Lung transplantation is a life-saving treatment for patients with end-stage lung disease; however, it is infrequently considered for patients with acute respiratory distress syndrome (ARDS) ...attributable to infectious causes. We aimed to describe the course of disease and early post-transplantation outcomes in critically ill patients with COVID-19 who failed to show lung recovery despite optimal medical management and were deemed to be at imminent risk of dying due to pulmonary complications.
We established a multi-institutional case series that included the first consecutive transplants for severe COVID-19-associated ARDS known to us in the USA, Italy, Austria, and India. De-identified data from participating centres-including information relating to patient demographics and pre-COVID-19 characteristics, pretransplantation disease course, perioperative challenges, pathology of explanted lungs, and post-transplantation outcomes-were collected by Northwestern University (Chicago, IL, USA) and analysed.
Between May 1 and Sept 30, 2020, 12 patients with COVID-19-associated ARDS underwent bilateral lung transplantation at six high-volume transplant centres in the USA (eight recipients at three centres), Italy (two recipients at one centre), Austria (one recipient), and India (one recipient). The median age of recipients was 48 years (IQR 41-51); three of the 12 patients were female. Chest imaging before transplantation showed severe lung damage that did not improve despite prolonged mechanical ventilation and extracorporeal membrane oxygenation. The lung transplant procedure was technically challenging, with severe pleural adhesions, hilar lymphadenopathy, and increased intraoperative transfusion requirements. Pathology of the explanted lungs showed extensive, ongoing acute lung injury with features of lung fibrosis. There was no recurrence of SARS-CoV-2 in the allografts. All patients with COVID-19 could be weaned off extracorporeal support and showed short-term survival similar to that of transplant recipients without COVID-19.
The findings from our report show that lung transplantation is the only option for survival in some patients with severe, unresolving COVID-19-associated ARDS, and that the procedure can be done successfully, with good early post-transplantation outcomes, in carefully selected patients.
National Institutes of Health. VIDEO ABSTRACT.
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.
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.
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.
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.
Case Presentation A 46-year-old man underwent redo bilateral sequential lung transplantation for rapidly progressive bronchiolitis obliterans syndrome that developed 3.5 years after initial ...transplantation. In the operating room, he was sedated and intubated with a dual lumen endotracheal tube with subsequent single right-lung ventilation and left allograft implantation. His pulmonary arterial pressure became elevated with reperfusion of the newly implanted left lung, which required initiation of cardiopulmonary bypass to facilitate implantation of the right lung. After implantation and reperfusion of the right lung, the patient was weaned from cardiopulmonary bypass. His chest was closed and he was transferred to the thoracic intensive care unit. On arrival to the intensive care unit, the patient was intubated, sedated, and had an oxygen saturation of 92% on a fraction of inspired oxygen of 100%, positive end-expiratory pressure of 10 cm H2 O, and 20 parts per million of inhaled nitric oxide. He had a Swan-Ganz catheter in the right internal jugular vein that measured a mean pulmonary arterial pressure of 33 mm Hg and a pulmonary arterial systolic pressure of 63 mm Hg, which remained persistently elevated and prompted further diagnostic evaluation.
Long-term survival after lung transplant remains severely limited by chronic lung allograft dysfunction. Antibody-mediated rejection of lung transplant allografts is usually caused by donor-specific ...antibodies (DSAs) directed toward donor human leukocyte antigens (HLAs). Typically, patients with antibody-mediated rejection have significantly higher circulating DSAs and increased mean fluorescence intensity than those without antibody-mediated rejection. However, some patients with antibody-mediated rejection have low mean fluorescence intensities, partly due to the “sponge effect” related to DSAs binding to HLA molecules within the lung. Herein, we report the case of an 18-year-old, female lung transplant recipient who required retransplantation and developed circulating DSAs directed toward the first allograft but detected in circulation only after retransplantation. The present case draws attention to a rare finding of sponge effect in a patient with antibody-mediated rejection leading to allograft failure.
Despite important improvements in the multimodal treatment of upper gastrointestinal tumors in recent years, surgery is still the standard of care and the best way to cure and palliate patients with ...esophageal cancer. There has been significant improvement in both clinical oncologic staging and functional preoperative evaluation of patients in the last few decades. Despite improvements, esophagectomy is still associated with high operative risk. Diligent perioperative evaluation and risk stratification lead to better outcomes.
