Publications by authors named "Steven R Buchman"

172 Publications

Intraoperative Stromal Vascular Fraction Therapy Improves Histomorphometric and Vascular Outcomes in Irradiated Mandibular Fracture Repair.

Plast Reconstr Surg 2021 04;147(4):865-874

From the Section of Plastic and Reconstructive Surgery, Michigan Medicine, C.S. Mott Children's Hospital.

Background: Cell-based treatments have demonstrated the capacity to enhance reconstructive outcomes in recent decades but are hindered in clinical utility by regulatory hurdles surrounding cell culture. This investigation examines the ability of a noncultured stromal vascular fraction derived from lipoaspirate to enhance bone healing during fracture repair to further the development of translatable cell therapies that may improve outcomes in irradiated reconstruction.

Methods: Isogenic male Lewis rats were divided into three groups: fracture, irradiated fracture, and irradiated fracture with stromal vascular fraction treatment. Irradiated groups received a fractioned dose of 35 Gy before mandibular osteotomy. Stromal vascular fraction was harvested from the inguinal fat of isogenic donors, centrifuged, and placed intraoperatively into the osteotomy site. All mandibles were evaluated for bony union and vascularity using micro-computed tomography before histologic analysis.

Results: Union rates were significantly improved in the irradiated fracture with stromal vascular fraction treatment group (82 percent) compared to the irradiated fracture group (25 percent) and were not statistically different from the fracture group (100 percent). Stromal vascular fraction therapy significantly improved all metrics of bone vascularization compared to the irradiated fracture group and was not statistically different from fracture. Osteocyte proliferation and mature bone formation were significantly reduced in the irradiated fracture group. Bone cellularity and maturity were restored to nonirradiated levels in the irradiated fracture with stromal vascular fraction treatment group despite preoperative irradiation.

Conclusions: Vascular and cellular depletion represent principal obstacles in the reconstruction of irradiated bone. This study demonstrates the efficacy of stromal vascular fraction therapy in remediating these damaging effects and provides a promising foundation for future studies aimed at developing noncultured, cell-based therapies for clinical implementation.
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http://dx.doi.org/10.1097/PRS.0000000000007781DOI Listing
April 2021

Computed Tomography in Patients With Craniosynostosis: A Survey to Ascertain Practice Patterns Among Craniofacial Surgeons.

Ann Plast Surg 2021 Feb 12. Epub 2021 Feb 12.

From the Section of Plastic Surgery, Department of Surgery Department of Neurosurgery, University of Michigan, Ann Arbor, MI.

Background: In patients with craniosynostosis, imaging remains up to the discretion of the plastic surgeon or neurosurgeon. To inform best practice guidelines, we sought to obtain data surrounding the frequency at which craniofacial surgeons order computed tomography (CT), as well as indications. We hypothesized that we would identify considerable variation in both imaging and associated indications.

Methods: We surveyed members of the American Society of Maxillofacial Surgeons and the American Society of Craniofacial Surgeons to measure the frequency of preoperative and postoperative head CTs, as well as indications. Initial items were piloted with 2 craniofacial surgeons and 1 neurosurgeon, using interviews to ensure content validity. χ2 Tests were used to measure associations between operative volume, years in practice, and imaging.

Results: Eighty-five craniofacial surgeons responded (13.8% response rate), with the majority (63.5%) having performed a craniosynostosis operation in the last month. Only 9.4% of surgeons never order preoperative CTs. Of those who do, the most common indications included diagnosis confirmation (31.2%) and preoperative planning (27.3%). About 25% of surgeons always obtain postoperative head CTs, usually to evaluate surgical outcomes (46.7%). Only 13.3% of respondents order 2 or more postoperative scans. Higher operative volume was associated with a lower likelihood of ordering preoperative head CTs (P = 0.008).

Conclusions: The majority of surgeons obtain preoperative head CTs, whereas only 25% obtain CTs postoperatively, often to evaluate outcomes. Because outcomes may be evaluated clinically, this is a poor use of resources and exposes children to radiation. Consensus guidelines are needed to create best practices and limit unnecessary studies.
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http://dx.doi.org/10.1097/SAP.0000000000002751DOI Listing
February 2021

Assessing the Key Predictors of an Academic Career after Craniofacial Surgery Fellowship.

Plast Reconstr Surg 2020 12;146(6):759e-767e

From the Department of Surgery, Section of Plastic and Reconstructive Surgery, Craniofacial Research Laboratory, University of Michigan Health System.

Background: As craniofacial fellowship positions outnumber the availability of academic craniofacial jobs, it is important to understand the factors associated with securing an academic position after fellowship. The purpose of this study was to evaluate the impact of bibliometric indices and trainee demographics on the ability to obtain a full-time academic plastic surgery position on completion of a craniofacial fellowship.

