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Study Objectives: Lung transplantation continues to be limited by the development of chronic allograft dysfunction in the form of bronchiolitis obliterans syndrome (BOS). The effect of a transplant operation on patients with BOS has not been well-studied, but patients who undergo double-lung transplantation have better long-term survival. We hypothesized that double-lung transplantation leads to decreased rates of BOS.Methods: A retrospective review of all lung transplant recipients at our institution, surviving for > 6 months after undergoing their transplant operation. Demographic data, information on other factors leading to the development of BOS, survival information, and data on the presence and timing of BOS were collected.Results: BOS occurred in 41.3% of the recipients (93 of 225 patients) at a median time of 4.2 years. Single-lung transplantation was associated with increased rates of BOS compared to double-lung transplantation (49.3% vs 31.7%, respectively; p = 0.007), at the time of the analysis. Single-lung and double-lung transplant recipients had different baseline characteristics, but after controlling for these factors the type of transplant remained a significant predictor of the length of time to the onset of BOS in a multivariable proportional hazard model.Conclusions: Double-lung transplantation is associated with a reduced risk for BOS in our study population. A multicenter study with complete BOS information on all patients with a single pretransplant diagnosis would be useful to confirm the above findings. Further research is needed to determine how the type of transplant contributes to the risk for BOS. [ABSTRACT FROM AUTHOR]

Acute formation of methemoglobin is a life-threatening condition caused by multiple medications. In this article we report the first case of methemoglobinemia in a patient with metastatic uterine leiomyosarcoma, after infusion of ifosfamide chemotherapy. The patient recovered after prompt diagnosis and treatment of the condition. A mechanism for the formation of methemoglobin as a result of the ifosfamide infusion is offered. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygen (ECMO) is increasingly used as a bridge to lung transplantation. Although other mechanical circulatory support devices have been associated with a transfusion-independent increase in calculated panel reactive antibodies (CPRA), it is unknown whether ECMO is a sensitizing exposure. In this single center retrospective cohort study of lung transplant candidates between 5/1/2015-6/30/2021, antibodies against human leukocyte antigens (HLA-Ab) were evaluated at the time of ECMO initiation and weekly thereafter. Multivariate logistic regression was used to evaluate associations between CPRA increase and ECMO exposure adjusting for a history of any packed red blood cell (PRBC) transfusion and female gender. Sixty-two candidates were placed on ECMO as a bridge to transplant. Of these, 39 (62.9%) either had available HLA-Ab screens from pre- and post-ECMO initiation or multiple HLA-Ab screens post-ECMO. Of the 250 non-ECMO exposed recipients, 224 (89.6%) had multiple pre-transplant screens and served as the comparison cohort. Nine (23.1%) ECMO bridged recipients had an increase in CPRA, compared to 16 (7.1%) of non-ECMO exposed recipients (Fisher's exact p=0.005). Among those with increased CPRA, the median increase was 6% in ECMO bridge patients and 9% in non-ECMO exposed patients. After adjusting for covariates, however, ECMO bridge was not an independent risk factor for increased CPRA (OR=1.85, 95% CI 0.58-5.95, p=0.30). A history of PRBC transfusion trended toward an association with increased CPRA (OR=2.93, 95% CI 0.98-8.78, p=0.06). Pre-lung transplant ECMO was not independently associated with an increase in CPRA when adjusting for PRBC transfusion, although the study was underpowered for small or moderate effect sizes. Where clinically appropriate, PRBC transfusions should be limited in these patients. [ABSTRACT FROM AUTHOR]

