Emerging concepts in the CanMEDS physician competency framework.

Background: The CanMEDS physician competency framework will be updated in 2025. The revision occurs during a time of disruption and transformation to society, healthcare, and medical education caused by the COVID-19 pandemic and growing acknowledgement of the impacts of colonialism, systemic discrimination, climate change, and emerging technologies on healthcare and training. To inform this revision, we sought to identify emerging concepts in the literature related to physician competencies. Methods: Emerging concepts were defined as ideas discussed in the literature related to the roles and competencies of physicians that are absent or underrepresented in the 2015 CanMEDS framework. We conducted a literature scan, title and abstract review, and thematic analysis to identify emerging concepts. Metadata for all articles published in five medical education journals between October 1, 2018 and October 1, 2021 were extracted. Fifteen authors performed a title and abstract review to identify and label underrepresented concepts. Two authors thematically analyzed the results to identify emerging concepts. A member check was conducted. Results: 1017 of 4973 (20.5%) of the included articles discussed an emerging concept. The thematic analysis identified ten themes: Equity, Diversity, Inclusion, and Social Justice; Anti-racism; Physician Humanism; Data-Informed Medicine; Complex Adaptive Systems; Clinical Learning Environment; Virtual Care; Clinical Reasoning; Adaptive Expertise; and Planetary Health. All themes were endorsed by the authorship team as emerging concepts. Conclusion: This literature scan identified ten emerging concepts to inform the 2025 revision of the CanMEDS physician competency framework. Open publication of this work will promote greater transparency in the revision process and support an ongoing dialogue on physician competence. Writing groups have been recruited to elaborate on each of the emerging concepts and how they could be further incorporated into CanMEDS 2025.

Contexte: Le référentiel de compétences CanMEDS pour les médecins sera mis à jour en 2025. Cette révision arrive à un moment où la société, les soins de santé et l'enseignement médical sont bouleversés et en pleine mutation à cause de la pandémie de la COVID-19. On est aussi à l'heure où l'on reconnaît de plus en plus les effets du colonialisme, de la discrimination systémique, des changements climatiques et des nouvelles technologies sur les soins de santé et la formation des médecins. Pour effectuer cette révision, nous avons avons extrait de la littérature scientifique les concepts émergents se rapportant aux compétences des médecins. Méthodes: Les concepts émergents ont été définis comme des idées ayant trait aux rôles et aux compétences des médecins qui sont débattues dans la littérature, mais qui sont absentes ou sous-représentées dans le cadre CanMEDS 2015. Nous avons réalisé une recherche documentaire, un examen des titres et des résumés, et une analyse thématique pour repérer les concepts émergents. Les métadonnées de tous les articles publiés dans cinq revues d'éducation médicale entre le 1er octobre 2018 et le 1er octobre 2021 ont été extraites. Quinze auteurs ont effectué un examen des titres et des résumés pour relever et étiqueter les concepts sous-représentés. Deux auteurs ont procédé à une analyse thématique des résultats pour dégager les concepts émergents. Une vérification a été faite par les membres de l'équipe. Résultats: Parmi les 4973 articles dépouillés, 1017 (20,5 %) abordaient un concept émergent. Les dix thèmes suivants sont ressortis de l'analyse thématique: l'équité, la diversité, l'inclusion et la justice sociale; l'antiracisme; l'humanité du médecin; la médecine fondée sur les données; les systèmes adaptatifs complexes; l'environnement de l'apprentissage clinique; les soins virtuels; le raisonnement clinique; l'expertise adaptative; et la santé planétaire. L'ensemble de ces thèmes ont été approuvés comme concepts émergents par l'équipe de rédaction. Conclusion: Cet examen de la littérature a permis de relever dix concepts émergents qui peuvent servir à éclairer la révision du référentiel de compétences CanMEDS pour les médecins qui aura lieu en 2025. La publication en libre accès de ce travail favorisera la transparence du processus de révision et le dialogue continu sur les compétences des médecins. Des groupes de rédaction ont été recrutés pour développer chacun des concepts émergents et pour examiner la façon dont ils pourraient être intégrés dans la version du référentiel CanMEDS de 2025.

Advance care planning conversations in primary care: a quality improvement project using the Serious Illness Care Program.

