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We model the evolution of eukaryotic protein-protein interaction (PPI) networks. In our model, PPI networks evolve by two known biological mechanisms: (1) Gene duplication, which is followed by rapid diversification of duplicate interactions. (2) Neofuncti

Compared with traditional open arthrodesis, arthroscopic ankle arthrodesis has been associated with similar rates of fusion, decreased time to union, decreased pain, shorter hospital stay, earlier mobilization, reliable clinical results, and fewer complications. The aim of this case-control study was to analyze cost differences between outpatient arthroscopic and inpatient open ankle arthrodesis. To this end, the authors analyzed 20 ankle arthrodesis procedures: 10 performed by one surgeon on an inpatient basis using an open approach, and 10 performed by another surgeon on an outpatient basis arthroscopically. Patient age, body mass index, tourniquet time, length of stay, complications, days to clinical union, and insurance type, as well as charges and reimbursements for the surgeons and the hospital or surgery center were abstracted from the records. Statistically significant differences were observed between the outpatient arthroscopic and inpatient open arthrodesis groups for total site charges ($3898 ± 0.00 versus $32,683 ± $12,762, respectively, P < .0001), reimbursement to the surgeon ($1567 ± $320 versus $1107 ± $278, respectively, P = .003), and reimbursement to the hospital or ambulatory surgery center ($1110 ± $287 versus $8432 ± $2626, respectively); the ratio of hospital/surgery center charges to hospital/surgery center reimbursements was 28.48% for the inpatient arthroscopic group and 25.80% for the inpatient open arthrodesis group. Outpatient arthroscopic ankle arthrodesis, compared with inpatient open ankle arthrodesis, appears to be less expensive for third party payers, and surgeons are paid more, whereas hospitals and ambulatory surgical centers get paid a greater proportion of the charges that they bill. [ABSTRACT FROM AUTHOR]

Diagnostic error, a cause of substantial morbidity and mortality, is largely discovered and evaluated through self-report and manual review, which is costly and not suitable to real-time intervention. Opportunities exist to leverage electronic health record data for automated detection of potential misdiagnosis, executed at scale and generalized across diseases. We propose a novel automated approach to identifying diagnostic divergence considering both diagnosis and risk of mortality. Our objective was to identify cases of emergency department infectious disease misdiagnoses by measuring the deviation between predicted diagnosis and documented diagnosis, weighted by mortality. Two machine learning models were trained for prediction of infectious disease and mortality using the first 24h of data. Charts were manually reviewed by clinicians to determine whether there could have been a more correct or timely diagnosis. The proposed approach was validated against manual reviews and compared using the Spearman rank correlation. We analyzed 6.5 million ED visits and over 700 million associated clinical features from over one hundred emergency departments. The testing set performances of the infectious disease (Macro F1 = 86.7, AUROC 90.6 to 94.7) and mortality model (Macro F1 = 97.6, AUROC 89.1 to 89.1) were in expected ranges. Human reviews and the proposed automated metric demonstrated positive correlations ranging from 0.231 to 0.358. The proposed approach for diagnostic deviation shows promise as a potential tool for clinicians to find diagnostic errors. Given the vast number of clinical features used in this analysis, further improvements likely need to either take greater account of data structure (what occurs before when) or involve natural language processing. Further work is needed to explain the potential reasons for divergence and to refine and validate the approach for implementation in real-world settings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Competing Interests: The authors declare no conflict of interest.

Background: The goal of interprofessional practice experiences in health professions programs is to develop interprofessional collaborative practice skills., Purpose: The purpose of the study was to explore the meaning final-semester Bachelor of Science in Nursing students attributed to interprofessional practice experiences during clinical immersion., Methods: The theoretical framework for this descriptive qualitative study was experiential learning theory. A sample of 12 participants was drawn from final-semester prelicensure Bachelor of Science in Nursing students at a college of nursing at a public research university. Data were collected through one-on-one semi-structured interviews and analyzed through inductive thematic analysis., Results: The analysis yielded four themes: professional and interprofessional identity, working with team members, communication practices, and trusting relationships. Patterns across themes were clinical environment culture, nursing school preparation, nurse preceptor role, fear/concern/worry, and night shift., Conclusion: Consistency in preceptors, welcoming clinical environments, and opportunities to practice communicating with team members contributed to interprofessional collaborative practice skill development and improved perceptions of readiness for practice. Academic and clinical educators may use findings to (a) identify immersion placements for interprofessional practice experiences, (b) design curricula reflective of interprofessional practice, (c) advance teaching strategies to promote interprofessional practice, and (d) create learning environments that aid in professional and interprofessional identity formation., Competing Interests: Declaration of competing interest The author has adjunct faculty appointment at the research site. Study design included strategies to mitigate potential conflict of interest such as expert review of data collection instrument; criteria to exclude students that may have had the faculty as an instructor or who knew her personally; and recruitment methods that included online notices posted by other faculty in their courses and e-flyers sent through distribution lists by student leaders and faculty advisors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Written clinical language embodies and reflects the clinician's mental models of disease. Prior to the COVID-19 pandemic, pneumonia was shifting away from concern for healthcare-associated pneumonia and toward recognition of heterogeneity of pathogens and host response. How these models are reflected in clinical language or whether they were impacted by the pandemic has not been studied. We aimed to assess changes in the language used to describe pneumonia following the COVID-19 pandemic.