Methods: Craniofacial fellowship graduates between 2009 and 2018 (n = 182) were identified. Initial job placement and demographic data were collected; bibliometric indices at fellowship completion were calculated. Chi-square and Fisher's exact tests and multivariable logistic regression were used to assess the association of select factors with job placement.

Results: Of the 48.9 percent of fellows that secured academic positions, 39.3 percent trained at five fellowship institutions. The majority of those completing residency at top institutions for academic surgery and research entered academic positions at fellowship completion. Geography influenced academic placement, as 72.7 percent of trainees in the Northeast secured academic positions. Only 20.3 percent of fellows completed dedicated postgraduate research time, but among these, 70.3 percent entered academic jobs. The h-index (OR, 1.14; p = 0.01) and total manuscripts (OR, 1.04; p = 0.02) were significantly associated with academic practice while adjusting for other covariates.

Conclusions: Although residency training institution, geographic location, and postgraduate research may influence academic placement, the h-index and total manuscripts represent the best predictors of academic careers after craniofacial fellowship. This information is valuable for applicants who aspire to be academic craniofacial surgeons, and for programs and educators who can use these data to identify applicants with a propensity for academics.
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http://dx.doi.org/10.1097/PRS.0000000000007340DOI Listing
December 2020

Complications and the Need for Long-Term Follow-Up after Secondary Speech Surgery: A National and Longitudinal Claims Analysis.

Plast Reconstr Surg 2020 12;146(6):1340-1346

From the Section of Plastic Surgery, Department of Surgery, University of Michigan.

Background: Although most patients attain normal speech after cleft palate repair, up to 20 percent require secondary speech surgery. Despite the frequency of these procedures, complications and rates of subsequent revisions of secondary speech surgery after all procedure types have never been reviewed using national, longitudinal data.

Methods: The authors examined insurance claims from Clinformatics Data Mart between 2001 and 2017. Cases were categorized as palatalprocedures (i.e., palatoplasty, revision palatoplasty, secondary lengthening, palatal island flap) or pharyngeal procedures (i.e., pharyngeal flap, dynamic sphincter pharyngoplasty) (n = 846). Continuous enrollment from 180 days before to 30 days after surgery was required. Patients were excluded if they underwent palatoplasty, or any surgery at less than 3 years of age, without a speech diagnosis. Outcomes included 30-day complications and rates of subsequent revision secondary speech surgery. Multivariable logistic regression was used to evaluate the relationship between procedure type and complications.

Results: In this cohort, 52.5 percent underwent pharyngeal procedures, and 47.5 percent underwent palatal procedures. Complications occurred in 10.9 percent of patients and included respiratory complications (4.0 percent), bleeding (1.2 percent), dehiscence (3.6 percent), and critical care episodes (3.0 percent). There was no difference in complications between procedure types (OR, 0.87; 95 percent CI, 0.56 to 1.37; p = 0.56). The subsequent revision rate was 12.7 percent, but was 21.7 percent in patients with 3 years of postoperative enrollment.

Conclusions: Although complication rates were comparable to those in recent literature, rates of subsequent revisions of secondary speech procedures were high in patients with longer postoperative enrollment. Thus, these patients merit prolonged follow-up, as velopharyngeal dysfunction may recur over time.

Clinical Question/level Of Evidence: Therapeutic, III.
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http://dx.doi.org/10.1097/PRS.0000000000007339DOI Listing
December 2020

Decision Making in Pediatric Plastic Surgery: Autonomy and Shared Approaches.

J Craniofac Surg 2020 Nov/Dec;31(8):2139-2143

Department of Surgery, Section of Plastic Surgery, University of Michigan Health System, Ann Arbor, MI.

Background: Although shared decision-making is essential to patient-centered healthcare, its role in pediatric plastic surgery remains unclear. The objective of this study was to define the preferred level of involvement in surgical decision-making among children, caregivers, and surgeons.

Methods: The authors surveyed pediatric plastic surgery patients (n = 100) and their caregivers regarding their preferences on child involvement during surgical decision-making. Fleiss' kappa was used to assess agreement between groups. Bivariate Chi-square tests and multinomial logistic regression were used to assess the relationship between decision-making preferences and select demographic factors.

Results: Only 34% of children and their caregivers agreed upon their decision-making preferences (k = 0.04). The majority of children (40%) and caregivers (67%) favored shared decision-making between the patient, caregiver, and surgeon. Only 16% of children preferred physician-driven decisions, while 20% of children desired complete autonomy. Children's preferences were significantly associated with their age; the relative risk of children deferring to caregivers or surgeons over a shared approach was lower for adolescents and teens compared to children under 10 years old (relative risk = 0.20; 95% confidence interval: 0.054-0.751; P = 0.02). Caregiver's preferences did not change based on the child's age, but rather were related to the child's gender. Caregivers were more likely to choose the option that gave the child more autonomy when the child was male.

