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Local delivery of adenosine receptor agonists to promote bone regeneration and defect healing
Lopez, Christopher D; Bekisz, Jonathan M; Corciulo, Carmen; Mediero, Aranzazu; Coelho, Paulo G; Witek, Lukasz; Flores, Roberto L; Cronstein, Bruce N
Adenosine receptor activation has been investigated as a potential therapeutic approach to heal bone. Bone has enhanced regenerative potential when influenced by either direct or indirect adenosine receptor agonism. As investigators continue to elucidate how adenosine influences bone cell homeostasis at the cellular and molecular levels, a small but growing body of literature has reported successful in vivo applications of adenosine delivery. This review summarizes the role adenosine receptor ligation plays in osteoblast and osteoclast biology and remodeling/regeneration. It also reports on all the modalities described in the literature at this point for delivery of adenosine through in vivo models for bone healing and regeneration.
PMID: 29913176
ISSN: 1872-8294
CID: 3157852
Assessment of American Cleft Palate-Craniofacial Association-Approved Teams' Websites for Patient-Oriented Content and Readability
Alfonso, Allyson R; DeMitchell-Rodriguez, Evellyn M; Ramly, Elie P; Noel, Daphney Y; Levy-Lambert, Dina; Wang, Maxime M; Kantar, Rami S; Flores, Roberto L
OBJECTIVE/UNASSIGNED:Informed decision-making relies on available information, including online resources. We evaluated the content and readability of websites published by American Cleft Palate-Craniofacial Association (ACPA)-approved cleft lip and/or palate (CLP) teams in the United States. DESIGN/UNASSIGNED:Team websites were reviewed, and teams with no accessible website or <30 sentences of content were excluded. Website content was scored by presence/absence of 20 variables derived from ACPA approval standards. Readability was evaluated with 8 scales. Readability was then compared to American Medical Association (AMA) recommendations. The relationship between website content and readability was assessed. MAIN OUTCOME MEASURE(S)/UNASSIGNED:Content and readability of team websites. RESULTS/UNASSIGNED:From 167 reviewed teams, 47 (28.1%) had nonfunctional links, 17 (10.2%) had no accessible website, and 39 (23.4%) had <30 sentences. The average content score for all 111 team websites included was 14.5 (2.6) of 20. The combined average reading level across all scales (10.7 [1.9]) exceeded the AMA-recommended sixth-grade reading level; this finding held true for each individual website. Children's Hospital-affiliated teams (n = 86) had a significantly higher content score (14.8 vs 13.5; P = .03) and better readability as evidenced by lower reading grade level (10.5 vs 11.4; P = .04). On linear regression, a higher content score significantly predicted better readability (β = -0.226; P < .001). CONCLUSIONS/UNASSIGNED:Websites published by ACPA-approved CLP teams vary in accessibility and content and exceed the recommended reading level. These findings could inform future efforts to improve patient-oriented resources.
PMID: 31129984
ISSN: 1545-1569
CID: 3948602
Nasolabial Aesthetics Following Cleft Repair: An Objective Evaluation of Subjective Assessment
Kantar, Rami S; Maliha, Samantha G; Alfonso, Allyson R; Wang, Maxime M; Ramly, Elie P; Eisemann, Bradley S; Shetye, Pradip R; Grayson, Barry H; Flores, Roberto L
OBJECTIVE/UNASSIGNED:Assess the weight and contribution of each of the parameters of the Asher-McDade Scale to overall subjective assessment of nasolabial aesthetics following cleft lip repair. DESIGN/UNASSIGNED:Retrospective cohort evaluation. SETTING/UNASSIGNED:Cleft and craniofacial center. PARTICIPANTS/UNASSIGNED:Forty-one patients who underwent unilateral cleft lip repair. INTERVENTIONS/UNASSIGNED:Unilateral cleft lip repair. MAIN OUTCOME MEASURES/UNASSIGNED:Nasolabial rating using the Asher-McDade scale and overall subjective assessment of nasolabial aesthetics using a rank score following unilateral cleft lip repair. RESULTS/UNASSIGNED:= .69; P < .001). CONCLUSION/UNASSIGNED:The parameters evaluated in the Asher-McDade scale have different weights and contribute differently to overall subjective assessment of nasolabial aesthetic outcomes following cleft lip repair. Adjusting for their weights results in a modified score that demonstrates superior correlation with overall subjective assessment of nasolabial aesthetic outcomes.
