Evaluation of a Pediatric Facial Paralysis Education and Family Support Day.

INTRODUCTION: Facial paralysis impairs the mimetic functions of the facial musculature. In pediatric patients, free functioning muscle transfer neurotized with an intact contralateral facial nerve is the gold standard for smile reanimation. In response to requests from families of children with facial paralysis, the Division of Plastic and Reconstructive Surgery at the Hospital for Sick Children hosted an inaugural "Facial Paralysis Family Day." The objective was to create an opportunity for families to meet, exchange stories, and build support networks. METHODS: This study was a quality improvement project to conduct a needs assessment and evaluate the feasibility and satisfaction of implementing a family support intervention for individuals living with facial paralysis. RESULTS: The needs assessment demonstrated that families were most interested in advances in medicine, therapy and coping sessions and meeting other families. The post-event evaluation questionnaire indicated that attendees enjoyed the event, would attend again and found it highly valuable connecting and networking other families. It also indicated that key needs identified were addressed, with excellent ratings for the presentation discussing advances in medicine (100% rated "good" or "very good"), the therapy sessions (92% rated "good" or "very good") and the presentations by patients and their families (100% rated "good" or "very good.") DISCUSSION:: Two areas of improvement highlighted were elaborating further on medical advances and facilitating interactions between families. Overall, this event was well regarded and will likely be repeated at our institution and serve as a valuable resource for other hospitals planning to organize a similar event.

Management of congenital melanocytic nevi in the plastic surgery clinic: Families' expectations and their persistent concern about malignancy.

BACKGROUND: Children with congenital melanocytic nevi (CMN) were historically managed with surgical removal to lower the risk of malignant transformation. The evolving literature over the last decade has indicated a significantly lower risk than previously estimated. Indications for excision currently revolve around aesthetic and psychosocial concerns. This study describes and evaluates the perspectives and expectations of patients and families referred to a pediatric plastic surgery clinic on CMN management. METHOD: A two-part questionnaire was administered before and after an initial clinic appointment to evaluate patient and family concerns of lesion growth, risk of malignancy, treatment expectations, and stigmatization. RESULTS: Thirty questionnaires were completed for 11 male and 19 female patients, mean age 9.2 years (1-25). Referring doctors (majority dermatologists) were rarely concerned about malignancy (8%), but parents listed it as a top reason for wanting the CMN removed (37%) and the most common expectation for the visit followed by information about surgical options and outcome. Before the clinic, 93% were at least "slightly" worried about CMN growth and 96% about malignancy, whereas 63% and 72%, respectively, after the clinic. CONCLUSIONS: Families want information about surgical excision and are concerned about malignancy, indicating lingering misinformation or misconception about melanoma risk. For the majority, CMN removal remains at least slightly important, presumably for aesthetic reasons and remaining concern about malignancy. Involved health care professionals should assure reliable and coherent patient information about MM risk, indications for surgery and expected outcome to best support families' decision-making.

Prehospital Identification of Underlying Coronary Artery Disease by Community Paramedics.

There is a lack of definitive evidence that preventative, in-home medical care provided by highly trained community paramedics reduces acute health care utilization and improves the overall well-being of patients suffering from chronic diseases. The Expanding Paramedicine in the Community (EPIC) trial is a randomized controlled trial designed to investigate the use of community paramedics in chronic disease management (ClinicalTrials.gov ID: NCT02034045). This case of a patient randomized to the intervention arm of the EPIC study demonstrates how the added layer of frequent patient contact by community paramedics and real-time electronic medical record (EMR) correspondence between the paramedics, physicians and other involved practitioners prevented possible life-threatening complications. The visiting community paramedic deduced the need for an electrocardiogram, which prompted the primary care physician to order a stress test revealing abnormalities and thus a coronary artery bypass graft was performed without emergency procedures, unnecessary financial expenditure or further health degradation such as a myocardial infarction.

Dynamic Reconstruction of Facial Paralysis in Craniofacial Microsomia.

BACKGROUND: Craniofacial microsomia is associated with maxillomandibular hypoplasia, microtia, soft-tissue deficiency, and variable severity of cranial nerve dysfunction, most often of the facial nerve. This study evaluated the incidence of facial paralysis in patients with craniofacial microsomia and outcomes after free functioning muscle transfer for dynamic smile reconstruction. METHODS: A single-center, retrospective, cross-sectional study was performed from 1985 to 2018 to identify pediatric patients with craniofacial microsomia and severe facial nerve dysfunction who underwent dynamic smile reconstruction with free functioning muscle transfer. Preoperative and postoperative facial symmetry and oral commissure excursion during maximal smile were measured using photogrammetric facial analysis software. RESULTS: This study included 186 patients with craniofacial microsomia; 41 patients (21 male patients, 20 female patients) had documented facial nerve dysfunction (22 percent) affecting all branches (51 percent) or the mandibular branch only (24 percent). Patients with severe facial paralysis (n = 8) underwent smile reconstruction with a free functioning muscle transfer neurotized either with a cross-face nerve graft (n = 7) or with the ipsilateral motor nerve to masseter (n =1). All patients achieved volitional muscle contraction with improvement in lip symmetry and oral commissure excursion (median, 8 mm; interquartile range, 3 to 10 mm). The timing of orthognathic surgery and facial paralysis reconstruction was an important consideration in optimizing patient outcomes. CONCLUSIONS: The authors' institution's incidence of facial nerve dysfunction in children with craniofacial microsomia is 22 percent. Free functioning muscle transfer is a reliable option for smile reconstruction in children with craniofacial microsomia. To optimize outcomes, a novel treatment algorithm is proposed for craniofacial microsomia patients likely to require both orthognathic surgery and facial paralysis reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

A cell-based drug delivery platform for treating central nervous system inflammation.