Lung transplant recipients with pre-transplant donor specific antibodies (DSA) are often treated with augmented immunosuppression. It is unknown whether some DSA can be safely crossed without additional therapies. We implemented a protocol allowing transplant when crossing select low level DSA (defined as mean fluorescence intensity (MFI) 1000-5000) without planned augmented immunosuppression. This was a single center retrospective cohort study between 4/1/2015-8/31/2020. All recipients received solumedrol and basiliximab induction without desensitization. Presence of low level pre-transplant DSA was recorded. All post-transplant DSA was monitored within 14 days of transplant and then at routine intervals. The primary study outcomes were overall survival, definite CLAD≥1-free survival, and definite antibody mediated rejection (AMR), all defined according to ISHLT consensus guidelines. Of the 453 recipients, 36 (7.9%) had a low-level pre-transplant DSA crossed at transplant (Table 1). 13 had Class I antibodies and 26 had Class II. The median historical DSA MFI was 1800 (IQR 1300-2400) and the median most recent MFI was 1200 (IQR 950-2000). Among recipients where pre-transplant DSA was crossed, 17 (47.2%) had persistent post-transplant DSA with a median peak MFI of 7400. Class II antibodies were more likely to be detected post-transplant than Class I (57.7% vs 15.4%, p=0.02). There was no statistical difference in definite AMR in recipients where pre-transplant DSA was and was not crossed (8.3% vs 3.1%, p=0.11). With a median follow-up time of 2.4 years, there were no differences in adjusted overall survival (HR=1.14, 95% CI=0.57-2.32, p=0.71) or CLAD≥1-free survival (HR=0.82, 95% CI=0.44-1.54, p=0.54). Lung transplantation in the presence of low level DSA without planned augmented immunosuppression was not associated with worse overall or CLAD-free intermediate-term survival but may be associated with increased AMR. [ABSTRACT FROM AUTHOR]

Antimicrobial overuse contributes to antimicrobial resistance in lung transplant recipients (LTRs). Guidance on assessment of the quantity and appropriateness of antimicrobial prescribing is required in LTRs for standardized management. This study aims to define the expected appropriate antibiotic prescribing of clinical scenarios in LTRs using a modified Delphi method. We developed an online questionnaire to solicit from ISHLT membership and Delphi Panel members regarding the appropriate treatment of 21 common clinical scenarios treated with systemic antimicrobials. Consensus was predefined as 80% agreement on the importance of each metric. The metrics that did not achieve the consensus on questionnaire were presented to an online multidisciplinary Delphi panel consisting of 25 experts from various disciplines (infectious diseases (6), pediatric infectious diseases (1), respirology (8), cardiology (2), cardiothoracic surgery (5), immunology (1) and pharmacy (1)) within ISHLT. An independent non-content expert conducted the panel. Following the initial online survey, 69 responses were received. Consensus on the antimicrobial management was reached on 20% (20/ 98) of questions related to 21 clinical scenarios. The survey was modified and shortened (based on relevancy, controversy of topic and consensus) to 38 questions in 10 clinical scenarios. Eleven further questions were removed due to redundancy. In total, 27 questions related to 10 clinical scenarios were discussed on-line among the Delphi Panel. Consensus was reached among 77% (21/ 27) of questions. Consensus was not reached regarding the antimicrobial management of the following 6 clinical syndromes: 1) CMV (duration of secondary prophylaxis); 2) Burkholderia cepacia pneumonia (duration of therapy); 3) RSV (duration of therapy); 4) Mycobacterium abscessus (intra operative antimicrobials); 5) Aspergillus (treatment of culture negative BAL but galactomannan BAL +) and 6) LVAD deep infection (initial empirical antimicrobial coverage). This study resulted in expert consensus for defined levels of appropriate antibiotic prescribing in majority of clinical scenarios assessed in LTRs. These results can be aid in antimicrobial stewardship adjudications in LTRs. [ABSTRACT FROM AUTHOR]

