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Rationale: Pulmonary hypertension from pulmonary arterial hypertension or parenchymal lung disease is associated with an increased risk for primary graft dysfunction after lung transplantation.Objective: We evaluated the clinical determinants of severe primary graft dysfunction in pulmonary hypertension and developed and validated a prognostic model.Methods: We conducted a retrospective cohort study of patients in the multicenter Lung Transplant Outcomes Group with pulmonary hypertension at transplant listing. Severe primary graft dysfunction was defined as PaO2/FiO2 ≤200 with allograft infiltrates at 48 or 72 hours after transplantation. Donor, recipient, and operative characteristics were evaluated in a multivariable explanatory model. A prognostic model derived using donor and recipient characteristics was then validated in a separate cohort.Results: In the explanatory model of 826 patients with pulmonary hypertension, donor tobacco smoke exposure, higher recipient body mass index, female sex, listing mean pulmonary artery pressure, right atrial pressure and creatinine at transplant, cardiopulmonary bypass use, transfusion volume, and reperfusion fraction of inspired oxygen were associated with primary graft dysfunction. Donor obesity was associated with a lower risk for primary graft dysfunction. Using a 20% threshold for elevated risk, the prognostic model had good negative predictive value in both derivation and validation cohorts (89.1% [95% confidence interval, 85.3-92.8] and 83.3% [95% confidence interval, 78.5-88.2], respectively), but low positive predictive value.Conclusions: Several recipient, donor, and operative characteristics were associated with severe primary graft dysfunction in patients with pulmonary hypertension, including several risk factors not identified in the overall transplant population. A prognostic model with donor and recipient clinical risk factors alone had low positive predictive value, but high negative predictive value, to rule out high risk for primary graft dysfunction. [ABSTRACT FROM AUTHOR]

As an originalist matter, what degree of logistical power did the Framers of the Reconstruction Amendments want Congress to have in actualizing the substantive guarantees of those amendments? In the 1990s the Court, seeking to revive its federalism vigilance, answered: "relatively limited power." Scholars pounced, and it quickly became "settled" in the scholarly literature that the Court had misread the historical record regarding the Framers' intent. Despite the scholarly reactions, the Roberts Court has carried the Rehnquist Court's torch on this interpretative matter. As such, strident accusations of conservative judicial activism toward the Roberts Court have paralleled the charges leveled at the Rehnquist Court since the 1990s. The scholars who claimed to settle the underlying issue via an originalist analysis of historical evidence are very respected scholars, and rightly so. However, this article constructively complicates things by highlighting that, when one takes a critical look at the very evidence these scholars invoked to "settle" the matter, the certitude of said scholars on the subject has been grossly unwarranted. That certitude has nevertheless spawned a vicious cycle of citation to a few scholarly works that, in turn, do not do justice to the complexity of the evidence. This, in turn, has bred within the scholarly climate an unwarranted and often shrill intolerance for judicial invocations of state sovereignty in cases implicating the Reconstruction Amendments. The goal here is to, by highlighting the relevant complexities, tame this shrillness and call for greater intellectual empathy toward (even if not agreement with) judicial sensitivity to federalism concerns. [ABSTRACT FROM AUTHOR]

The article discusses the concept of penumbral federalism in America in relation to rulings by the U.S. Supreme Court (USSC) under the leadership of USSC Chief Justice John Roberts in cases such as Shelby County v. Holder which deals with the nation's Voting Rights Act (VRA) and the equal protection matter United States v. Windsor which addresses the U.S. Defense of Marriage Act (DOMA). State sovereign immunity and a personal jurisdiction legal doctrine are assessed.

Introduction: Primary graft dysfunction (PGD) is a significant contributor to early morbidity and mortality after lung transplantation. Increased vascular permeability in the allograft has been identified as a possible mechanism leading to PGD. Angiopoietin-2 serves as a partial antagonist to the Tie-2 receptor and induces increased endothelial permeability. We hypothesized that elevated Ang2 levels would be associated with development of PGD. Methods: We performed a case-control study, nested within the multi-center Lung Transplant Outcomes Group cohort. Plasma angiopoietin-2 levels were measured pre-transplant and 6 and 24 hours post-reperfusion. The primary outcome was development of grade 3 PGD in the first 72 hours. The association of angiopoietin-2 plasma levels and PGD was evaluated using generalized estimating equations (GEE). Results: There were 40 PGD subjects and 79 non-PGD subjects included for analysis. Twenty-four PGD subjects (40%) and 47 non-PGD subjects (59%) received a transplant for the diagnosis of idiopathic pulmonary fibrosis (IPF). Among all subjects, GEE modeling identified a significant change in angiopoietin-2 level over time in cases compared to controls (p = 0.03). The association between change in angiopoietin-2 level over the perioperative time period was most significant in patients with a pre-operative diagnosis of IPF (p = 0.02); there was no statistically significant correlation between angiopoietin-2 plasma levels and the development of PGD in the subset of patients transplanted for chronic obstructive pulmonary disease (COPD) (p = 0.9). Conclusions: Angiopoietin-2 levels were significantly associated with the development of PGD after lung transplantation. Further studies examining the regulation of endothelial cell permeability in the pathogenesis of PGD are indicated. [ABSTRACT FROM AUTHOR]