PMID: 31117813
ISSN: 1545-1569
CID: 4055152
Dipyridamole Augments Three-Dimensionally Printed Bioactive Ceramic Scaffolds to Regenerate Craniofacial Bone
Lopez, Christopher D; Diaz-Siso, J Rodrigo; Witek, Lukasz; Bekisz, Jonathan M; Gil, Luiz F; Cronstein, Bruce N; Flores, Roberto L; Torroni, Andrea; Rodriguez, Eduardo D; Coelho, Paulo G
BACKGROUND:Autologous bone grafts remain a standard of care for the reconstruction of large bony defects, but limitations persist. The authors explored the bone regenerative capacity of customized, three-dimensionally printed bioactive ceramic scaffolds with dipyridamole, an adenosine A2A receptor indirect agonist known to enhance bone formation. METHODS:Critical-size bony defects (10-mm height, 10-mm length, full-thickness) were created at the mandibular rami of rabbits (n = 15). Defects were replaced by a custom-to-defect, three-dimensionally printed bioactive ceramic scaffold composed of β-tricalcium phosphate. Scaffolds were uncoated (control), collagen-coated, or immersed in 100 μM dipyridamole. At 8 weeks, animals were euthanized and the rami retrieved. Bone growth was assessed exclusively within scaffold pores, and evaluated by micro-computed tomography/advanced reconstruction software. Micro-computed tomographic quantification was calculated. Nondecalcified histology was performed. A general linear mixed model was performed to compare group means and 95 percent confidence intervals. RESULTS:Qualitative analysis did not show an inflammatory response. The control and collagen groups (12.3 ± 8.3 percent and 6.9 ± 8.3 percent bone occupancy of free space, respectively) had less bone growth, whereas the most bone growth was in the dipyridamole group (26.9 ± 10.7 percent); the difference was statistically significant (dipyridamole versus control, p < 0.03; dipyridamole versus collagen, p < 0.01 ). There was significantly more residual scaffold material for the collagen group relative to the dipyridamole group (p < 0.015), whereas the control group presented intermediate values (nonsignificant relative to both collagen and dipyridamole). Highly cellular and vascularized intramembranous-like bone healing was observed in all groups. CONCLUSION:Dipyridamole significantly increased the three-dimensionally printed bioactive ceramic scaffold's ability to regenerate bone in a thin bone defect environment.
PMID: 31033822
ISSN: 1529-4242
CID: 3854182
Long-term speech and functional outcomes of bilateral intraoral myomucosal flaps for velopharyngeal insufficiency [Meeting Abstract]
Ramly, E; Kantar, R; Alfonso, A; Eisemann, B; Wang, M; Flores, R; Leblanc, E
Background/Purpose: Intraoral myomucosal flaps such as the facial artery myomucosal (FAMM) flap and the buccal flap can provide effective palatal lengthening for the management of velopharyngeal insufficiency (VPI). This surgical approach is not without limitations and can result in increased postoperative burden to the patient and caregiver and frequently involves a second anesthetic event for pedicle division and flap inset. We sought to analyze the postoperative speech and functional outcomes of patients undergoing such procedures at our institution. Methods/Description: A retrospective assessment of all patients undergoing intraoral myomucosal flaps by a single surgeon at a tertiary academic institution was conducted. Only patients undergoing bilateral FAMM or buccal flaps for VPI were included. Data included demographic characteristics, flap-related complications, and postoperative speech and oral function. Results were compared between 2 age groups (group 1: <13, group 2: >=13). Analysis was performed over 5 clinical time points: preoperatively (T0), and postoperatively at 1 to 4 weeks (T1), 3 to 6 months (T2), and 1 to 3 years (T3).
