Using HCV-viremic organs for lung transplantation does not confer higher rejection rates compared to HCV-negative organs.

BACKGROUND: National data demonstrate that hepatitis C virus (HCV)-infected organ donors are increasingly being used in the US, including for lung transplantation. We aimed to assess whether there were any differences in the acute or chronic rejection rates at 1 year following lung transplantation from HCV-viremic versus uninfected donors. METHODS: We retrospectively reviewed all lung transplant recipients at our institution from April 1, 2017 to October 1, 2020 and then assessed various outcomes between those who received a transplant from HCV-viremic donors versus HCV-negative donors. Primary outcome was to determine if there was a higher incidence of acute and/or chronic allograft rejection when using HCV NAT+ lung donation. We carried out univariate and multivariate analyses. RESULTS: We transplanted 135 patients during the study period, including 18 from HCV-viremic donors. Standard induction therapy with basiliximab and maintenance triple drug immunosuppression was utilized per UC San Diego protocol. All 17 patients receiving HCV-viremic organs developed acute HCV infection and were treated in the postoperative period with 12 weeks of direct acting antivirals (DAA). HCV genotypes included 1, 2, and 3. DAA used included glecaprevir/pibrentasvir (12), sofosbuvir/velpatasvir (1), and ledipasvir/sofosbuvir (2) with drug choice determined by patient's medical insurance coverage. Sustained virological response at 12 weeks after end of DAA therapy (SVR12), indicative of a cure, was achieved in all (100%) recipients. No recipient had a serious adverse event related to HCV infection. The lung transplant recipient (LTR) HCV-viremic donors had lower rates of clinically significant rejection (5.9% vs. 11% LTR HCV-nonviremic donors), and no chronic lung allograft dysfunction at 1 year (vs. 5.9% LTR HCV-nonviremic donors). One-year survival was 100% in the LTR HCV-viremic donors compared to 95.8% in the LTR HCV-nonviremic donors. CONCLUSIONS: We demonstrate the feasibility and success of using HCV NAT + donors with excellent results and without a higher incidence of rejection. Longer term follow-up and a larger sample size are needed to allow this to be a more widely accepted practice for lung transplant programs and payors.

Outcomes following lung transplantation for American Indians/Alaska Natives in the United States.

Limited data is available for American Indians/Alaska Natives (AI/AN) undergoing lung transplant. The goal of our study was to assess outcomes for AI/AN lung transplant recipients (LTR). A retrospective review of data from the Organ Procurement and Transplant Network was performed comparing AI/AN (n = 88) and Caucasian (n = 22,767) LTRs between May 4, 2005 and October 31, 2019. AI/AN LTRs had worse functional parameters prior to transplantation but had similar post-transplant outcomes compared to Caucasians LTRs.

An Unexpected Cause of Lung Disease Identified After Lung Transplantation.

CASE PRESENTATION: A 54-year-old woman with systemic lupus erythematosus with associated interstitial lung disease (ILD) presented to the lung transplant clinic for assessment of candidacy for transplantation. She was initially diagnosed with ILD based on clinical and radiographic features (never underwent lung biopsy). In addition, she had associated mixed group I/III pulmonary arterial hypertension. The patient had no family history of pulmonary disease and had never used tobacco and did not have a history of illicit drug use. She was maintained on systemic immunosuppression with hydroxychloroquine, mycophenolate mofetil, and nintedanib for ILD as well as inhaled treprostinil, sildenafil, and macitentan for pulmonary arterial hypertension. Given her progressive symptoms on maximal medical therapy, she was referred for consideration to undergo lung transplantation.

Tolerability and Feasibility of the Upper Esophageal Sphincter Assist Device in Preventing Acute and Chronic Allograft Rejection Among Lung Transplant Recipients.

GOALS: We aimed to evaluate a novel upper esophageal sphincter (UES) assist device loaner program for the prevention of acute cellular rejection and chronic lung allograft dysfunction among lung transplant (LTx) recipients. BACKGROUND: Laryngopharyngeal reflux can lead to chronic microaspiration and LTx rejection. The UES assist device applies external pressure at the level of UES to decrease reflux. STUDY: We prospectively enrolled and issued UES assist devices to consecutive transplant patients referred for gastrointestinal motility testing from 2016 to 2020. Device tolerability was defined by successful utilization as a bridge to ambulatory pH monitoring and/or antireflux procedure, or as permanent therapy. Incidence of rejection was analyzed before, during, and after device implementation. RESULTS: Twenty-six participants were issued devices (15 pathologic, 5 physiological, 6 unknown reflux status), none of whom developed acute rejection episodes or chronic lung allograft dysfunction while using the device. Thirteen adopted the device promptly after transplantation (mean 1.7 mo) and remained free of rejection episodes over a mean 24.7 months of follow-up. Among those with pathologic reflux, lag time to device adoption strongly correlated with the development of rejection ( r =0.8, P =0.0006). There was no such correlation among those with physiological reflux. Five developed acute rejection after device return. CONCLUSIONS: The device was tolerated by a majority of LTx patients and appears feasible as a barrier measure in the prevention of rejection. Delayed treatment of laryngopharyngeal reflux may lead to early allograft failure; therefore, the UES assist device should be given important consideration in transplant protection.

