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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

Comparing Reconstructive Outcomes in Patients with Gustilo Type IIIB Fractures and Concomitant Arterial Injuries

Ricci, Joseph A; Stranix, John T; Lee, Z-Hye; Jacoby, Adam; Anzai, Lavinia; Thanik, Vishal D; Saadeh, Pierre B; Levine, Jamie P
BACKGROUND:The Gustilo classification serves as a proxy for injury severity, but recent data suggest rising complications with decreasing arterial runoff. This study aims to compare different microsurgical anastomosis options based on the number of patent vessels in the lower extremity. METHODS:A single-center retrospective review of 806 lower extremity free flaps performed from 1976 to 2016 was performed. Patients with Gustilo type IIIB injuries were grouped based on the number of patent vessels in the leg (three, two, or one). Patients were compared based on the type of anastomosis performed, evaluating for perioperative complications and flap failures. RESULTS:Perioperative complications occurred in 111 flaps (27 percent): 71 take-backs (17 percent), 45 partial losses (11 percent), and 37 complete losses (9 percent). Among patients with three-vessel runoff (61.8 percent), there was no difference in take-backs or flap loss between those with end-to-end versus end-to-side anastomoses. In 68 patients (18.7 percent) with two-vessel runoff, no difference between take-backs or flap loss was noted when comparing any anastomosis (i.e., end-to-end into an injured vessel, end-to-end into an uninjured vessel, or end-to-side into an uninjured vessel), although vein grafts were required more often in the end-to-side groups (p < 0.01). Finally, in 39 patients (10.7 percent) with single-vessel runoff, no difference was seen between end-to-end anastomosis into an injured vessel or end-to-side anastomosis into an uninjured vessel in terms of take-backs or flap loss. CONCLUSION:Higher rates of flap failure correlated with decreasing numbers of patent vessels in the leg, but neither type of microvascular anastomosis nor vessel selection demonstrated any impact on reconstructive outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE:Therapeutic, III.
PMID: 31033835
ISSN: 1529-4242
CID: 3854382

Proximal Row Carpectomy versus Four-Corner Arthrodesis for the Treatment of Scapholunate Advanced Collapse/Scaphoid Nonunion Advanced Collapse Wrist: A Cost-Utility Analysis

Daar, David A; Shah, Ajul; Mirrer, Joshua T; Thanik, Vishal; Hacquebord, Jacques
BACKGROUND:Two mainstay surgical options for salvage in scapholunate advanced collapse and scaphoid nonunion advanced collapse are proximal row carpectomy and four-corner arthrodesis. This study evaluates the cost-utility of proximal row carpectomy versus three methods of four-corner arthrodesis for the treatment of scapholunate advanced collapse/scaphoid nonunion advanced collapse wrist. METHODS:A cost-utility analysis was performed in accordance with the Second Panel on Cost-Effectiveness in Health and Medicine. A comprehensive literature review was performed to obtain the probability of potential complications. Costs were derived using both societal and health care sector perspectives. A visual analogue scale survey of expert hand surgeons estimated utilities. Overall cost, probabilities, and quality-adjusted life-years were used to complete a decision tree analysis. Both deterministic and probabilistic sensitivity analyses were performed. RESULTS:Forty studies yielding 1730 scapholunate advanced collapse/scaphoid nonunion advanced collapse wrists were identified. Decision tree analysis determined that both four-corner arthrodesis with screw fixation and proximal row carpectomy were cost-effective options, but four-corner arthrodesis with screw was the optimal treatment strategy. Four-corner arthrodesis with Kirschner-wire fixation and four-corner arthrodesis with plate fixation were dominated (inferior) strategies and therefore not cost-effective. One-way sensitivity analysis demonstrated that when the quality-adjusted life-years for a successful four-corner arthrodesis with screw fixation are lower than 26.36, proximal row carpectomy becomes the optimal strategy. However, multivariate probabilistic sensitivity analysis confirmed the results of our model. CONCLUSIONS:Four-corner arthrodesis with screw fixation and proximal row carpectomy are both cost-effective treatment options for scapholunate advanced collapse/scaphoid nonunion advanced collapse wrist because of their lower complication profile and high efficacy, with four-corner arthrodesis with screw as the most cost-effective treatment. Four-corner arthrodesis with plate and Kirschner-wire fixation should be avoided from a cost-effectiveness standpoint.
PMID: 31033826
ISSN: 1529-4242
CID: 3854372

Clinical experience with mechanically coupled anastomoses in skull base reconstruction [Meeting Abstract]