Result(s): Of 54 patients reviewed, 24 met inclusion criteria: fourteen (58.3%) underwent bilateral FAMM flaps and 10 (41.7%) buccal flaps. Group 1 included 15 (62.5%) patients (median age: 6; range: 4-12) and group 2 included 9 (37.5%; median age: 23; range: 13-52). Group 1 patients were more likely to undergo buccal (60%), whereas group 2 were more likely to undergo FAMM flaps (88.9%). No intraor postoperative donor site complications, bleeding, flap necrosis, or dehiscence were noted. Subsequent pedicle division was performed in 66.7% of patients in group 1 (median: 35 days, range: 18-174) and 55.6% in group 2 (median: 46 days, range: 35-980) for interference with mastication in 10 (41.7%) patients, timing with other elective procedures in 3 (12.5%), or molar eruption in 1 patient. Ten (41.7%) patients had longitudinal speech follow-up, 70% of which were from group 1. Structural hypernasality had completely resolved in 80% of patients at T1, and in the rest by T3. At T1, >50% displayed abnormal occlusion or tongue placement and weak articulatory contact, which subsequently resolved. Dysphagia, drooling, or reduced oral opening were noted at T1 in most patients but had largely resolved on follow-up.
Conclusion(s): FAMM and buccal flaps are effective palatal lengthening procedures with 100% resolution of structural hypernasality and minimal complications in our series. Patient age and timing of division of flap pedicles may have an effect on postoperative oral function. Our findings support the early division of FAMM and buccal flap pedicles
EMBASE:629086211
ISSN: 1545-1569
CID: 4070942
Pediatric bone tissue engineering of the calvarium with dipyridamole-coated, 3D printed bioceramic scaffolds: Long-term analysis on facial growth, suture patency, and absorption kinetics in a growing cranial model [Meeting Abstract]
Colon, R R; Wang, M; Kurgansky, G; Witek, L; Torroni, A; Cronstein, B; Flores, R; Coelho, P
Background/Purpose: Our tissue engineering laboratory has previously demonstrated that dipyridamole-coated, 3D printed bioceramic (3DPBC) scaffolds comprised of B-tricalcium phosphate generate significantly more bone compared to negative controls in short-term growing animal model studies. No detrimental effects to the cranial suture were observed in any experimental animals. The longterm osteogenic efficacy and safety of our 3DPBC scaffold for tissue engineering in growing calvaria was assessed by describing bone regeneration compared to autogenous bone graft, scaffold degradation kinetics, and the effects of the construct on cranial growth over time. Methods/Description: Twenty-two 1-month-old (immature) New Zealand white rabbits underwent unilateral 11-mm craniotomy within 2 mm of the coronal and sagittal sutures. Rabbits' calvarial defects were repaired by 1 of 2 interventions: 3DPBC scaffolds coated with 1000 mM dipyridamole (n = 14) or autogenous calvarial bone graft (n = 8). Six rabbits from the 3DPBC scaffold group were sacrificed at 8 weeks. The remaining rabbits (n = 8 each group) were observed until craniofacial growth was completed (6 months) and then euthanized. Bone regeneration, scaffold degradation, and cranial suture patency were analyzed in Amira software using reconstructed microcomputed tomography (muCT) images. Cranial growth was assessed by comparing bilateral cephalometric measurements based on muCT images. Bone growth and suture patency were qualitatively evaluated through histologic analysis.
Result(s): After 6 months of healing, animals with defects repaired with 3DPBC scaffolds regenerated an average of 53.9% +/- 3.6% (mean +/- SEM) bone, compared to 53.5% +/- 3.6% in defects repaired with bone graft (P = .95). Unoperated calvarial bone porosity was 49.4%+/-2.0%. Scaffolds showed significant degradation at 6 months (15.1% +/-0.7%) compared to 8 weeks (23.2% +/- 0.9%; P<=.001). Comparative measurements of operated and unoperated sides showed no significant differences in asymmetry between scaffold and bone graft animals (P > .24). Analysis of histologic sections revealed well-vascularized, organized bone formation within scaffold interstices with no evidence of ectopic bone formation, excess inflammatory cells, or suture fusion.
