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Little is known about the effects of hepatitis C viremia on immunologic outcomes in the era of direct-acting antivirals. We conducted a prospective, single-arm trial of lung transplantation from hepatitis C-infected donors into hepatitis C-naïve recipients (n = 21). Recipients were initiated on glecaprevir-pibrentasvir immediately post-transplant and were continued on therapy for a total of 8 weeks. A control group of recipients of hepatitis C-negative lungs were matched 1:1 on baseline variables (n = 21). The primary outcome was the frequency of acute cellular rejection over 1-year post-transplant. Treatment with glecaprevir-pibrentasvir was well tolerated and resulted in viremia clearance after a median of 16 days of therapy (IQR 10-24 days). At one year, there was no difference in incidence of acute cellular rejection (71.4% vs. 85.7%, P = .17) or rejection requiring treatment (33.3% vs. 57.1%, P = .12). Mean cumulative acute rejection scores were similar between groups (.46 [SD ± .53] vs. .52 [SD ± .37], P = .67). Receipt of HCV+ organs was not associated with acute rejection on unadjusted Cox regression analysis (HR .55, 95% CI .28-1.11, P = .09), or when adjusted for risk factors known to be associated with acute rejection (HR .57, 95% CI .27-1.21, P = .14). Utilization of hepatitis C infected lungs with immediate treatment leads to equivalent immunologic outcomes at 1 year.

Objectives Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may develop end-stage lung disease requiring lung transplantation. We report the clinical course, pulmonary pathology with radiographic correlation, and outcomes after lung transplantation in three patients who developed chronic respiratory failure due to postacute sequelae of SARS-CoV-2 infection. Methods A retrospective histologic evaluation of explanted lungs due to coronavirus disease 2019 was performed. Results None of the patients had known prior pulmonary disease. The major pathologic findings in the lung explants were proliferative and fibrotic phases of diffuse alveolar damage, interstitial capillary neoangiogenesis, and mononuclear inflammation, specifically macrophages, with varying numbers of T and B lymphocytes. The fibrosis varied from early collagen deposition to more pronounced interstitial collagen deposition; however, pulmonary remodeling with honeycomb change was not present. Other findings included peribronchiolar metaplasia, microvascular thrombosis, recanalized thrombi in muscular arteries, and pleural adhesions. No patients had either recurrence of SARS-CoV-2 infection or allograft rejection following transplant at this time. Conclusions The major pathologic findings in the lung explants of patients with SARS-CoV-2 infection suggest ongoing fibrosis, prominent macrophage infiltration, neoangiogenesis, and microvascular thrombosis. Characterization of pathologic findings could help develop novel management strategies.

Background Several studies have described improved survival with double lung transplant (DLT) compared with single lung transplant (SLT) in pulmonary fibrosis. To avoid the innate selection bias of including patients exclusively listed for SLT or DLT, this study analyzed those deemed appropriate for either procedure at time of listing. Methods All consecutive adult lung transplants for idiopathic pulmonary fibrosis provided by the Scientific Registry of Transplant Recipients were retrospectively reviewed (2007-2017). Isolated lobar transplants (n = 11) or patients listed only for SLT (n = 1834) or DLT (n = 2372) were excluded. Group stratification was based on the ultimate procedure (SLT vs DLT). Group propensity matching was performed based on 24 recipient and donor characteristics. Recipient demographics, donor demographics, and outcomes were compared between groups. Results During the study period 45% (974/2179) and 55% (1205/2179) of patients ultimately received SLT and DLT, respectively. After propensity matching 466 matched patients remained in each group. SLT patients were less likely to require prolonged (>48 hours) ventilator support than DLT patients. There was also a trend toward reduced rates of posttransplant renal failure and hospital length of stay in SLT recipients. Whether analyzed by time of listing or time of transplant, survival was similar between groups. Conclusions In recipients concurrently listed for SLT and DLT overall survival was similar regardless of the eventual procedure. These data suggest that the previously purported survival advantage for DLT may purely represent selection bias and should not preclude the use of SLT in appropriately selected idiopathic pulmonary fibrosis patients.