BACKGROUND: Advance care planning (ACP) conversations are associated with improved end-of-life healthcare outcomes and patients want to engage in ACP with their healthcare providers. Despite this, ACP conversations rarely occur in primary care settings. The objective of this study was to implement ACP through adapted Serious Illness Care Program (SICP) training sessions, and to understand primary care provider (PCP) perceptions of implementing ACP into practice. METHODS: We conducted a quality improvement project guided by the Normalization Process Theory (NPT), in an interprofessional academic family medicine group in Hamilton, Ontario, Canada. NPT is an explanatory model that delineates the processes by which organizations implement and integrate new work. PCPs (physicians, family medicine residents, and allied health care providers), completed pre- and post-SICP self-assessments evaluating training effectiveness, a survey evaluating program implementability and sustainability, and semi-structured qualitative interviews to elaborate on barriers, facilitators, and suggestions for successful implementation. Descriptive statistics and pre-post differences (Wilcoxon Sign-Rank test) were used to analyze surveys and thematic analysis was used to analyze qualitative interviews. RESULTS: 30 PCPs participated in SICP training and completed self-assessments, 14 completed NoMAD surveys, and 7 were interviewed. There were reported improvements in ACP confidence and skills. NoMAD surveys reported mixed opinions towards ACP implementation, specifically concerning colleagues' abilities to conduct ACP and patients' abilities to participate in ACP. Physicians discussed busy clinical schedules, lack of patient preparedness, and continued discomfort or lack of confidence in having ACP conversations. Allied health professionals discussed difficulty sharing patient prognosis and identification of appropriate patients as barriers. CONCLUSIONS: Training in ACP conversations improved PCPs' individual perceived abilities, but discomfort and other barriers were identified. Future iterations will require a more systematic process to support the implementation of ACP into regular practice, in addition to addressing knowledge and skill gaps.

Health TAPESTRY: Exploring the Potential of a Nursing Student Placement Within a Primary Care Intervention for Community-Dwelling Older Adults.

The increasing prevalence of chronic diseases in aging places demands on primary care. Nurses are the major nonphysician primary care workforce. Baccalaureate nursing programs should expose students to primary care and older adults to support these demands and help recruit new graduates to this setting. However, many baccalaureate nursing programs focus on acute care and placements aimed at older adults are viewed negatively. To address these curriculum challenges, third-year Canadian baccalaureate nursing students were placed in an innovative primary care program-Health TAPESTRY-for community-dwelling older adults. Health TAPESTRY involves an interprofessional primary care team, trained lay volunteers conducting home visits, system navigation, and an online software application. The goal of this study was to explore third-year baccalaureate nursing students' perceptions of this unique clinical primary care placement. This qualitative descriptive study explored students' perceptions of this placement's strengths, weaknesses, opportunities, threats (SWOT), and outcomes. Nursing students participated in focus groups (n = 14) or an interview (n = 1) and five completed narrative summaries following visits. Qualitative content analysis was supported by NVivo 10. Strengths of the clinical placement included training for the intervention; new insights about older adults; and experience with home visiting, interprofessional team functions, and community resources. Weaknesses included limited exposure to older adult clients, lack of role clarity, lack of registered nurse role models, and technology challenges. Opportunities included more exposure to primary care, interprofessional teams, and community resources. No threats were described. Nursing students' clinical experiences can be enhanced through engagement in innovative primary care programs. Adequate exposure to clients, including older adults; interprofessional teams; mentoring by registered nurses or advanced practice nurse preceptors; and role clarity for students in the primary care team should be considered in supporting baccalaureate nursing students in primary care clinical placements.

Healthcare Burden, Risk Factors, and Outcomes of Mucosal Barrier Injury Laboratory-Confirmed Bloodstream Infections after Stem Cell Transplantation.