Benjamin, C; Delacure, M
Background: The reconstruction of major skull base, scalp and calvarial defects with microvascular free flaps has revolutionized the predictable and safe conduct of multidisciplinary oncologic surgery of this region. While extended resections can be more confidently completed, this has not necessarily been accompanied by increased local control or cure. This is due to limitations of radiation tolerance of surrounding tissues, necessary acceptance of involved microscopically close or involved margins, tolerable morbidity, and the lack of specific medical oncologic agents for benign and malignant CNS tumors. Use of coupler devices in routine head and neck defects evolved into use in skull base, calvarial, and intracranial settings where flap loss can be catastrophic.
Method(s): Mechanical microvascular anastomosis became increasingly widely used in head and neck reconstruction in the late 1980s and 1990s as a method to speed the process, and perhaps patency over hand-sewn anastomoses. These have been incorporated primarily in venous interposition graft and end-to-end, and end-to side venous configurations facilitated by vessel pliability and the ability to evert vessel walls over coupler pins. The coupler itself is constructed of 2 polyethylene rings and staggered ferromagnetic pins which match holes on the opposing ring through a friction fit, thus joining the vessels. Because of its construction, and the increased use and preference of MRI for perioperative evaluation early concern for heating and/or rotation, torquing or disruption of new anastomoses, it was studied in a relevant model and found in clinical experience, to be irrelevant.[1]
Conclusion(s): The use of the superficial temporal vessels for recipients is often preferred to save pedicle length, minimize the need for interposition vein grafts (doubling the number of anastomoses and thrombotic opportunity/risk), and often influenced by prior treatment (bicoronal flaps) in which ligation and scar may limit suitability. Additionally, the vein is often thin-walled and technically unusable. The incision for access to these vessels is usually placed immediately in the junctional creases of the ear and cheek, and thus several millimeters removed from the actual course of the vessels. In a broad and significant experience spanning 25 years including 40 skull base microvascular reconstructions, 15 of which used temporal recipient vessels, there have been 2 cases (one calvarial, one intracranial) where the coupler rings have eroded through the temporal skin, and self-ejected, without flap loss, and implying the acquisition of adequate venous supply to support flap survival. Given this observation, unique to this region, hand-sewn anastomoses are specifically recommended when using these vessels so as to minimize potentially catastrophic flap loss. Our experience in microvascular skull base reconstruction in this context is reviewed in support of this recommendation
EMBASE:627318551
ISSN: 2193-6331
CID: 3831702

Ridge Architecture Preservation Following Minimally Traumatic Exodontia Techniques and Guided Tissue Regeneration

Faciola Pessôa de Oliveira, Paula Gabriela; Pedroso Bergamo, Edmara Tatiely; Bordin, Dimorvan; Arbex, Leticia; Konrad, Danielle; Gil, Luiz Fernando; Neiva, Rodrigo; Tovar, Nick; Witek, Lukasz; Coelho, Paulo Guilherme
OBJECTIVE:To compare hard-tissue healing after 3 exodontia approaches. MATERIALS AND METHODS/METHODS:Premolars of dogs were extracted: (1) flapless, (2) flap, and (3) flap + socket coverage with polytetrafluoroethylene (dPTFE) nonresorbable membrane (flap + dPTFE). Animals were euthanized at 1 and 4 weeks. Amount of bone formation within socket and socket total area were measured. RESULTS:Amount of bone formation revealed significant difference between 1 and 4 weeks; however, there was no differences among groups. Socket total area decreased after 4 weeks, and the flap + dPTFE group showed significantly higher socket total area. As a function of time and group, flap + dPTFE 4 weeks presented similar socket total area values relative to flap + dPTFE at 1 week, and significantly higher socket total area than flapless and flap. The histological sections revealed almost no bone formation within socket after 1 week, which increased for all groups at 4 weeks. CONCLUSION/CONCLUSIONS:Socket coverage with polytetrafluoroethylene (dPTFE) membrane showed to effectively preserve bone architecture. Bone formation within sockets was not influenced by tooth extraction technique.
PMID: 31008823
ISSN: 1538-2982
CID: 3821152

Three-Dimensional Affordable Stone Models for Cleft Lip Markings: A Prospective Study of Learner Satisfaction

