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PD-1 blockade unleashes CD8 T cells1, including those specific for mutation-associated neoantigens (MANA), but factors in the tumour microenvironment can inhibit these T cell responses. Single-cell transcriptomics have revealed global T cell dysfunction programs in tumour-infiltrating lymphocytes (TIL). However, the majority of TIL do not recognize tumour antigens2, and little is known about transcriptional programs of MANA-specific TIL. Here, we identify MANA-specific T cell clones using the MANA functional expansion of specific T cells assay3 in neoadjuvant anti-PD-1-treated non-small cell lung cancers (NSCLC). We use their T cell receptors as a 'barcode' to track and analyse their transcriptional programs in the tumour microenvironment using coupled single-cell RNA sequencing and T cell receptor sequencing. We find both MANA- and virus-specific clones in TIL, regardless of response, and MANA-, influenza- and Epstein-Barr virus-specific TIL each have unique transcriptional programs. Despite exposure to cognate antigen, MANA-specific TIL express an incompletely activated cytolytic program. MANA-specific CD8 T cells have hallmark transcriptional programs of tissue-resident memory (TRM) cells, but low levels of interleukin-7 receptor (IL-7R) and are functionally less responsive to interleukin-7 (IL-7) compared with influenza-specific TRM cells. Compared with those from responding tumours, MANA-specific clones from non-responding tumours express T cell receptors with markedly lower ligand-dependent signalling, are largely confined to HOBIThigh TRM subsets, and coordinately upregulate checkpoints, killer inhibitory receptors and inhibitors of T cell activation. These findings provide important insights for overcoming resistance to PD-1 blockade.
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Antígenos de Neoplasias/imunologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Regulação da Expressão Gênica , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Antígenos de Neoplasias/genética , Linfócitos T CD8-Positivos/imunologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/imunologia , Células Cultivadas , Humanos , Memória Imunológica , Neoplasias Pulmonares/genética , Receptor de Morte Celular Programada 1/antagonistas & inibidores , RNA-Seq , Receptores de Interleucina-7/imunologia , Análise de Célula Única , Transcriptoma/genética , Microambiente TumoralRESUMO
INTRODUCTION: We evaluated equity in access to esophagectomy after Maryland's 2014 "Global Budget Revenue" (GBR) implementation, which equalizes reimbursement rates irrespective of patient insurance and employs an annual hospital revenue ceiling to incentivize reductions in unnecessary resource utilization. We hypothesized that more traditionally underserved patients would undergo surgical treatment for esophageal cancers after GBR. METHODS: Using Maryland's Health Services Cost Review Commission database, we retrospectively analyzed patient demographics, insurance statuses, inflation-adjusted hospital charges, postoperative outcomes, and discharge dispositions for esophagectomies for neoplasms between 2012 and 2018. RESULTS: Four hundred eighty six patients were included: 22.0% (107) pre-GBR and 78.0% (379) post-GBR. The proportion of African-American patients increased post-GBR (5.6% versus 12.9%, P = 0.035) and subsequently exhibited year-over-year increases. While not statistically significant, the proportion of Medicaid patients increased from 4.7% to 10.0% (P = 0.085). The post-GBR era also saw patients from 10 new counties, six of which were in Maryland's bottom half of counties ranked by median household income, receive operative esophageal cancer treatment without losing representation from pre-GBR counties. Patient age and sex were comparable between the two groups, and there were no significant differences in mortality or 30-day readmissions. Inflation-adjusted hospital charges and length of hospital stay did not appreciably change post-GBR, including after adjusting for age, comorbidities, and surgical approach. CONCLUSIONS: GBR increased access to esophagectomy for African-Americans, those insured by Medicaid, and those from lower socioeconomic status counties. Contrary to prior studies of outpatient and emergency room settings, we found the GBR program's goal of reduction of resource utilization and cost were not apparent in this complex surgical population.