Conclusion(s): Dipyridamole-coated 3D-printed bioceramic scaffolds bone regeneration is comparable to autogenous bone graft without showing signs of adverse events such as premature cranial suture fusion, or detrimental effects to facial growth. The scaffold demonstrates favorable absorption kinetics, highlighting the potential for this technology in pediatric bone tissue engineering
EMBASE:629085209
ISSN: 1545-1569
CID: 4071012
Foundation-Based Cleft Care in Developing Countries
Kantar, Rami S; Cammarata, Michael J; Rifkin, William J; Diaz-Siso, J Rodrigo; Hamdan, Usama S; Flores, Roberto L
BACKGROUND:Cleft deformities of the lip and palate affect nearly one in 500 to 700 births, and lead to increased morbidity and mortality if untreated. Nevertheless, significant global disparities in access to timely and appropriate care still exist. The relatively basic infrastructure required to surgically correct these deformities and large unmet disease burden have resulted in a significant number of foundation-based cleft care initiatives focused on developing countries. In this study, the authors evaluate the peer-reviewed literature generated by these foundations in an attempt to assess their clinical, scientific, educational, and economic impact. METHODS:A comprehensive review of the literature was performed using key search terms, and the level of evidence of identified articles was determined. Data were then analyzed to determine the different models of foundation-based cleft care in developing countries, and their clinical, scientific, educational, and economic impact. RESULTS:A total of 244 articles were identified through the authors' search and reviewed. Foundation-based cleft care initiatives in developing countries have significantly contributed to a better understanding of disease epidemiology, barriers to care, safety considerations, complications and outcomes, and international and local cleft surgery education. The cleft care center model is more cost-effective than the surgical mission model and provides more sustainable care. CONCLUSIONS:Foundation-based cleft care prevents significant morbidity in developing countries and has provided valuable resources for capacity building. The surgical mission model should be considered as a transitory conduit for establishing the more effective and sustainable cleft care center model of care.
PMID: 30921141
ISSN: 1529-4242
CID: 3778902
A Simple Protective Splint for Infant Nasal Reconstruction
Rifkin, William J; Maroutsis, Sandra; Bohsali, Sabrina A; Flores, Roberto L
Nasal trauma is a common complication of nasal continuous positive airway pressure (NCPAP) and may range from erythema, edema, and skin breakdown to columellar necrosis. Although rare, columellar necrosis can be a devastating complication following NCPAP, and surgical repair remains challenging due to contour and color-match difficulties, tenuous vascularity, and limited available adjacent skin. In addition, because operative site protection is critical to a successful repair, many surgeons opt to delay surgical intervention from infancy until a later age so that the patient does not inadvertently injure and compromise the graft during the early postoperative period. Here, we present a case of composite nasal reconstruction in an infant following columellar necrosis secondary to NCPAP, along with the design and implementation of a simple, inexpensive, and protective nasal splint that allows for early repair at the time of infancy.
PMID: 31136558
ISSN: 1550-1841
CID: 3957912
Assessment of patient-oriented online resources provided by american cleft palate-craniofacial association approved teams [Meeting Abstract]
Alfonso, A; DeMitchell-Rodriguez, E; Ramly, E; Noel, D; Levy-Lambert, D; Wang, M; Kantar, R; Flores, R
Background/Purpose: Informed decision-making in cleft care relies heavily on available information, including online resources. The American Medical Association (AMA) recommends that the readability of these resources does not exceed the sixth grade reading level. We evaluated the comprehensiveness and readability of patientoriented online resources provided by American Cleft Palate- Craniofacial Association (ACPA) Approved cleft lip and/or palate (CLP) Teams in the United States. Methods/Description: ACPA Approved CLP Team listings were reviewed between July 16, 2018, and July 30, 2018. Listings with nonfunctional website links prompted an Internet search for the corresponding websites. Teams with no accessible website or <30 sentences of content were excluded. Content comprehensiveness was scored by presence/absence of 20 variables derived from ACPA team approval standards. Content readability, defined as estimated reading grade level, was evaluated with 8 validated scales using a Professional Readability Software (Oleander Software, Ltd, Vandalia, Ohio). Readability was then compared to AMA recommendations. Linear regression was used to assess the relationship between comprehensiveness and readability.