Kantar, Rami S; Gonchar, Marina; Maliha, Samantha G; Ramly, Elie P; Alfonso, Allyson R; Cohen, Oriana; Eisemann, Bradley S; Diaz-Siso, J Rodrigo; Saadeh, Pierre B; Flores, Roberto L
INTRODUCTION/BACKGROUND:Knowledge of surgical markings for unilateral cleft lip (UCL) repair is critical for surgical competency. However, few appropriate models are accessible to residents and affordable and accurately reproduce this 3-dimensional (3D) deformity. We propose that cleft care units have the capability of creating affordable 3D stone models to teach UCL markings. METHODS:Polyvinyl siloxane and SnapStone were used to create UCL stone models. Thirteen plastic surgery residents were prospectively recruited, provided with a textbook chapter and online module for studying surgical markings for UCL repair, and then asked to perform the markings on a UCL stone model and standardized patient photograph. Learner satisfaction was evaluated using a modified survey based on the Student Evaluation of Educational Quality survey. RESULTS:The production time of each model was 10 minutes, whereas the cost was $1.84. Participants reported that the stone model was more stimulating (4.77 ± 0.44 vs 3.92 ± 0.86; U = 38.0; P = 0.008), increased their interest more (4.70 ± 0.48 vs 3.53 ± 1.20; U = 33.5; P = 0.005), allowed better learning (4.61 ± 0.51 vs 3.08 ± 0.86; U = 10.0; P < 0.001), was clearer (4.62 ± 0.51 vs 3.15 ± 0.90; U = 12.5; P < 0.001), and was more effective for learning cleft lip markings (4.77 ± 0.44 vs 3.08 ± 1.04; U = 9.0; P < 0.001). They were also more likely to recommend it (4.85 ± 0.38 vs 3.15 ± 1.07; U = 7.0; P < 0.001). CONCLUSIONS:Plastic surgery residents report that 3D cleft lip stone models are superior training tools to learn cleft lip markings compared with patient photographs. These educational tools have the potential to overcome significant financial, logistic, and time constraints in teaching cleft lip surgery markings.
PMID: 31008789
ISSN: 1536-3708
CID: 3821312

Midface Growth in Patients With Unilateral Cleft Lip and Palate Treated With a Nasoalveolar Molding Protocol

Rubin, Marcie S; Clouston, Sean A P; Esenlik, Elçin; Shetye, Pradip R; Flores, Roberto L; Grayson, Barry H
This retrospective cohort study aimed to determine the impact of a nasoalveolar molding (NAM) protocol on midface growth in school-aged children with non-syndromic unilateral cleft lip and palate (UCLP). Data from 56 consecutively treated, NAM-prepared, Caucasian patients with non-syndromic UCLP from a single US cleft palate center were compared to pooled center data based on 56 patients with non-syndromic UCLP treated at 2 Eurocleft centers that did not use presurgical infant orthopedics (non-PSIO). Lateral cephalograms were obtained and 28 landmarks were identified. Published cephalometric measurements from Eurocleft centers were used for comparison. Seven cephalometric measurements (SNA, SNB, ANB, A'N'B', G'-Sn'-Pg', Sn-CT-LS, ANS-Me/N-Me%), available or derivable for both centers, were analyzed. Means and standard deviations for the 7 measurements were calculated for the NAM center. Student's t-tests were used to compare group means for 6 of the measures and a test of proportion was used for ANS-Me/N-Me%. No significant differences were found between the NAM protocol-prepared group and the Eurocleft non-PSIO centers on any of the 7 analyzed cephalometric relationships after accounting for false discovery rate. The NAM treatment protocol does not appear to impact skeletal or soft tissue facial growth in school-aged children with non-syndromic UCLP.
PMID: 30950956
ISSN: 1536-3732
CID: 3826272

A Call to Action for Male Surgeons in the Wake of the #MeToo Movement: Mentor Female Surgeons

Daar, David A; Abdou, Salma A; Wilson, Stelios C; Hazen, Alexes; Saadeh, Pierre B
PMID: 30998536
ISSN: 1528-1140
CID: 3810612

Targeted TNF-α Overexpression Drives Salivary Gland Inflammation

Limaye, A; Hall, B E; Zhang, L; Cho, A; Prochazkova, M; Zheng, C; Walker, M; Adewusi, F; Burbelo, P D; Sun, Z J; Ambudkar, I S; Dolan, J C; Schmidt, B L; Kulkarni, A B
Chronic inflammation of the salivary glands from pathologic conditions such as Sjögren's syndrome can result in glandular destruction and hyposalivation. To understand which molecular factors may play a role in clinical cases of salivary gland hypofunction, we developed an aquaporin 5 (AQP5) Cre mouse line to produce genetic recombination predominantly within the acinar cells of the glands. We then bred these mice with the TNF-αglo transgenic line to develop a mouse model with salivary gland-specific overexpression of TNF-α; which replicates conditions seen in sialadenitis, an inflammation of the salivary glands resulting from infection or autoimmune disorders such as Sjögren's syndrome. The resulting AQP5-Cre/TNF-αglo mice display severe inflammation in the salivary glands with acinar cell atrophy, fibrosis, and dilation of the ducts. AQP5 expression was reduced in the salivary glands, while tight junction integrity appeared to be disrupted. The immune dysregulation in the salivary gland of these mice led to hyposalivation and masticatory dysfunction.
PMID: 30958728
ISSN: 1544-0591
CID: 3809552

Can intraoral photography replace plaster and digital models in clinical practice? A preliminary investigation

Jerrold, Laurance; Schulte, Michael; Isaacs Henry, Jessie
PMID: 30978721
ISSN: 0022-3875
CID: 3809452