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INTRODUCTION: Pulmonary lobectomy can result in intercostal nerve injury, leading to denervation of the rectus abdominis (RA) resulting in asymmetric muscle atrophy or an abdominal bulge. While there is a high rate of intercostal nerve injury during thoracic surgery, there are no studies that evaluate the magnitude and predisposing factors for RA atrophy in a large cohort. METHODS: A retrospective chart review was conducted of 357 patients who underwent open, thoracoscopic or robotic pulmonary lobectomy at a single academic center. RA volumes were measured on computed tomography scans preoperatively and postoperatively on both the operated and nonoperated sides from the level of the xiphoid process to the thoracolumbar junction. RA volume change and association of surgical/demographic characteristics was assessed. RESULTS: Median RA volume decreased bilaterally after operation, decreasing significantly more on the operated side (-19.5%) versus the nonoperated side (-6.6%) (P < 0.0001). 80.4% of the analyzed cohort experienced a 10% or greater decrease from preoperative RA volume on the operated side. Overweight individuals (body mass index 25.5-29.9) experienced a 1.7-fold greater volume loss on the operated side compared to normal weight individuals (body mass index 18.5-24.9) (P = 0.00016). In all right-sided lobectomies, lower lobe resection had the highest postoperative volume loss (Median (interquartile range): -28 (-35, -15)) (P = 0.082). CONCLUSIONS: This study of postlobectomy RA asymmetry includes the largest cohort to date; previous literature only includes case reports. Lobectomy operations result in asymmetric RA atrophy and predisposing factors include demographics and surgical approach. Clinical and quality of life outcomes of RA atrophy, along with mitigation strategies, must be assessed.
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Atrofia Muscular , Pneumonectomia , Reto do Abdome , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Reto do Abdome/patologia , Reto do Abdome/inervação , Reto do Abdome/cirurgia , Reto do Abdome/diagnóstico por imagem , Pneumonectomia/efeitos adversos , Pneumonectomia/métodos , Atrofia Muscular/etiologia , Atrofia Muscular/patologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Tomografia Computadorizada por Raios X , AdultoRESUMO
PURPOSE: Guanfacine is an α2A-adrenergic receptor agonist, FDA-approved to treat attention-deficit hyperactivity disorder and high blood pressure, typically as an extended-release formulation up to 7 mg/day. In our dysautonomia clinic, we observed that off-label use of short-acting guanfacine at 1 mg/day facilitated symptom relief in two families with multiple members presenting with severe generalized anxiety. We also noted anecdotal improvements in associated dysautonomia symptoms such as hyperhidrosis, cognitive impairment, and palpitations. We postulated that a genetic deficit existed in these patients that might augment guanfacine susceptibility. METHODS: We used whole-exome sequencing to identify mutations in patients with shared generalized anxiety and dysautonomia symptoms. Guanfacine-induced changes in the function of voltage-gated Na+ channels were investigated using voltage-clamp electrophysiology. RESULTS: Whole-exome sequencing uncovered the p.I739V mutation in SCN9A in the proband of two nonrelated families. Moreover, guanfacine inhibited ionic currents evoked by wild-type and mutant NaV1.7 encoded by SCN9A, as well as other NaV channel subtypes to a varying degree. CONCLUSION: Our study provides further evidence for a possible pathophysiological role of NaV1.7 in anxiety and dysautonomia. Combined with off-target effects on NaV channel function, daily administration of 1 mg short-acting guanfacine may be sufficient to normalize NaV channel mutation-induced changes in sympathetic activity, perhaps aided by partial inhibition of NaV1.7 or other channel subtypes. In a broader context, expanding genetic and functional data about ion channel aberrations may enable the prospect of stratifying patients in which mutation-induced increased sympathetic tone normalization by guanfacine can support treatment strategies for anxiety and dysautonomia symptoms.