Purpose Azole antifungals are commonly prescribed for fungal prophylaxis (ppx) following lung transplant, but have many side effects and drug interactions. Isavuconazole, a new broad-spectrum azole antifungal, may obviate these issues. Methods We retrospectively reviewed all lung transplant recipients (LTR) from February 2018 through September 2019 who received either ISA or POS for fungal ppx for 3 months post-transplant. Prior to February 2019 all patients received POS for ppx. Starting February 2019, POS was replaced by ISA at standard dosing. All patients received basiliximab induction and standard triple immunosuppression post-transplant. Surveillance bronchoscopies were performed at 1, 3, 6, and 12 months post-transplant. Results In total, we reviewed 24 LTR who received ISA and 29 who received POS. Baseline characteristics were similar between groups. Median duration of follow-up was significantly shorter for the ISA group (137 vs. 340 days, p Conclusion Breakthrough fungal infections were similar between LTR receiving ISA or POS for fungal ppx. Longer follow-up of ISA patients is needed for definitive comparison of long-term infection risk. POS was discontinued in more patients due to drug interactions. ISA is a reasonable choice for primary fungal ppx in LTR.

We conducted a retrospective review of thoracic transplant recipients (22 heart and 16 lung transplant recipients) prospectively enrolled in a single-center observational study of HCV NAT+ organ transplantation in HCV NAT- recipients. All recipients were treated with 8 weeks of glecaprevir-pibrentasvir (GP) for HCV viremia in addition to standard triple immunosuppression post-transplant. Thoracic transplant recipients of HCV NAT- organs were used as a control (24 heart and 22 lung transplant recipients). Our primary outcome was to assess the effect of GP on tacrolimus dose requirements. Secondary objectives included assessing drug interactions with common post-transplant medications, adverse effects, and the need to hold or discontinue GP therapy. The median tacrolimus concentration-to-dose ratio (CDR) in the cohort was 184 (99-260) during GP therapy and 154 (78-304) over the first month after GP (P = .79). Trends in median tacrolimus CDR were similar on a per-week basis and per-patient basis. In three instances, concomitant posaconazole and GP led to hyperbilirubinemia and interruption of posaconazole. GP therapy was held in one heart transplant recipient and discontinued in another due to unresolving hyperbilirubinemia. Utilization of GP to treat HCV viremia post-thoracic transplant is feasible and safe, but requires modifications to post-transplant pharmacotherapy and careful monitoring for adverse effects.

Background The lung allocation score (LAS) was designed to optimize the use of pulmonary allografts based on anticipated pretransplant survival and posttransplant outcome. Hospital admission status, not included in the LAS, has not been comprehensively investigated with regard to organ allocation. The objective of this study was to determine whether pretransplant hospital admission status was independently associated with posttransplant mortality and whether high center volume was associated with improved survival in that cohort. Methods All consecutive adult lung transplants provided by the Scientific Registry of Transplant Recipients were retrospectively reviewed (from 2007 to 2017). Group stratification was performed based on admission status at the time of transplantation. A Cox proportional hazard regression was used to determine independent associations with posttransplant mortality. Results During the study period, 3747 of 18,416 recipients (20%) were admitted to the hospital at the time of transplantation. Compared with nonadmitted recipients, LAS were significantly higher and waitlist times significantly shorter. Admitted recipients had higher rates of prolonged mechanical ventilation, higher rates of posttransplant dialysis, and longer posttransplant lengths of stay. Pretransplant admission to a low-volume center conferred significantly worse survival compared with nonadmitted patients, and high-volume centers were independently associated with improved survival compared with low-volume centers. Conclusions Hospital admission status is associated with increased posttransplant mortality independent of the LAS and the factors from which it is calculated. However, adjusted survival analysis demonstrates that admission to a high-volume center appears to be independently associated with improved survival compared with low-volume centers.

