival was 100%. <h3>Conclusion</h3> Real-time lung weight measurement during EVLP is feasible. Our data suggest that donor lung weight gain in the earliest phase of EVLP correlates with decreased lung transplant suitability and PGD. Further studies are needed to define the significance of lung weight gain early during EVLP.

High Grade Primary Graft Dysfunction after Lung Transplantation is Associated with Acute Rejection but Not Chronic Allograft Dysfunction

Purpose Evidence suggests that high grade primary graft dysfunction after lung transplantation (LTx) is a major threat for early and late outcomes. Herein, we aim to examine the risk factors and clinical impact of PGD in a contemporary cohort at a single center. Methods From 1/2008 to 7/2018, 1147 LTx procedures were performed at our institution. Clinical data was prospectively collected and PGD defined according to ISHLT criteria. Median follow up was 3.3 years (interquartile range 1.2 - 7.4). Multi-variable analysis utilizing recipient, donor, and LTx procedure variables was performed to assess risk factors for PGD, acute rejection, chronic lung allograft dysfunction (CLAD), early mortality, and late survival. Results Out of 1147 LTx procedures, 61% were bilateral. The incidence of PGD (grade II & III) was 13% & 15% at 24 hr , 12% & 14% at 48 hr , and 12% & 14% at 72 hr, respectively. Multi-variable analysis identified cardiopulmonary bypass usage/duration, single LTx, recipient pulmonary arterial hypertension, longer ischemic time, earlier year of LTx, older donor, higher Lung Allocation Score, and higher ratio of recipient/donor weight as risk factors for high grade PGD (grade II or III at 48-72 hr). Notably, recipient body mass index, donor smoking history, and diabetes were not significant risk factors for high grade PGD. Further analysis demonstrated that PGD II or III at 48-72 hr were independent significant risk factors for early mortality and higher acute rejection grades, while not significantly associated with CLAD or late survival. PGD grade II or III at 24 hr were not significant risk factors for early mortality, acute rejection, CLAD, or late survival. Conclusion This single-center data analysis of > 1000 contemporary lung transplants identified risk factors for high grade PGD. While high grade PGD at 48-72 hr was associated with higher risk of early mortality and acute rejection, in contrast to previous studies, it was not associated with a higher risk of CLAD or late survival, perhaps due to evolving management strategies.

Use of Ex Vivo Lung Perfusion for Lung Transplantation: Midterm Results

Purpose Ex vivo lung perfusion (EVLP) offers a unique potential in evaluation, optimization and transplantation of lungs that would otherwise potentially be rejected. Between 2016 and 2020 208 lung transplants (LuTx) were performed and 22 donor lungs were evaluated by EVLP of which 16 were transplanted. Aim of the study was to compare mid-term results in LuTx recipients with or without the use of EVLP. Methods In a retrospective single-center analysis data from a prospectively collected database were analysed. The EVLP group (n=16) consisted of donor lungs classified as marginal and were evaluated by EVLP and afterwards transplanted. The non EVLP group (n=16) consisted of conventional LuTx recipients matched for age and pulmonary disease. Both groups were compared for the endpoints survival, primary graft dysfunction, rejection episodes and chronic allograft dysfunction. Results Recipient age was 55 ± 6 years in EVLP group and 57 ± 5 years non EVLP group (n.s.). Female gender was present in 36% EVLP patients and 50% non EVLP (n.s.). The rate PGD grade 1 at 72 h post-LTx was 14% in both groups (each2/16). In non EVLP group 1recipient was PGD 2 (7%). PGD3 was present only in the EVLP group 14% (2/16) vs. 0% in control. At last visit, post-LuTx, forced expiratory volume in 1 s (FEV1%) as percentage of predicted best was similar in the EVLP and non-EVLP group (77% vs. 78%). Chronic lung allograft dysfunction was diagnosed in one non EVLP patient and one EVLP patient during follow up post-LuTx. In the EVLP group 2 patients had rejection episodes subjected to treatment and 6 patients in the non EVLP group (n.s.). Survival at 1 year was 81% for the EVLP group and 94% in non EVLP group (n.s.). Conclusion Recipients transplanted with extended criteria donor lungs, thoroughly evaluated by EVLP show similar mid term outcomes as conventionally transplanted lungs from standard donors. EVLP shall increase the number of acceptable donor lungs. Future clinical trials will bring further evidence; clear guidelines regarding application of machine perfusion have to be developed.