Nursing professional development practitioners are integral leaders who continue to seek tangible ways to show their value. A tool was designed to capture workload based upon the scope and standards of nursing professional development practice and successfully captured the workload of over 200 practitioners. The measures used in this project can serve as a guide for others to describe nursing professional development practitioner workload., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The vast majority of ankle arthritis is post-traumatic in nature, with rates of 60% to 80%. Symptoms include pain, decreased range of motion, and joint effusion. Diagnostic imaging is helpful in determining the degree of joint degeneration, with MRI and CT scan being the most sensitive. Conservative treatment modalities are targeted at reducing symptoms and improving function. Injectable therapy has gained popularity over the last few decades, with advancements in biologic treatments. Corticosteroids, hyaluronic acid, platelet-rich plasma, and amniotic tissue-derived products can be used to reduce inflammation in the joint, as well as prevent cartilage degeneration., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The impact of social inequity on the collective health of a society is well documented and, despite decades of research, the problem persists on a global scale. Nurse practitioners are competent to treat the downstream health effects of social inequity, but nursing students may lack the structural awareness to accurately target primary prevention efforts., Objective: The authors discuss faculty preparation and pedagogical considerations when incorporating social justice learning into a graduate and post-graduate psychiatric nurse practitioner course., Design/methods: Guided by Walter's Emancipatory Nursing Praxis model, several pedagogical strategies were developed to enhance graduate nursing students' awareness of oppressive and unjust realities in the healthcare setting., Conclusion: Emancipatory pedagogical strategies in competency-based graduate nursing education can enhance the transformative social learning essential for the development of health equity praxis., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: This article summarizes our approach to extracting medication and corresponding attributes from clinical notes, which is the focus of track 1 of the 2022 National Natural Language Processing (NLP) Clinical Challenges(n2c2) shared task., Methods: The dataset was prepared using Contextualized Medication Event Dataset (CMED), including 500 notes from 296 patients. Our system consisted of three components: medication named entity recognition (NER), event classification (EC), and context classification (CC). These three components were built using transformer models with slightly different architecture and input text engineering. A zero-shot learning solution for CC was also explored., Results: Our best performance systems achieved micro-average F1 scores of 0.973, 0.911, and 0.909 for the NER, EC, and CC, respectively., Conclusion: In this study, we implemented a deep learning-based NLP system and demonstrated that our approach of (1) utilizing special tokens helps our model to distinguish multiple medications mentions in the same context; (2) aggregating multiple events of a single medication into multiple labels improves our model's performance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the feasibility, accuracy, and interoperability of a natural language processing (NLP) system that extracts diagnostic assertions of pneumonia in different clinical notes and institutions., Materials and Methods: A rule-based NLP system was designed to identify assertions of pneumonia in 3 types of clinical notes from electronic health records (EHRs): emergency department notes, radiology reports, and discharge summaries. The lexicon and classification logic were tailored for each note type. The system was first developed and evaluated using annotated notes from the Department of Veterans Affairs (VA). Interoperability was assessed using data from the University of Utah (UU)., Results: The NLP system was comprised of 782 rules and achieved moderate-to-high performance in all 3 note types in VA (precision/recall/f1: emergency = 88.1/86.0/87.1; radiology = 71.4/96.2/82.0; discharge = 88.3/93.0/90.1). When applied to UU data, performance was maintained in emergency and radiology but decreased in discharge summaries (emergency = 84.7/94.3/89.3; radiology = 79.7/100.0/87.9; discharge = 65.5/92.7/76.8). Customization with 34 additional rules increased performance for all note types (emergency = 89.3/94.3/91.7; radiology = 87.0/100.0/93.1; discharge = 75.0/95.1/83.4)., Conclusion: NLP can be used to accurately identify the diagnosis of pneumonia across different clinical settings and institutions. A limited amount of customization to account for differences in lexicon, clinical definition of pneumonia, and EHR structure can achieve high accuracy without substantial modification., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Background: Deaths from pneumonia were decreasing globally prior to the COVID-19 pandemic, but it is unclear whether this was due to changes in patient populations, illness severity, diagnosis, hospitalization thresholds, or treatment. Using clinical data from the electronic health record among a national cohort of patients initially diagnosed with pneumonia, we examined temporal trends in severity of illness, hospitalization, and short- and long-term deaths., Design: Retrospective cohort PARTICIPANTS: All patients >18 years presenting to emergency departments (EDs) at 118 VA Medical Centers between 1/1/2006 and 12/31/2016 with an initial clinical diagnosis of pneumonia and confirmed by chest imaging report., Exposures: Year of encounter., Main Measures: Hospitalization and 30-day and 90-day mortality. Illness severity was defined as the probability of each outcome predicted by machine learning predictive models using age, sex, comorbidities, vital signs, and laboratory data from encounters during years 2006-2007, and similar models trained on encounters from years 2015 to 2016. We estimated the changes in hospitalizations and 30-day and 90-day mortality between the first and the last 2 years of the study period accounted for by illness severity using time covariate decompositions with model estimates., Results: Among 196,899 encounters across the study period, hospitalization decreased from 71 to 63%, 30-day mortality 10 to 7%, 90-day mortality 16 to 12%, and 1-year mortality 29 to 24%. Comorbidity risk increased, but illness severity decreased. Decreases in illness severity accounted for 21-31% of the decrease in hospitalizations, and 45-47%, 32-24%, and 17-19% of the decrease in 30-day, 90-day, and 1-year mortality. Findings were similar among underrepresented patients and those with only hospital discharge diagnosis codes., Conclusions: Outcomes for community-onset pneumonia have improved across the VA healthcare system after accounting for illness severity, despite an increase in cases and comorbidity burden., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Objective: Analyze responses to a national request for information (RFI) to uncover gaps in policy, practice, and understanding of veteran suicide to inform federal research strategy., Data Source: An RFI with 21 open-ended questions generated from Presidential Executive Order #1386, administered nationally from July 3 to August 5, 2019., Study Design: Semi-structured, open-ended responses analyzed using a collaborative qualitative and text-mining data process., Data Extraction Methods: We aligned traditional qualitative methods with natural language processing (NLP) text-mining techniques to analyze 9040 open-ended question responses from 722 respondents to provide results within 3 months. Narrative inquiry and the medical explanatory model guided the data extraction and analytic process., Results: Five major themes were identified: risk factors, risk assessment, prevention and intervention, barriers to care, and data/research. Individuals and organizations mentioned different concepts within the same themes. In responses about risk factors, individuals frequently mentioned generic terms like "illness" while organizations mentioned specific terms like "traumatic brain injury." Organizations and individuals described unique barriers to care and emphasized ways to integrate data and research to improve points of care. Organizations often identified lack of funding as barriers while individuals often identified key moments for prevention such as military transitions and ensuring care providers have military cultural understanding., Conclusions: This study provides an example of a rapid, adaptive analysis of a large body of qualitative, public response data about veteran suicide to support a federal strategy for an important public health topic. Combining qualitative and text-mining methods allowed a representation of voices and perspectives including the lived experiences of individuals who described stories of military transition, treatments that worked or did not, and the perspective of organizations treating veterans for suicide. The results supported the development of a national strategy to reduce suicide risks for veterans as well as civilians., (© 2022 Health Research and Educational Trust.)