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Doenças do Sistema Nervoso Autônomo , Guanfacina , Humanos , Guanfacina/uso terapêutico , Canal de Sódio Disparado por Voltagem NAV1.7/genética , Mutação , Ansiedade/tratamento farmacológico , Ansiedade/genética , Agonistas alfa-AdrenérgicosRESUMO
INTRODUCTION: The coronavirus disease-2019 (COVID-19) pandemic has substantially affected the delivery of healthcare globally. The purpose of this study was to evaluate the association of this era with the timeline of care in esophageal cancer patients. METHODS: We performed a retrospective chart-review of patients presenting to a single high-volume tertiary care center with the diagnosis of esophageal cancer. COVID era was defined as March 2020-December 2020 and compared with the year before (3/2019-12/2019). RESULTS: In total, 117 patients presented in the COVID-era versus 190 in pre-COVID. Stage 3 + 4 disease was found in 77.8% of the patients in the COVID-era compared to 68.9% in the pre-COVID era (P = 0.34). Diagnoses through emergency department admission were 35.5% in the COVID versus 26.7% in the pre-COVID group (P = 0.15). In the COVID era it took a median of 78 d to visit primary care provider (versus 52 d, P = 0.12 in pre-COVID), 45 d to endoscopy (versus 18 d, P = 0.004) and 38 d to treatment initiation (versus 36 d, P = 0.48). Thirty-five percent of the patients underwent esophagectomy compared to 26% in the pre-COVID-era. Median days of intensive-care-unit (ICU) (2 versus 3, P = 0.16) and hospital stay (14 versus 15, P = 0.28) were similar in both groups as well as postoperative 30-day morbidities (63 versus 63%, P = 0.48). One-year follow-up showed 83.7% (95% confidence interval [CI]: 73.8%-90.1%) survival in the COVID-group compared to 76.4% (95% CI: 66.9%-83.5%) in the pre-COVID-group (P = 0.58). Only three patients had a positive COVID result. CONCLUSIONS: Our institution treated fewer esophageal cancer patients during COVID-19 accompanied by a delay in endoscopic diagnosis. Postoperative outcomes and 1-year survival remained similar.
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COVID-19 , Neoplasias Esofágicas , Humanos , Estudos Retrospectivos , Neoplasias Esofágicas/cirurgia , Hospitalização , Teste para COVID-19RESUMO
Lung transplantation is accepted as a well-established and effective treatment for patients with end-stage lung disease. While the number of candidates added to the waitlist continues to rise, the number of transplants performed remains limited by the number of suitable organ donors. Ex vivo lung perfusion (EVLP) emerged as a method of addressing the organ shortage by allowing the evaluation and potential reconditioning of marginal donor lungs or minimizing risks of prolonged ischemic time due to logistical challenges. The currently available FDA-approved EVLP systems have demonstrated excellent outcomes in clinical trials, and retrospective studies have demonstrated similar post-transplant survival between recipients who received marginal donor lungs perfused using EVLP and recipients who received standard criteria lungs stored using conventional methods. Despite this, widespread utilization has plateaued in the last few years, likely due to the significant costs associated with initiating EVLP programs. Centralized, dedicated EVLP perfusion centers are currently being investigated as a potential method of further expanding utilization of this technology. In the preclinical setting, potential applications of EVLP that are currently being studied include prolongation of organ preservation, reconditioning of unsuitable lungs, and further enhancement of already suitable lungs. As adoption of EVLP technology becomes more widespread, we may begin to see future implementation of these potential applications into the clinical setting.
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Transplante de Pulmão , Pulmão , Humanos , Perfusão/métodos , Estudos Retrospectivos , Pulmão/cirurgia , Circulação Extracorpórea/métodos , Transplante de Pulmão/métodos , Preservação de Órgãos/métodosRESUMO
INTRODUCTION: Esophageal cancer is an aggressive malignancy with high mortality. Optimal treatment of esophageal cancer remains an elusive goal. Ribonucleic acid (RNA) interference is a novel potential targeted approach to treat esophageal cancer. Targeting oncogenes that can alter critical cellular functions with silencing RNA molecules is a promising approach. The silencing of specific oncogenes in esophageal cancer cells in the experimental setting has been shown to decrease the expression of oncogenic proteins. This has resulted in cell apoptosis, reduction in cell proliferation, reduced invasion, migration, epithelial-mesenchymal transition, decrease in tumor angiogenesis and metastasis, and overcoming drug resistance. The Hedgehog (Hh) signaling pathway has been shown to be involved in esophageal adenocarcinoma formation in a reflux animal model. In addition to Hh, we will focus on other targets with clinical potential in the treatment of esophageal cancer. MATERIALS AND METHODS: We searched for articles published from 2005 to August 2020 that studied the siRNA effects on inhibiting esophageal cancer formation in experimental settings. We used combinations of the following terms for searching: "esophageal cancer," "RNA interference," "small interfering RNA," "siRNA," "silencing RNA," "Smoothened (Smo)," "Gli," "Bcl-2," "Bcl-XL," "Bcl-W,â³ "Mcl-1," "Bfl-1," "STAT3,"and "Hypoxia inducible factor (HIF)". A total of 21 relevant articles were found. RESULTS AND CONCLUSIONS: Several proto-oncogenes/oncogenes including Hh pathway mediators, glioma-associated oncogene homolog 1 (Gli-1), Smoothened (Smo), and antiapoptotic Bcl-2 have potential as targets for silencing RNA in the treatment of esophageal cancer.
