Faculty Bibliography

Human fibrin hydrogels are a popular choice for use as a biomaterial within tissue engineered constructs because they are biocompatible, nonxenogenic, autologous use compatible, and biodegradable. We have recently demonstrated the ability to culture induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium on fibrin hydrogels. However, iPSCs themselves have relatively few substrate options (e.g., laminin) for expansion in adherent cell culture for use in cell therapy. To address this, we investigated the potential of culturing iPSCs on fibrin hydrogels for three-dimensional applications and further examined the use of fibrinogen, the soluble precursor protein, as a coating substrate for traditional adherent cell culture. iPSCs successfully adhered to and proliferated on fibrin hydrogels. The two-dimensional culture with fibrinogen allows for immediate adaption of culture models to a nonxenogeneic model. Similarly, multiple commercially available iPSC lines adhered to and proliferated on fibrinogen coated surfaces. iPSCs cultured on fibrinogen expressed similar levels of the pluripotent stem cell markers SSea4 (98.7% ± 1.8%), Oct3/4 (97.3% ± 3.8%), TRA1-60 (92.2% ± 5.3%), and NANOG (96.0% ± 3.9%) compared with iPSCs on Geltrex. Using a trilineage differentiation assay, we found no difference in the ability of iPSCs grown on fibrinogen or Geltrex to differentiate to endoderm, mesoderm, or ectoderm. Finally, we demonstrated the ability to differentiate iPSCs to endothelial cells using only fibrinogen coated plates. On the basis of these data, we conclude that human fibrinogen provides a readily available and inexpensive alternative to laminin-based products for the growth, expansion, and differentiation of iPSCs for use in research and clinical cell therapy applications. Stem Cells Translational Medicine 2019;8:512-521.

OBJECTIVE:To summarise the literature on the barriers to athletes seeking mental health treatment and cultural influencers of mental health in elite athletes. DESIGN/METHODS:Systematic review DATA SOURCES: PubMed, Cochrane, Scopus, SportDiscus (Ebsco), and PsycINFO (ProQuest) up to November 2018. ELIGIBILITY CRITERIA FOR SELECTING STUDIES/UNASSIGNED:Qualitative and quantitative original studies of elite athletes (those who competed at the professional, Olympic, or collegiate/university levels), published in any language. RESULTS:Stigma, low mental health literacy, negative past experiences with mental health treatment-seeking, busy schedules, and hypermasculinity are barriers to elite athletes seeking mental health treatment. Cultural influencers of mental health in elite athletes include: (1) the lack of acceptance of women as athletes; (2) lower acceptability of mental health symptoms and disorders among non-white athletes; (3) non-disclosure of religious beliefs; and (4) higher dependence on economic benefits. Coaches have an important role in supporting elite athletes in obtaining treatment for mental illness. Brief anti-stigma interventions in elite athletes decrease stigma and improve literary about mental health. CONCLUSION/CONCLUSIONS:There is a need for various actors to provide more effective strategies to overcome the stigma that surrounds mental illness, increase mental health literacy in the athlete/coach community, and address athlete-specific barriers to seeking treatment for mental illness. In this systematic review, we identified strategies that, if implemented, can overcome the cultural factors that may otherwise limit athletes seeking treatment. Coaches are critical for promoting a culture within elite athletes' environments that encourages athletes to seek treatment.

Background/UNASSIGNED:Patients with biopsy-proven systemic sarcoidosis who develop a chronic CNS disorder are often presumed to have neurosarcoidosis (NS), however, the possibility of comorbid neurologic disease, such as MS, must be considered if presentation and course are not typical for NS. Methods/UNASSIGNED:Retrospective chart review across 4 academic MS centers was undertaken to identify patients with diagnosis of MS (2017 McDonald criteria) and biopsy-confirmed extraneural sarcoidosis. Data were abstracted from each chart using a case report form that systematically queried for demographic, clinical, and paraclinical characteristics relevant to NS and MS. Results/UNASSIGNED:Ten patients met our inclusion criteria (mean age 47.7 [±5.9] years; 80% female). Noncaseating granulomas consistent with sarcoidosis were found on biopsy in all cases (lung 7/10, mediastinum 2/10, liver 1/10, spleen 1/10, and skin 1/10). Diagnosis of MS was based on clinical history of MS-like relapses and MRI findings characteristic of demyelination and typical disease evolution during follow-up (average of 7 years). No patient developed features of NS that could be considered a "red flag" against the diagnosis of MS (such as meningeal enhancement, hydrocephalus, and pituitary involvement). All patients were treated with disease-modifying therapy for MS. Conclusions/UNASSIGNED:We propose a rational diagnostic approach to patients with sarcoidosis who may have comorbid MS. When the clinical picture is equivocal, the presence of multiple "MS-typical lesions" and the absence of any "NS-typical lesions" on MRI favor diagnosis of MS. Close follow-up is required to ascertain whether clinical and radiologic disease evolution and response to MS therapies conform to the proposed diagnosis of MS.

Mental health emergencies require a rapid, effective response. We searched the literature on mental health emergencies in athletes and found five papers. None of these addressed elite athletes. Nonetheless, common mental health emergencies may present in the sports environment and may place the athlete and others at risk. Sports teams and organisations should anticipate which emergencies are likely and how medical and support staff can best respond. Responses should be based on general non-sporting guidelines. We stress the importance of clinicians following standard procedures.

OBJECTIVE:The impetus for this consensus discussion was to recommend clinical trial designs that can deliver high-quality data for effective therapies for pediatric patients, in a reasonable timeframe, with a key focus on short- and long-term safety. METHODS:The International Pediatric Multiple Sclerosis Study Group convened a meeting of experts to review the advances in the understanding of pediatric-onset multiple sclerosis (MS) and the advent of clinical trials for this population. RESULTS:In the last few years, convincing evidence has emerged that the biological processes involved in MS are largely shared across the age span. As such, treatments proven efficacious for the care of adults with MS have a biological rationale for use in pediatric MS given the relapsing-remitting course at onset and high relapse frequency. There are also ethical considerations on conducting clinical trials in this age group including the use of placebo owing to highly active disease. It is imperative to reconsider study design and implementation based on what information is needed. Are studies needed for efficacy or should safety be the primary goal? Further, there have been major recruitment challenges in recently completed and ongoing pediatric MS trials. Phase 3 trials for every newly approved therapy for adult MS in the pediatric MS population are simply not feasible. CONCLUSIONS:A primary goal is to ensure high-quality evidence-based treatment for children and adolescents with MS, which will improve our understanding of the safety of these agents and remove regulatory or insurance-based limitations in access to treatment.

Facial transplant (FT) is a viable option for patients with severe craniomaxillofacial deformities. Transplant imaging requires coordination between radiologists and surgeons and an understanding of the merits and limitations of imaging modalities. Digital subtraction angiography and CT angiography are critical to mapping vascular anatomy, while volume-rendered CT allows evaluation of osseous defects and landmarks used for surgical cutting guides. This article highlights the components of successful FT imaging at two institutions and in two index cases. A deliberate stepwise approach to performance and interpretation of preoperative FT imaging, which consists of the modalities and protocols described here, is essential to seamless integration of the multidisciplinary FT team. ^©RSNA, 2019 See discussion on this article by Lincoln .