Competing Interests: The authors declare no conflicts of interest.

Competing Interests: The authors declare no conflicts of interest.

Despite impressive success of machine learning algorithms in clinical natural language processing (cNLP), rule-based approaches still have a prominent role. In this paper, we introduce medspaCy, an extensible, open-source cNLP library based on spaCy framework that allows flexible integration of rule-based and machine learning-based algorithms adapted to clinical text. MedspaCy includes a variety of components that meet common cNLP needs such as context analysis and mapping to standard terminologies. By utilizing spaCy's clear and easy-to-use conventions, medspaCy enables development of custom pipelines that integrate easily with other spaCy-based modules. Our toolkit includes several core components and facilitates rapid development of pipelines for clinical text., (©2021 AMIA - All rights reserved.)

Abundant literature supports the value of interprofessional education (IPE) in health profession programs, but few studies focus on undergraduate honors students. The goals of this academic-practice partnership quality improvement project were to increase awareness of IPE, provide experiential opportunities to learn the principles of interprofessional practice, assess perceptions of readiness for practice, and to explore motivations and learning expectations of undergraduate nursing and pre-medical honors students. Average scores on the Readiness for Interprofessional Learning Scale (RIPLS) increased in several areas after the IPE simulation experiences, with small to medium effect sizes (Cohen's d) on individual items and two subscales (Teamwork & Collaboration and Positive Professional Identity). Themes identified in the narrative data were opportunity, fun, self-awareness, situational awareness, and the value of teamwork. These findings add to literature on honor students' expectations and motivations for learning and can be used in designing interprofessional collaborative learning activities for undergraduate health profession students., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Rationale: Computerized severity assessment for community-acquired pneumonia could improve consistency and reduce clinician burden. Objectives: To develop and compare 30-day mortality-prediction models using electronic health record data, including a computerized score with all variables from the original Pneumonia Severity Index (PSI) except confusion and pleural effusion ("ePSI score") versus models with additional variables. Methods: Among adults with community-acquired pneumonia presenting to emergency departments at 117 Veterans Affairs Medical Centers between January 1, 2006, and December 31, 2016, we compared an ePSI score with 10 novel models employing logistic regression, spline, and machine learning methods using PSI variables, age, sex and 26 physiologic variables as well as all 69 PSI variables. Models were trained using encounters before January 1, 2015; tested on encounters during and after January 1, 2015; and compared using the areas under the receiver operating characteristic curve, confidence intervals, and patient event rates at a threshold PSI score of 970. Results: Among 297,498 encounters, 7% resulted in death within 30 days. When compared using the ePSI score (confidence interval [CI] for the area under the receiver operating characteristic curve, 0.77-0.78), performance increased with model complexity (CI for the logistic regression PSI model, 0.79-0.80; CI for the boosted decision-tree algorithm machine learning PSI model using the Extreme Gradient Boosting algorithm [mlPSI] with the 19 original PSI factors, 0.83-0.85) and the number of variables (CI for the logistic regression PSI model using all 69 variables, 0.84-085; CI for the mlPSI with all 69 variables, 0.86-0.87). Models limited to age, sex, and physiologic variables also demonstrated high performance (CI for the mlPSI with age, sex, and 26 physiologic factors, 0.84-0.85). At an ePSI score of 970 and a mortality-risk cutoff of <2.7%, the ePSI score identified 31% of all patients as being at "low risk"; the mlPSI with age, sex, and 26 physiologic factors identified 53% of all patients as being at low risk; and the mlPSI with all 69 variables identified 56% of all patients as being at low risk, with similar rates of mortality, hospitalization, and 7-day secondary hospitalization being determined. Conclusions: Computerized versions of the PSI accurately identified patients with pneumonia who were at low risk of death. More complex models classified more patients as being at low risk of death and as having similar adverse outcomes.

Background: Patient travel history can be crucial in evaluating evolving infectious disease events. Such information can be challenging to acquire in electronic health records, as it is often available only in unstructured text., Objective: This study aims to assess the feasibility of annotating and automatically extracting travel history mentions from unstructured clinical documents in the Department of Veterans Affairs across disparate health care facilities and among millions of patients. Information about travel exposure augments existing surveillance applications for increased preparedness in responding quickly to public health threats., Methods: Clinical documents related to arboviral disease were annotated following selection using a semiautomated bootstrapping process. Using annotated instances as training data, models were developed to extract from unstructured clinical text any mention of affirmed travel locations outside of the continental United States. Automated text processing models were evaluated, involving machine learning and neural language models for extraction accuracy., Results: Among 4584 annotated instances, 2659 (58%) contained an affirmed mention of travel history, while 347 (7.6%) were negated. Interannotator agreement resulted in a document-level Cohen kappa of 0.776. Automated text processing accuracy (F1 85.6, 95% CI 82.5-87.9) and computational burden were acceptable such that the system can provide a rapid screen for public health events., Conclusions: Automated extraction of patient travel history from clinical documents is feasible for enhanced passive surveillance public health systems. Without such a system, it would usually be necessary to manually review charts to identify recent travel or lack of travel, use an electronic health record that enforces travel history documentation, or ignore this potential source of information altogether. The development of this tool was initially motivated by emergent arboviral diseases. More recently, this system was used in the early phases of response to COVID-19 in the United States, although its utility was limited to a relatively brief window due to the rapid domestic spread of the virus. Such systems may aid future efforts to prevent and contain the spread of infectious diseases., (©Kelly S Peterson, Julia Lewis, Olga V Patterson, Alec B Chapman, Daniel W Denhalter, Patricia A Lye, Vanessa W Stevens, Shantini D Gamage, Gary A Roselle, Katherine S Wallace, Makoto Jones. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 24.03.2021.)