Conclusions: While most caregivers preferred a shared approach to decision-making, children desired greater autonomy, particularly with increasing age. Since there was limited agreement between caregivers and children, surgeons must be cognizant of differing preferences when discussing treatment plans to optimize both patient and parent satisfaction.
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http://dx.doi.org/10.1097/SCS.0000000000006738DOI Listing
March 2021

Reply: Age at Craniosynostosis Surgery and Its Impact on Ophthalmologic Diagnoses: A Single-Center Retrospective Review.

Plast Reconstr Surg 2020 09;146(3):376e-377e

Department of Surgery, Division of Plastic Surgery, Pediatric Plastic Surgery Service, University of Michigan, Ann Arbor, Mich.

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http://dx.doi.org/10.1097/PRS.0000000000007114DOI Listing
September 2020

Achieving the Optimal Aesthetic Benefit While Correcting Midface Deficiency: Utilizing A High Winged Le Fort I in Cleft and Craniofacial Patients.

J Craniofac Surg 2021 Jan-Feb 01;32(1):46-50

Department of Surgery, Section of Plastic and Reconstructive Surgery.

Abstract: Craniofacial anomalies are congenital disorders that affect the cranium and facial bones, with cleft lip and palate being the most common. These anomalies are often associated with abnormal development of pharyngeal arches and can result in the development of class III malocclusion and severe maxillary retrusion. Current treatment includes orthodontic decompensation and Le Fort I osteotomy to correct the maxillomandibular relationship. However, the traditional Le Fort I (LFI) advancement does not fully address the lack of skeletal volume in the midface. The high winged Le Fort I osteotomy (HWLFI) is an excellent surgical option for simultaneous correction of the midface deficiency and malocclusion while restoring optimal esthetic convexity. A retrospective chart review was conducted to include all cleft and craniofacial patients who underwent HWLFI advancement from 2002 to 2018. Patients had a minimum of 12 months of follow-up. Patient data and complications were reviewed. Standardized facial photographs were analyzed for esthetic improvement, occlusion, and beneficial salutary effects on the midface. Forty-three patients met the inclusion criteria. The mean age at surgery was 18.9 years. The mean follow-up was 32 months. Early complications included infection (9.3%) and temporary nerve paresthesia (2.3%). Late complications included infection (6.5%), wound dehiscence (4.3%), and painful hardware (2.3%). One patient (2.3 percent) had clinically significant relapse that required surgery. Postoperatively, patients demonstrated excellent midface projection and correction of the skeletal malocclusion. The HWLFI advancement significantly improves both the malocclusion and esthetic concerns of cleft and craniofacial patients by reestablishing maximal midfacial support. Important advantages of the HWLFI are avoidance of alloplastic implant use and extensive and potentially unstable surgical procedures that increase orbital volume.
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http://dx.doi.org/10.1097/SCS.0000000000006871DOI Listing
August 2020

Sociodemographic Predictors of Patient Age at Time of Cleft Lip and Palate Repair.

Cleft Palate Craniofac J 2020 12 13;57(12):1402-1409. Epub 2020 Aug 13.

Section of Plastic and Reconstructive Surgery, 1259University of Michigan, Ann Arbor, MI, USA.

Objective: To identify the impact of sociodemographic and health variables on the age at which patients undergo cleft lip repair, cleft palate repair, and primary speech evaluation.

Design: A retrospective, noninterventional quality assessment, and quality improvement study was designed.

Setting: This institutional study was performed at Michigan Medicine in Ann Arbor, MI.

Patients: All patients born between 2011 and 2014 who received surgical cleft repair, excluded those who were adopted (n = 165).

Main Outcome Measure: The age at which patients undergo cleft lip repair, cleft palate repair, and primary speech evaluation.

Results: Cleft lip repair was performed significantly later for patients identifying as Asian (18 weeks, = .01), patients with Child Protective Services contact (19 weeks, = .01), patients with a significant comorbidity (14 weeks, = .02), and patients who underwent preliminary lip adhesion surgery (19 weeks, < .01). Cleft palate repair was performed significantly later for patients identifying racially as Asian (19 weeks, = .03) and other (22 weeks, = .03). Preliminary speech and language evaluation were performed significantly later for patients identifying as black (55 weeks, = .03) and patients diagnosed with an isolated cleft lip (71 weeks, < .01).