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Neoplasias Esofágicas , Proteínas Hedgehog , Animais , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/terapia , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Interferente Pequeno/metabolismo , Proteína GLI1 em Dedos de Zinco/genéticaRESUMO
BACKGROUND: Previous studies suggest double-lung transplant (DLT) may be associated with superior survival compared to single-lung transplantation (SLT) in chronic obstructive pulmonary disease (COPD) recipients. The purpose of this study was to compare survival in patients with COPD undergoing DLT versus SLT since the inception of the lung allocation score. METHODS: We used the United Network for Organ Sharing database to retrospectively identify adult patients with COPD who underwent isolated lung transplantation from 5/4/2005-12/31/2014. We then separated patients into DLT versus SLT. Short-term (1 y) and long-term survival (5 y) were compared between DLT and SLT cohorts by the method of Kaplan-Meier, and Cox proportional hazards modeling was used to adjust for case mix. RESULTS: Four thousand eight hundred thirty-two COPD patients were listed, and 3554 underwent lung transplantation over the study period, including 1358 SLTs (38%) and 2196 DLTs (62%). Survival 1 y after listing was 93% for those remaining wait listed (n = 1892) versus 91% for SLT (n = 1093) versus 89% for DLT (n = 1847) (log-rank P < 0.01). Survival at 1 y after transplant was 88% for both SLT and DLT groups (log-rank P = 0.93); however, 5-y survival was significantly lower after SLT (51% versus 59%, log-rank P < 0.01). After risk adjustment, hazard for 1-y mortality after DLT was not significantly reduced compared to SLT (hazard ratio 0.89 [0.69-1.14], P = 0.36) but was significantly reduced 5 y after DLT (hazard ratio 0.88 [0.78-0.99], P = 0.04). CONCLUSIONS: In the largest survival analysis of COPD recipients since the inception of the lung allocation score, the hazard for 5-y mortality was significantly reduced in recipients who underwent DLT as compared to SLT.
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Transplante de Pulmão/métodos , Doença Pulmonar Obstrutiva Crônica/mortalidade , Idoso , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/cirurgia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Listas de Espera/mortalidadeAssuntos
Asiático , Racismo , Cirurgiões , Centros Médicos Acadêmicos , Mobilidade Ocupacional , Humanos , Liderança , Estados UnidosRESUMO
PURPOSE: Currently, nearly 1 in 5 Americans is at least 60 years of age. Bone atrophy, decreased capacity for tissue repair, and chronic disease are known to influence fracture patterns and operative algorithms in this age group. This study presents craniofacial trauma injury patterns and treatment in an elderly population at a major urban trauma center. METHODS: Patient records were retrospectively reviewed from February 1998 through December 2010. Patients at least 60 years of age who met the inclusion criteria for craniofacial fractures identified by International Classification of Diseases, Ninth Revision code review and confirmed by author review of available computed tomograms were studied. Demographic information, fracture type, concomitant injuries, and management were recorded. RESULTS: Of 11,084 patients presenting with facial fracture, 1,047 were older than 60 years. The most common mechanism of injury was falls (50%), and most patients were men (59%). Commonly fractured areas included the nose (n = 452, 43%), maxilla (316, 30%), zygoma (312, 30%), orbital floor (280, 27%), and mandible (186, 18%), with 51 patients (5%) having a concomitant basilar skull fracture. Inpatient mortality and length of stay were significantly increased compared with the nongeriatric population (P < .01), although only 5% of all fractures were treated operatively. CONCLUSIONS: Fractures in the elderly tend to be minimally displaced midfacial fractures that do not warrant surgical intervention. Despite conservative management, the elderly are hospitalized longer than their younger counterparts, have increased critical care needs, and have higher mortality. These data support national medical preparedness in anticipating the craniofacial trauma needs of the aging US population and can be used to update treatment algorithms for these patients.