Mucosal barrier injury laboratory-confirmed bloodstream infections (MBI-LCBIs) lead to significant morbidity, mortality, and healthcare resource utilization in hematopoietic stem cell transplant (HSCT) patients. Determination of the healthcare burden of MBI-LCBIs and identification of patients at risk of MBI-LCBIs will allow researchers to identify strategies to reduce MBI-LCBI rates. The objective of our study was to describe the incidence, risk factors, timing, and outcomes of MBI-LCBIs in hematopoietic stem cell transplant patients. We performed a retrospective analysis of 374 patients who underwent HSCT at a large free-standing academic children's hospital to determine the incidence, risk factors, and outcomes of patients that developed a bloodstream infection (BSI) including MBI-LCBI, central line-associated BSI (CLABSI), or secondary BSI in the first year after HSCT. Outcome measures included nonrelapse mortality (NRM), central venous catheter removal within 7 days of positive culture, shock, admission to the pediatric intensive care unit (PICU) within 48 hours of positive culture, and death within 10 days of positive culture. One hundred seventy BSIs were diagnosed in 100 patients (27%): 80 (47%) MBI-LCBIs, 68 (40%) CLABSIs, and 22 (13%) secondary infections. MBI-LCBIs were diagnosed at a significantly higher rate in allogeneic HSCT patients (18% versus 7%, P = .007). Reduced-intensity conditioning (OR, 1.96; P = .015) and transplant-associated thrombotic microangiopathy (OR, 2.94; P = .0004) were associated with MBI-LCBI. Nearly 50% of all patients with a BSI developed septic shock, 10% died within 10 days of positive culture, and nearly 25% were transferred to the PICU. One-year NRM was significantly increased in patients with 1 (34%) and more than 1 (56%) BSIs in the first year post-HSCT compared with those who did not develop BSIs (14%) (P ≤ .0001). There was increased 1-year NRM in patients with at least 1 MBI-LCBI (OR, 1.94; P = .018) and at least 1 secondary BSI (OR, 2.87; P = .0023) but not CLABSIs (OR, 1.17; P = .68). Our data demonstrate that MBI-LCBIs lead to substantial use of healthcare resources and are associated with significant morbidity and mortality. Reduction in frequency of MBI-LCBI should be a major public health and scientific priority.

Short-term donor site morbidity: A comparison of the anterolateral thigh and radial forearm fasciocutaneous free flaps.

BACKGROUND: Donor site morbidity is an important consideration in the overall decision-making algorithm for fasciocutaneous free flap reconstruction of the head and neck. METHODS: A retrospective case series was conducted of donor site complications occurring within 30 days of surgery among 226 consecutive anterolateral thigh (ALT) or radial forearm free flap (RFFF) microvascular free tissue transfers performed by multiple reconstructive surgeons between 2005 and 2010. RESULTS: A greater number of donor site complications occurred among patients undergoing RFFF versus ALT free flaps (40; 35.4%; vs 14; 12.4%; p < .001). Wound dehiscence occurred significantly more frequently among patients undergoing RFFF versus ALT free flap reconstruction (34; 30%; vs 6; 5%; p < .001). Tendon exposure occurred in 16 of the 113 RFFFs (14.1%). Seromas occurred more commonly in the ALT group (6; 5%; vs 2; 1.7%; p = .280). CONCLUSION: Although short-term donor site morbidity was low in both groups, the ALT was associated with a significantly lower incidence of wound dehiscence with or without tendon exposure. © 2015 Wiley Periodicals, Inc. Head Neck 38: E945-E948, 2016.

NF-κB decoy oligodeoxynucleotide enhanced osteogenesis in mesenchymal stem cells exposed to polyethylene particle.

Excessive generation of wear particles after total joint replacement may lead to local inflammation and periprosthetic osteolysis. Modulation of the key transcription factor NF-κB in immune cells could potentially mitigate the osteolytic process. We previously showed that local delivery of ultrahigh-molecular-weight polyethylene (UHMWPE) particles recruited osteoprogenitor cells and reduced osteolysis. However, the biological effects of modulating the NF-κB signaling pathway on osteoprogenitor/mesenchymal stem cells (MSCs) remain unclear. Here we showed that decoy oligodeoxynucleotide (ODN) increased cell viability when primary murine MSCs were exposed to UHMWPE particles, but had no effects on cellular apoptosis. Decoy ODN increased transforming growth factor-beta 1 (TGF-ß1) and osteoprotegerin (OPG) in MSCs exposed to UHMWPE particles. Mechanistic studies showed that decoy ODN upregulated OPG expression through a TGF-ß1-dependent pathway. By measuring the alkaline phosphatase activity, osteocalcin levels, Runx2 and osteopontin expression, and performing a bone mineralization assay, we found that decoy ODN increased MSC osteogenic ability when the cells were exposed to UHMWPE particles. Furthermore, the cellular response to decoy ODN and UHMWPE particles with regard to cell phenotype, cell viability, and osteogenic ability was confirmed using primary human MSCs. Our results suggest that modulation of wear particle-induced inflammation by NF-κB decoy ODN had no adverse effects on MSCs and may potentially further mitigate periprosthetic osteolysis by protecting MSC viability and osteogenic ability.

