Thromboelastography profiles for controlled circulatory death donors: Validating the role of heparin.

Controlled donation after circulatory death (cDCD) liver transplants are associated with increased ischemic-type biliary complications. Microvascular thrombosis secondary to decreased donor fibrinolysis may contribute to bile duct injury. We hypothesized that cDCD donors are hypercoagulable with impaired fibrinolysis and aim to use thromboelastography to characterize cDCD coagulation profiles.

A pattern-matched Twitter analysis of US cancer-patient sentiments.

BACKGROUND: Twitter has been recognized as an important source of organic sentiment and opinion. This study aimed to (1) characterize the content of tweets authored by the United States cancer patients; and (2) use patient tweets to compute the average happiness of cancer patients for each cancer diagnosis. METHODS: A large sample of English tweets from March 2014 through December 2014 was obtained from Twitter. Using regular expression software pattern matching, the tweets were filtered by cancer diagnosis. For each cancer-specific tweetset, individual patients were extracted, and the content of the tweet was categorized. The patients' Twitter identification numbers were used to gather all tweets for each patient, and happiness values for patient tweets were calculated using a quantitative hedonometric analysis. RESULTS: The most frequently tweeted cancers were breast (n = 15,421, 11% of total cancer tweets), lung (n = 2928, 2.0%), prostate (n = 1036, 0.7%), and colorectal (n = 773, 0.5%). Patient tweets pertained to the treatment course (n = 73, 26%), diagnosis (n = 65, 23%), and then surgery and/or biopsy (n = 42, 15%). Computed happiness values for each cancer diagnosis revealed higher average happiness values for thyroid (h_avg = 6.1625), breast (h_avg = 6.1485), and lymphoma (h_avg = 6.0977) cancers and lower average happiness values for pancreatic (h_avg = 5.8766), lung (h_avg = 5.8733), and kidney (h_avg = 5.8464) cancers. CONCLUSIONS: The study confirms that patients are expressing themselves openly on social media about their illness and that unique cancer diagnoses are correlated with varying degrees of happiness. Twitter can be employed as a tool to identify patient needs and as a means to gauge the cancer patient experience.

Dealing with the struggling learner.

Every resident will inevitably struggle with some aspect of training. The degree and severity of the struggle, however, will vary and the struggling residents will fall along a continuum. The struggles of a few will not be evident to those in program leadership. One of the most challenging aspects of managing a struggling resident's remediation is the early identification of one who is faltering. We identify best practices in identification and remediation.

Evaluating the educational effectiveness of an 8-week patient management course for surgical interns: A nine-year analysis.

INTRODUCTION: Our general surgery program mandates an 8-week "intern school" (IS) for matriculating surgery interns. The course consists of a pre-test, didactics, and a post-test. We hypothesized IS exam performance would correlate with American Board of Surgery In Training Examination (ABSITE) scores.∖ METHODS: This was a retrospective analysis of IS pre- and post-tests and ABSITE scores for all OHSU surgery interns from 2010 to 2018. McNemar's, chi-square, and Pearson tests were calculated. RESULTS: The pre and post-test pass rate for 293 interns was 26% vs. 86% (p < 0.001). Categorical interns were more likely to pass the pre-test (33% vs 11% p = 0.004), and the post-test (96% vs 83% p = 0.007) than non-designated interns and more likely to pass the post-test than designated preliminary intern (96% vs 80%, p = 0.0014). There was no correlation between IS exams and ABSITE performance. DISCUSSION: IS improves exam performance, but IS test scores do not correlate with ABSITE scores, and the program is not a means to identify interns at risk of poor ABSITE performance.

Design of an entrustable professional activity for adult extracorporeal membrane oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation supports severe cardiac or pulmonary failure. There are currently no competency-based standards for extracorporeal membrane oxygenation training. METHODS: Extracorporeal membrane oxygenation experts were interviewed using a structured interview. Responses were audio recorded, transcribed, and validated by respondents. Interviews were coded using grounded theory with a constant comparison method. Themes were developed and used to construct the entrustable professional activity, which was reviewed by the extracorporeal membrane oxygenation experts. RESULTS: Nine experts were interviewed; all had experience with trainees. Interview themes identified include patient selection, circuit and medical management, multidisciplinary communication, problem-based learning and simulation, and entrustment decisions. Essential functions of the entrustable professional activity were patient selection, circuit management, cannula selection, responding to circuit emergencies/complications, anticoagulation management, weaning, and family/team communication. CONCLUSIONS: Essential functions of an extracorporeal membrane oxygenation entrustable professional activity were defined using data from structured interviews. The resultant entrustable professional activity could be implemented by critical-care programs as a scaffolding for competency-based fellow training.

Mucosal delivery of a double-stapled RSV peptide prevents nasopulmonary infection.

Respiratory syncytial virus (RSV) infection accounts for approximately 64 million cases of respiratory disease and 200,000 deaths worldwide each year, yet no broadly effective prophylactic or treatment regimen is available. RSV deploys paired, self-associating, heptad repeat domains of its fusion protein, RSV-F, to form a fusogenic 6-helix bundle that enables the virus to penetrate the host cell membrane. Here, we developed hydrocarbon double-stapled RSV fusion peptides that exhibit stabilized α-helical structure and striking proteolytic resistance. Pretreatment with double-stapled RSV peptides that specifically bound to the RSV fusion bundle inhibited infection by both laboratory and clinical RSV isolates in cells and murine infection models. Intranasal delivery of a lead double-stapled RSV peptide effectively prevented viral infection of the nares. A chitosan-based nanoparticle preparation markedly enhanced pulmonary delivery, further preventing progression of RSV infection to the lung. Thus, our results provide a strategy for inhibiting RSV infection by mucosal and endotracheal delivery of double-stapled RSV fusion peptides.

Chemical synthesis of hydrocarbon-stapled peptides for protein interaction research and therapeutic targeting.

The peptide α-helix represents one of nature's most featured protein shapes and is employed in a diversity of protein architectures, from the cytoskeletal infrastructure to the most intimate contact points between crucial signaling proteins. By installing an all-hydrocarbon crosslink into native sequences, the shape and biological activity of natural peptide α-helices can be recapitulated, yielding a chemical toolbox that can be used both to interrogate the protein interactome and to modulate interaction networks for potential therapeutic benefit. Here, current methodology for synthesizing stabilized α-helices (SAH) corresponding to key protein interaction domains is described. A stepwise approach is taken for the production of crosslinking non-natural amino acids, incorporation of the residues into peptide templates, and application of ruthenium-catalyzed ring-closing metathesis to generate hydrocarbon-stapled peptides. Through facile derivatization and functionalization steps, SAHs can be tailored for a broad range of applications in biochemical, structural, proteomic, cellular, and in vivo studies. Curr. Protoc. Chem. Biol. 3:99-117 © 2011 by John Wiley & Sons, Inc.