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Idoso/estatística & dados numéricos , Envelhecimento , Traumatismos Cranianos Fechados/epidemiologia , Acidentes por Quedas/estatística & dados numéricos , Idoso de 80 Anos ou mais , Traumatismos Faciais/epidemiologia , Feminino , Escala de Coma de Glasgow , Traumatismos Cranianos Fechados/mortalidade , Hospitalização/estatística & dados numéricos , Humanos , Escala de Gravidade do Ferimento , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Razão de Masculinidade , Fraturas Cranianas/epidemiologia , Centros de Traumatologia/estatística & dados numéricos , Traumatismos do Sistema Nervoso/epidemiologia , Estados Unidos/epidemiologiaRESUMO
Objective: The "July Effect" is a theory that the influx of trainees from July to September negatively impacts patient outcomes. We aimed to study this theoretical phenomenon in lung transplant recipients given the highly technical nature of thoracic procedures. Methods: Adult lung transplant hospitalizations were identified within the National Inpatient Sample (2005-2020). Recipients were categorized as academic Q1 (July to September) or Q2-Q4 (October to June). In-hospital mortality, operator-driven complications (pneumothorax, dehiscence including wound dehiscence, bronchial anastomosis, and others, and vocal cord/diaphragm paralysis, all 3 treated as a composite outcome), length of stay, and inflation-adjusted hospitalization charges were compared between both groups. Multivariable logistic regression was performed to assess the association between academic quarter and in-hospital mortality and operator-driven complications. The models were adjusted for recipient demographics and transplant characteristics. Subgroup analysis was performed between academic and nonacademic hospitals. Results: Of 30,788 lung transplants, 7838 occurred in Q1 and 22,950 occurred in Q2-Q4. Recipient demographic and clinical characteristics were similar between groups. Dehiscence (n = 922, 4% vs n = 236, 3%), post-transplant cardiac arrest (n = 532, 2% vs n = 113, 1%), and pulmonary embolism (n = 712, 3% vs n = 164, 2%) were more common in Q2-Q4 versus Q1 recipients (all P < .05). Other operator-driven complications, in-hospital mortality, and resource use were similar between groups (P > .05). These inferences remained unchanged in adjusted analyses and on subgroup analyses of academic versus nonacademic hospitals. Conclusions: The "July Effect" is not evident in US lung transplantation recipient outcomes during the transplant hospitalization. This suggests that current institutional monitoring systems for trainees across multiple specialties, including surgery, anesthesia, critical care, nursing, and others, are robust.
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Extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplant (BTT) has been used for critically ill candidates with excellent outcomes, but data on this strategy in older recipients remain limited. We compared outcomes of no BTT, mechanical ventilation (MV)-only BTT, and ECMO BTT in recipients of greater than or equal to 65 years. Lung-only recipients of greater than or equal to 65 years in the United Network for Organ Sharing database between 2008 and 2022 were included and stratified by bridging strategy. Of the 9,936 transplants included, 226 (2.3%) were MV-only BTT and 159 (1.6%) were ECMO BTT. Extracorporeal membrane oxygenation BTT recipients were more likely to have restrictive disease pathology, had higher median lung allocation score, and spent fewer days on the waitlist (all p < 0.001). Compared to no-BTT recipients, ECMO BTT recipients were more likely to be intubated or on ECMO at 72 hours posttransplant and had longer hospital lengths of stay (all p < 0.001). Extracorporeal membrane oxygenation BTT recipients had increased risk of 3 years mortality compared to both no-BTT (adjusted hazard ratio [aHR] = 1.48 [95% confidence interval {CI}: 1.14-1.91], p = 0.003) and MV-only recipients (aHR = 1.50 [95% CI: 1.08-2.07], p = 0.02). Overall, we found that ECMO BTT in older recipients is associated with inferior posttransplant outcomes compared to MV-only or no BTT, but over half of recipients remained alive at 3 years posttransplant.
