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.

Difference in immunosuppressant dose requirement when transitioning to isavuconazole from other azoles in thoracic transplant recipients.

The triazole antifungal isavuconazole (ISAVU) is used for prevention and treatment of fungal infections in solid organ transplant (SOT). SOT recipients commonly need to transition from one azole to another due to breakthrough infection, toxicity, or other reasons. The purpose of our study was to evaluate the effect of ISAVU on immunosuppressant concentrations in thoracic transplant recipients when ISAVU was started de novo or transitioned from another azole. We conducted a single-center retrospective cohort study including 68 patients (51 lung, 14 heart, and 3 heart/lung transplant). Concentration to dosage ratios (C/D) of immunosuppressants were assessed at baseline, day 3, and weekly for 9 weeks. When starting ISAVU de novo, we observed a temporary doubling of tacrolimus exposure. Cyclosporine and sirolimus required dose decreases. Tacrolimus C/D increased by 110% at day 3 in patients started on ISAVU de novo then returned to baseline C/D ± 17% weeks 2-9 (n = 8). One cyclosporine patient started on ISAVU de novo had variable C/D, and C/D increased by 219% ± 72% in 2 sirolimus patients. When transitioning from other azoles, tacrolimus and cyclosporine required about twice the initial dose. After week 1, tacrolimus C/D decreased by 53% ± 6% in patients transitioned from posaconazole (n = 33), voriconazole (n = 14), or fluconazole (n = 2). Cyclosporine C/D decreased by 45% ± 16% in patients transitioning from other azoles (posaconazole [n = 2], voriconazole [n = 2], fluconazole [n = 1]). Sirolimus C/D decreased by 73% ± 13% in patients transitioned from posaconazole (n = 7). Aside from the initial loading phase, ISAVU had a lesser degree of interaction with immunosuppressants than other azoles in loading phase, ISAVU had a lesser degree of interaction with immunosuppressants than other azoles in adjustments for the 4-week period after initiating antifungal therapy with ISAVU or switching from another agent.

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.

Pre-arterialization of coronary veins prior to retroperfusion of ischemic myocardium: percutaneous closure device.

Background: Chronic coronary retroperfusion to treat myocardial ischemia has previously failed due to edema and hemorrhage of coronary veins suddenly exposed to arterial pressures. The objective of this study was to selectively adapt the coronary veins to become arterialized prior to coronary venous retroperfusion to avoid vascular edema and hemorrhage. Methods and results: In 32 animals (Group I = 19 and Group II = 13), the left anterior descending (LAD) artery was occluded using an ameroid occlusion model. In Group I, the great cardiac vein was blocked with suture ligation (Group IA = 11) or with occlusion device (Group IB = 8) to arterialize the venous system within 2 weeks at intermediate pressure (between arterial and venous levels) before a coronary venous bypass graft (CVBG) was implemented through a left internal mammary artery (LIMA) anastomosis. Group II only received the LAD artery occlusion and served as control. Serial echocardiograms showed recovery of left ventricular (LV) function with this adaptation-arterialization approach, with an increase in ejection fraction (EF) in Group I from 38% ± 5% after coronary occlusion to 53% ± 7% eight weeks after CVBG, whereas in Group II the EF never recovered (41% ± 2%-33% ± 7%). The remodeling of the venous system not only allowed restoration of myocardial function when CVBG was implemented but possibly promoted a novel form of "collateralization" between the native arterioles and the newly arterialized venules, which revascularized the ischemic myocardium. Conclusions: These findings form a potential rationale for a venous arterialization-revascularization treatment for the refractory angina and the "no-option" patients using a hybrid percutaneous (closure device for arterialization)/surgical approach (CVBG) to revascularize the myocardium.

Sirolimus Long-Term Tolerability and Impact on Kidney Function in Lung Transplantation: A Single-Center Experience.