Pre-transplant antiphospholipid antibodies (aPLab), including anticardiolipin (aCL) and anti-B2 glycoprotein-I (aB2GPI), may be associated with thrombotic complications and graft loss in kidney and liver transplant recipients. The objective of this study was to evaluate the prevalence and impact of aPLab on post-operative thrombotic and bleeding complications in lung transplant recipients. This was a single center retrospective cohort study of patients who were evaluated and transplanted between 1/1/2018-11/30/20. All candidates were screened for aPLab. We compared post-operative arterial and venous thrombotic events, treated as a combined endpoint, in recipients with and without aPLab (Fisher's exact test). Among recipients with aPLab, we recorded major bleeding events—defined as requiring blood transfusion or surgical exploration—while on therapeutic or prophylactic dose anticoagulation (AC). There were 100 patients who were evaluated and transplanted during the study period, 19 (19.0%) of whom had aPLab (Figure 1). Among these, 7 (36.8%) had pre-transplant deep vein thrombosis (DVT) or arterial thrombotic events. After transplant, 7 (36.8%) had new symptomatic DVT or arterial thromboses compared to 20 (24.7%) recipients without aPLab (p=0.39). Ten patients with aPLab were fully anticoagulated post-transplant, either because of prior or new thrombotic events. Of these, 6 (60.0%) had major bleeding. One aPLab patient had major bleeding on prophylactic AC. The majority (85.7%) of patients with major bleeding were on renal replacement therapy or had an eGFR <30. The one-year survival rate among recipients with aPLab was 89.5%. The presence of a pre-transplant aPLab was not associated with an increase in new symptomatic DVT or arterial thrombotic events following lung transplant although the study was underpowered for small or moderate effects. The decision to anticoagulate patients with aPLab should account for other risk factors for bleeding including renal insufficiency. [ABSTRACT FROM AUTHOR]

Background: Lung transplantation has emerged as a viable therapeutic option for patients with a variety of end-stage pulmonary diseases. As immediate posttransplant surgical outcomes have improved, the greatest limitation of lung transplantation remains chronic allograft dysfunction. Gastroesophageal reflux disease (GERD) with resultant aspiration has been implicated as a potential contributing factor in allograft dysfunction. GERD is prevalent in end-stage lung disease patients, and it is even more common in patients after transplantation. We report here on the safety of laparoscopic fundoplication surgery for the treatment of GERD in lung transplant patients. Methods: Eighteen of the 298 lung transplants performed at Duke University Medical Center underwent antireflux surgery for documented severe GERD. The safety and benefit of laparoscopic fundoplications in this population was evaluated. Results: The antireflux surgeries included 13 laparoscopic Nissen fundoplications, four laparoscopic Toupets, and one open Nissen (converted secondary to extensive adhesions). Two of the 18 patients reported recurrence of symptoms (11%), and two others reported minor GI complaints postoperatively (nausea, bloating). There were no deaths from the antireflux surgery. After fundoplication surgery, 12 of the 18 patients showed measured improvement in pulmonary function (67%). Conclusions: GERD occurs commonly in the posttransplant lung population. Laparoscopic fundoplication surgery, when indicated, can be done safely with minimal morbidity and mortality. In addition to the resolution of reflux symptoms, improvement in pulmonary function may be seen in this population after fundoplication. Lung transplant patients with severe GERD should be strongly considered for antireflux surgery. [ABSTRACT FROM AUTHOR]

Rates of deep vein thrombosis (DVT) range from 20-60% in patients undergoing extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome. Data on the rates of DVT in lung transplant recipients bridged with ECMO is limited. The objective of this study was to report incidence and outcomes, including use of anticoagulation and subsequent bleeding rates, of DVT in ECMO-bridged transplant recipients. This was a single center retrospective cohort study of all adult ECMO-bridged lung transplant recipients from 5/1/15 to 9/30/19. Recipients underwent routine ultrasound screening for upper extremity (UE) and lower extremity (LE) DVT following ECMO decannulation. Of the 45 ECMO-bridged recipients, 3 died before ECMO decannulation and 4 did not have screening ultrasounds, leaving 38 patients in the cohort. The majority (81.5%) were bridged using venovenous ECMO and most (63%) were decannulated immediately following transplant (Table 1). Among remaining recipients, mean time to decannulation was 4 days. Among recipients with adequate studies, the incidence of LE DVT was 26.4% and the incidence of UE DVT was 63.6%. Neither total time on ECMO, cannula size, nor need for femoral vein cannulation was associated with LE or UE DVT. All of the recipients with LE DVT but two, were anticoagulated. Three needed an inferior vena cava filter placed. Of recipients with UE DVT only, 43.75% were anticoagulated. Among all anticoagulated recipients, five (31.25%) had significant bleeding during their initial hospitalization requiring cessation of anticoagulation. DVTs are common in patients bridged to lung transplantation with ECMO, particularly in the upper extremity. Bleeding poses further challenges for systemic anticoagulation in this high risk population. Additional studies are needed to identify risk factors for both LE DVT and for bleeding to help guide decisions for systemic anticoagulation in this population. [ABSTRACT FROM AUTHOR]

