Rajat Walia

Donor-Derived Exosomes With Lung Self-Antigens in Human Lung Allograft Rejection.

The immunological role of exosomes in allograft rejection remains unknown. We sought to determine whether exosomes are induced during lung allograft rejection and to define the antigenic compositions of HLA, lung‐associated self‐antigens (SAgs) and microRNAs (miRNAs). Exosomes were isolated from sera and bronchoalveolar lavage fluid from 30 lung transplant recipients (LTxRs) who were stable or who had acute rejection (AR) or bronchiolitis obliterans syndrome (BOS). Exosomes were defined by flow cytometry for CD63 and western blotting for annexin V SAgs, collagen V (Col‐V) and Kα1 tubulin were examined by electron microscopy; miRNAs were profiled by a miRNA array. Donor HLA and SAgs were detected on exosomes from LTxRs with AR and BOS but not from stable LTxRs. Exosomes expressing Col‐V were isolated from sera from LTxRs 3 mo before AR and 6 mo before BOS diagnosis, suggesting that exosomes with SAgs may be a noninvasive rejection biomarker. Exosomes isolated from LTxRs with AR or BOS also contained immunoregulatory miRNAs. We concluded that exosomes expressing donor HLA, SAgs and immunoregulatory miRNAs are present in the circulation and local site after human lung transplantation and play an important role in the immune pathogenesis of acute allograft rejection and BOS.

Extracorporeal membrane oxygenation as a bridge to lung transplantation: A single-center experience in the present era

Objective: Extracorporeal membrane oxygenation has been used as a bridge to lung transplantation in patients with rapid pulmonary function deterioration. The reported success of this modality and perioperative and functional outcomes are varied. Methods: We retrospectively reviewed all patients who underwent lung transplantation at our institution over 1 year (January 1, 2015, to December 31, 2015). Patients were divided into 2 groups depending on whether they required extracorporeal membrane oxygenation support as a bridge to transplant; preoperative characteristics, lung transplantation outcomes, and survival were compared between groups. Results: Of the 93 patients, 12 (13%) received bridge to transplant, and 81 (87%) did not. Patients receiving bridge to transplant were younger, had higher lung allocation scores, had lower functional status, and were more often on mechanical ventilation at listing. Most patients who received bridge to transplant (n = 10, 83.3%) had pulmonary fibrosis. Mean pretransplant extracorporeal membrane oxygenation support was 103.6 hours in duration (range, 16‐395 hours). All patients who received bridge to transplant were decannulated immediately after lung transplantation but were more likely to return to the operating room for secondary chest closure or rethoracotomy. Grade 3 primary graft dysfunction within 72 hours was similar between groups. Lung transplantation success and hospital discharge were 100% in the bridge to transplant group; however, these patients experienced longer hospital stays and higher rates of discharge to acute rehabilitation. The 1‐year survival was 100% in the bridge to transplant group and 91% in the non–bridge to transplant group (log‐rank, P = .24). The 1‐year functional status was excellent in both groups. Conclusions: Extracorporeal membrane oxygenation can be used to safely bridge high‐acuity patients with end‐stage lung disease to lung transplantation with good 30‐day, 90‐day, and 1‐year survival and excellent 1‐year functional status. Long‐term outcomes are being studied.

Gastroparesis is common after lung transplantation and may be ameliorated by botulinum toxin-A injection of the pylorus

aPTT may be falsely elevated and may lead to insufficient anticoagulation if dosing UFH from aPTT levels. This is a preliminary report in a small number of patients. However, the incidence of thrombosis is high in LVAD patients and all potential causes need to be reported quickly so that they can be investigated in larger numbers and at multiple institutions. Several hypotheses need to be tested in LVAD patients, including: exclusive monitoring of anti-Xa levels (or a combination of anti-Xa and aPTT) and the increased risk of bleeding when monitoring anti-Xa levels. Our results suggest that aPTT levels underestimate anti-coagulation in LVAD patients and monitoring UFH with anti-Xa levels more accurately reflects the level of anti-coagulation.

Lung Transplant Recipient with Pulmonary Alveolar Proteinosis

Pulmonary alveolar proteinosis (PAP) is a progressive lung disease characterized by accumulated surfactant-like lipoproteinaceous material in the alveoli and distal bronchioles. This accumulation is the result of impaired clearance by alveolar macrophages. PAP has been described in 11 solid organ transplant recipients, 9 of whom were treated with mammalian target of rapamycin inhibitors. We report a case of a lung transplant recipient treated with prednisone, mycophenolate mofetil (MMF), and tacrolimus who ultimately developed PAP, which worsened when MMF was replaced with everolimus.