BACKGROUND: After lung transplant, 2 common complications are calcineurin inhibitor (CNI) induced nephrotoxicity and bronchiolitis obliterans syndrome. The objective of this study was to investigate the long-term effects of sirolimus conversion after lung transplantation. METHODS: This was a retrospective cohort study of patients who had undergone lung transplantation at a single center from June 2003 to December 2016. We compared patients converted to a sirolimus-based regimen to those maintained on our standard tacrolimus-based regimen. Kidney function, pulmonary function, and immunosuppression concentrations were compared between the groups. Additionally, indications, toxicity monitoring parameters, and discontinuation rates for sirolimus were collected. RESULTS: During the study period, 176 of the 205 patients who underwent lung transplants were converted to a sirolimus-containing regimen (86%). The most common reason for sirolimus initiation was impairment of kidney function or CNI-associated neurotoxicity. Sirolimus was initiated at a median of 150 days post-transplantation and continued for a medium time of 5.02 (2.27-7.85) years. Of those patients converted to sirolimus, 39 (22%) had sirolimus subsequently discontinued secondary to an adverse event. No difference in pulmonary function was found between the groups at 1- and 3-years post-transplantation. In the sirolimus group, the median estimated glomerular filtration rate improved by 8.6 mL/min/1.73 m2 at 3 months post-conversion (P < .001), which was maintained at both 1 and 3 years (P = .014 and .025, respectively). CONCLUSION: Sirolimus is a viable immunosuppressant option after lung transplant, which successfully allows for the reduction or withdrawal of the CNI, resulting in sustained improvement in kidney function.

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.

Development of Host Immune Response to Bacteriophage in a Lung Transplant Recipient on Adjunctive Phage Therapy for a Multidrug-Resistant Pneumonia.

Bacteriophage therapy is the use of viruses to kill bacteria for the treatment of antibiotic-resistant infections. Little is known about the human immune response following phage therapy. We report the development of phage-specific CD4 T cells alongside rising phage-specific immunoglobulin G and neutralizing antibodies in response to adjunctive bacteriophage therapy used to treat a multidrug-resistant Pseudomonas aeruginosa pneumonia in a lung transplant recipient. Clinically, treatment was considered a success despite the development phage-specific immune responses.

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.

A Pilot Trial for Prevention of Hepatitis C Virus Transmission From Donor to Organ Transplant Recipient With Short-Course Glecaprevir/Pibrentasvir.

A 7-day course of glecaprevir/pibrentasvir started in the preoperative period prevented transmission of hepatitis C virus (HCV) from viremic donors to 10 HCV-negative recipients (2 heart, 1 lung, 6 kidney, 1 heart/kidney) with 100% sustained virological response at 12 weeks.

Novel Biomaterial for Artery Patch in Swine Model With High-Fat Diet.

OBJECTIVE: We evaluated swine and bovine pulmonary visceral pleura (PVP) in artery patch-angioplasty in swine model of high-fat diet. BACKGROUND: Arterial patch-angioplasty is frequently used for repair or reconstruction of arteries. An autologous patch is often limited by the number and dimension of donor tissue and can result in donor complications. Furthermore, mechanical mismatch is a cause of poor performance of vascular reconstruction. Here, we introduce a readily available patch biomaterial with similar compliance as native arteries. METHODS: The PVP was peeled from swine and bovine lungs by hydro-dissection. The swine and bovine PVPs were crosslinked with glutaraldehyde and then sterilized. The swine PVP (sPVP) patches were implanted in the carotid and femoral arteries of six Yorkshire pigs that were fed a regular diet and euthanized at 2 and 4 months postoperative. The bovine PVP (bPVP) patches were implanted in the carotid artery of six Yucatan pigs that were fed a high-fat diet and euthanized at 4 months postoperative. Patency was evaluated by ultrasound and angiography. Neo-endothelium and media were evaluated by histologic examination. RESULTS: All arteries in patch-angioplasties remained patent with no adhesions, inflammation, or aneurysms. Biomarkers of endothelial cells (e.g., Factor VIII and eNOS) were detected in the neo-endothelial cells. We observed endothelial cell-cell junctions in the confluent neo-endothelium in the PVP patches. Neo-media composed of vascular smooth muscle developed similar as native arteries. In the hypercholesterolemic model, we observed the accumulation of cholesterol in both arterial tissues and in the neo-vascular tissues in the PVP patches. Protein expressions of lipid transport and metabolism (e.g., APOE-1, ABCA, and PACK9) were also observed in both arterial and neo-vascular tissues. CONCLUSION: The PVP patch-angioplasty overcomes the pitfalls of compliance mismatch of synthetic patches and has a non-thrombogenic surface. The proliferation of vascular cells assembled to generate the neo-endothelium and media in the patch-angioplasties to support long-term patency. The neo-vascular tissue in PVP patch-angioplasty also developed similar cellular functions for lipid transport and metabolism compared with native arteries in hypercholesterolemia.