Objective To determine the optimal hemoglobin A1c (HgbA1c) level to screen for Cystic Fibrosis Related Diabetes (CFRD) in a population of adults with cystic fibrosis (CF). Methods All oral glucose tolerance test (OGTT) results completed between 2012 and 2014 and HgbA1c tests within 3 months of the OGTT were included. HgbA1c levels were categorized as U5.5%, 5.6–6.4% and ≥6.5%. Chi-square analysis was used to compare HgbA1c categories to the following: 1. presence of CFRD, 2. 1 hour OGTT results >199 mg/dL, and 3. 1 hour OGTT results >155 mg/dL. Results The number of OGTT tests performed per year is described in Poster Table 1. Descriptive statistics for the sample variables are described in Poster Table 2. Statistical significance was achieved comparing HgbA1c category with 2 hour OGTT results (p = 0.002). Of the patients with an HgbA1c ≤5.5%, 4.8% met criteria for CFRD, as did 16.7% with a HgbA1c between 5.6–6.4% and 60% with a HgbA1c ≥6.5%. Hypoglycemia occurred in 28.6% of patients with a HgbA1c U5.5% having a 2 hour OGTT result <70 mg/dL (p = 0.028) compared to 10% in the group with a HgbA1c between 5.6–6.4%. Comparison of HgbA1c and 1 hour OGTT >199 mg/dL achieved statistical significance (p = 0.008). Conclusion Based on the results of this observation, using HgbA1c levels as a screening tool may be useful in determining which patients may be appropriate for OGTT testing. Using this method may have the added benefits of decreasing the incidence of hypoglycemia in the population of patients with normal HgbA1c who are most at risk. Using the HgbA1c test may increase the likelihood of patients completing OGTT test and improve utilization of hospital costs and resources. [ABSTRACT FROM AUTHOR]

Purpose: Provision of palliative and end-of-life care is of special importance for patients awaiting lung transplantation. However, lung transplant program practices may be at odds with palliative care principles. We examined perceived barriers to delivery of palliative care to lung transplant candidates and sought strategies to improve such care. Methods and Materials: An anonymized e-mail questionnaire was sent to all members of the American College of Chest Physicians Transplant NetWork and of the Pulmonary Council of the ISHLT. It included demographic and practice-related questions, questions about barriers to palliative care of lung transplant candidates, availability of services and utility of strategies to improve palliative care. Transplant program practitioners were eligible for this study. Results: There were 158 eligible responses. Respondents were in practice 11.3 (±9) years. 70% were pulmonologists, 17% surgeons and 13% other care providers, including coordinators and nurse practitioners. Barriers that were considered at least moderate by >50% of respondents were classified as significant. These included unrealistic patient/family expectations about survival until and after transplant, patient/family unwillingness to plan end-of-life care, patient concerns about inappropriate care or abandonment after enrollment in a palliative care program and family disagreements about care goals. Among program policy barriers, the requirement for weight loss or gain was identified. Clinician barriers included competing time demands and seemingly contradictory goals of transplantation and palliative care. Helpful strategies included routine advanced care planning assistance for listed patients, access to palliative care consultants, training of transplant physicians in symptom management and regular meetings between transplant physicians, nurses, patients and families. Conclusions: Clinicians providing care to lung transplant candidates perceive important barriers to the delivery and acceptance of palliative care and believe that there are specific strategies that may improve such care. [Copyright &y& Elsevier]