Background Anastomotic complications occur in 7% to 18% of lung transplant recipients, among which airway dehiscence (AD) is particularly catastrophic. Using multi-institutional registry data, this study compared preoperative recipient/donor risk factors and outcomes in patients with and without AD and analyzed the effect of extracorporeal membrane oxygenation (ECMO) on the incidence of AD. Methods Data on adult lung transplants from 2007 to 2017 were provided by the Scientific Registry of Transplant Recipients. Patients receiving isolated lobar transplantation and patients with unknown AD status were excluded. Multivariable logistic regression identified independent risk factors for AD. Kaplan-Meier curves and log-rank tests describe mortality and graft survival. Results Of 18 122 lung transplants, 275 (1.5%) experienced AD. While the incidence of ECMO steadily increased from 0.7% to 5.9% over the study period, the incidence of AD remained relatively constant. Multivariable analysis revealed recipient male gender and prolonged ( > 48 hours) posttransplant mechanical ventilation as independent predictive factors for AD, while advanced donor age and single left lung transplant were protective factors. Recipient chronic steroid use, recipient diabetes, donor diabetes, and donor smoking history were not predictive of AD. Mortality and graft failure were significantly worse in the AD group. Conclusions Despite increased ECMO utilization, the incidence of AD has remained stable. Multiple independent risk factors for AD were identified and poor postoperative outcomes confirmed. However, many known impediments to wound healing such as recipient chronic steroid use, recipient and donor diabetes, and donor smoking were not identified as risk factors for AD, reinforcing the critical role of technical performance.

Purpose Clostridium difficile infection (CDI) is associated with increased morbidity and mortality after thoracic transplant. In response to a series of cases, our institution implemented primary CDI prophylaxis with oral vancomycin 125 mg twice daily. Methods We retrospectively reviewed all thoracic transplant recipients from January 2018 to March 2020. Exclusion criteria included postoperative antibiotics Results In total, we reviewed 164 thoracic transplant recipients. We excluded 55 patients for a final cohort of 109 patients. There were 63 lung and 46 heart transplant recipients. Twenty-two patients (20%) received prophylaxis and 87 patients (80%) did not. Baseline demographics and hospitalization or receipt of antibiotics within prior 90 days did not differ between groups. Median length of stay was 30 and 43 days in the No PPX and OVP groups, respectively (p=0.01). Post-transplant, more patients in the OVP group were mechanically ventilated greater than 72 hours (16% vs. 46%, p=0.003) or on ECMO (7% vs. 27%, p=0.006). Median duration of antibiotics was 18 and 28 days in the No PPX and OVP groups, respectively (p=0.002). OVP overlapped a median of 95% of antibiotic days and continued for a median of 4 days after antibiotic discontinuation. During hospitalization, CDI occurred in 6 patients (7%) in the No PPX arm and 0 patients in the OVP arm (p=0.35). CDI-free survival did not differ between groups based on the Kaplan-Meier survival analysis (p=0.16). Conclusion Despite a higher degree of post-transplant organ support and significantly longer duration of antibiotics and length of stay, the incidence of CDI trended lower with the use of OVP. Primary OVP should be investigated in larger cohorts.

Purpose 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. Methods 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. Results 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. Conclusion 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.

Introduction Hemophagocytic Lymphohistiocytosis (HLH) is a rare life-threatening hyperinflammatory syndrome. Few case reports exist describing this entity in lung transplant recipients. Case Report A 56-year-old woman with scleroderma and pulmonary hypertension presented two months after double lung transplantation with acute onset abdominal pain, nausea, and vomiting. Her physical examination was notable for mild tenderness to palpation over right upper quadrant. Admission laboratory values revealed aspartate transaminase of 337 U/L, alanine aminotransferase of 430 U/L, alkaline phosphatase of 1083 U/L, total bilirubin of 3.9 mg/dL, and direct bilirubin of 2.9 mg/dL. Abdominal computed tomography (CT) was unremarkable aside from prior cholecystectomy. Subsequent liver biopsy was consistent with drug-induced liver injury, which led to discontinuation of possible culprits. There was no evidence of a hemophagocytic process. As her transaminases recovered to near-normal, she abruptly became leukopenic to 0.1 × 103μ/L and thrombocytopenic to 17 × 109μ/L. She developed new parotid lymphadenopathy and was febrile. Further work-up showed hyperferritinemia of 21899 ng/mL, hypertriglyceridemia of 294 mg/dL, and elevated soluble CD25 of 17780 IU/mL. Repeat abdominal CT showed splenic enhancement. A bone marrow biopsy revealed numerous histiocytes with hemophagocytosis (see image). She was treated with high dose steroids, cyclophosphamide, and a dose of rituximab for Epstein-Barr virus PCR of 390 copies/mL. As all her markers worsened, she began therapy with anakinra. Concurrently, she developed polymicrobial bacteremia, fungemia, and renal failure. Despite aggressive efforts, she deteriorated and passed away. Summary HLH carries a high mortality rate and is commonly underrecognized due to the non-specific nature of its clinical and laboratory findings. Particularly in transplant recipients, where differentials are broader at baseline, early consideration, rapid diagnosis, and prompt treatment are critical.