Conclusions: Timing of cleft lip, cleft palate repair, and primary speech and language evaluation are subject to variation which may be predicted by clinically accessible factors. By identifying race, Child Protective Services contact, and care variables as significant predictors of increased patient age at time of intervention, multidisciplinary cleft care teams can proactively allocate patient support resources.
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http://dx.doi.org/10.1177/1055665620949119DOI Listing
December 2020

Saving Face: Patient Strategies to Reduce Stigma and Barriers to Effective Decision-Making Among Children With Cleft Lip.

J Craniofac Surg 2020 Sep;31(6):1608-1612

Center for Healthcare Outcomes and Policy, University of Michigan, Ann Arbor, MI.

Facial differences associated with cleft lips are often stigmatizing and can negatively impact psychosocial development and quality of life. However, little is known regarding patients' responses to societal expectations of appearance, or how these responses may impact utilization of revision surgery. Thus, patients with cleft lips at least 8 years of age (n = 31) were purposively sampled for semi-structured interviews. After verbatim transcription, first cycle coding proceeded with a semantic approach, which revealed patterns that warranted second cycle coding. The authors utilized an eclectic coding design to capture deeper meanings in thematic analysis. Additionally, survey data from a separate study were examined to evaluate participants' interest in improving appearance. Three major themes emerged, all of which reflected a desire to "save face" when interacting with society: (1) Cultural Mantras, which included societal mottos that minimized the importance of appearance; (2) Toughening Up, wherein the participants downplayed the difficulty of having a cleft; and (3) Deflection, wherein the participants took pride in facial features unrelated to their clefts. Despite these efforts to "save face," 78% of participants expressed interest in improving their appearance in the separate survey data.In conclusion, children with cleft lips try to "save face" when interacting with society by depreciating appearance, making light of clefts, and focusing on non-cleft related features. Paradoxically, many desired improvements of their appearance in an earlier survey. Awareness of these coping strategies is critical, as they may negatively impact surgeon-patient communication and inhibit patients from expressing interest in revision surgery.
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http://dx.doi.org/10.1097/SCS.0000000000006520DOI Listing
September 2020

A Simplified Approach to Myelomeningocele Defect Repair.

Ann Plast Surg 2021 01;86(1):58-61

From the Section of Plastic Surgery.

Background: Repair of the soft tissue defect in myelomeningoceles remains challenging. The literature currently lacks a systematic approach, reporting high rates of complications. We present outcomes from the largest series to date and describe a simplified approach that minimizes morbidity and streamlines decision making.

Methods: Patients 1 year or younger who underwent myelomeningocele repair between 2008 and 2018 were reviewed. Flap types were categorized by tissue composition. Complications were dichotomized into early and late (<30 days and >30 days postoperative, respectively). Logistic regression was used to measure the impact of flap tissue composition and skin closure technique on odds of postoperative complications.

Results: Ninety-seven patients met inclusion criteria. Reoperation was required in only 3 (3.0%) patients-1 for wound dehiscence and 2 for surgical site infections. Zero cases of tethered cord or cerebrospinal fluid leak occurred. The most common minor complications were early wound complications (n = 18, 18.6%) and early infection (n = 5, 5.2%). Fascia-only flaps and muscle + other tissue flaps were not associated with higher odds of complications compared with muscle-only flaps (odds ratio [OR], 2.13; 95% confidence interval [CI], 0.53-8.50, P = 0.29; OR = 2.87, 95% CI 0.66-12.51, P = 0.16, respectively). Rhomboid flaps for skin closure were associated with higher odds of complications (OR, 4.47; 95% CI, 1.00-19.97; P = 0.05).

Conclusions: Our approach to myelomeningocele repair demonstrated no cases of secondary tethered cord or cerebrospinal fluid leak, and reoperative rates were extremely low. Because complications were unrelated to flap type, we recommend a simplified approach using any tissue type for dural coverage and 2-layer primary closure of the skin.
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http://dx.doi.org/10.1097/SAP.0000000000002374DOI Listing
January 2021

Noncultured Minimally Processed Adipose-Derived Stem Cells Improve Radiated Fracture Healing.

Ann Plast Surg 2020 07;85(1):83-88

From the Craniofacial Research Laboratory.