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Oxigenação por Membrana Extracorpórea , Transplante de Pulmão , Resultado do Tratamento , Oxigenação por Membrana Extracorpórea/efeitos adversos , Estudos Retrospectivos , Transplante de Pulmão/efeitos adversos , Modelos de Riscos ProporcionaisRESUMO
OBJECTIVE: End-stage lung disease from severe COVID-19 infection is an increasingly common indication for lung transplantation (LT), but there are limited data on outcomes. We evaluated 1-year COVID-19 LT outcomes. METHODS: We identified all adult US LT recipients January 2020 to October 2022 in the Scientific Registry for Transplant Recipients, using diagnosis codes to identify recipients transplanted for COVID-19. We used multivariable regression to compare in-hospital acute rejection, prolonged ventilator support, tracheostomy, dialysis, and 1-year mortality between COVID-19 and non-COVID-19 recipients, adjusting for donor, recipient, and transplant characteristics. RESULTS: LT for COVID-19 increased from 0.8% to 10.7% of total LT volume during 2020 to 2021. The number of centers performing LT for COVID-19 increased from 12 to 50. Recipients transplanted for COVID-19 were younger; were more likely to be male and Hispanic; were more likely to be on a ventilator, extracorporeal membrane oxygenation support, and dialysis pre-LT; were more likely to receive bilateral LT; and had higher lung allocation score and shorter waitlist time than other recipients (all P values < .001). COVID-19 LT had higher risk of prolonged ventilator support (adjusted odds ratio, 2.28; P < .001), tracheostomy (adjusted odds ratio 5.3; P < .001), and longer length of stay (median, 27 vs 19 days; P < .001). Risk of in-hospital acute rejection (adjusted odds ratio, 0.99; P = .95) and 1-year mortality (adjusted hazard ratio, 0.73; P = .12) were similar for COVID-19 LTs and LTs for other indications, even accounting for center-level differences. CONCLUSIONS: COVID-19 LT is associated with higher risk of immediate postoperative complications but similar risk of 1-year mortality despite more severe pre-LT illness. These encouraging results support the ongoing use of LT for COVID-19-related lung disease.
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COVID-19 , Pneumopatias , Transplante de Pulmão , Adulto , Humanos , Masculino , Feminino , Diálise Renal , Transplante de Pulmão/efeitos adversos , Doadores de Tecidos , Pneumopatias/cirurgia , Estudos RetrospectivosRESUMO
OBJECTIVE: To determine whether allograft ischemic times affect outcomes following bilateral, single, and redo lung transplantation. METHODS: A nationwide cohort of lung transplant recipients from 2005 through 2020 was examined using the Organ Procurement and Transplantation Network registry. The effects of standard (<6 hours) and extended (≥6 hours) ischemic times on outcomes following primary bilateral (n = 19,624), primary single (n = 688), redo bilateral (n = 8461), and redo single (n = 449) lung transplantation were analyzed. A priori subgroup analysis was performed in the primary and redo bilateral-lung transplant cohorts by further stratifying the extended ischemic time group into mild (≥6 and <8 hours), moderate (≥8 and <10 hours), and long (≥10 hours) subgroups. Primary outcomes included 30-day mortality, 1-year mortality, intubation at 72 hours' posttransplant, extracorporeal membrane oxygenation (ECMO) support at 72 hours' posttransplant, and a composite variable of intubation or ECMO at 72 hours' posttransplant. Secondary outcomes included acute rejection, postoperative dialysis, and hospital length of stay. RESULTS: Recipients of allografts with ischemic times ≥6 hours experienced increased 30-day and 1-year mortality following primary bilateral-lung transplantation, but increased mortality was not observed following primary single, redo bilateral, or redo single-lung transplants. Extended ischemic times correlated with prolonged intubation or increased postoperative ECMO support in the primary bilateral, primary single, and redo bilateral-lung transplant cohorts but did not affect these outcomes following redo single-lung transplantation. CONCLUSIONS: Since prolonged allograft ischemia correlates with worse transplant outcomes, the decision to use donor lungs with extended ischemic times must consider the specific benefits and risks associated with individual recipient factors and institutional expertise.
