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The number of available donor organs limits lung transplantation, the only lifesaving therapy for the increasing population of patients with end-stage lung disease. A prevalent etiology of injury that renders lungs unacceptable for transplantation is gastric aspiration, a deleterious insult to the pulmonary epithelium. Currently, severely damaged donor lungs cannot be salvaged with existing devices or methods. Here we report the regeneration of severely damaged lungs repaired to meet transplantation criteria by utilizing an interventional cross-circulation platform in a clinically relevant swine model of gastric aspiration injury. Enabled by cross-circulation with a living swine, prolonged extracorporeal support of damaged lungs results in significant improvements in lung function, cellular regeneration, and the development of diagnostic tools for non-invasive organ evaluation and repair. We therefore propose that the use of an interventional cross-circulation platform could enable recovery of otherwise unsalvageable lungs and thus expand the donor organ pool. Gastric aspiration severely injures donor lungs, frequently making them unacceptable for transplantation. Here the authors show that an interventional cross-circulation platform enables the regeneration of severely damaged lungs in a swine model of gastric aspiration injury.

Engineered tissues can be used to model human pathophysiology and test the efficacy and safety of drugs. Yet, to model whole-body physiology and systemic diseases, engineered tissues with preserved phenotypes need to physiologically communicate. Here we report the development and applicability of a tissue-chip system in which matured human heart, liver, bone and skin tissue niches are linked by recirculating vascular flow to allow for the recapitulation of interdependent organ functions. Each tissue is cultured in its own optimized environment and is separated from the common vascular flow by a selectively permeable endothelial barrier. The interlinked tissues maintained their molecular, structural and functional phenotypes over 4 weeks of culture, recapitulated the pharmacokinetic and pharmacodynamic profiles of doxorubicin in humans, allowed for the identification of early miRNA biomarkers of cardiotoxicity, and increased the predictive values of clinically observed miRNA responses relative to tissues cultured in isolation and to fluidically interlinked tissues in the absence of endothelial barriers. Vascularly linked and phenotypically stable matured human tissues may facilitate the clinical applicability of tissue chips. Tissue chips with matured human heart, liver, bone and skin tissue niches linked by recirculating vascular flow recapitulate interdependent functions of these organs.

A diagnostic test accuracy study provides evidence on how well a test correctly identifies or rules out disease and informs subsequent decisions about treatment for clinicians, their patients, and healthcare providers. The authors highlight several different ways in which data from diagnostic test accuracy studies can be presented and interpreted, and discuss their advantages and disadvantages.

Objective Improving prognostication to direct personalised therapy remains an unmet need. This study prospectively investigated promising CT, genetic, and immunohistochemical markers to improve the prediction of colorectal cancer recurrence. Material and methods This multicentre trial (ISRCTN 95037515) recruited patients with primary colorectal cancer undergoing CT staging from 13 hospitals. Follow-up identified cancer recurrence and death. A baseline model for cancer recurrence at 3 years was developed from pre-specified clinicopathological variables (age, sex, tumour-node stage, tumour size, location, extramural venous invasion, and treatment). Then, CT perfusion (blood flow, blood volume, transit time and permeability), genetic (RAS, RAF, and DNA mismatch repair), and immunohistochemical markers of angiogenesis and hypoxia (CD105, vascular endothelial growth factor, glucose transporter protein, and hypoxia-inducible factor) were added to assess whether prediction improved over tumour-node staging alone as the main outcome measure. Results Three hundred twenty-six of 448 participants formed the final cohort (226 male; mean 66 ± 10 years. 227 (70%) had ≥ T3 stage cancers; 151 (46%) were node-positive; 81 (25%) developed subsequent recurrence. The sensitivity and specificity of staging alone for recurrence were 0.56 [95% CI: 0.44, 0.67] and 0.58 [0.51, 0.64], respectively. The baseline clinicopathologic model improved specificity (0.74 [0.68, 0.79], with equivalent sensitivity of 0.57 [0.45, 0.68] for high vs medium/low-risk participants. The addition of prespecified CT perfusion, genetic, and immunohistochemical markers did not improve prediction over and above the clinicopathologic model (sensitivity, 0.58–0.68; specificity, 0.75–0.76). Conclusion A multivariable clinicopathological model outperformed staging in identifying patients at high risk of recurrence. Promising CT, genetic, and immunohistochemical markers investigated did not further improve prognostication in rigorous prospective evaluation. Clinical relevance statement A prognostic model based on clinicopathological variables including age, sex, tumour-node stage, size, location, and extramural venous invasion better identifies colorectal cancer patients at high risk of recurrence for neoadjuvant/adjuvant therapy than stage alone. Key Points Identification of colorectal cancer patients at high risk of recurrence is an unmet need for treatment personalisation . This model for recurrence, incorporating many patient variables, had higher specificity than staging alone . Continued optimisation of risk stratification schema will help individualise treatment plans and follow-up schedules .