Adipose-derived stem cells mitigate deleterious effects of radiation on bone and enhance radiated fracture healing by replacing damaged cells and stimulating angiogenesis. However, adipose-derived stem cell harvest and delivery techniques must be refined to comply with the US Food and Drug Administration restrictions on implantation of cultured cells into human subjects prior to clinical translation. The purpose of this study is to demonstrate the preservation of efficacy of adipose-derived stem cells to remediate the injurious effects of radiation on fracture healing utilizing a novel harvest and delivery technique that avoids the need for cell culture. Forty-four Lewis rats were divided into 4 groups: fracture control (Fx), radiated fracture control (XFx), radiated fracture treated with cultured adipose-derived stem cells (ASC), and radiated fracture treated with noncultured minimally processed adipose-derived stem cells (MP-ASC). Excluding the Fx group, all rats received a fractionated human-equivalent dose of radiation. All groups underwent mandibular osteotomy with external fixation. Following sacrifice on postoperative day 40, union rate, mineralization, and biomechanical strength were compared between groups at P < 0.05 significance. Compared with Fx controls, the XFx group demonstrated decreased union rate (100% vs 20%), bone volume fraction (P = 0.003), and ultimate load (P < 0.001). Compared with XFx controls, the MP-ASC group tripled the union rate (20% vs 60%) and demonstrated statistically significant increases in both bone volume fraction (P = 0.005) and ultimate load (P = 0.025). Compared with the MP-ASC group, the ASC group showed increased union rate (60% vs 100%) and no significant difference in bone volume fraction (P = 0.936) and ultimate load (P = 0.202). Noncultured minimally processed adipose-derived stem cells demonstrate the capacity to improve irradiated fracture healing without the need for cell proliferation in culture. Further refinement of the cell harvest and delivery techniques demonstrated in this report will enhance the ability of noncultured minimally processed adipose-derived stem cells to improve union rate and bone quality, thereby optimizing clinical translation.
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http://dx.doi.org/10.1097/SAP.0000000000002354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293584PMC
July 2020

Therapeutic Interventions to Reduce Radiation Induced Dermal Injury in a Murine Model of Tissue Expander Based Breast Reconstruction.

Ann Plast Surg 2020 11;85(5):546-552

From the Section of Plastic Surgery Craniofacial Research Laboratory, Department of Surgery, University of Michigan Health System, Ann Arbor, MI.

Background: Radiation therapy (XRT) induced dermal injury disrupts type I collagen architecture. This impairs cutaneous viscoelasticity, which may contribute to the high rate of complications in expander-based breast reconstruction with adjuvant XRT. The objective of this study was to further elucidate the mechanism of radiation-induced dermal injury and to determine if amifostine (AMF) or deferoxamine (DFO) mitigates type I collagen injury in an irradiated murine model of expander-based breast reconstruction.

Methods: Female Lewis rats (n = 20) were grouped: expander (control), expander-XRT (XRT), expander-XRT-AMF (AMF), and expander-XRT-DFO (DFO). Expanders were surgically placed. All XRT groups received 28 Gy of XRT. The AMF group received AMF 30 minutes before XRT, and the DFO group used a patch for delivery 5 days post-XRT. After a 20-day recovery period, skin was harvested. Atomic force microscopy and Raman spectroscopy were performed to evaluate type I collagen sheet organization and tissue compositional properties, respectively.

Results: Type I collagen fibril disorganization was significantly increased in the XRT group compared with the control (83.8% vs 22.4%; P = 0.001). Collagen/matrix ratios were greatly reduced in the XRT group compared with the control group (0.49 ± 0.09 vs 0.66 ± 0.09; P = 0.017). Prophylactic AMF demonstrated a marked reduction in type I collagen fibril disorganization on atomic force microscopy (15.9% vs 83.8%; P = 0.001). In fact, AMF normalized type I collagen organization in irradiated tissues to the level of the nonirradiated control (P = 0.122). Based on Raman spectroscopy, both AMF and DFO demonstrated significant differential protective effects on expanded-irradiated tissues. Collagen/matrix ratios were significantly preserved in the AMF group compared with the XRT group (0.49 ± 0.09 vs 0.69 ± 0.10; P = 0.010). β-Sheet/α-helix ratios were significantly increased in the DFO group compared with the XRT group (1.76 ± 0.03 vs 1.86 ± 0.06; P = 0.038).

Conclusions: Amifostine resulted in a significant improvement in type I collagen fibril organization and collagen synthesis, whereas DFO mitigated abnormal changes in collagen secondary structure in an irradiated murine model of expander-based breast reconstruction. These therapeutics offer the ability to retain the native microarchitecture of type I collagen after radiation. Amifostine and DFO may offer clinical utility to reduce radiation induced dermal injury, potentially decreasing the high complication rate of expander-based breast reconstruction with adjuvant XRT and improving surgical outcomes.
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http://dx.doi.org/10.1097/SAP.0000000000002264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487044PMC
November 2020

Amifostine Prophylaxis in Irradiated Breast Reconstruction: A Study of Oncologic Safety In Vitro.

Ann Plast Surg 2020 10;85(4):424-429

From the Section of Plastic Surgery.