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Transplante de Pulmão , Diálise Renal , Humanos , Estudos Retrospectivos , Fatores de Tempo , Transplante de Pulmão/efeitos adversos , Isquemia , AloenxertosRESUMO
BACKGROUND: With the increasing age of lung transplant candidates, we studied waitlist and posttransplantation outcomes of candidates ≥70 years during the Lung Allocation Score era. METHODS: Adult lung transplant candidates from 2005 to 2020 in the United Network for Organ Sharing database were included and stratified on the basis of age at listing into 18 to 59 years old, 60 to 69 years old, and ≥70 years old. Baseline characteristics, waitlist outcomes, and posttransplantation outcomes were assessed. RESULTS: A total of 37,623 candidates were included (52.3% aged 18-59 years, 40.6% aged 60-69 years, 7.1% aged ≥70 years). Candidates ≥70 years were more likely than younger candidates to receive a transplant (81.9% vs 72.7% [aged 60-69 years] vs 61.6% [aged 18-59 years]) and less likely to die or to deteriorate on the waitlist within 1 year (9.1% vs 10.1% [aged 60-69 years] vs 12.2% [aged 18-59 years]; P < .001). Donors for older recipients were more likely to be extended criteria (75.7% vs 70.1% [aged 60-69 years] vs 65.7% [aged 18-59 years]; P < .001). Recipients ≥70 years were found to have lower rates of acute rejection (6.7% vs 7.4% [aged 60-69 years] vs 9.2% [aged 18-59 years]; P < .001) and prolonged intubation (21.7% vs 27.4% [aged 60-69 years] vs 34.5% [aged 18-59 years]; P < .001). Recipients aged ≥70 years had increased 1-year (adjusted hazard ratio [aHR], 1.19 [95% CI, 1.06-1.33]; P < .001), 3-year (aHR, 1.28 [95% CI, 1.18-1.39]; P < .001), and 5-year mortality (aHR, 1.29 [95% CI, 1.21-1.38]; P < .001) compared with recipients aged 60 to 69 years. CONCLUSIONS: Candidates ≥70 years had favorable waitlist and perioperative outcomes despite increased use of extended criteria donors. Careful selection of candidates and postoperative surveillance may improve posttransplantation survival in this population.
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Transplante de Pulmão , Doadores de Tecidos , Adulto , Humanos , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Modelos de Riscos Proporcionais , Sistema de Registros , Listas de Espera , Pulmão , Estudos RetrospectivosRESUMO
OBJECTIVES: Concomitant heart and lung recovery can result in increased operative complexity, ischemic time, and competition for resources and anatomic territory. Dual thoracic recovery from circulatory death donors may have additional risks that are not fully understood. We investigated the effects of dual heart and lung recovery from circulatory death donors on thoracic transplant outcomes. METHODS: Using the United Network for Organ Sharing database, we categorized all adult thoracic circulatory death donor transplants from 2019 to 2023 by whether the donor heart, lung, or both (dual donors) were recovered. Heart and lung transplant outcomes were compared between dual recovery donors and heart-only or lung-only donors, respectively, using multivariable analyses. RESULTS: Of the 2513 donors included, 42.9% were heart-only, 45.0% were lung-only, and 12.0% were dual donors. Recipients of dual versus heart-only donors had similar likelihood of post-transplant dialysis (18.9% vs 18.3%, P = .84), likelihood of stroke (2.9% vs 4.7%, P = .34), and 2-year risk of mortality (adjusted hazard ratio, 1.15 [95% CI, 0.90-1.47], P = .26), but lower likelihood of acute rejection (10.2% vs 16.1%, P = .04). Recipients of dual and lung-only donors had similar likelihood of predischarge acute rejection (7.6% vs 8.5%, P = .70), intubation at 72 hours (38.9% vs 45.1%, P = .13), and extracorporeal membrane oxygenation at 72 hours (13.1% vs 18.1%, P = .11), as well as 2-year risk of mortality (adjusted hazard ratio, 1.16 [95% CI, 0.74-1.82], P = .52). CONCLUSIONS: Recovering both the heart and lungs from a circulatory death donor does not negatively impact transplant outcomes. Outcomes in this population should continue to be investigated as more data and longer-term follow-up become available.
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BACKGROUND: This study compared utilization and outcomes of the 2 widely utilized ex vivo lung perfusion (EVLP) platforms in the United States: a static platform and a portable platform. METHODS: Adult (age 18 years or older) bilateral lung-only transplants utilizing EVLP between February 28, 2018, and December 31, 2022, in the United Network for Organ Sharing database were included. Predischarge acute rejection, intubation at 72 hours posttransplant, extracorporeal membrane oxygenation at 72 hours posttransplant, primary graft dysfunction grade 3 at 72 hours posttransplant, 30-day mortality, and 1-year mortality were evaluated using multivariable regressions. RESULTS: Overall, 607 (6.3%) lung transplants during the study period used EVLP (51.2% static, 48.8% portable). Static EVLP was primarily utilized in the eastern United States, whereas portable EVLP was primarily utilized in the western United States. Static EVLP donors were more likely to be donation after circulatory death (33.4% vs 26.0%; P = .005), have a >20 pack-year smoking history (13.5% vs 6.5%; P = .005), and be extended criteria donors (92.3% vs 85.0%; P = .013), whereas portable EVLP donors were more likely to be older than age 55 years (14.2% vs 8.0%; P = .02). Transplants utilizing the static and portable platforms had similar risk of acute rejection, intubation at 72 hours, extracorporeal membrane oxygenation at 72 hours, primary graft dysfunction grade 3 at 72 hours, and posttransplant mortality at 30 days and 1 year (all P values > .05). CONCLUSIONS: The static and portable platforms had significant differences in donor characteristics and geographic distributions of utilization. Despite this, posttransplant survival was similar between the 2 EVLP platforms.