Heart and Lung Transplant for Mixed Connective Tissue Disease: A Case Report and Implications for Pretransplant Testing.

We present a case of end-stage lung disease secondary to mixed connective tissue disease (MCTD) with concomitant myocarditis found on explant at time of transplant. The patient is a 37-year-old man who was first diagnosed with interstitial lung disease secondary to MCTD at 30 years of age. He underwent en bloc heart-lung transplant for progressive decline in left ventricular ejection fraction and severe pulmonary fibrosis despite immunosuppression with hydroxychloroquine, mycophenolate, and azathioprine. Cardiac MRI failed to demonstrate findings suggestive of myocarditis; however, explant demonstrated significant lymphocytic infiltrate with myocyte damage and areas of fibrosis with myocyte hypertrophy. In patients presenting with unexplained systolic dysfunction in the setting of MCTD, fluorodeoxyglucose-positron emission tomography may be a screening tool and if myocardial inflammation is noted, there may be a role for increased immunosuppression. While this strategy was not employed in our patient, his improvement in left ventricular ejection fraction while on mycophenolate mofetil as compared with HCQ and explant histology suggests a process that may have been further responsive to escalation of immunosuppression.

Use of low-dose thrombolytics for treatment of intracardiac thrombus and massive pulmonary embolus after aborted liver transplant leads to recovery of right ventricular function and redo liver transplantation.

This is a 61-year-old man with end-stage liver disease who experienced cardiac arrest secondary to a massive pulmonary embolus and intracardiac thrombus during cannulation for veno-venous extracorporeal membrane oxygenation (ECMO) in preparation for orthotopic liver transplantation (OLT). Surgery was aborted and the patient was taken back to the intensive care unit in cardiogenic shock on multiple vasopressors. The patient was unresponsive to heparin bolus and too high risk for systemic thrombolytics or embolectomy. He was ultimately treated with 12 mg total of alteplase through his pulmonary artery catheter over 3 hours. He had subsequent resolution of his cardiogenic shock and proceeded with successful liver transplantation 5 days after his initial event without any bleeding complications. Low-dose thrombolytic therapy in the setting of absolute contraindications to thrombolysis allowed for recovery of cardiac function and, ultimately redo OLT in a patient with otherwise little hope of survival.

Resolution of a Mobile Right Atrial Thrombus Complicating Acute Pulmonary Embolism With Low-Dose Tissue Plasminogen Activator in a Patient With Recent Craniotomy.

Right heart thrombus in transit (RHTT) is a rare, severe form of venous thromboembolism that carries a high mortality rate. The optimal treatment for RHTT has not been well established. Thrombolysis is a therapeutic modality for RHTT but carries the risk of bleeding complications including intracranial hemorrhage. Low-dose thrombolysis has been shown to be effective in treating submassive pulmonary emboli without an increased risk in bleeding complications, but it has not been studied in patients with RHTT. Here, we discuss the case of a 74-year-old male with lung cancer and recent craniotomy with metastasectomy 30 days prior to admission presenting with RHTT and bilateral pulmonary emboli (PE). He was treated successfully with low-dose thrombolysis, despite his relative contraindication to thrombolytics. To our knowledge, this is the first reported case of low-dose alteplase (tissue plasminogen activator [tPA]) used to treat an in-transit PE in the setting of recent craniotomy with metastasectomy.

Activation of aortic endothelial cells by oxidized phospholipids: a phosphoproteomic analysis.

Previous studies have shown that oxidized products of the phospholipid PAPC (Ox-PAPC) are strong activators of aortic endothelial cells and play an important role in atherosclerosis and other inflammatory diseases. We and others have demonstrated that Ox-PAPC activates specific signaling pathways and regulates a large number of genes. Using a phosphoproteomic approach based on phosphopeptide enrichment and mass spectrometry analysis, we identified candidate changes in Ox-PAPC-induced protein phosphorylation of 228 proteins. Functional annotation of these proteins showed an enrichment of the regulation of cytoskeleton, junctional components, and tyrosine kinases, all of which may contribute to the phenotypic and molecular changes observed in endothelial cells treated with Ox-PAPC. Many changes in protein phosphorylation induced by Ox-PAPC are reported here for the first time and provide new insights into the mechanism of activation by oxidized lipids, including phosphorylation-based signal transduction.