Obesity is a serious chronic disease whose prevalence has grown to epidemic proportions over the past five decades and is a major contributor to the global burden of most common cancers, heart disease, Type 2 diabetes, liver disease, and sleep apnea. Primary care clinicians, including physicians, nurse practitioners, and physician assistants, are often the first health care professionals to identify obesity or overweight during routine long-term care and have the opportunity to intervene to prevent and treat disease. However, they often lack the training and skills needed to deliver scientifically validated, behavior-based treatments. These gaps must be addressed in order to treat the obesity epidemic. The Society of Behavioral Medicine strongly urges health professional educators and accrediting agencies to include obesity and overweight management education for primary care clinicians. Additionally, we support promoting referrals and reimbursement for psychologists, dieticians, and other health care professionals as critical members of the care team and improving reimbursement levels for behavioral obesity and overweight management treatment., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society of Behavioral Medicine.)

Background: Due to the difficulty of studying incentives in practice, there is limited empirical evidence of the full-impact pay-for-performance (P4P) incentive systems., Objective: To evaluate the impact of P4P in a controlled, simulated environment., Design: We employed a simulation-based randomised controlled trial with three standardised patients to assess advanced practice providers' performance. Each patient reflected one of the following: (A) indicated for P4P screenings, (B) too young for P4P screenings, or (C) indicated for P4P screenings, but screenings are unrelated to the reason for the visit. Indication was determined by the 2016 Centers for Medicare and Medicaid Services quality measures., Intervention: The P4P group was paid $150 and received a bonus of $10 for meeting each of five outcome measures (breast cancer, colorectal cancer, pneumococcal, tobacco use and depression screenings) for each of the three cases (max $300). The control group received $200., Setting: Learning resource centre., Participants: 35 advanced practice primary care providers (physician assistants and nurse practitioners) and 105 standardised patient encounters., Measurements: Adherence to incentivised outcome measures, interpersonal communication skills, standards of care, and misuse., Results: The Type a patient was more likely to receive indicated P4P screenings in the P4P group (3.82 out of 5 P4P vs 2.94 control, p=0.02), however, received lower overall standards of care under P4P (31.88 P4P vs 37.06 control, p=0.027). The Type b patient was more likely to be prescribed screenings not indicated, but highlighted by P4P: breast cancer screening (47% P4P vs 0% control, p<0.01) and colorectal cancer screening (24% P4P vs 0% control, p=0.03). The P4P group over-reported completion of incentivised measures resulting in overpayment (average of $9.02 per patient)., Limitations: A small sample size and limited variability in patient panel limit the generalisability of findings., Conclusions: Our findings caution the adoption of P4P by highlighting the unintended consequences of the incentive system., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The academic-practice partnership began in 2005 with a collaborative Pre-licensure Bachelor of Science in Nursing (BSN) program. Since that time the partnership has broadened to include faculty development, evidence-based practice, interprofessional education, and research initiatives., Purpose: The purpose is to share the outcomes of this academic-practice partnership and to provide a model for other institutions., Methods: This successful partnership is grounded in the American Association of Colleges of Nursing and the American Organization of Nurse Executives' eight guiding principles for academic-practice partnerships. The cornerstones to the partnership are communication, collaboration, and mutual respect., Results: The initial outcomes of this collaboration increased enrollment, thereby increasing the number of BSN prepared registered nurses; created opportunities for clinical nurses to teach; increased the number of nursing faculty; and capitalized on the strengths of each partner., Conclusion: The most exciting aspect of this partnership is the shared commitment to decrease the gap between nursing education and practice; thus, improving the quality of nursing education, advancing the practice of nursing and healthcare delivery, and enhancing the health of our community. Consistent with the AACN-AONE recommendations, this academic-practice partnership prepares nurses of the future to be evidence-based practitioners and creates opportunities for nurses to achieve educational and career advancements., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Identifying occurrences of medication side effects and adverse drug events (ADEs) is an important and challenging task because they are frequently only mentioned in clinical narrative and are not formally reported., Methods: We developed a natural language processing (NLP) system that aims to identify mentions of symptoms and drugs in clinical notes and label the relationship between the mentions as indications or ADEs. The system leverages an existing word embeddings model with induced word clusters for dimensionality reduction. It employs a conditional random field (CRF) model for named entity recognition (NER) and a random forest model for relation extraction (RE)., Results: Final performance of each model was evaluated separately and then combined on a manually annotated evaluation set. The micro-averaged F1 score was 80.9% for NER, 88.1% for RE, and 61.2% for the integrated systems. Outputs from our systems were submitted to the NLP Challenges for Detecting Medication and Adverse Drug Events from Electronic Health Records (MADE 1.0) competition (Yu et al. in http://bio-nlp.org/index.php/projects/39-nlp-challenges , 2018). System performance was evaluated in three tasks (NER, RE, and complete system) with multiple teams submitting output from their systems for each task. Our RE system placed first in Task 2 of the challenge and our integrated system achieved third place in Task 3., Conclusion: Adding to the growing number of publications that utilize NLP to detect occurrences of ADEs, our study illustrates the benefits of employing innovative feature engineering.

This article expands upon previous work by the authors to develop a model of nursing essential and effective freedom to facilitate nursing action in behalf of social justice. The article proposes that while social justice is rooted in nursing's ontological, epistemological, and moral foundations, the discipline's social justice mandate is constrained by its historical and contemporary location within an institutionalized medical paradigm. We present a model of nursing "essential" and "effective" freedom based on the philosophy of Bernard Lonergan to illustrate how nursing can transcend these barriers. This humanizing model is illustrated through personal narratives of the authors.