The Clinical Significance of Donor Lung Weight at Procurement and during Ex Vivo Lung Perfusion

<h3>Purpose</h3> Elevated donor lung weight can result from excess extravascular lung water and adversely affect transplant suitability and post-transplant outcomes. We sought to define the impact of lung weight on 1) donor lung suitability and 2) post-transplant graft dysfunction in lungs transplanted with and without ex vivo lung perfusion (EVLP). <h3>Methods</h3> From Feb 2016 to Aug 2020, 365 human lung donors were reviewed. Of 365, 239 were transplanted without EVLP, 74 treated with acellular EVLP (50 went on to transplant), and 52 declined for transplant without EVLP. Lung weights were measured at two time points: at 0 hr (LW0; after lung explant or start of EVLP), and after EVLP was completed (LWend). LW0 data were divided into 4 quartiles (Category 1=0-25%, Category 2=25-50%, Category 3=50-75%, and Category 4=75-100%) within 3 height groups (< 160, 160-180, and ≥ 180 cm) [Figure]. LWend data were also divided into the same 4 quartiles as LW0 data. <h3>Results</h3> For LW0 Category 4, EVLP was utilized more frequently (45 vs. 17%, p < 0.05). Higher rates of Grade 3 PGD at 72 hrs (18 vs. 9%, p = 0.44), longer times to extubation, and longer ICU/hospital days (p < 0.05, each) were observed vs. LW0 Categories 1-3. For lungs treated with EVLP, LW0 Category 4 lungs were associated with a significantly lower transplant suitability rate (57 vs. 75%, p = 0.02) and higher incidence of PGD grade 3 at 72 hrs vs. LW0 Categories 1-3 (26 vs. 3%, p < 0.05). LWend Category 4 lungs were also associated with lower transplant suitability after EVLP (55 vs. 90%, p < 0.01), and an increased incidence of PGD grade 3 at 72 hrs (21 vs. 0%, p < 0.01), compared to LWend Categories 1-3. <h3>Conclusion</h3> Donor lungs in the highest quartile of lung weight are associated with increased need for EVLP, but lower transplant suitability rates after EVLP when compared to lungs with lower weight. Donor lungs in the highest quartile are also associated with higher Grade 3 PGD rates and longer ICU/hospital stay. These findings should be taken into account when high weight donor lungs are considered for clinical use.

Contemporary Indications for Heart-Lung Transplantation

<h3>Purpose</h3> Currently, there are patients who meet criteria for lung transplant who are denied listing because of underlying heart disease. Likewise, there are patients who meet criteria for heart transplant but are denied listing because of lung disease. In addition, end-stage pulmonary hypertension has become more commonly treated with bilateral lung transplantation. From 2006 to 2018, no adult heart-lung transplantation (HLT) was performed in New York State. Given this unmet need our center has renewed interest in HLT. <h3>Methods</h3> All patients who underwent HLT from 06/2019 to 09/2020 were reviewed. Patients were listed per standard UNOS guidelines. The primary outcome was hospital and 1year survival. <h3>Results</h3> 10 patients (50% male; mean age 54±8 years) underwent HLT during this period. All patients had been deemed not appropriate candidates for isolated heart or lung transplant at more than one transplant center. The indication for HLT was interstitial lung disease (ILD) with ischemic cardiomyopathy (n=4), nonischemic cardiomyopathy with PAH (n=2), PAH with RV failure (n=2), and ILD with RV failure (n=2). Median lung allocation score and heart waitlist status were 71 (IQR: 41-85) and 2 (IQR: 1-3) respectively. Three patients had re-operative sternotomies. Two patients bridged to transplant with VA-ECMO, two with VV-ECMO and three patients required IABP. One patient received a DCD donor heart-lung block utilizing normothermic regional perfusion, and two patients received Hep C+ donor organs. One patient was left on central VA-ECMO postoperatively for early lung PGD. No lung PGD grade 3 at 72 hours or significant heart PGD at any time point were observed. At a median follow up of 287 (IQR: 108-401 days), all patients are alive at home. <h3>Conclusion</h3> Our initial center experience demonstrates that appropriately selected patients with end stage heart and lung disease who would otherwise die without transplantation can be offered HLT with excellent short-term outcomes.