Implementation and Outcomes of a Mobile Extracorporeal Membrane Oxygenation Program in the United States During the Coronavirus Disease 2019 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic began in the United States around March 2020. Because of limited access to extracorporeal membrane oxygenation (ECMO) in the authors' region, a mobile ECMO team was implemented by April 2020 to serve patients with COVID-19. Several logistical and operational needs were assessed and addressed to ensure a successful program, including credentialing, equipment management, and transportation. A multidisciplinary team was included in the planning, decision-making, and implementation of the mobile ECMO. From April 2020 to January 2021, mobile ECMO was provided to 22 patients in 13 facilities across four southern California counties. The survival to hospital discharge of patients with COVID-19 who received mobile ECMO was 52.4% (11 of 21) compared with 45.2% (14 of 31) for similar patients cannulated in-house. No significant patient or transportation complications occurred during mobile ECMO. Neither the ECMO nor transport teams experianced unprotected exposures to or infections with severe acute respiratory syndrome coronavirus 2. Herein, the implementation of the mobile ECMO team is reviewed, and patient characteristics and outcomes are described.

Treatment of Bronchopleural and Alveolopleural Fistulas in Acute Respiratory Distress Syndrome With Extracorporeal Membrane Oxygenation, a Case Series and Literature Review.

OBJECTIVES: To describe a ventilator and extracorporeal membrane oxygenation management strategy for patients with acute respiratory distress syndrome complicated by bronchopleural and alveolopleural fistula with air leaks. DESIGN SETTING AND PARTICIPANTS: Case series from 2019 to 2020. Single tertiary referral center-University of California, San Diego. Four patients with various etiologies of acute respiratory distress syndrome, including influenza, methicillin-resistant Staphylococcus aureus pneumonia, e-cigarette or vaping product use-associated lung injury, and coronavirus disease 2019, complicated by bronchopleural and alveolopleural fistula and chest tubes with air leaks. MEASUREMENTS AND MAIN RESULTS: Bronchopleural and alveolopleural fistula closure and survival to discharge. All four patients were placed on extracorporeal membrane oxygenation with ventilator settings even lower than Extracorporeal Life Support Organization guideline recommended ultraprotective lung ventilation. The patients bronchopleural and alveolopleural fistulas closed during extracorporeal membrane oxygenation and minimal ventilatory support. All four patients survived to discharge. CONCLUSIONS: In patients with acute respiratory distress syndrome and bronchopleural and alveolopleural fistula with persistent air leaks, the use of extracorporeal membrane oxygenation to allow for even lower ventilator settings than ultraprotective lung ventilation is safe and feasible to mediate bronchopleural and alveolopleural fistula healing.

Vertebral Artery Stump Syndrome Due to Chronic Complicated Aortic Dissection.

BACKGROUND: Vertebral artery (VA) stump syndrome arises when thrombi of an occluded proximal VA propagate to the brain and cause posterior circulation strokes. This phenomenon has been described in limited reports to date. CASE DESCRIPTION: A 39-year-old man with a remote history of endovascular repair of a type B aortic dissection experienced type Ia endoleak causing expansion of the false lumen associated with the dissection. This required combined open debranching and endovascular reconstruction of the thoracic aortic arch. He experienced recurrent posterior circulation strokes 6 months postoperatively. The left VA origin was occluded and remained sequestered to the proximal subclavian artery, in continuity with the false lumen of the dissection. We suspected the aortic dissection extended into the VA and caused the occlusion, while pressure from the false lumen propelled thrombi from the occluded VA stump into the posterior circulation. Repeat imaging shortly after symptom onset showed spontaneous recanalization of the VA. Open surgical ligation of the proximal left VA led to symptom resolution. CONCLUSIONS: We describe a unique mechanism of VA stump syndrome due to VA occlusion and pressure waves from an aortic dissection and present the first report of VA stump syndrome treatment by surgical exclusion of the VA.

E-cigarette, or vaping, product use-associated lung injury (EVALI) treated with veno-venous extracorporeal membrane oxygenation (VV-ECMO) and ultra-protective ventilator settings.

A 19-year-old man vaping with tetrahydrocannabinol presented with dyspnoea and right pneumothorax. History, imaging and negative infectious workup were consistent with E-cigarette, or vaping, product use-associated lung injury (EVALI). Treated with systemic steroids, he developed acute respiratory distress syndrome and was intubated requiring veno-venous extracorporeal membrane oxygenation (VV-ECMO) by hospital day 3. Using VV-ECMO, very-low tidal volume ventilation of 1.5 cc/kg was achieved, as was daily ambulation. VV-ECMO was decannulated on hospital day 9 and the patient was extubated the next day. He was discharged home on hospital day 13 without oxygen. At post-intensive care unit clinic follow-up, he had lost 20 kg of weight while hospitalised and reported nightmares. Patients with EVALI may be supported with VV-ECMO, which allows ultra-lung-protective mechanical ventilation that may minimise ventilator-induced lung injury. Follow-up in patients with EVALI is essential to diagnose and treat comorbidities, follow lung function and prevent relapses.