Background. Persistent orthostatic hypotension (OH) is a lesser-known complication of lung transplantation (LTx). In this retrospective case series, we describe the clinical manifestations, ...complications, and treatment of persistent OH in 13 LTx recipients. Methods. We identified LTx recipients who underwent transplantation between March 1, 2018, and March 31, 2020, with persistent symptomatic OH and retrospectively queried the records for clinical information. Results. Thirteen patients were included in the analysis, 9 (69%) had underlying pulmonary fibrosis, and 12 (92%) were male. The median age, height, and body mass index at LTx were 68 years, 70 inches, and 27 kg/m2, respectively. Six (46%) patients were deceased at the time of chart abstraction with a median (IQR) posttransplant survival of 12.6 months (6, 21); the 7 remaining living patients were a median of 19.6 months (18, 32) posttransplant. Signs and symptoms of OH developed a median of 60 (7, 75) days after transplant. Patients were treated with pharmacological agents and underwent extensive physical therapy. Most patients required inpatient rehabilitation (n = 10, 77%), and patients commonly developed comorbid conditions including weight loss, renal insufficiency with eGFR <50 (n = 13, 100%), gastroparesis (n = 7, 54%), and tachycardia-bradycardia syndrome (n = 2, 15%). Falls were common (n = 10, 77%). The incidence of OH in LTx recipients at our center during the study period was 5.6% (13/234). Conclusions. Persistent OH is a lesser-known complication of LTx that impacts posttransplant rehabilitation and may lead to comorbidities and shortened survival. In addition, most LTx recipients with OH at our center were tall, thin men with underlying pulmonary fibrosis, which may offer an opportunity to instate pretransplant OH screening of at-risk patients.
Surgical procedures to treat reflux disease are common, but good outcomes rely on both a thorough preoperative workup and careful surgical techniques. Although complications are uncommon, surgeons ...should recognize these and possess the skills to overcome them in clinical practice.
Chronic lung allograft dysfunction (CLAD) is nonreversible and remains the biggest obstacle to long-term survival after lung transplantation (LTx). Retransplantation is the sole definitive ...therapeutic option for CLAD. We analyzed our single-center experience with retransplantation as a treatment option for CLAD.
From March 1, 2010, to May 31, 2016, 419 consecutive patients underwent LTx at our institution; 29 of these procedures were retransplantations for CLAD. We analyzed demographic characteristics, lung allocation score, operation type, length of stay, and perioperative outcomes. Actuarial survival was estimated using Kaplan-Meier survival curves.
In total, 29 of 419 patients (6.9%) underwent retransplantation for CLAD. Median time from primary LTx to retransplantation was 1,163 days (range: 304 to 3,971 days). Patients undergoing retransplantation were younger and had higher lung allocation scores than primary transplantation patients. Most LTx procedures were bilateral (93% of retransplantations, 95% of primary LTx). Rates of cardiopulmonary bypass, extracorporeal membrane oxygenation support for severe primary graft dysfunction, and re-exploration for bleeding were higher in retransplantation patients (p = 0.010, p = 0.019, and p = 0.029, respectively). One- and 5-year survival rates in the retransplantation group were similar to those of the primary LTx group (89.2% and 64.3% versus 89.7% and 58.2%, respectively; p = 0.79).
Lung retransplantation is a viable treatment option for CLAD after LTx. In this study, retransplantation patients were younger, had higher lung allocation scores, and were more likely to require cardiopulmonary bypass and postoperative extracorporeal membrane oxygenation support than primary LTx patients. Postoperative length of stay and short- and mid-term survival were comparable with those of primary LTx patients.
To elucidate the deregulated functional modules that drive clear cell renal cell carcinoma (ccRCC), we performed comprehensive genomic, epigenomic, transcriptomic, proteomic, and phosphoproteomic ...characterization of treatment-naive ccRCC and paired normal adjacent tissue samples. Genomic analyses identified a distinct molecular subgroup associated with genomic instability. Integration of proteogenomic measurements uniquely identified protein dysregulation of cellular mechanisms impacted by genomic alterations, including oxidative phosphorylation-related metabolism, protein translation processes, and phospho-signaling modules. To assess the degree of immune infiltration in individual tumors, we identified microenvironment cell signatures that delineated four immune-based ccRCC subtypes characterized by distinct cellular pathways. This study reports a large-scale proteogenomic analysis of ccRCC to discern the functional impact of genomic alterations and provides evidence for rational treatment selection stemming from ccRCC pathobiology.
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•Integrated proteogenomic characterization in 103 ccRCC cases•Delineation of chromosomal translocation events leading to chromosome 3p loss•Tumor-specific proteomic/phosphoproteomic alterations unrevealed by mRNA analysis•Immune-based subtypes of ccRCC defined by mRNA, proteome, and phosphoproteome
Comprehensive proteogenomic characterization in 103 treatment-naive clear cell renal cell carcinoma patient samples highlights tumor-specific alterations at the proteomic level that are unrevealed by transcriptomic profiling and proposes a revised subtyping scheme based on integrated omics analysis.
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