Influence of Donor-Recipient Age Mismatch in Young Lung Transplant Recipients

Purpose Lack of organ donors demands transplantation of older lungs into younger recipients. Providing that other general organ donor selection criteria are fulfilled; it still remains questionable whether high age mismatch negatively affects short- and long-term outcomes. Here we investigate outcomes of lung recipients aged between 0 and 50 years whose donors had a high or low age mismatch compared to their respective recipients. Methods Records of patients aged between 0 and 50 years (33±12 years) and transplanted between 2005 and 2020 were retrospectively reviewed. Two groups were formed, one including recipients who received organs from donors at least 20 years older (high-mismatch group) and the other group including recipients whose donors were not older than 10 years (low-mismatch group) compared to their corresponding recipients. Donor smoking status, pO2-pressure and ventilation time (days) were evaluated. Incidence of Primary Graft Dysfunction grade 3 (PGD 3), ICU stay, ventilation time, perioperative hospital stay, chronic lung allograft dysfunction (CLAD) and graft survival were compared using Chi-Square test, Mann-Whitney-U test and Kaplan-Meier analysis, respectively. Results During the study period, among the 1722 patients transplanted at our institution, 172 (9.9 %) patients form the high-mismatch group and 212 (12.3%) patients the low mismatch group. Prevalence of donor smoking history was higher in low-mismatch recipients (34% vs. 46%; p=0.024). PO2-pressure (390 vs. 405 mmHg; p=0.39) and median ventilation time (4 vs. 4 days; p=0.898) prior organ procurement did not differ between groups. Incidence of PGD Grade 3 after 48 (11% vs. 6%; p=0.078) and 72 (11% vs. 6%; p=0.078) hours was not significantly different. Median mechanical ventilation (14 vs. 14 hours; p=0.76), ICU stay (4 vs. 4 days; p=0.6) and postoperative hospital stay times (25 vs. 24 days; p=0.17) did not differ between groups. At 5- and 10-year follow-up, overall graft survival (66.3% vs. 67.3%, 54% vs. 48%, p=0.956), patient survival conditioned to hospital discharge (75.7% vs. 79.2%, 62.9% vs. 64.1%, p=0.541) and freedom from CLAD (57.6% vs. 62.9%, 47% vs. 38%, p=0.944) was comparable between the groups. Conclusion Age mismatch alone is not a limiting factor for accepting donor lungs. Long term survival and incidence of CLAD are not affected providing general donor organ selection criteria are considered.

Respiratory mechanic evaluation using an esophageal balloon catheter in patient receiving lung transplantation. Observational study. Preliminary results

Introduction Mechanical ventilation (MV) plays a crucial role during the early post-operative period of lung transplantation (LTx). An accurate setting of MV is important in order to prevent ventilation-induced lung injury, which may lead to Primary Graft Dysfunction (PDG), and to set a protective ventilation strategy whenever this complication occurs. Unfortunately, respiratory mechanics may be unpredictable: these patients receive lungs which may not perfectly match their chest walls, causing a patient-donor size-mismatch, is conventionally defined by the ratio between recipient and donor lungs predicted-Total Lung Capacity (r-pTLC and d-pTLC, respectively) and may modify the distribution of pressures inside the respiratory system between lung and chest wall. In order to improve our understanding of the LTx respiratory mechanics and to evaluate whether ventilation setting was dangerous for the transplanted lungs, we placed an Esophageal Balloon Catheter (EBC) and analysed the esophageal pressure (Pes) in the early post-operative period of patients receiving bilateral sequential single LTx (BSSLTx). Methods We observed the respiratory mechanics of patients receiving BSSLTx over 1-year period at Molinette Hospital (Ospedale Molinette, Citta della Salute e della Scienza, Turin, Italy). For each patient respiratory mechanics was evaluated at least two times in the post-transplant period: intraoperatively (T0), just before the chest closure, and post-operatively (T1), in ICU. Patients and donors data, recipient-donor size-matching and outcomes were compared with respiratory mechanics. Results Between November 2018 and October 2019, we included 22 patients receiving LTx. Among them, 9 were excluded: 6 were single LTx, 1 was a paediatric patient and 2 patients had incomplete data. Among the 13 patients included, 3 (23%) developed PGD: 5 patients were best matched (d/pTLC 0,9 – 1,1; 5/13, 38,4%), 6 were undersized (d/pTLC 1,1; 2/13, 15,3%) but no correlation was found between size-matching and incidence of high-grade PGD (PGD grade 2 or 3) (Fig.1). We found no statistically significant difference in transpulmonary pressure (PTP i, PTP e, PTP drive), transpulmonary compliance (CTP) or chest elastance (ECW) at T0 or T1 in patients who developed PGD compared to those without PGD. However, we noticed an early raise of PTP i in patients who were going to develop PGD (no PGD δ% t0-t1 PTP i – 14,6% vs PGD δ% t0-t1 PTP i + 14,0%; p=0,1402) (Fig. 2). Moreover, we found that this early raising in PTP i (δ% t0-t1 PTP i) was statistically related with the ICU-length-of-stay (ICU-LOS) (r2=0,57; p=0,050) (Fig. 3) Discussion The overall incidence of PGD in our centre was 23%, however no correlation with patient-donor size-matching. An early raise of transpulmonary pressure was observed among patients who developed PGD and it was statistically correlated with higher ICU-LOS.