Spontaneous Left Atrial Thrombus Formation on the Catheter Delivery System During WATCHMAN Implantation.

We present a rare complication of spontaneous thrombus formation on the WATCHMAN delivery system, on both the right- and left-sided systemic circulation. We also describe the multidisciplinary team approach and the use of percutaneous vacuum-assisted aspiration system (AngioVac, AngioDynamics, Latham, New York) for successful thrombus removal. (Level of Difficulty: Intermediate.).

Homologous and heterologous assessment of a novel biomaterial for venous patch.

OBJECTIVE: This study evaluated swine and bovine pulmonary visceral pleura (PVP) as a vascular patch. Venous patches are frequently used in surgery for repair or reconstruction of veins. Autologous patches are often limited by the number and dimension of donor tissue and can result in donor complications. Bovine pericardium is the most common heterologous patch used by vascular surgeons. Researchers, however, are continually seeking to improve heterologous and synthetic patches for improved outcome. METHODS: The PVP was peeled from swine and bovine lungs and cross-linked with glutaraldehyde. After sterilization and rinsing, the PVP patches were implanted in the jugular vein (10 × 35 mm) of pigs and dogs. Patency was evaluated by ultrasound, and animals were euthanized at 2 and 4 months. Neoendothelium and neomedia were evaluated by histologic analysis. RESULTS: The jugular vein patched by PVP in pigs and dogs remained patent at 2 and 4 months with no adhesions, inflammation, or aneurysm in the patches. The biomarkers of endothelial cells-factor VIII, platelet/endothelial cell adhesion molecule 1, and endothelial nitric oxide synthase-were detected in the neoendothelial cells. The expression of vascular smooth muscle cell (VSMC) α-actin was robust in the neomedia at 2 and 4 months. Neomedia composed of VSMCs developed to nearly double the thickness of adjacent jugular vein. The circumferential orientation of VSMCs in neomedia further increased in the 4-month group. CONCLUSIONS: The cross-linked swine and bovine PVP patch has a nonthrombogenic surface that maintains patency. The PVP patch may overcome the pitfall of compliance mismatch of synthetic patches. The proliferation of vascular cells assembled in the neoendothelium and neomedia in the patches may support long-term patency.

Novel Use of Cangrelor With Heparin During Cardiopulmonary Bypass in Patients With Heparin-Induced Thrombocytopenia Who Require Cardiovascular Surgery: A Case Series.

Optimal anticoagulation strategy during cardiopulmonary bypass (CPB) remains uncertain in patients with heparin-induced thrombocytopenia (HIT) who require urgent/emergent cardiac surgery. We describe our strategy and experience with utilizing cangrelor in combination with heparin for anticoagulation during CPB in patients with different phases of HIT undergoing a wide range of urgent/emergent cardiovascular surgery. Cangrelor is an intravenous direct-acting P2Y12 platelet receptor antagonist that achieves therapeutic effect and eliminates rapidly. Its antiplatelet activity is unaffected by stagnation of blood, nor is it influenced by patient's sex, age, renal status, or hepatic function. Our institutional alternative intraoperative anticoagulation strategy for HIT patients is to administer cangrelor with a loading dose of 30 µg/kg, followed by continuous infusion of 4 µg/kg/min throughout CPB via a dedicated intravenous access. VerifyNow P2Y12 reaction unit point-of-care assay is utilized to monitor platelet inhibition throughout surgery. Cangrelor infusion is discontinued 10 minutes prior to heparin reversal with protamine. Ten urgent/emergent cardiovascular surgeries were performed at our institution using cangrelor with heparin for anticoagulation during CPB, and the majority were pulmonary thromboendarterectomy (60%). HIT was confirmed in 3 cases and was suspected in 4 which was found to be negative after the operation. One case of subacute B HIT and 2 cases of remote HIT were included in this series. This novel alternative intraoperative anticoagulation strategy was well tolerated by all patients. There was neither serious postoperative thrombotic event nor major postoperative bleeding complication that required reoperation. One death occurred in a patient with advanced intracardiac malignancy, whose life support was ultimately withdrawn postoperatively. Median postoperative intensive care unit stay was 7.2 ± 5.5 days, while median postoperative hospital stay was 16.3 ± 10.8 days. In patients with various phases of HIT who require urgent/emergent on-pump cardiovascular surgery, the use of cangrelor with heparin may be a convenient, safe, and effective alternative intraoperative anticoagulation strategy providing acceptable outcomes.