Normothermic Ex Vivo Lung Perfusion (Novel) as an Assessment of Extended Criteria Donor Lungs: A Prospective Multi-Center Clinical Trial

Purpose: Ex vivo lung perfusion (EVLP) allows re-evaluation of extended criteria/marginal donor lungs. This can increase the number of lung transplants. However, the long-term outcomes of transplanting EVLP-screened lungs in a multicenter setting are unknown. We proposed to evaluate the short- and long-term outcomes of EVLP performed at multiple centers. Methods: This is a prospective, nonrandomized clinical trial. Seventeen lung transplant centers in the United States. Adult patients with end-stage pulmonary disease requiring lung transplant from May 2011 to December 2017 were eligible. Lung allografts initially deemed extended criteria/marginal (n=216) were placed on EVLP and re-evaluated prior to transplant. Patients received either standard donors (n=116) or lungs screened with EVLP (n=110). Results: Half of the lung grafts (110/216, 50.9%) placed on EVLP were transplanted. The incidence of primary graft dysfunction 24 hours post-transplant was higher in the EVLP group (25.5% vs 10.3%, p=0.003), but was not significantly different 48 hours (EVLP: 15.5%, control: 9.5%, p=0.49) and 72 hours (13.6% vs 6.9%, p=0.34) post-transplant. Survival was not significantly different between the 2 groups 1 year (n=226, EVLP: 86%, control: 94%, p=0.06), 3 years (n=226, EVLP: 68%, control: 76%, p=0.16, Figure), or 5 years (n=159, EVLP: 59%, control: 65%, p=0.68) post-transplant. There were also no differences in pulmonary function, the incidence of chronic lung allograft dysfunction or quality of life measures post-transplant. Conclusion: In this multicenter study, recipients of lungs that were re-evaluated on EVLP and deemed suitable for transplant had similar outcomes as a recipients of a standard lung transplants. EVLP offers the opportunity to screen donated lungs initially considered high risk and can safely increase the availability of transplantable lungs without compromising outcomes

Cohort profile: a collaborative multicentre study of retinal optical coherence tomography in 539 patients with neuromyelitis optica spectrum disorders (CROCTINO)

PURPOSE: Optical coherence tomography (OCT) captures retinal damage in neuromyelitis optica spectrum disorders (NMOSD). Previous studies investigating OCT in NMOSD have been limited by the rareness and heterogeneity of the disease. The goal of this study was to establish an image repository platform, which will facilitate neuroimaging studies in NMOSD. Here we summarise the profile of the Collaborative OCT in NMOSD repository as the initial effort in establishing this platform. This repository should prove invaluable for studies using OCT to investigate NMOSD. PARTICIPANTS: The current cohort includes data from 539 patients with NMOSD and 114 healthy controls. These were collected at 22 participating centres from North and South America, Asia and Europe. The dataset consists of demographic details, diagnosis, antibody status, clinical disability, visual function, history of optic neuritis and other NMOSD defining attacks, and OCT source data from three different OCT devices. FINDINGS TO DATE: The cohort informs similar demographic and clinical characteristics as those of previously published NMOSD cohorts. The image repository platform and centre network continue to be available for future prospective neuroimaging studies in NMOSD. For the conduct of the study, we have refined OCT image quality criteria and developed a cross-device intraretinal segmentation pipeline. FUTURE PLANS: We are pursuing several scientific projects based on the repository, such as analysing retinal layer thickness measurements, in this cohort in an attempt to identify differences between distinct disease phenotypes, demographics and ethnicities. The dataset will be available for further projects to interested, qualified parties, such as those using specialised image analysis or artificial intelligence applications

The oxygenating constituent of 3,6-diketocamphane monooxygenase from the CAM plasmid of Pseudomonas putida: the first crystal structure of a type II Baeyer-Villiger monooxygenase. Corrigendum

: A statement is amended in the article by Isupov et al. [(2015). Acta Cryst. D71, 2344-2353]

The oxygenating constituent of 3,6-diketocamphane monooxygenase from the CAM plasmid of Pseudomonas putida: The first crystal structure of a type II Baeyer-Villiger monooxygenase

The three-dimensional structures of the native enzyme and the FMN complex of the overexpressed form of the oxygenating component of the type II Baeyer-Villiger 3,6-diketocamphane monooxygenase have been determined to 1.9\uc5 resolution. The structure of this dimeric FMN-dependent enzyme, which is encoded on the large CAM plasmid of Pseudomonas putida, has been solved by a combination of multiple anomalous dispersion from a bromine crystal soak and molecular replacement using a bacterial luciferase model. The orientation of the isoalloxazine ring of the FMN cofactor in the active site of this TIM-barrel fold enzyme differs significantly from that previously observed in enzymes of the bacterial luciferase-like superfamily. The Ala77 residue is in a cis conformation and forms a \u3b2-bulge at the C-terminus of \u3b2-strand 3, which is a feature observed in many proteins of this superfamily.Peer reviewed: YesNRC publication: Ye

The oxygenating constituent of 3,6-diketocamphane monooxygenase from the CAM plasmid of Pseudomonas putida: The first crystal structure of a type II Baeyer-Villiger monooxygenase

The three-dimensional structures of the native enzyme and the FMN complex of the overexpressed form of the oxygenating component of the type II Baeyer-Villiger 3,6-diketocamphane monooxygenase have been determined to 1.9\uc5 resolution. The structure of this dimeric FMN-dependent enzyme, which is encoded on the large CAM plasmid of Pseudomonas putida, has been solved by a combination of multiple anomalous dispersion from a bromine crystal soak and molecular replacement using a bacterial luciferase model. The orientation of the isoalloxazine ring of the FMN cofactor in the active site of this TIM-barrel fold enzyme differs significantly from that previously observed in enzymes of the bacterial luciferase-like superfamily. The Ala77 residue is in a cis conformation and forms a \u3b2-bulge at the C-terminus of \u3b2-strand 3, which is a feature observed in many proteins of this superfamily.Peer reviewed: YesNRC publication: Ye