Background: Implant survivorship is dependent on accuracy of implantation and successful soft tissue balancing. System instrumentation for total ankle arthroplasty implantation has a key influence on surgeon accuracy and reproducibility. The purpose of this study was to determine the accuracy and reproducibility of implant position with patient-specific guides for total ankle arthroplasty across multiple surgeons at multiple facilities., Methods: This retrospective, multicenter study included 44 patients who received a total ankle implant (INBONE II Total Ankle System; Wright Medical Technology, Memphis, TN) using PROPHECY patient-specific guides from January 2012 to December 2014. Forty-four patients with an average age of 63.0 years underwent total ankle arthroplasty using this preoperative patient-specific system. Preoperative computed tomography (CT) scans were obtained to assess coronal plane deformity, assess mechanical and anatomic alignment, and build patient-specific guides that referenced bony anatomy. The mean preoperative coronal deformity was 4.6 ± 4.6 degrees (range, 14 degrees varus to 17 degrees valgus). The first postoperative weightbearing radiographs were used to measure coronal and sagittal alignment of the implant vs the anatomic axis of the tibia., Results: In 79.5% of patients, the postoperative implant position of the tibia corresponded to the preoperative plan of the tibia within 3 degrees of the intended target, within 4 degrees in 88.6% of patients, and within 5 degrees in 100% of patients. The tibial component coronal size was correctly predicted in 98% of cases, whereas the talar component was correctly predicted in 80% of cases., Conclusion: The use of patient-specific instrumentation for total ankle arthroplasty provided reliable alignment and reproducibility in the clinical situation similar to that shown in cadaveric testing. This study has shown that the preoperative patient-specific instrumentation provided for accuracy and reproducibility of ankle arthroplasty implantation in a cohort across multiple surgeons and facilities., Level of Evidence: Level III, retrospective comparative series.

Lateral column lengthening is a common procedure for correction of pes planovalgus. A tricortical bone graft has been a standard among foot and ankle surgeons. The purpose of the present study was to compare the union rates and complications between the 2 forms of fixation for lateral column lengthening. The present study was a retrospective medical record and radiograph review of 52 patients divided into 2 equal groups, allograft (group A) and opening wedge plate (group B). The radiographic analyses compared the preoperative, postoperative and long-term measurements of cuboid abduction and talonavicular angles. The outcome measures included nonunion, hardware removal, and infection. The median follow-up duration for each group was 34.5 (range 6.3 to 89.5) months and 12.6 (range 6.5 to 56.8) months for groups A and B, respectively. Group A had 4 nonunions (15.4%) and group B had 2 nonunions (7.7%). The mean radiographic measurements of cuboid abduction and talonavicular articulation for each group improved significantly. The incidence of hardware removal was greater for group A than for group B (30.8% versus 15.4%), although the difference was not statistically significant. The median time to osseous healing for group A was 12.0 (range 8.0 to 80.0) weeks and for group B was 10.0 (range 6.0 to 36.0) weeks. The interposition plating techniques for lateral column lengthening procedures had a lower nonunion rate and incidence of hardware removal compared with the traditional use of tricortical bone grafting. The findings from the present study will aid surgeons in alternative fixation for lateral column lengthening procedures., (Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Total ankle replacement (TAR) is a viable alternative to ankle fusion in certain patients with end-stage ankle arthritis. Despite the importance of understanding alignment and movement of the prosthesis, there is no standardized radiographic method for evaluating the position and movement of the INBONE 2 prosthesis. The aims of this study were to describe a radiographic measurement protocol for INBONE 2 for clinical practice and research while determining the interobserver and intraobserver reliability using standard weightbearing radiographs. Fifteen patients were randomly selected with operative dates from January 2011 to January 2014 who underwent primary TAR using the INBONE 2 prosthesis. Most recent preoperative and first postoperative weightbearing anteroposterior and lateral radiographs were pulled and deidentified. Three foot and ankle surgeons blinded from the patient selection and deidentification, measured the described measurements on separate occasions. Intraobserver reliability: surgeon 1 had acceptable reliability for 9 of 13 continuous radiographic measurements (69.2%), surgeon 2 had acceptable reliability for 8 of 13 measurements (61.5%), and surgeon 3 had acceptable reliability for 12 of 13 measurements (92.3%). Interobserver reliability: among the first measurements, 6 of 13 continuous radiographic measurements (46.2%) had acceptable reliability. Among the second measurements, 7 of 13 measurements (53.8%) had acceptable reliability. Among the first and second measurements combined, 7 of 13 measurements (53.8%) had acceptable reliability. This study promotes the need for meticulous evaluation of annual radiographic findings following TAR in an effort to avoid catastrophic failure and represents moderate agreement can be obtained by employing the proposed measurements for surveillance of INBONE 2 TAR at annual postoperative visits. Measurements on the anteroposterior radiograph appear to demonstrate more consistent results for surveillance than lateral measurements. The intraobserver reliability results were somewhat superior to the interobserver reliability, implying more relevance for a single surgeon applying these measurements annually for postoperative surveillance., Levels of Evidence: Diagnostic, Level III.