Endoscopic forehead approach for minimally invasive benign tumor excisions.

IMPORTANCE: Direct transcutaneous resection has been a widely accepted standard for the removal of benign forehead lesions. In recent years, the endoscopic approach has become more prevalent because of its noninvasiveness. To date, only a few studies with limited case numbers have reported on this technique. We report our findings from one of the largest cohorts of patients undergoing tumor resection of the forehead via the endoscopic approach. OBJECTIVES: To evaluate results of the endoscopic forehead approach for benign tumor excisions, to give a more nuanced insight into this procedure, and to discuss technical pearls and potential pitfalls from our experience. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, retrospective case study at 2 university centers and 1 private practice among 36 patients aged 18 to 72 years (mean age, 44 years) who underwent the endoscopic forehead approach for benign tumor resections. MAIN OUTCOMES AND MEASURES: Symptoms at presentation, surgical procedure and duration, type of lesions, intraoperative and postoperative complications, recurrences, and patient satisfaction. RESULTS: In total, 34 patients had an asymptomatic forehead mass, while 2 patients reported discomfort and headache. Among all patients, complete tumor excision was achieved endoscopically. The mean operative time was 36 minutes. Histopathological examination revealed 18 lipomas, 13 osteomas, 2 dermoid cysts, and 1 bone fragment after previous rhinoplasty. In 2 patients, no specimen was submitted. No hematomas, infections, scalp numbness, contour irregularities, temporal branch paralysis, or tumor recurrences occurred. One patient had a prolonged area of alopecia, which resolved on its own. All patients attested to a high satisfaction rate. CONCLUSIONS AND RELEVANCE: The endoscopic approach offers excellent aesthetic results and allows for safe tumor removal. It has proven to be an effective and minimally invasive alternative to the conventional open approach. LEVEL OF EVIDENCE: 4.

The extended SMAS approach to neck rejuvenation.

Jowling, submental lipoptosis, and platysmal banding can affect self-image and reduce quality of life, leading one to seek facial and neck rejuvenation. With realistic expectations, a facelift can provide the desired improvement in appearance and sense of well-being. Before any intervention, a detailed history, focused examination, communication of expected outcomes with the assistance of preoperative digital imaging, and discussion of perioperative instructions are of utmost importance. Although many techniques exist, the modified deep plane extended superficial muscular aponeurotic system rhytidectomy with submentoplasty reliably delivers a significant improvement with lasting results.

Chronic inflammation in biomaterial-induced periprosthetic osteolysis: NF-κB as a therapeutic target.

Biomaterial-induced tissue responses in patients with total joint replacement are associated with the generation of wear particles, which may lead to chronic inflammation and local bone destruction (periprosthetic osteolysis). Inflammatory reactions associated with wear particles are mediated by several important signaling pathways, the most important of which involves the transcription factor NF-κB. NF-κB activation is essential for macrophage recruitment and maturation, as well as the production of pro-inflammatory cytokines and chemokines such as TNF-α, IL-1ß, IL-6 and MCP1. In addition, NF-κB activation contributes to osteoclast differentiation and maturation via RANK/RANKL signaling, which increases bone destruction and reduces bone formation. Targeting individual downstream cytokines directly (such as TNF-α or IL-1ß) may not effectively prevent wear particle induced osteolysis. A more logical upstream therapeutic approach may be provided by direct modulation of the core IκB/IKKα/ß/NF-κB signaling pathway in the local environment. However, the timing, dose and strategy for administration should be considered. Suppression of chronic inflammation via inhibition of NF-κB activity in patients with malfunctioning joint replacements may be an effective strategy to mitigate wear particle induced periprosthetic osteolysis.

Mutant monocyte chemoattractant protein 1 protein attenuates migration of and inflammatory cytokine release by macrophages exposed to orthopedic implant wear particles.