It is no secret that formalist methodologies like originalism are not nearly as scientific as they pretend to be. Banking on this fact, pragmatism offers a prescriptive alternative: instead of expending intellectual energy attempting "fidelity" to antecedent "authority" (precedent, Framers' intent, etc.), judges should embrace their inevitable roles as de facto policy makers, and focus on producing the best social results they can through the cases they decide. This Article discusses the current state of legal pragmatism, with a focus on the archetypal species espoused by Judge Richard Posner, and asks whether it has proven itself capable of contributing anything useful to modern adjudication. Through a dissection of the essentials of Posner's pragmatism, the Article demonstrates that pragmatism serves only as a method of justifying outcomes that comport with the personal temperament and intuitions of those applying it. The Article then explores how the increasing obviousness of pragmatism's failings has renewed interest in a concept central to formalist approaches: "fidelity" to exalted principles of political theory. Thus, the Article concludes that a primary legacy of pragmatism will be its contribution to the advent of "soft formalism," characterized by an insistence that indeterminacy and subjectivity in law does not excuse the abandonment of fidelity as a central hallmark of legitimate adjudication. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory distress syndrome (ARDS) is a severe form of lung injury characterized by damage to the epithelial barrier with subsequent pulmonary edema and hypoxic respiratory failure. ARDS is a significant medical problem in intensive care units with associated high care costs. There are many potential causes of ARDS; however, alveolar injury associated with mechanical ventilation, termed ventilator-induced lung injury (VILI), remains a well-recognized contributor. It is thus critical to understand the mechanism of VILI. Based on our published preliminary data, we hypothesized that the endoplasmic reticulum (ER) stress response molecule Protein Kinase R-like Endoplasmic Reticulum Kinase (PERK) plays a role in transmitting mechanosensory signals the alveolar epithelium.Methods: ER stress signal responses to mechanical stretch were studied in ex-vivo ventilated pig lungs. To explore the effect of PERK inhibition on VILI, we ventilated live rats and compared lung injury parameters to non-ventilated controls. The effect of stretch-induced epithelial ER Ca2+ signaling on PERK was studied in stretched alveolar epithelial monolayers. To confirm the activation of PERK in human disease, ER stress signaling was compared between ARDS and non-ARDS lungs.Results: Our studies revealed increased PERK-specific ER stress signaling in response to overstretch. PERK inhibition resulted in dose-dependent improvement of alveolar inflammation and permeability. Our data indicate that stretch-induced epithelial ER Ca2+ release is an activator of PERK. Experiments with human lung tissue confirmed PERK activation by ARDS.Conclusion: Our study provides evidences that PERK is a mediator stretch signals in the alveolar epithelium. [ABSTRACT FROM AUTHOR]

Bronchoalveolar lavage (BAL) is a key clinical and research tool in lung transplantation (LTx). However, BAL collection and processing are not standardized across LTx centers. This International Society for Heart and Lung Transplantation–supported consensus document on BAL standardization aims to clarify definitions and propose common approaches to improve clinical and research practice standards. The following 9 areas are covered: (1) bronchoscopy procedure and BAL collection, (2) sample handling, (3) sample processing for microbiology, (4) cytology, (5) research, (6) microbiome, (7) sample inventory/tracking, (8) donor bronchoscopy, and (9) pediatric considerations. This consensus document aims to harmonize clinical and research practices for BAL collection and processing in LTx. The overarching goal is to enhance standardization and multicenter collaboration within the international LTx community and enable improvement and development of new BAL-based diagnostics. [ABSTRACT FROM AUTHOR]