Mesenchymal stem cells (MSCs) are promising candidates for the development of cell-based drug delivery systems for autoimmune inflammatory diseases, such as multiple sclerosis (MS). Here, we investigated the effect of Ro-31-8425, an ATP-competitive kinase inhibitor, on the therapeutic properties of MSCs. Upon a simple pretreatment procedure, MSCs spontaneously took up and then gradually released significant amounts of Ro-31-8425. Ro-31-8425 (free or released by MSCs) suppressed the proliferation of CD4+ T cells in vitro following polyclonal and antigen-specific stimulation. Systemic administration of Ro-31-8425-loaded MSCs ameliorated the clinical course of experimental autoimmune encephalomyelitis (EAE), a murine model of MS, displaying a stronger suppressive effect on EAE than control MSCs or free Ro-31-8425. Ro-31-8425-MSC administration resulted in sustained levels of Ro-31-8425 in the serum of EAE mice, modulating immune cell trafficking and the autoimmune response during EAE. Collectively, these results identify MSC-based drug delivery as a potential therapeutic strategy for the treatment of autoimmune diseases. KEY MESSAGES: MSCs can spontaneously take up the ATP-competitive kinase inhibitor Ro-31-8425. Ro-31-8425-loaded MSCs gradually release Ro-31-8425 and exhibit sustained suppression of T cells. Ro-31-8425-loaded MSCs have more sustained serum levels of Ro-31-8425 than free Ro-31-8425. Ro-31-8425-loaded MSCs are more effective than MSCs and free Ro-31-8425 for EAE therapy.

Oxandrolone in the Treatment of Burn Injuries: A Systematic Review and Meta-analysis.

Severe burns induce a profound hypermetabolic response, leading to a prolonged state of catabolism associated with organ dysfunction and delay of wound healing. Oxandrolone, a synthetic testosterone analog, may alleviate the hypermetabolic catabolic state thereby decreasing associated morbidity. However, current literature has reported mixed outcomes on complications following Oxandrolone use, specifically liver and lung function. We conducted an updated systematic review and meta-analysis studying the effects of Oxandrolone on mortality, length of hospital stay, progressive liver dysfunction, and nine secondary outcomes. We searched Pubmed, EMBASE, Web of Science, CINAHL, and Cochrane Databases of Systematic Reviews and Randomized Controlled Trials. Thirty-one randomized control trials and observational studies were included. Basic science and animal studies were excluded. Only studies comparing Oxandrolone to standard of care, or placebo, were included. Oxandrolone did not affect rates of mortality (relative risk [RR]: 0.72; 95% confidence interval [CI]: 0.47 to 1.08; P = .11) or progressive liver dysfunction (RR: 1.04; 95% CI: 0.59 to 1.85; P = .88), but did decrease length of stay in hospital. Oxandrolone significantly increased weight regain, bone mineral density, percent lean body mass, and decreased wound healing time for donor graft sites. Oxandrolone did not change the incidence of transient liver dysfunction or mechanical ventilation requirements. There is evidence to suggest that Oxandrolone is a beneficial adjunct to the acute care of burn patients; shortening hospital stays and improving several growth and wound healing parameters. It does not appear that Oxandrolone increases the risk of progressive or transient liver injury, although monitoring liver enzymes is recommended.

Shattering barriers toward clinically meaningful MSC therapies.

More than 1050 clinical trials are registered at FDA.gov that explore multipotent mesenchymal stromal cells (MSCs) for nearly every clinical application imaginable, including neurodegenerative and cardiac disorders, perianal fistulas, graft-versus-host disease, COVID-19, and cancer. Several companies have or are in the process of commercializing MSC-based therapies. However, most of the clinical-stage MSC therapies have been unable to meet primary efficacy end points. The innate therapeutic functions of MSCs administered to humans are not as robust as demonstrated in preclinical studies, and in general, the translation of cell-based therapy is impaired by a myriad of steps that introduce heterogeneity. In this review, we discuss the major clinical challenges with MSC therapies, the details of these challenges, and the potential bioengineering approaches that leverage the unique biology of MSCs to overcome the challenges and achieve more potent and versatile therapies.

A prodrug-doped cellular Trojan Horse for the potential treatment of prostate cancer.

Despite considerable advances in prostate cancer research, there is a major need for a systemic delivery platform that efficiently targets anti-cancer drugs to sites of disseminated prostate cancer while minimizing host toxicity. In this proof-of-principle study, human mesenchymal stem cells (MSCs) were loaded with poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) that encapsulate the macromolecule G114, a thapsigargin-based prostate specific antigen (PSA)-activated prodrug. G114-particles (∼950 nm in size) were internalized by MSCs, followed by the release of G114 as an intact prodrug from loaded cells. Moreover, G114 released from G114 MP-loaded MSCs selectively induced death of the PSA-secreting PCa cell line, LNCaP. Finally, G114 MP-loaded MSCs inhibited tumor growth when used in proof-of-concept co-inoculation studies with CWR22 PCa xenografts, suggesting that cell-based delivery of G114 did not compromise the potency of this pro-drug in-vitro or in-vivo. This study demonstrates a potentially promising approach to assemble a cell-based drug delivery platform, which inhibits cancer growth in-vivo without the need of genetic engineering. We envision that upon achieving efficient homing of systemically infused MSCs to cancer sites, this MSC-based platform may be developed into an effective, systemic 'Trojan Horse' therapy for targeted delivery of therapeutic agents to sites of metastatic PCa.