Purpose We hypothesize that home monitoring and telehealth utilizing data from a mobile healthcare application in conjunction with laboratory values and chest imaging, can replace an outpatient appointment. Methods Our study is comprised of patients who have received a single or bilateral lung transplant or a heart/lung transplant.Before our patients are discharged from their inpatient stay after Transplantation, the application for home monitoring is installed on their smart phone. This application was specifically designed for Lung Transplant Patients. A blood pressure cuff and spirometer are provided and linked to their mobile device using Bluetooth. A weighing scale is also provided which uses a cellular connection to a secure cloud relaying data to the patient's phone and to EPIC. Additional data including (e.g. temperature, pulse oximetry) are manually entered into the application. Physical fitness (steps) is also monitored. The team who created the application enabled the data to flow from the application to our electronic medical record. Alerts are set for each piece of data and any abnormal value is sent to our team's EPIC in-basket for further action.Patients who are compliant with their home monitoring are offered telehealth. Patients are sent for laboratory testing and imaging the week of the appointment close to their home. Results As of October 1, 2019, we have enrolled fifty patients in our home monitoring program. Fourteen patients are now one - year post transplant. Twelve of these patients are compliant with home monitoring. Eight of them have had telehealth visits throughout the year with five receiving the majority of their care utilizing home monitoring and telehealth. These visits occur bimonthly for the first three months after transplant and then monthly for the first year. Conclusion Home monitoring and telehealth visits can replace outpatient visits in the first year following lung transplantation. Patients find the devices easy to use and are satisfied with the care they receive during their telehealth visits. Additionally, telehealth improves patient quality of life by reducing visits to the medical center and avoiding additional costs such as parking and time off work. It also limits pathogen exposure. Long term use may enable early detection of rejection or infection.

Purpose Adequate pain control is essential following lung transplantation to reduce patient stress and minimize perioperative complications. Enhanced recovery after surgery (ERAS) protocols have demonstrated improvements in patient experience and reduced length of stay. However, the implementation of these protocols has not yet extended to the lung transplant population. Methods We retrospectively reviewed all lung transplant recipients (LTR) at our institution from February 2018 to August 2019. An opioid-sparing, multimodal pain regimen was implemented that included preemptive analgesia with gabapentin and acetaminophen (APAP) pre-transplant; liposomal bupivacaine intercostal nerve block (INB) in the operating room; and a combination of APAP, gabapentin, and methocarbamol post-op with opioids given as indicated. Serratus anterior plane block was used for refractory pain. Results In total, we reviewed 48 LTR. The mean LAS was 43.74 and 21% were on mechanical ventilation or ECMO pre-transplant. Frequency of protocol adherence for each agent was as follows: liposomal bupivacaine INB (71%), APAP (100%), gabapentin (98%), methocarbamol (27%), and ketorolac (33%). Seven patients (15%) required a serratus plane block for refractory pain. Pain scores peaked at a median of 5 on postoperative day (POD) 1 and declined to a median of 3 by POD 3. By POD 4 only 54% of patients were still receiving opioids at a median of 15 mg oral morphine equivalents per day (IQR, 0-59). Only 3 patients were discharged on opioids and they were all on opioids pre-transplant. The median duration of mechanical ventilation was 1 day (IQR, 0.64-1.69) and 81% were extubated before 48 hours. The median hospital length of stay was 8 days (IQR, 6-15) and 30-day mortality was 0%. Conclusion Enhanced recovery and opioid-sparing pain protocols are feasible in LTR leading to minimal opioid use and acceptable pain scores. Outcomes with ERAS protocols should be compared to standard-of-care postoperative management.