Background: Indications for adjuvant radiation therapy (XRT) in breast cancer have expanded. Although highly effective, XRT damages surrounding tissues and vasculature, often resulting in delayed or compromised breast reconstruction. Thus, effective yet safe methods of radiation injury prophylaxis would be desirable. Amifostine is a Food and Drug Administration-approved radioprotectant; however, concerns about its potential to also protect cancer remain. The purpose of this study was to evaluate the oncologic safety of amifostine (AMF) in vitro and determine its effect on human breast cancer cells in the setting of XRT.

Methods: One ER+/PR+/Her2- (MCF-7) and two ER-/PR-Her2- (MDA-MB-231, MDA-MB-468) breast cancer cell lines were investigated. Female fibroblasts were used as controls. Cells were treated with WR-1065, the active metabolite of AMF, 20 minutes before 0Gy, 10Gy, or 20Gy XRT. Live and dead cells were quantified; percent cell death was calculated.

Results: WR-1065 treatment significantly preserved viability and reduced healthy female fibroblasts death after XRT compared with untreated controls. All three breast cancer cells lines exhibited radiosensitivity with substantial cell death. Cancer cells retained their radiosensitivity despite WR-1065 pretreatment, achieving the same degree of cell death as untreated controls.

Conclusions: This study demonstrated the proficiency of AMF to selectively protect healthy cells from XRT while breast cancer cells remained radiosensitive. These results support the oncologic safety of AMF in breast cancer in vitro. Further investigation is now warranted in vivo to ascertain the translational potential of using AMF as a radioprotectant to improve breast reconstruction after radiation treatment.
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http://dx.doi.org/10.1097/SAP.0000000000002110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295666PMC
October 2020

Variation in the Utilization of Postoperative Computed Tomography for Patients With Nonsyndromic Craniosynostosis: A National Claims Analysis.

Cleft Palate Craniofac J 2020 03 24;57(3):288-295. Epub 2019 Oct 24.

Section of Plastic Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.

Objective: Routine postoperative computed tomography (CT) imaging in nonsyndromic craniosynostosis remains controversial due to the hazards of radiation exposure. The extent to which postoperative head CTs are performed remains unknown. Therefore, we sought to measure the use of postoperative CTs in this population.

Design: The authors reviewed insurance claims from OptumInsight, using Current Procedural Terminology codes to identify procedures and postoperative imaging. Multilevel logistic regression was used to describe the odds of undergoing postoperative CTs, adjusting for patient and provider covariates.

Participants: Craniosynostosis patients who underwent reconstruction between 2001 and 2017 were reviewed. Patients older than 5 years at surgery, postoperative lengths of stay >15 days, syndromic diagnoses, operative complications within 30 days of surgery, and cranial bone grafting merited exclusion.

Main Outcome Measure: Odds of postoperative head CTs after cranial vault reconstruction.

Results: In this cohort (n = 1150), 326 (28.4%) patients underwent postoperative head CTs. The number of CTs ranged from 0 to 14. Older age at surgery (odds ratio [OR]: 1.32, = .002), increasing years of follow-up (OR: 1.12, < .001), and increasing comorbidities (OR: 1.21, = .017) were associated with postoperative CTs. After adjusting for patient factors, provider factors accounted for 31.3% of variation in imaging.

Conclusions: Over a quarter of patients underwent head CTs following reconstruction, and provider factors accounted for a large percentage of the variation. Given the risks of radiation, neurosurgeons and craniofacial surgeons face a critical need to establish postoperative imaging protocols to reduce unnecessary imaging in these vulnerable patients.
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http://dx.doi.org/10.1177/1055665619882568DOI Listing
March 2020

The Impact of Ethnicity on Craniosynostosis in the United States.

J Craniofac Surg 2019 Nov-Dec;30(8):2526-2529

Division of Plastic and Reconstructive Surgery, Washington University, St. Louis Children's Hospital, St. Louis, MO.

While many studies have examined potential risk factors for nonsyndromic craniosynostosis, there have been no publications to date investigating the role of ethnicity in the United States. The current study was undertaken as the first multi-center investigation to examine the relationship between ethnicity and nonsyndromic craniosynostosis, looking at both overall prevalence as well as potential correlation between ethnicity and pattern of affected suture site. A chart review of patients diagnosed with nonsyndromic craniosynostosis treated at four major children's hospitals was performed to obtain ethnicity data. Analysis was preformed based on ethnic group as well as suture site affected. To account for potentialOne regional selection bias, the KID database (1997-2012) was utilized to identify all cases of craniosynostosis on a national level. This data was analyzed against birth rates by ethnicity obtained from CDC WONDER natality database.Amongst the 2112 cases of nonsyndromic craniosynostosis at all institutions, Caucasians and African Americans were consistently the predominant ethnic groups. There was a statistically significant difference in the distribution of affected suture type with African Americans more likely to present with unicoronal synostosis and Caucasians more likely to present with metopic synostosis (P = 0.005). The national data revealed that there were more cases of craniosynostosis in Caucasians and fewer in African Americans than expected when compared to population birth rates. Our findings demonstrate that the Caucasian race is associated with increased rates of synostosis.
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http://dx.doi.org/10.1097/SCS.0000000000006009DOI Listing
January 2020

Age at Craniosynostosis Surgery and Its Impact on Ophthalmologic Diagnoses: A Single-Center Retrospective Review.