Early protein expression profile in bronchoalveolar lavage fluid and clinical outcomes in primary graft dysfunction after lung transplantation.

Primary graft dysfunction (PGD) remains a major post-transplant complication and is associated with increased morbidity and mortality. Mechanisms evoking PGD are not completely clear, but inflammation plays a central role. We investigated the association between PGD and inflammatory proteins present in immediate postoperative bronchoalveolar lavage. All double-lung recipients transplanted at our institution from 2002 to 2018 were included in our study. We retrospectively selected 80 consecutive lung transplant recipients with different PGD grades (n = 20 for each PGD grades 0-1 to 2-3). In bronchoalveolar lavage performed within the first 24 h after donor aortic cross-clamping following lung transplantation, concentrations of 30 cytokines, chemokines and growth factors were assessed by enzyme-linked immunosorbent assay (ELISA) and correlated with donor and recipient demographics and outcomes. For analysis, 2 groups were defined: 'mild' PGD (grade 0-1) and 'severe' PGD (grades 2-3). Significant differences between mild and severe PGD were found in 8 biomarkers [interleukin (IL)-6, IL-10, IL-13, eotaxin, granulocyte colony-stimulating factor, interferon γ, macrophage inflammatory protein 1α, surfactant protein D (SP-D); P < 0.05]. Increased IL-10 and IL-13, but none of the other proteins, were associated with short-term outcome (longer time to extubation; P = 0.005 and P < 0.0001; increased intensive care unit stay; P = 0.012 and P < 0.0001; and hospital stay; P = 0.041 and P = 0.002). There were no significant differences in donor and recipient characteristics between the groups. Expression profiles of key inflammatory mediators in bronchoalveolar lavage fluid differed significantly between lung transplant recipients with severe versus mild PGD and correlated with clinical outcome variables. Further research should focus on the early mechanisms leading to PGD.

Respiratory Failure Treated by ECLS in Previously Unscreened Patients - Is Lung Transplantation Feasible?

ECLS is increasingly used to bridge deteriorating candidates to LTx. Most centers would only bridge patients previously approved for Tx and on the waiting list. Our center has accepted to transplant patients supported with ECLS device previously unknown to the transplant team. Unscreened patients on ECLS for respiratory failure were included in this retrospective single-center analysis. Criteria to accept patients for Tx were: preserved kidney and liver function, acceptable muscular reserve, no systemic disorders, no significant CV comorbidities. This group was compared to deteriorating patients on the waiting list and bridged to their Tx. Ninety-six patients were bridged by ECLS to primary LTx between 2005 and 2018. This included 37 (38%) unscreened patients with a median age was 30 years (13-65). The main diagnosis was CF (14, 38%) followed by fibrosis (11, 30%) and ARDS (6, 16%). Median ECLS bridging time was was similar in both groups (5 vs 7 days). Thirty (81%) patients listed during ECLS were intubated prior to implantation of ECLS device. Seven of them (19%) could be weaned from invasive ventilation and could be bridged awake to Tx compared to 17 (32%) patients in the control group. Among the 37 unscreened patients, 13 (35%) were on VA ECMO, 13 (35%) on VV double site ECMO and 7 (19%) on a combination of modalities. 32/37 patients (90%) reached Tx. At 72 hours PGD grade 3 was observed in 2 recipients in the group evaluated during ECLS period compared to 1 recipient in the other group. No differences were found in terms of length of mechanical ventilation after Tx among the two groups: 2 days (1-15) vs 4 days (1-37). One and 5-year survival rate per intention to treat were: 57% vs 64 % and 45% vs 50% (p=0.414), respectively. Long-term results of Tx for previously unscreened patients on ECLS are comparable to ECLS bridged patients already on the waiting list. Our data provide evidence that this group of patients should not be excluded from a life-saving transplantation.