Ex vivo lung perfusion (EVLP) allows for a reassessment of lung grafts initially deemed unsuitable for transplantation, increasing the available donor pool; however, this requires a pre- and post-EVLP period of cold ischemic time (CIT). Paucity of data exists on how the sequence of cold normothermic–cold preservations affect outcomes. A total of 110 patients were retrospectively analyzed. Duration of 3 preservation phases was measured: cold pre-EVLP, EVLP, and cold post-EVLP. The donor and recipient clinical data were collected. Primary graft dysfunction (PGD) and survival were monitored. Risk of mortality or PGD was calculated using Cox proportional hazards and logistic regression models to adjust for baseline characteristics. Using the highest quartile, patients were stratified into extended vs non-extended pre-EVLP (<264 vs ≥264 minutes) and post-EVLP (<287 vs ≥287 minutes) CIT. The rates of 1-year mortality (8.4% vs 29.6%, p = 0.013), PGD 2-3 (20.5% vs 52%, p = 0.002), and PGD 3 (8.4% vs 29.6%, p = 0.005) at 72 hours were increased in the extended post-EVLP CIT group. After adjusting for baseline risk factors, the extended group remained an independent predictor of PGD ≥2 (odd ratio: 6.18, 95% CI: 1.88–20.3, p = 0.003) and PGD 3 (odd ratio: 20.4, 95% CI: 2.56–161.9, p = 0.004) at 72 hours and 1-year mortality (hazard ratio: 17.9, 95% CI: 3.36–95.3, p = 0.001). Cold pre-EVLP was not a significant predictor of primary outcomes. Extended cold post-EVLP preservation is associated with a risk for PGD and 1-year mortality. Pre-EVLP CIT does not increase mortality or high-grade PGD. These findings from a multicenter trial should caution on the implementation of extended cold preservation after EVLP. [ABSTRACT FROM AUTHOR]

Background Delirium significantly affects post-operative outcomes, but the incidence, risk factors, and long-term impact of delirium in lung transplant recipients have not been well studied. Methods We analyzed 155 lung transplant recipients enrolled in the Lung Transplant Outcomes Group (LTOG) cohort at a single center. We determined delirium incidence by structured chart review, identified risk factors for delirium, determined whether plasma concentrations of 2 cerebral injury markers (neuron-specific enolase [NSE] and glial fibrillary acidic protein [GFAP]) were associated with delirium, and determined the association of post-operative delirium with 1-year survival. Results Fifty-seven (36.8%) patients developed post-operative delirium. Independent risk factors for delirium included pre-transplant benzodiazepine prescription (relative risk [RR] 1.82; 95% confidence interval [CI] 1.08 to 3.07; p = 0.025), total ischemic time (RR 1.10 per 30-minute increase; 95% CI 1.01 to 1.21; p = 0.027), duration of time with intra-operative mean arterial pressure <60 mm Hg (RR 1.07 per 15-minute increase; 95% CI 1.00 to 1.14; p = 0.041), and Grade 3 primary graft dysfunction (RR 2.13; 95% CI 1.27 to 3.58; p = 0.004). Ninety-one (58.7%) patients had plasma available at 24 hours. Plasma GFAP was inconsistently detected, whereas NSE was universally detectable, with higher NSE concentrations associated with delirium (risk difference 15.1% comparing 75th and 25th percentiles; 95% CI 2.5 to 27.7; p = 0.026). One-year mortality appeared higher among delirious patients, 12.3% compared with 7.1%, but the difference was not significant ( p = 0.28). Conclusions Post-operative delirium is common in lung transplant recipients, and several potentially modifiable risk factors deserve further study to determine their associated mechanisms and predictive values. [ABSTRACT FROM AUTHOR]

Mechanical circulatory support (MCS) as a bridge to lung transplant is an infrequent but accepted pathway in patients who have refractory end-stage pulmonary failure. The American Association of Thoracic Surgeons Expert Consensus Guidelines, published in 2023, recommends venovenous (VV) extracorporeal membrane oxygenation (ECMO) as the initial configuration for those patients who have failed conventional medical therapy, including mechanical ventilation, while waiting for lung transplantation and needing MCS. Alternatively, venoarterial (VA) ECMO can be used in patients with acute right ventricular failure, hemodynamic instability, or refractory respiratory failure. With the advancement in percutaneous venopulmonary (VP) ECMO cannulation techniques, this option is becoming an attractive configuration as bridge to lung transplantation. This configuration enhances stability of the right ventricle, prevents recirculation with direct introduction of pulmonary artery oxygenation, and promotes hemodynamic stability during mobility, rehabilitation, and sedation-weaning trials before lung transplantation. Here, we present a case series of eight percutaneous VP ECMO as bridge to lung transplant with all patients mobilized, awake, and successfully transplanted with survival to hospital discharge., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)