Objective We aimed to identify the effect of computer-aided detection (CAD) on visual search and performance in CT Colonography (CTC) of inexperienced and experienced readers. Methods Fifteen endoluminal CTC examinations were recorded, each with one polyp, and two videos were generated, one with and one without a CAD mark. Forty-two readers (17 experienced, 25 inexperienced) interpreted the videos during infrared visual search recording. CAD markers and polyps were treated as regions of interest in data processing. This multi-reader, multi-case study was analysed using multilevel modelling. Results CAD drew readers’ attention to polyps faster, accelerating identification times: median ‘time to first pursuit’ was 0.48 s (IQR 0.27 to 0.87 s) with CAD, versus 0.58 s (IQR 0.35 to 1.06 s) without. For inexperienced readers, CAD also held visual attention for longer. All visual search metrics used to assess visual gaze behaviour demonstrated statistically significant differences when “with” and “without” CAD were compared. A significant increase in the number of correct polyp identifications across all readers was seen with CAD (74 % without CAD, 87 % with CAD; p  < 0.001). Conclusions CAD significantly alters visual search and polyp identification in readers viewing three-dimensional endoluminal CTC. For polyp and CAD marker pursuit times, CAD generally exerted a larger effect on inexperienced readers. Key Points • Visual gaze is attracted by computer - assisted detection ( CAD ) marks on polyps • Inexperienced readers ’ gaze is affected more by CAD than experienced readers . • CAD marks could mean that the unannotated endoluminal surface is relatively neglected . • Correct polyp identification is increased significantly by CAD .

Background Crohn’s disease (CD) is a lifelong, relapsing and remitting inflammatory condition of the intestine. Medical imaging is crucial for diagnosis, phenotyping, activity assessment and detecting complications. Diverse small bowel imaging tests are available but a standard algorithm for deployment is lacking. Many hospitals employ tests that impart ionising radiation, of particular concern to this young patient population. Magnetic resonance enterography (MRE) and small bowel ultrasound (USS) are attractive options, as they do not use ionising radiation. However, their comparative diagnostic accuracy has not been compared in large head to head trials. METRIC aims to compare the diagnostic efficacy, therapeutic impact and cost effectiveness of MRE and USS in newly diagnosed and relapsing CD. Methods METRIC (ISRCTN03982913) is a multicentre, non-randomised, single-arm, prospective comparison study. Two patient cohorts will be recruited; those newly diagnosed with CD, and those with suspected relapse. Both will undergo MRE and USS in addition to other imaging tests performed as part of clinical care. Strict blinding protocols will be enforced for those interpreting MRE and USS. The Harvey Bradshaw index, C-reactive protein and faecal calprotectin will be collected at recruitment and 3 months, and patient experience will be assessed via questionnaires. A multidisciplinary consensus panel will assess all available clinical and imaging data up to 6 months after recruitment of each patient and will define the standard of reference for the presence, localisation and activity of disease against which the diagnostic accuracy of MRE and USS will be judged. Diagnostic impact of MRE and USS will be evaluated and cost effectiveness will be assessed. The primary outcome measure is the difference in per patient sensitivity between MRE and USS for the correct identification and localisation of small bowel CD. Discussion The trial is open at 5 centres with 46 patients recruited. We highlight the importance of stringent blinding protocols in order to delineate the true diagnostic accuracy of both imaging tests and discuss the difficulties of diagnostic accuracy studies in the absence of a single standard of reference, describing our approach utilising a consensus panel whilst minimising incorporation bias. Trial registration METRIC - ISRCTN03982913 – 05.11.13.