Tibiotalocalcaneal arthrodesis is a salvage procedure for severe hindfoot/ankle deformities, arthritis, avascular necrosis of the talus, failed total ankle replacement, and Charcot neuroarthropathy. The methods for fixation include anterior and lateral plates, screws, retrograde intramedullary nails, and external fixation. The purpose of the present report was to describe the short-term radiographic outcomes and technique using a posterior approach with an anatomic-specific locking plate for tibiotalocalcaneal arthrodesis. Nine patients underwent tibiotalocalcaneal arthrodesis using a posterior locking plate. The medical records and radiographs were retrospectively reviewed for patient demographics, fusion rate, complications, and patient satisfaction. The mean patient age was 57.89 ± 10.8 years, and the follow-up period was 11.11 ± 4.74 months for the patients undergoing posterior tibiotalocalcaneal arthrodesis. The mean time to weightbearing in a shoe with a brace was 16.68 weeks. The ankle and subtalar joints had healed within a mean duration of 13.61 ± 2.96 weeks. Two patients (22%) developed nonunion, 1 at both the ankle and subtalar joint and 1 at the ankle only. The present report demonstrates an alternative posterior approach to joint preparation and fixation. Direct visualization of both joints and soft tissue coverage provide a viable option for posterior fusion in patients with compromised anterior and/or lateral skin envelopes., (Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Calcaneonavicular coalitions can lead to a painful, rigid pes planovalgus deformity. Historical treatment of coalitions recommends resection. A newer concept in coalition treatment includes concomitant flatfoot reconstruction. In the present study, we hoped to demonstrate the ability to reconstruct a flatfoot deformity with concomitant calcaneonavicular coalition resection. We performed a retrospective comparative study of patients undergoing isolated calcaneonavicular bar excision (group A) with those undergoing calcaneonavicular bar excision and concomitant pes planovalgus reconstruction (group B). The radiographic parameters of pes planovalgus correction were measured on the pre- and postoperative radiographs, including talar head uncoverage, calcaneal inclination, and anteroposterior and lateral talo-first metatarsal angle. Calcaneonavicular coalition resection was performed using a standard technique with or without biologic spacers. Associated flatfoot reconstruction included posterior muscle group lengthening, calcaneal osteotomy, and/or midfoot osteotomy. Of the 27 patients, 20 were included in group A and 7 in group B. Their mean age was 18.1 years. Improvement was seen in the radiographic parameters for patients undergoing calcaneonavicular bar excision with concomitant flatfoot procedures, with statistical significance found in the calcaneal inclination (p = .013). Talar head uncoverage improved in both groups (p = .011). No change was found in the radiographic angles in patients undergoing isolated calcaneonavicular bar excision. No patients in either group developed recurrence of the coalition. The results of the present study demonstrated radiographic improvement in patients undergoing calcaneonavicular bar excision with concomitant pes planovalgus reconstruction. Hindfoot reconstruction with joint sparing osteotomies during coalition excision is a reasonable option to improve alignment and avoid arthrodesis., (Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Severe hallux valgus deformity with proximal instability creates pain and deformity in the forefoot. First tarsometatarsal joint arthrodesis is performed to reduce the intermetatarsal angle and stabilize the joint. Dorsomedial locking plate fixation with adjunctive lag screw fixation is used because of its superior construct strength and healing rate. Despite this, questions remain regarding whether this hardware is more prominent and more likely to need removal. The purpose of the present study was to determine the incidence of symptomatic hardware at the first tarsometatarsal joint and to determine the incidence of hardware removal resulting from prominence and/or discomfort. A review of 165 medical records of consecutive patients who had undergone first tarsometatarsal joint arthrodesis with plate fixation was conducted. The outcome of interest was the incidence of symptomatic hardware removal in patients with clinical union. The mean age was 55 (range 18.4 to 78.8) years. The mean follow-up duration was 65.9 ± 34.0 (range 7.0 to 369.0) weeks. In our cohort, 25 patients (15.2%) had undergone hardware removed because of pain and irritation. Of these patients, 18 (72.0%) had a locking plate and lag screw removed, and 7 (28.0%) had crossing lag screws removed. The fixation of a first tarsometatarsal joint fusion poses a difficult situation owing to minimal soft tissue coverage and the inherent need for robust fixation to promote fusion. Hardware can become prominent postoperatively and can become painful and/or induce cutaneous compromise. The results of the present observational investigation imply that surgeons can reasonably inform patients that the incidence of symptomatic hardware removal after first tarsometatarsal arthrodesis is approximately 15% within a median duration of 9.0 months after surgery., (Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Nonunion, delayed union, and refracture after operative treatment of acute proximal fifth metatarsal fractures in athletes is uncommon. This study was a failure analysis of operatively managed acute proximal fifth metatarsal fractures in healthy athletes. We identified 149 patients who underwent operative treatment for fifth metatarsal fractures. Inclusion criteria isolated skeletally mature, athletic patients under the age of 40 with a minimum of 1-year follow-up. Patients were excluded with tuberosity fractures, fractures distal to the proximal metaphyseal-diaphyseal region of the fifth metatarsal, multiple fractures or operative procedures, fractures initially treated conservatively, and medical comorbidities/risk factors for nonunion. Fifty-five patients met the inclusion/exclusion criteria. Four (7.3%) patients required a secondary operative procedure due to refracture. The average time to refracture was 8 months. All refractures were associated with bent screws and occurred in male patients who participated in professional basketball, professional volleyball, and college football. The average time for release to progressive weight-bearing was 6 weeks. Three patients were revised to a bigger size screw and went on to union. One patient was revised to the same-sized screw and required a second revision surgery for nonunion. All failures were refractures in competitive athletes who were initially treated with small diameter solid or cannulated stainless steel screws. The failures were not associated with early postoperative weight-bearing protocol. Maximizing initial fixation stiffness may decrease the late failure rate in competitive athletes. More clinical studies are needed to better understand risk factors for failure after screw fixation in the competitive, athletic population., Level of Evidence: Prognostic, Level IV: Case series., (© 2015 The Author(s).)

Unlabelled: Moderate to severe hallux valgus (HV) has traditionally been treated with a corrective osteotomy or a tarsometatarsal arthrodesis. Tarsometatarsal arthrodesis can be performed as a planar wedge resection or using a joint curettage technique. Little is known about whether adequate correction can be obtained with purely a joint curettage technique. The purpose of this study is to evaluate the corrective power of a first tarsometatarsal joint (TMTJ) arthrodesis using a nonplanar wedge curettage technique. A retrospective radiograph and chart review was performed on 99 consecutive patients (110 feet) who underwent a first TMTJ arthrodesis for primary HV correction utilizing a curettage technique. The radiographic measurements collected were the first intermetatarsal angle, HV angle, and tibial sesamoid position and were obtained at the following intervals: preoperative, immediate postoperative, and 6 months postoperative. In all, 91 patients (100 feet) qualified for statistical analysis. There was a significant decrease in all 3 measurements from the preoperative throughout the entire postoperative time period (P < .001). The authors demonstrate the ability to achieve significant angular correction with a joint curettage method for a tarsometatarsal arthrodesis., Levels of Evidence: Therapeutic, Level IV: Case series., (© 2014 The Author(s).)