Plast Reconstr Surg 2019 09;144(3):696-701

From the Section of Plastic Surgery, Department of Surgery, the Department of Ophthalmology, and the Section of Plastic Surgery, University of Michigan; and the University of Toledo College of Medicine and Life Sciences.

Background: Ocular abnormalities in craniosynostosis are a persistent concern for patients and providers, and some surgeons feel that early surgical intervention for synostosis alleviates the progression of ophthalmologic abnormalities. In contradistinction, the authors hypothesize that operating early will have no bearing on postoperative ophthalmologic outcomes.

Methods: Single-suture craniosynostosis patients who underwent surgical correction between 1989 and 2015 were reviewed. Patients with multisuture craniosynostosis, syndromic diagnoses, no preoperative ophthalmology evaluation, and less than 2 years of follow-up were excluded. Logistic regression was used to determine odds of preoperative and postoperative ophthalmologic abnormalities by age, while controlling for patient-level covariates.

Results: One hundred seventy-two patients met inclusion criteria. The median age at surgery was 10 months (interquartile range, 7 to 12.9 months). Increasing age at the time of surgery was associated with increased odds of preoperative ophthalmologic diagnoses (OR, 1.06; p = 0.037) but not postoperative diagnoses (OR, 1.00; p = 0.91). Increasing age at surgery was also not associated with increased odds of ophthalmologic diagnoses, regardless of timing (OR, 1.04; p = 0.08). Patients with coronal synostosis (OR, 3.94; p = 0.036) had significantly higher odds of preoperative ophthalmologic diagnoses. Patients with metopic (OR, 5.60; p < 0.001) and coronal (OR, 7.13; p < 0.001) synostosis had significantly higher odds of postoperative ophthalmologic diagnoses.

Conclusions: After reviewing an expansive cohort, associations of both overall and postoperative ophthalmologic diagnoses with age at surgery were not found. The authors' findings thus run counter to the theory that early surgical intervention lessens the likelihood of postoperative ophthalmologic diagnoses and improves ophthalmologic outcomes.

Clinical Question/level Of Evidence: Risk, III.
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http://dx.doi.org/10.1097/PRS.0000000000005915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6729144PMC
September 2019

Decision-Making in Cleft-Related Surgery: A Qualitative Analysis of Patients and Caregivers.

Cleft Palate Craniofac J 2020 02 5;57(2):161-168. Epub 2019 Aug 5.

Section of Plastic Surgery, University of Michigan, Ann Arbor, MI, USA.

Objective: Preference-sensitive surgical decisions merit shared decision-making, as decision engagement can reduce decisional conflict and regret. Elective cleft-related procedures are often preference sensitive, and therefore, we sought to better understand decision-making in this population.

Design: Semistructured interviews were conducted to elicit qualitative data. A hierarchical codebook was developed through an iterative process in preparation for thematic analysis. Thematic analysis was performed to examine differences between patients and caregivers.

Setting: Multidisciplinary cleft clinic at a tertiary care center.

Participants: Patients with cleft lip aged 8 and older (n = 31) and their caregivers (n = 31) were purposively sampled. Inability to converse in English, intellectual disability, or syndromic diagnoses resulted in exclusion.

Main Outcome Measures: Preferences surrounding surgical decision-making identified during thematic analysis.

Results: Mean patient age was 12.7 (standard deviation: 3.1). Most had unilateral cleft lip and palate (43.8%). Three themes emerged: Insufficient Understanding of Facial Difference and Treatment, Diversity of Surgical Indications, and Barriers to Patient Autonomy. Almost half of caregivers believed their children understood their clefts, but most of these children failed to provide information about their cleft. Although many patients and caregivers acknowledged that surgery addressed function and/or appearance, patients and caregivers exhibited differences regarding the necessity of surgery. Furthermore, a large proportion of patients believed their opinions mattered in decisions, but less than half of caregivers agreed.

Conclusions: Patients with clefts desire to participate in surgical decisions but have limited understanding of their facial difference and surgical indications. Cleft surgeons must educate patients and facilitate shared decision-making.
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http://dx.doi.org/10.1177/1055665619866552DOI Listing
February 2020

Variation in the Desire for Cleft Revision Surgery among Children, Caregivers, and Surgeons.