Wear particles generated from total joint replacements can stimulate macrophages to release chemokines, such as monocyte chemoattractant protein 1 (MCP-1), which is the most important chemokine regulating systemic and local cell trafficking and infiltration of monocyte/macrophages in chronic inflammation. One possible strategy to curtail the adverse events associated with wear particles is to mitigate migration and activation of monocyte/macrophages. The purpose of this study is to modulate the adverse effects of particulate biomaterials and inflammatory stimuli such as endotoxin by interfering with the biological effects of the chemokine MCP-1. In the current study, the function of MCP-1 was inhibited by the mutant MCP-1 protein called 7ND, which blocks its receptor, the C-C chemokine receptor type 2 (CCR2) on macrophages. Addition of 7ND decreased MCP-1-induced migration of THP-1 cells in cell migration experiments in a dose-dependent manner. Conditioned media from murine macrophages exposed to clinically relevant polymethylmethacrylate (PMMA) particles with/without endotoxin [lipopolysaccharide (LPS)] had a chemotactic effect on human macrophages, which was decreased dramatically by 7ND. 7ND demonstrated no adverse effects on the viability of macrophages, and the capability of mesenchymal stem cells (MSCs) to form bone at the doses tested. Finally, proinflammatory cytokine production was mitigated when macrophages were exposed to PMMA particles with/without LPS in the presence of 7ND. Our studies confirm that the MCP-1 mutant protein 7ND can decrease macrophage migration and inflammatory cytokine release without adverse effects at the doses tested. Local delivery of 7ND at the implant site may provide a therapeutic strategy to diminish particle-associated periprosthetic inflammation and osteolysis.

Mutant MCP-1 protein delivery from layer-by-layer coatings on orthopedic implants to modulate inflammatory response.

Total joint replacement (TJR) is a common and effective surgical procedure for hip or knee joint reconstruction. However, the production of wear particles is inevitable for all TJRs, which activates macrophages and initiates an inflammatory cascade often resulting in bone loss, prosthetic loosening and eventual TJR failure. Macrophage Chemoattractant Protein-1 (MCP-1) is one of the most potent cytokines responsible for macrophage cell recruitment, and previous studies suggest that mutant MCP-1 proteins such as 7ND may be used as a decoy drug to block the receptor and reduce inflammatory cell recruitment. Here we report the development of a biodegradable, layer-by-layer (LBL) coating platform that allows efficient loading and controlled release of 7ND proteins from the surface of orthopedic implants using as few as 14 layers. Scanning electron microscopy and fluorescence imaging confirmed effective coating using the LBL procedure on titanium rods. 7ND protein loading concentration and release kinetics can be modulated by varying the polyelectrolytes of choice, the polymer chemistry, the pH of the polyelectrolyte solution, and the degradation rate of the LBL assembly. The released 7ND from LBL coating retained its bioactivity and effectively reduced macrophage migration towards MCP-1. Finally, the LBL coating remained intact following a femoral rod implantation procedure as determined by immunostaining of the 7ND coating. The LBL platform reported herein may be applied for in situ controlled release of 7ND protein from orthopedic implants, to reduce wear particle-induced inflammatory responses in an effort to prolong the lifetime of implants.

Suprastomal cutaneous monitoring paddle for free flap reconstruction of laryngopharyngectomy defects.

IMPORTANCE: Method of direct clinical monitoring of tissue perfusion in free tissue reconstruction of pharyngeal defects. OBJECTIVE: To describe a novel and effective method of incorporating a cutaneous skin paddle into laryngopharyngectomy reconstruction for direct clinical monitoring of anterolateral thigh free flaps. DESIGN: Retrospective review of pharyngoesophageal reconstruction for laryngopharyngectomy defects performed between August 1, 2008, and March 1, 2011, using the anterolateral thigh flap. SETTING: Tertiary care academic medical center. PARTICIPANTS: Consecutive patients undergoing laryngopharyngectomy where free tissue transfer is indicated. INTERVENTIONS: Anterolateral thigh free flap reconstruction with suprastomal cutaneous monitoring paddle. MAIN OUTCOME MEASURES: Postoperative complications, including flap failure, fistula, and stricture. Postoperative functional outcomes of swallowing and vocal capability were also measured. RESULTS: Twenty-one patients (mean age, 62.2 years; range, 39-81 years) underwent total laryngectomy with near-total or total pharyngectomy and immediate reconstruction with an anterolateral thigh free flap. The reconstructions included a cutaneous monitor paddle distal to the pharyngoesophageal anastomosis. Twenty patients were treated for squamous cell carcinoma and received either adjuvant or neoadjuvant radiation therapy. There were no partial or total flap losses. A late pharyngocutaneous fistula occurred at 6 weeks in 1 patient (5%), requiring exploration, and anastomotic stricture occurred in 4 patients (19%). All patients except 1 were able to swallow solid foods at a mean follow-up of 11.1 months. Nineteen patients (90%) underwent tracheoesophageal puncture and attained an intelligible voice. One patient (5%) had stomal stenosis requiring surgical management. CONCLUSIONS AND RELEVANCE: The suprastomal cutaneous monitoring paddle enables direct monitoring of an otherwise buried reconstructive flap. This method allows direct clinical observation for microvascular compromise without a need for further procedures and without any increase in morbidity or compromise of speech and swallow functions. LEVEL OF EVIDENCE: 4.

