Faculty Bibliography

Rates of lung donation have increased over the past several years. This has been accomplished through the utilization of donors with extended criteria, the creation of donor hospitals or centers, and the optimization of lungs through the implementation of donor management protocols. These measures have resulted in augmenting the pool of available donors thereby decreasing the wait time for lung transplantation candidates. Although transplant programs vary significantly in their acceptance rates of these organs, studies have not shown any difference in the incidence of primary graft dysfunction or overall mortality for the recipient when higher match-run sequence organs are accepted. Yet, the level of comfort in accepting these donors varies among transplant programs. This deviation in practice results in these organs going to lower-priority candidates thereby increasing the waitlist time of other recipients and ultimately has a deleterious effect on an institution's waitlist mortality.

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/OBJECTIVE: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.

Introduction: Community-acquired Cytomegalovirus (CMV) infection in a seronegative transplant recipient (R) from a seronegative donor (D) is a rare occurrence that carries significant clinical and prognostic implications. Few case reports exist describing this entity in lung transplant recipients. Case Report: A 58-year-old man with bilateral lung transplant for sarcoidosis presented with three days of diarrhea and dyspnea. He underwent an uneventful bilateral lung transplantation (CMV D-/R-) six weeks prior, receiving basiliximab and methylprednisolone for induction. He was discharged two weeks later on tacrolimus, mycophenolate motefil, and prednisone taper as maintenance immunosuppression. He was receiving acyclovir for herpes viruses prophylaxis. He was seen weekly post-discharge and continued to have clear chest radiographs and unremarkable bloodwork. On presentation, his physical examination was notable for decreased breath sounds at the right base. His laboratory values revealed creatinine of 2.4 mg/dL. His chest radiograph showed new right pleural effusion. He was admitted for hydration and diarrhea work up. Abdominal computed tomography (CT) revealed mild diverticulitis with no colitis and his stool studies were positive for Clostridium difficile. Chest CT showed hazy and linear markings with thin-walled cysts in right lower lobe, adjacent to a moderate pleural effusion. CMV by polymerase chain reaction resulted at 318,200 copies/mL. He was treated with intravenous ganciclovir and underwent a thoracenthesis. Half a liter of clear pleural fluid was removed and was notable for lymphocytic predominance of 72% as well as polytypic plasma cells and a small number of B lymphocytes with no surface immunoglobulins on flow cytometry. Subsequent radiograph showed completely re-expanded lung. Within two days, the effusion re-accumulated and additional half a liter were drained, revealing of 95% lymphocytes, with complete re-expansion of the lung. Concomitant viral load remained elevated at 150,328 copies/mL. He was discharged on valganciclovir, his viral load decreased to an undetectable level, and his radiographs have remained free of effusion. While primary CMV infection is rare in low-risk lung transplant recipients, CMV disease should be considered in the differential diagnosis of early post-operative pleural effusion.
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Opioid analgesics are commonly used post-lung transplant, but have many side effects and are associated with worse outcomes. We conducted a retrospective review of all lung transplant recipients who were treated with a multimodal opioid-sparing pain protocol. The use of liposomal bupivacaine intercostal nerve block was variable due to hospital restrictions. The primary objective was to describe opioid requirements and patient-reported pain scores early post-lung transplant and to assess the impact of intraoperative liposomal bupivacaine intercostal nerve block. We treated 64 lung transplant recipients with our protocol. Opioid utilization decreased to a mean of 43 milligram oral morphine equivalents by postoperative day 4. Median pain scores peaked at 4 on postoperative day 1 and decreased thereafter. Only three patients were discharged home with opioids, all of whom were taking opioid agonist therapy pre-transplant for opioid use disorder. Patients who received liposomal bupivacaine intercostal nerve block in the operating room had a significant reduction in opioid consumption over postoperative day 1 through 4 (228 mg vs. 517 mg, P= .032). A multimodal opioid-sparing pain management protocol is feasible and resulted in weaning of opioids prior to hospital discharge.

BACKGROUND:The lung allocation score (LAS) was designed to optimize the utilization of pulmonary allografts based on anticipated pre-transplant survival and post-transplant outcome. Hospital admission status, not included in the LAS, has not been comprehensively investigated with regards to organ allocation. The objective of this study was to determine if pre-transplant hospital admission status is independently associated with post-transplant mortality and to determine if high center volume is associated with improved survival in that cohort.background METHODS: All consecutive adult lung transplants provided by the Scientific Registry of Transplant Recipients were retrospectively reviewed (2007-2017). 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 post-transplant mortality. RESULTS:During the study period, 20% (3,747/18,416) of recipients were admitted to the hospital at the time of transplantation. Compared to non-admitted recipients, LAS were significantly higher and waitlist times significantly shorter. Admitted recipients had higher rates of prolonged mechanical ventilation, higher rates of post-transplant dialysis, and longer post-transplant lengths of stay. Pre-transplant admission to a low volume center conferred significantly worse survival compared to non-admitted patients, and high volume centers were independently associated with improved survival compared to low volume centers.results CONCLUSIONS: Hospital admission status is associated with increased post-transplant mortality independent from 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 to low volume centers. CONCLUSION/CONCLUSIONS/:

BACKGROUND:The Lung Allocation Score (LAS) significantly improved outcomes and waitlist mortality in lung transplantation. However, mortality remains high for the sickest waitlist candidates despite additional changes to allocation distance. Regulatory considerations of overhauling the current lung allocation system has met significant resistance, and would require years to implement. This study evaluates if a modest change to the current system by prioritization of only high-LAS lung transplant candidates would result in lowered waitlist mortality. METHODS:The Thoracic Simulated Allocation Model was used to evaluate all lung transplant candidates and donor lungs recovered between July 1, 2009 and June 30, 2011. Current lung allocation rules (initial offer within 250 nautical-mile radius for ABO-identical then compatible offers) were run. Allocation was then changed for only patients with an LAS≥50 (high-LAS) to be prioritized within a 500 nautical-mile radius with no stratification between ABO-identical and compatible offers. Ten iterations of each model were run. Primary endpoints were waitlist mortality and post-transplant 1-year survival. RESULTS:6,538 waitlist candidates and transplant recipients were evaluated per iteration, for a total of 130,760 simulated patients. Compared with current allocation, the adjusted model had a 23.3% decrease in waitlist mortality. Post-transplant 1-year survival was minimally affected. CONCLUSIONS:Without overhauling the entire system, simple prioritization changes to the allocation system for high-LAS candidates may lead to decreased waitlist mortality and increased organ utilization. Importantly, these changes do not appear to lead to clinically significant changes in post-transplant 1-year survival.

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 (CDR) in the cohort was 184 (99-260) during GP therapy and 154 (78-304) over the first month after GP (p=0.79). 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.

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.
METHOD(S): 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.
RESULT(S): 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(S): 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.
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