Incidental extensive adenocarcinoma in lungs explanted from a transplant recipient with an idiopathic pulmonary fibrosis flare-up: A clinical dilemma

Patients under consideration for lung transplantation as treatment for end-stage lung diseases such as idiopathic pulmonary fibrosis (IPF) often have risk factors such as a history of smoking or concomitant emphysema, both of which can predispose the patient to lung cancer. In fact, IPF itself increases the risk of lung cancer development by 6.8% to 20%. Solid organ malignancy (non-skin) is an established contraindication for lung transplantation. We encountered a clinical dilemma in a patient who presented with an IPF flare-up and underwent urgent evaluation for lung transplantation. After transplant, the patients explanted lungs showed extensive adenocarcinoma in situ, with the foci of invasion and metastatic adenocarcinoma in N1-level lymph nodes, as well as usual interstitial pneumonia. Retrospectively, we saw no evidence to suggest malignancy in addition to the IPF flare-up. Clinical diagnostic dilemmas such as this emphasize the need for new noninvasive testing that would facilitate malignancy diagnosis in patients too sick to undergo invasive tissue biopsy for diagnosis. Careful pathological examination of explanted lungs in patients with IPF is critical, as it can majorly influence immunosuppressive regimens, surveillance imaging, and overall prognosis after lung transplant.

Pneumatosis intestinalis in solid organ transplant recipients

Pneumatosis intestinalis (PI) is an uncommon medical condition in which gas pockets form in the walls of the gastrointestinal tract. The mechanism by which this occurs is poorly understood; however, it is often seen as a sign of serious bowel ischemia, which is a surgical emergency. Since the early days of solid organ transplantation, PI has been described in recipients of kidney, liver, heart, and lung transplant. Despite the dangerous connotations often associated with PI, case reports dating as far back as the 1970s show that PI can be benign in solid organ transplant recipients. This is an important observation, as operative intervention in these patients carries greater risk than surgical procedures in the general population. The higher operative risks in the transplant population are partly due to their immunosuppressed status and poor wound healing. Furthermore, no clear consensus exists on the optimal management of PI. Various treatment strategies such as bowel rest, antibiotics, and parenteral feeding have been implemented with similar levels of success. With the increasing use of solid organ transplantation, PI is being recognized with increasing frequency. In this review, we provide a summary of the incidence, presentation, diagnosis, and management of PI, particularly as it affects recipients of solid organ transplantation.

Electromagnetic navigational bronchoscopy for diagnosing peripheral lung lesions in lung transplant recipients: a singlecenter experience

Lung nodules are common in lung transplant recipients (1), but the immunosuppressed status of these patients means that diagnosing these nodules is urgent. Differential diagnoses in lung transplant recipients with lung nodules include infection (i.e., bacterial, fungal, mycobacterial), malignancy [e.g., bronchogenic, post-transplant lymphoproliferative disorder (PTLD), or metastatic malignancy], and hemorrhage after previous transbronchial biopsies (1,2).

Outcomes of lung transplant recipients with preoperative atrial fibrillation

Background Preoperative atrial fibrillation is associated with poor outcomes after cardiac surgery, but its effect on lung transplantation outcomes remains unknown. Methods We retrospectively reviewed the charts of 235 patients who underwent lung transplantation in our institution from 2013 to 2015, analyzing demographics, length of stay, survival, readmissions, and cardiac events. Mean recipient age was 59 ± 11 years, and 142 (60.4%) were men. Patients were grouped according to pre-transplantation atrial fibrillation status (atrial fibrillation/no atrial fibrillation). Results The atrial fibrillation group (n = 38; 16.2%) was significantly older with a longer ischemic time, more postoperative atrial arrhythmias (73.7% vs. 20.8%, p = 0.01), and a longer median postoperative length of stay (16 vs. 13 days, p = 0.02). The median total hospital stay in the first postoperative year was also higher in the atrial fibrillation group (27 vs. 21 days, p = 0.25). Short-term survival and survival during follow-up did not differ significantly between groups. Conclusions Lung transplant recipients with preoperative atrial fibrillation are at increased risk of adverse cardiovascular outcomes and longer hospital stay. Preoperative atrial fibrillation may portend adverse events after lung transplantation.

The Imitation Game: A 55-Year-Old Man With a Lung and Adrenal Mass

To the Editor:Infections can often cause pulmonary lesions that resemble cancer.1 Extrathoracic dissemination raises the suspicion for malignancy. The adrenals are a common site of occult lung cancer metastases, and fluorodeoxyglucose positron emission tomography (FDG-PET) has a high sensitivity and