Co-culture of adipose derived stem cells and chondrocytes with surface modifying proteins induces enhanced cartilage tissue formation.

OBJECTIVES: Current treatments for focal cartilage defects include osteochondral allograft transplants-a common treatment for large defects and revisions of previously autografted joints. Allografts with weak osseous regions are usable, since bone remodeling replaces inferior quality bone. However, poor quality chondral surfaces on grafts preclude their use, leading to grafting material shortages. Endogenous adult stem cells can make hyaline-like cartilage tissue on scaffolds. To increase the number of usable allografts, tissue culture methods using adipose derived stem cells (ASCs) were developed to grow cartilage on grafts. METHODS: Co-cultures utilized living chondrocytes in host cartilage, modeling in vivo conditions, and ASCs seeded on the allografts. Sterilized allografts were treated with Poly-L-Lysine and ProNectin. Tissue growth was analyzed and quantified with histological techniques. RESULTS AND CONCLUSIONS: Monoculture experiments produced tenuous cartilage formation when proteins were utilized and allograft surfaces were perforated. Extensive tissue formation was observed with co-culture and the presence of type II collagen was confirmed with immunohistochemistry. Results demonstrate that co-culture techniques offer a better means of growing tissue on allograft cartilage surfaces. Additionally, the use of proteins to facilitate surface attachment produced more tissue formation demonstrating that cell attachment is crucial when growing cartilage on allografts. Development of new culture techniques to evaluate treatment strategies will accelerate the rate at which cartilage procedures using endogenous cells are possible. This will increase the number of usable grafts and allow critical selection of grafts to fit specific surfaces increasing surgical success by returning the joint to its native structure.

Orbitomaxillary reconstruction using the layered fibula osteocutaneous flap.

OBJECTIVE: To describe a surgical technique for total palatomaxillary and orbital reconstruction using a fibula osteocutaneous free flap in a layered fashion. METHODS: Case series from a tertiary care facial plastic and reconstructive surgical practice including patients with postextirpative Brown 3a and 3b orbitopalatomaxillary defects undergoing immediate microvascular reconstruction. Application of the layered fibula free flap to composite maxillary defects permits single-stage, optimal reconstruction of contiguous orbitomaxillary defects, reconstitution of midface 3-dimensional contour, and restoration of the anterior alveolar arch with robust bone, thereby providing for potential sequential dental rehabilitation with osseointegrated implants. RESULTS: This technique demonstrates excellent long-term symmetry, support, function, and aesthetic contour. Although patients may need minor, adjunctive procedures, this technique is flexible in design and offers reliable outcomes with a minimum of morbidity. CONCLUSION: The fibula osteocutaneous free flap, because of its design flexibility and ability to provide structural support, is an excellent reconstructive option for total maxillary defects, including those that involve the orbit.

Bone regeneration in a rabbit critical-sized calvarial model using tyrosine-derived polycarbonate scaffolds.