Result(s): From 167 reviewed teams, 47 (28.1%) had nonfunctional links. After an Internet search, 17 (10.2%) had no accessible website, and 39 (23.4%) had <30 sentences. A total of 56 teams were thus excluded. The average comprehensiveness score for all 111 team websites included was 14.5 +/- 2.6 out of 20. The combined average reading level across all scales (10.7 +/- 1.9) exceeded the AMArecommended sixth grade reading level; this finding held true for each individual website. Children's Hospital-affiliated teams (n = 86) had a significantly higher comprehensiveness score (14.8 vs 13.5; P = .03) and better readability as evidenced by lower reading grade level (10.5 vs 11.4; P = .04). On linear regression, a higher comprehensiveness score significantly predicted better readability (beta = -0.226; P < .001; 95% CI: -0.359 to -0.092).
Conclusion(s): Online resources of ACPA Approved CLP Teams vary in accessibility and comprehensiveness, and exceed the recommended reading level. In order to better serve and educate patients with cleft lip and/or palate and their caregivers, future efforts should be directed toward developing standardized, comprehensive, accessible, and intelligible online resources, while ensuring validation of their content and language
EMBASE:629085085
ISSN: 1545-1569
CID: 4071042
Learner satisfaction with 3-dimensional affordable stone models for cleft lip markings: Results from a prospective study [Meeting Abstract]
Kantar, R; Gonchar, M; Maliha, S; Ramly, E; Alfonso, A; Eisemann, B; Shetye, P; Grayson, B; Saadeh, P; Flores, R
Background/Purpose: Knowledge of cleft lip (CL) surgical markings is essential prior to performing the repair. Work hours restrictions, increased patient care documentation time, and requests by patients not to have trainees involved in their care are limiting the acquisition of this skill in the operating room. Textbooks provide 2-dimensional illustrations of CL markings; while the cost of 3-dimensional (3D) printed CL models prohibit their widespread utilization for this purpose. We propose 3D stone models as simple and affordable tools to teach surgical trainees unilateral CL markings. Methods/Description: Polyvinyl siloxane (PVS) impression material was used to create a negative of a patient with unilateral CL. Snapstone mixed with water was poured into the PVS impression to create unilateral CL stone models. Eleven plastic surgery residents were prospectively recruited in the study. They were provided with a textbook chapter and online module detailing surgical markings for unilateral CL repair, and were given 15 minutes of study time, before providing them with a unilateral CL stone model for performing the CL markings within 10 minutes. The participants were then provided with a standardized patient photograph for the same purpose. Learner satisfaction with the stone model and patient photograph as educational tools for learning surgical markings were evaluated using a modified survey based on the Student Evaluation of Educational Quality (SEEQ) survey, a validated tool for measuring higher education student satisfaction. Learner satisfactions with each tool were compared using a Mann-Whitney U test.
Result(s): The total production time of one stone model, including the PVS impression, was 10 minutes. The cost of one PVS impression and one stone model were 64 and 83 cents respectively, for a total of $1.47. Participants reported that when compared to the standardized patient photograph, the stone model was more stimulating (4.72 +/- 0.47 vs 3.82+/-0.87; U = 25.5; P = .01), increased their interest in the subject (4.63 +/- 0.50 vs 3.45 +/- 1.29; U = 26.5; P = .02), allowed better learning of the subject matter (4.54 +/- 0.52 vs 2.91 +/- 0.83; U = 5.0; P < .001), had greater clarity (4.64 +/- 0.50 vs 3.00 +/- 0.89; U = 6.0; P < .001), and was a more effective means of teaching CL markings (4.73 +/- 0.47 vs 2.91 +/- 1.04; U = 6.0; P < .001). Participants were also more likely to recommend the stone model (4.82+/-0.40) over the standardized patient photograph (3.00 +/- 1.10; U = 5.0; P < .001).
Conclusion(s): 3D stone models of the unilateral cleft lip deformity are affordable and simple to produce. Plastic surgery residents report that these models are superior training tools to learn cleft lip markings compared to patient photographs. These educational tools have the potential to overcome significant financial, logistic, and time constraints in teaching cleft lip surgery markings
EMBASE:629085954
ISSN: 1545-1569
CID: 4070972