Flexible adult acquired flatfoot disorder is commonly treated with the use of osteotomies in the calcaneus and medial column. The combination of these joint-preserving osteotomies with additional soft-tissue procedures allows realignment of the hindfoot with the goal of preventing further deformity or degenerative joint disease. A thorough understanding of each patient's condition allows the surgeon to match the correct osteotomy to the clinical indication, while also successfully executing the planned surgery., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Malreduction of the syndesmosis can lead to increased peak pressures and subsequent arthritis. The purpose of this study was to evaluate the initial syndesmotic reduction and radiographic maintenance when using a knotless suture button fixation device for treatment of syndesmotic injury., Methods: A retrospective chart and radiographic review was performed to identify patients who underwent open reduction internal fixation of ankle syndesmosis ruptures treated with a knotless, suture button fixation system. Radiographic measurements included medial clear space, tibiofibular overlap, tibiofibular clear space, and the distance between buttons. Fifty-six patients underwent repair of an ankle fracture with syndesmotic rupture over a 3-year period, with a mean follow-up of 160.9 days., Results: The tibiofibular clear space and tibiofibular overlap significantly improved from pre- to first postoperative, but also demonstrated some loss of fixation at final follow-up (P < .001). The distance between the buttons increased on average 1.1 mm from immediate postoperative to final follow-up, demonstrating some postoperative creep and loss of fixation in the system. A low complication rate and need for a revision operation was found in our patient cohort. Some loss of reduction did occur postoperatively, although this did not correlate to adverse patient outcomes., Conclusion: Syndesmotic stabilization, using a knotless suture button fixation device demonstrated adequate initial syndesmotic reduction, but also exhibited an increase in the tibiofibular clear space and tibiofibular overlap, relative to initial postfixation position, at short-term follow-up., Level of Evidence: Level IV, retrospective case series., (© The Author(s) 2015.)

Charcot neuroarthropathy is frequently recognized as a major cause of morbidity in patients with neuropathic diabetes mellitus. Recently, intramedullary beam screw fixation has been used for midfoot Charcot reconstructions. Ten below-the-knee cadaveric specimens were used to demonstrate an antegrade, posterior approach for placement of a medial column beam screw, with specific attention to the proximity of the anatomic structures at risk. Six structures at risk were identified, including the sural nerve, ankle joint, flexor hallucis longus tendon, Achilles tendon, neurovascular bundle, and peroneal tendon sheath. The sural nerve was the most commonly injured structure, injured in 50% of the limbs. The Achilles and flexor hallucis longus tendons were injured in 20% and the ankle joint in 10% of the limbs. The neurovascular bundle and peroneal tendon sheath were located over 1 cm from the reference guidewire and were considered safe structures in this approach. Our results have demonstrated an alternative posterior approach to the delivery of an intramedullary medial column beam screw, instead of a retrograde technique beginning in the metatarsal heads. Our results have also made clear the need to be aware of the potential for damage to the sural nerve, Achilles tendon, flexor hallucis longus tendon, and ankle joint., (Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

The Achilles tendon is among the most commonly injured tendons in the human body. The most common reason for delayed treatment is a missed diagnosis or a deficiency in presentation. The neglected or chronically ruptured Achilles tendon presents a unique treatment challenge. The surgical approach varies greatly depending on the extent of degeneration and the resultant gap between the opposing tendon ends. Most surgeons have recommended the use of a tendon transfer or augmentation to strengthen the Achilles tendon repair. The following technique uses a flexor hallucis longus tendon transfer with gastrocnemius aponeurosis turndown flap augmentation. This technique has been commonly performed by us with success., (Copyright © 2014 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Adult acquired flatfoot deformity is a debilitating musculoskeletal condition affecting the lower extremity. Posterior tibial tendon dysfunction (PTTD) is the primary etiology for the development of a flatfoot deformity in an adult. PTTD is classified into 4 stages (with stage IV subdivided into stage IV-A and IV-B). This classification is described in detail in this article., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Combined ankle and subtalar joint instability can lead to severe disability of the lower extremity. Multiple procedures have been described for hindfoot and ankle instability, including anatomic and non-anatomic reconstructions. The authors present their technique consisting of a free autogenous split peroneus longus tendon graft combined with a modified Brostrom-Gould repair., (Copyright © 2013 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: Acute Hemorrhagic Leukoencephalitis (AHLE) is a rare demyelinating disorder of acute onset, rapid deterioration and significant morbidity and mortality. Most often described as a post-infectious complication of an upper respiratory illness, its precise pathophysiology remains unclear. We describe two pediatric patients with AHLE with partial complement factor I (FI) deficiency whose successful treatment included the interleukin-1 (IL-1) receptor antagonist, anakinra, implicating a role for FI and IL-1 in this disorder., Methods: Extensive clinical workup of two patients presenting with AHLE revealed complement abnormalities, specifically related to the alternative pathway and its regulator, FI. Aggressive management with steroids, immunoglobulin, and anakinra ultimately led to improvement of clinical status and near return to neurologic baseline in both patients. Genetic sequencing of the FI coding regions of the patients and their families was performed. In vitro protein expression studies and immunohistochemistry of fixed brain tissue was used to investigate pathogenic mechanisms., Results: Two novel mutations in FI were identified in our patients, which result in failure to secrete FI. Immunohistochemical evaluation of brain tissue demonstrated positive staining for C3, membrane attack complex (MAC) and IL-1., Conclusions: We propose AHLE is an unreported, rare phenotype for partial FI deficiency. The upregulation of C3, MAC and IL-1 with subsequent demyelination support a pathologic role for complement activation in AHLE, and suggest anakinra as an important adjunctive therapy in this disease.

Significant patient morbidity and mortality is associated with the development of venous thromboembolism (VTE) following orthopedic surgery. The majority of the literature supports proper prophylaxis following major orthopedic surgery involving hip and knee procedures. Foot and ankle surgery, however, is starkly contrasted because of the lack of recommendations. This article provides a comprehensive overview of the risk factors and incidence of VTE in foot and ankle surgery while also outlining the newest literature guidelines for prophylaxis.