Porous three-dimensional tyrosine-derived polycarbonate (TyrPC) scaffolds with a bimodal pore distribution were fabricated to mimic bone architecture using a combination of salt-leaching and phase separation techniques. TyrPC scaffolds degraded in register with bone regeneration during the 6-week study period and compressive moduli of the scaffolds were maintained >0.5 MPa at 6 weeks of incubation in PBS at 37 °C. The TyrPC scaffolds either unsupplemented or supplemented with recombinant human bone morphogenetic protein-2 (rhBMP-2) were implanted in a rabbit calvarial critical-sized defect (CSD) model and the TyrPC scaffolds treated with rhBMP-2 or TyrPC coated with calcium phosphate scaffold alone promoted bone regeneration in a rabbit calvarial CSD at 6 weeks postimplantation. A synthetic TyrPC polymeric scaffold either without a biological supplement or with a minimal dose of rhBMP-2 induced bone regeneration comparable to a commercially available bone graft substitute in a nonrodent CSD animal model.

Osteoblast growth and bone-healing response to three-dimensional poly(ε-caprolactone fumarate) scaffolds.

Poly(ε-caprolactone fumarate) (PCLF) scaffold formulations were assessed as a delivery system for recombinant human bone morphogenetic protein (rhBMP-2) for bone tissue engineering. The formulations included PCLF with combinations of poly(vinyl alcohol) (PVA) and hydroxyapatite (HA). The assessments included in vitro and in vivo assays. In vitro assays validated cell attachment using a pre-osteoblast cell line (MC3T3-E1). Additionally, in vitro release profiles of rhBMP-2 from PCLF scaffolds were determined up to 21 days. The data suggested that PCLF incorporated with PVA and HA accelerated rhBMP-2 release and that the released protein was bioactive. For the in vivo study, a critical-sized defect (CSD) model in rabbit calvaria was used to test PCLF scaffolds. At 6 weeks post-implantation, significantly more bone formation was measured in PCLF scaffolds containing rhBMP-2 than in scaffolds without rhBMP-2. In conclusion, we demonstrated that PCLF delivered biologically active rhBMP-2, promoted bone healing in a CSD and has potential as a bone tissue engineering scaffold.

Botulinum toxin treatment of adductor spasmodic dysphonia: longitudinal functional outcomes.

OBJECTIVES: Laryngeal botulinum toxin (BoNT) injection is a well-established symptomatic treatment for adductor spasmodic dysphonia (AdSD). Injections may be followed by a period of muscle weakness characterized by breathiness, voice weakness, and dysphagia for liquids. A recent study described some detriment and limited functional improvement with "good voice" for only one-third of the period between successive injections. Our objective was to examine the longitudinal effect of BoNT treatment for AdSD upon functional outcomes and quality of life when using a patient-specific dosing regimen. STUDY DESIGN: Prospective cohort study. METHODS: Patients presenting for BoNT treatment of AdSD were asked to complete evaluation of voice function after each injection using the percentage of normal function (PNF) scale (daily for two weeks, then weekly). Other parameters measured included voice handicap index (VHI), duration of effect, and complications. RESULTS: A total of 133 patients treated continuously between January 2006 and January 2009 with an individuated regime (dose, pattern, and schedule) were included. Of 1,457 treatments, 50.9% experienced some breathiness. Mean VHI improvement was 9.6%. Mean PNF improvement was 30.3%. There was correlation between the two scales. Dysphagia to liquids was reported after 14.2% of treatments. We describe two distinct types of functional outcome curve. A total of 28.5% of treatments were followed by initial functional decline. Mean time below baseline function was 5.7%. Mean proportion of time in plateau phase was 42.5%. CONCLUSIONS: It is important to consider longitudinal functional outcomes in BoNT treatment of AdSD. An individuated dosing regimen helps minimize side effects and maximize functional and quality-of-life outcomes.

Does HPV have a presence in diffuse high grade pre-malignant lesions of the larynx?

OBJECTIVE: To describe the incidence of HPV in diffuse high grade pre-cancerous lesions of the larynx. METHODS: Patient charts were searched for those who presented between October 2008 and June 2009 with diffuse vocal fold leukoplakia. Biopsy proven laryngeal lesions with high grade dysplasia or carcinoma-in-situ (CIS) were examined for patient characteristics and presence of high-risk type HPV detected by in situ hybridization technique. RESULTS: Fifteen patients with precancerous lesions were identified. Average age was 63 years and 13 were male. One lesion was identified as positive for high-risk HPV, all other lesions were negative. At current follow up, no patient has demonstrated progression to invasive carcinoma. CONCLUSION: HPV may not play a role in non-progressing diffuse high-grade lesions of the larynx.