Assuntos
Transplante de Pulmão , Perfusão , Humanos , Transplante de Pulmão/mortalidade , Transplante de Pulmão/estatística & dados numéricos , Transplante de Pulmão/tendências , Masculino , Feminino , Pessoa de Meia-Idade , Estados Unidos , Adulto , Perfusão/métodos , Perfusão/mortalidade , Perfusão/efeitos adversos , Perfusão/instrumentação , Resultado do Tratamento , Estudos Retrospectivos , Fatores de Tempo , Bases de Dados Factuais , Fatores de Risco , Rejeição de Enxerto , Sobrevivência de Enxerto , IdosoRESUMO
Objective: A novel simulator developed to offer hands-on practice for the stapled side-to-side cervical esophagogastric anastomosis was tested previously in a single-center study that supported its value in surgical education. This multi-institutional trial was undertaken to evaluate validity evidence from 6 independent thoracic surgery residency programs. Methods: After a virtual session for simulation leaders, learners viewed a narrated video of the procedure and then alternated as surgeon or first assistant. Using an online survey, perceived value was measured across fidelity domains: physical attributes, realism of materials, realism of experience, value, and relevance. Objective assessment included time, number of sutures tearing, bubble test, and direct inspection. Comparison across programs was performed using the Kruskal-Wallis test. Results: Surveys were completed by 63 participants as surgeons (17 junior and 20 senior residents, 18 fellows, and 8 faculty). For 3 of 5 tasks, mean ratings of 4.35 to 4.44 correlated with "somewhat easy" to "very easy" to perform. The interrupted outer layer of the anastomosis rated lowest, suggesting this task was the most difficult. The simulator was rated as a highly valuable training tool. For the objective measurements of performance, "direct inspection" rated highest followed by "time." A total of 90.5% of participants rated the simulator as ready for use with only minor improvements. Conclusions: Results from this multi-institutional study suggest the cervical esophagogastric anastomosis simulator is a useful adjunct for training and assessment. Further research is needed to determine its value in assessing competence for independent operating and associations between improved measured performance and clinical outcomes.
RESUMO
OBJECTIVE: On November 24, 2017, lung transplant allocation switched from donation service area to a 250-nautical mile radius policy to improve equity in access to lung transplantation. Given the growing consideration of healthcare costs, we evaluated changes in hospitalization costs after this policy change. METHODS: Lung transplant hospitalizations were identified within the National Inpatient Sample from 2005 to 2020. Recipients were categorized as donation service area era (August 2015 to October 2017) or non-donation service area era (December 2017 to February 2020). Median total hospitalization costs (inflation adjusted) were compared by era nationally and regionally. Multivariable generalized linear regression was performed to determine if the removal of the donation service area was associated with total hospitalization costs. The model was adjusted for recipient demographics, Charlson Comorbidity Index, hospitalization region, transplant type (single, double), and use of extracorporeal membrane oxygenation, ex vivo lung perfusion, and mechanical ventilation. RESULTS: We analyzed 12,985 lung transplant recipients (median age of 61 years, 66% were male): 7070 in the donation service area era and 5915 in the non-donation service area era. Demographics were not different between recipients in both eras. Non-donation service area era recipients had greater extracorporeal membrane oxygenation use, mechanical ventilation (<24 hours), and longer length of stay than donation service area era recipients. Median total hospitalization costs for non-donation service area versus donation service area era recipients increased by $24,198 ($157,964 vs $182,162, percentage change = 15.32%, P < .001). Median costs increased in East North Central ($42,281) and Mountain ($35,521) regions (both P < .01). After adjustment, median costs for non-donation service area versus donation service area era recipients still increased ($19,168, 95% CI, 145-38,191, P = .048). CONCLUSIONS: Hospitalization costs for lung transplant hospitalizations have increased from 2015 to 2020. The transition from donation service area-based allocation to the non-donation service area system may have contributed to this increase after 2017 by increasing access to transplant for sicker recipients.