We model the evolution of eukaryotic protein-protein interaction (PPI) networks. In our model, PPI networks evolve by two known biological mechanisms: (1) Gene duplication, which is followed by rapid diversification of duplicate interactions. (2) Neofunctionalization, in which a mutation leads to a new interaction with some other protein. Since many interactions are due to simple surface compatibility, we hypothesize there is an increased likelihood of interacting with other proteins in the target protein's neighborhood. We find good agreement of the model on 10 different network properties compared to high-confidence experimental PPI networks in yeast, fruit flies, and humans. Key findings are: (1) PPI networks evolve modular structures, with no need to invoke particular selection pressures. (2) Proteins in cells have on average about 6 degrees of separation, similar to some social networks, such as human-communication and actor networks. (3) Unlike social networks, which have a shrinking diameter (degree of maximum separation) over time, PPI networks are predicted to grow in diameter. (4) The model indicates that evolutionarily old proteins should have higher connectivities and be more centrally embedded in their networks. This suggests a way in which present-day proteomics data could provide insights into biological evolution.

Deep venous thrombosis after foot and ankle surgery is a serious complication that can have potentially life-threatening complications, such as pulmonary embolus. Genetic mutations have been reported in the published data to cause an increased risk of developing deep vein thrombosis. Two such genetic mutations are the methylenetetrahydrofolate reductase gene variant C677T and the 4G/5G polymorphism of the plasminogen activator inhibitor gene. This case report presents a female patient who developed a postoperative deep vein thrombosis after hallux valgus reconstruction. A hypercoagulable panel revealed the 2 mentioned genetic mutations. We hope this case study will highlight the importance of ascertaining all patient risk factors and the relation to perioperative deep vein thrombosis prophylaxis., (Copyright © 2011 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

We report a case of pneumonia in a 13 month old male child with partial DiGeorge syndrome who died after inadvertently receiving live viral vaccines. Although live viral vaccines have been used safely in some children with DiGeorge syndrome, there are insufficient data to recommend their routine use in those with severe immunodeficiency.

We completed a phase I trial of indole-3-carbinol (I3C) in 17 women (1 postmenopausal and 16 premenopausal) from a high-risk breast cancer cohort. After a 4-week placebo run-in period, subjects ingested 400 mg I3C daily for 4 weeks followed by a 4-week period of 800 mg I3C daily. These chronic doses were tolerated well by all subjects. Hormonal variables were measured near the end of the placebo and dosing periods, including determination of the urinary 2-hydroxyestrone/16alpha-hydroxyestrone ratio. Measurements were made during the follicular phase for premenopausal women. Serum estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, and sex hormone binding globulin showed no significant changes in response to I3C. Caffeine was used to probe for cytochrome P450 1A2 (CYP1A2), N-acetyltransferase-2 (NAT-2), and xanthine oxidase. Comparing the results from the placebo and the 800 mg daily dose period, CYP1A2 was elevated by I3C in 94% of the subjects, with a mean increase of 4.1-fold. In subjects with high NAT-2 activities, these were decreased to 11% by I3C administration but not altered if NAT-2 activity was initially low. Xanthine oxidase was not affected. Lymphocyte glutathione S-transferase activity was increased by 69% in response to I3C. The apparent induction of CYP1A2 was mirrored by a 66% increase in the urinary 2-hydroxyestrone/16alpha-hydroxyestrone ratio in response to I3C. The maximal increase was observed with the 400 mg daily dose of I3C, with no further increase found at 800 mg daily. If the ratio of hydroxylated estrone metabolites is a biomarker for chemoprevention, as suggested, then 400 mg I3C daily will elicit a maximal protective effect.

The molecular pathogenesis of focal/diffuse proliferative lupus glomerulonephritis was studied by cDNA microarray analysis of gene expression in glomeruli from clinical biopsies. Transcriptional phenotyping of glomeruli isolated by laser-capture microscopy revealed considerable kidney-to-kidney heterogeneity in increased transcript expression, resulting in four main gene clusters that identified the presence of B cells, several myelomonocytic lineages, fibroblast and epithelial cell proliferation, matrix alterations, and expression of type I IFN-inducible genes. Glomerulus-to-glomerulus variation within a kidney was less marked. The myeloid lineage transcripts, characteristic of those found in isolated activated macrophages and myeloid dendritic cells, were widely distributed in all biopsy samples. One major subgroup of the samples expressed fibrosis-related genes that correlated with pathological evidence of glomerulosclerosis; however, decreased expression of TGF-beta1 argued against its role in lupus renal fibrosis. Expression of type I IFN-inducible transcripts by a second subset of samples was associated with reduced expression of fibrosis-related genes and milder pathological features. This pattern of gene expression resembled that exhibited by activated NK cells. A large gene cluster with decreased expression found in all samples included ion channels and transcription factors, indicating a loss-of-function response to the glomerular injury.

The CD8 alphabetaT cell receptor repertoire in joint fluid of individuals with active psoriatic arthritis contained an average of 32 major oligoclonal expansions in many variable genes of the TCR beta chain (BV) families, as shown by beta-chain CDR3 length analysis. Interestingly, a small number of oligoclonal expansions were shared between simultaneous samples of joint fluid and blood; however, most expansions found in joint fluid were not identifiable in blood emphasizing the immunologic specificity of the clonal events for the inflamed joint at a given point of time. The CD4 T cell joint fluid repertoire contained fewer and smaller oligoclonal expansions also largely restricted to the joint, suggesting that CD4 T cells participate perhaps by interacting cognitively to generate the CD8 clones. The inferred amino acid sequence of a single CD8 oligoclonal expansion revealed that they usually are composed of one or a few structurally related clones at the amino acid sequence level with beta-chains that encode identical or highly homologous CDR3 motifs. These were not shared among patients. Moreover, several clones that encoded the same amino acid sequence were found to be structurally distinct at the nucleotide level, strongly implying clonal selection and expansion is operating at the level of specific TCR-peptide interactions. The findings support a model of psoriatic arthritis inflammation involving extensive and selective Ag, likely autoantigen, driven intra-articular CD4, and CD8 T cell clonal expansions.