Developing DSA Post-Lung Transplant - Identifying Risk Factors

Purpose Donor specific antibodies (DSA) to mismatched human leukocyte antigens have been reported to adversely affect the outcomes of lung transplantation. This study aimed to identify the risk factors for the development of DSA within 1-year post-transplant and examine its impact on recipients’ medium-term survival. Methods Recipients’ age, type of transplantation (single lung or bilateral lungs), pre-existing antibodies, post-op DSA, method of transplantation (ECMO, off-pump or on-pump), primary graft failure (PGD) grade 3 at 72hrs, blood transfusion, post-op ITU stay, ECMO usage and renal support, and survival status were collected from the unit's database. Binary logistic regression was used to identify risk factors for the development of post-op DSA within 1-year post-transplant. Multivariable Cox regression was performed to identify risk factors for survival. Results From January 2012 to October 2017, 259 adult patients received lung transplantation in our unit and 242 (93.4%) survived beyond 30-day post-op. Recipients who died within 30-day post-transplant were not included, as the causes of their death were less likely to be influenced by or associated with post-op DSA. Among these 242 recipients, 46 (19.0%) had pre-existing antibodies and 129 (53.3%) had DSA detected within 1-year post-transplant. Among all the potential risk factors, transplantation performed with ECMO (p = 0.007, OR 3.06, 95% CI: 1.36-6.90) are significantly associated with post-op DSA within 1-year post-transplant. Age (p = 0.009, OR 1.03, 95% CI: 1.01-1.05), post-op renal support (p = 0.015, OR 2.23, 95% CI: 1.17-4.26), PGD grade 3 at 72hrs (p = 0.001, OR 2.79, 95% CI: 1.54-5.05), and red blood cell transfusion (p < 0.001, OR 1.17, 95% CI: 1.11-1.23) are associated with worse medium-term survival, but neither pre-existing antibodies (p = 0.454) or post-op DSA (p = 0.479) has an impact on survival. Conclusion Use of ECMO for lung transplantation is associated with DSA development within 1-year post-transplantation. However, the presence of DSA within 1-year post-transplant has no impact on medium-term survival in this cohort. Further study is required to look at the effect of DSA on the development of chronic lung allograft dysfunction and long-term survival. Donor specific antibodies (DSA) to mismatched human leukocyte antigens have been reported to adversely affect the outcomes of lung transplantation. This study aimed to identify the risk factors for the development of DSA within 1-year post-transplant and examine its impact on recipients’ medium-term survival. Recipients’ age, type of transplantation (single lung or bilateral lungs), pre-existing antibodies, post-op DSA, method of transplantation (ECMO, off-pump or on-pump), primary graft failure (PGD) grade 3 at 72hrs, blood transfusion, post-op ITU stay, ECMO usage and renal support, and survival status were collected from the unit's database. Binary logistic regression was used to identify risk factors for the development of post-op DSA within 1-year post-transplant. Multivariable Cox regression was performed to identify risk factors for survival. From January 2012 to October 2017, 259 adult patients received lung transplantation in our unit and 242 (93.4%) survived beyond 30-day post-op. Recipients who died within 30-day post-transplant were not included, as the causes of their death were less likely to be influenced by or associated with post-op DSA. Among these 242 recipients, 46 (19.0%) had pre-existing antibodies and 129 (53.3%) had DSA detected within 1-year post-transplant. Among all the potential risk factors, transplantation performed with ECMO (p = 0.007, OR 3.06, 95% CI: 1.36-6.90) are significantly associated with post-op DSA within 1-year post-transplant. Age (p = 0.009, OR 1.03, 95% CI: 1.01-1.05), post-op renal support (p = 0.015, OR 2.23, 95% CI: 1.17-4.26), PGD grade 3 at 72hrs (p = 0.001, OR 2.79, 95% CI: 1.54-5.05), and red blood cell transfusion (p < 0.001, OR 1.17, 95% CI: 1.11-1.23) are associated with worse medium-term survival, but neither pre-existing antibodies (p = 0.454) or post-op DSA (p = 0.479) has an impact on survival. Use of ECMO for lung transplantation is associated with DSA development within 1-year post-transplantation. However, the presence of DSA within 1-year post-transplant has no impact on medium-term survival in this cohort. Further study is required to look at the effect of DSA on the development of chronic lung allograft dysfunction and long-term survival.