Therapies targeting inflammation reveal inconsistent results in idiopathic pulmonary fibrosis (IPF). Aerosolised interferon (IFN)-γ has been proposed as a novel therapy. Changes in the host airway microbiome are associated with the inflammatory milieu and may be associated with disease progression. Here, we evaluate whether treatment with aerosolised IFN-γ in IPF impacts either the lower airway microbiome or the host immune phenotype. Patients with IPF who enrolled in an aerosolised IFN-γ trial underwent bronchoscopy at baseline and after 6 months. 16S rRNA sequencing of bronchoalveolar lavage fluid (BALF) was used to evaluate the lung microbiome. Biomarkers were measured by Luminex assay in plasma, BALF and BAL cell supernatant. The compPLS framework was used to evaluate associations between taxa and biomarkers. IFN-γ treatment did not change α or β diversity of the lung microbiome and few taxonomic changes occurred. While none of the biomarkers changed in plasma, there was an increase in IFN-γ and a decrease in Fit-3 ligand, IFN-α2 and interleukin-5 in BAL cell supernatant, and a decrease in tumour necrosis factor-β in BALF. Multiple correlations between microbial taxa common to the oral mucosa and host inflammatory biomarkers were found. These data suggest that the lung microbiome is independently associated with the host immune tone and may have a potential mechanistic role in IPF., Lower airway microbiome and immunological tone are associated in IPF, an effect independent of IFN-γ treatment http://ow.ly/cTDo30bsJiN

Purpose Controversy remains over the mortality benefit of single (SLT) versus double lung transplantation (DLT) in idiopathic pulmonary fibrosis (IPF). Independent of this controversy, hesitancy to perform SLT in this population exists on the basis of unclear one year functional status. We compared functional status at one year between IPF patients listed for both who ultimately received SLT or DLT. Methods All consecutive adult lung transplants for IPF provided by the Scientific Registry of Transplant Recipients were retrospectively reviewed (2007-2017). Isolated lobar transplants (n=4), patients listed only for SLT (n=1834) or DLT (n=2372), and patients with missing functional status data (n=715) were excluded. Group stratification was based on the ultimate procedure (SLT or DLT). Group propensity matching was performed based on 25 recipient/donor characteristics. We compared ‘good functional status’, defined as >70%, at one year. Results During the study period, 45% (660/1464) and 55% (804/1464) of patients listed for both procedures ultimately received SLT and DLT, respectively. After propensity matching, 341 matched patients remained in each group. Donor and recipient characteristics were similar (Table). There was no statistically significant difference in ‘good functional status’ at one year between SLT (77%, 264/341) and DLT (81%, 275/341) (p=0.301). The same trend is present for patients younger than 50 who receive SLT (82%, 23/28) versus DLT (94%, 34/36) (p=0.225), and patients between 50 and 60 who receive SLT (78%, 86/110) versus DLT (84%, 97/115) (p=0.305). The opposite trend is noted in patients older than 70 who receive SLT (72%, 13/18) versus DLT (61%, 11/18) (p=0.725). Conclusion In this cohort of lung transplant recipients listed for both SLT and DLT, functional status was statistically similar between groups, even in younger recipients. This data suggests that SLT should not be precluded in IPF patients on the basis of expected functional status at one year.

Background: Therapies targeting the inflammatory process revealed inconsistent results in Idiopathic Pulmonary Fibrosis (IPF). Aerosolized Interferon Gamma (IFN-y) has been proposed as a novel therapy. Additionally, changes in the host airway microbiome have been associated with inflammatory tone and, in IPF, may be associated with disease progression. We evaluate whether …