Plast Reconstr Surg 2019 07;144(1):171-178

From the Section of Plastic Surgery, Department of Surgery, and the Department of Physical Medicine and Rehabilitation, Michigan Medicine; and the University of Michigan Medical School.

Background: Although revision surgery is part of the reconstructive process for children with cleft lip and/or cleft palate, the indications for revision vary, and the extent to which surgeons and families agree on appearance is unclear. The authors sought to understand the extent to which children with cleft lip and/or cleft palate, surgeons, caregivers, and control observers agree on satisfaction with appearance and the desire for revision.

Methods: Children with cleft lip and/or cleft palate (n = 100) and their caregivers (n = 100) were surveyed regarding satisfaction with appearance using the Cleft Evaluation Profile. Surgeons (n = 10) and control observers (n = 10) rated photographs of these children using questions analogous to the Cleft Evaluation Profile. General linear model repeated measures analysis of variance were used to detect significant differences between raters, with an alpha of 0.05.

Results: The children reported greater satisfaction with appearance across all domains compared with surgeons (nose, 7.77 versus 5.51, p < 0.001; lip, 7.94 versus 5.90, p < 0.001; maxilla, 8.16 versus 6.56, p < 0.001) and general observers (nose, 7.78 versus 6.00, p < 0.001; lip, 7.80 versus 6.12, p < 0.001; maxilla, 8.16 versus 7.40, p < 0.001). Children and caregivers expressed similar degrees of satisfaction with appearance of the lip (5.48 ± 1.69 versus 5.6 ± 1.49, p > 0.5) and maxilla (6.08 ± 1.1 versus 5.8 ± 1.2, p = 0.07). There was no significant relationship between children and surgeons in terms of the desire for revision surgery (p = 0.44).

Conclusions: All groups expressed differing levels of satisfaction with cleft-specific aspects of appearance. Importantly, children were more satisfied than all other groups. Care must be taken to evaluate perceptions of all stakeholders before moving forward with cleft revision surgery.
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http://dx.doi.org/10.1097/PRS.0000000000005722DOI Listing
July 2019

Implantable hyaluronic acid-deferoxamine conjugate prevents nonunions through stimulation of neovascularization.

NPJ Regen Med 2019 21;4:11. Epub 2019 May 21.

1Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI 48109 USA.

Approximately 6.3 million fractures occur in the U.S. annually, with 5-10% resulting in debilitating nonunions. A major limitation to achieving successful bony union is impaired neovascularization. To augment fracture healing, we designed an implantable drug delivery technology containing the angiogenic stimulant, deferoxamine (DFO). DFO activates new blood vessel formation through iron chelation and upregulation of the HIF-1α pathway. However, due to its short half-life and rapid clearance, maintaining DFO at the callus site during peak fracture angiogenesis has remained challenging. To overcome these limitations, we composed an implantable formulation of DFO conjugated to hyaluronic acid (HA). This compound immobilizes DFO within the fracture callus throughout the angiogenic window, making it a high-capacity iron sponge that amplifies blood vessel formation and prevents nonunions. We investigated implanted HA-DFO's capacity to facilitate fracture healing in the irradiated rat mandible, a model whereby nonunions routinely develop secondary to obliteration of vascularity. HA-DFO implantation significantly improved radiomorphometrics and metrics of biomechanical strength. In addition, HA-DFO treated mandibles exhibited a remarkable 91% bone union rate, representing a 3.5-fold improvement over non-treated/irradiated controls (20% bone union rate). Collectively, our work proposes a unique methodology for the targeted delivery of DFO to fracture sites in order to facilitate neovascularization. If these findings are successfully translated into clinical practice, millions of patients will benefit from the prevention of nonunions.
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http://dx.doi.org/10.1038/s41536-019-0072-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529413PMC
May 2019

The Role of Deferoxamine in Irradiated Breast Reconstruction: A Study of Oncologic Safety.

Plast Reconstr Surg 2019 06;143(6):1666-1676

From the Department of Surgery, Section of Plastic and Reconstructive Surgery, and the Department of Pharmacology, University of Michigan.

Background: Radiotherapy plays an essential role in the oncologic management of breast cancer. However, patients who undergo radiotherapy experience significantly more wound complications during the reconstructive process. Deferoxamine has immense potential to up-regulate angiogenesis and improve reconstructive outcomes. The purpose of this study was to determine the impact of deferoxamine on breast cancer cell proliferation in vitro, to delineate oncologic safety concerns regarding the use of deferoxamine as a regenerative therapeutic.

Methods: The dose-dependent effect of radiation and deferoxamine on two triple-negative breast cancer cell lines (MDA-MB-231 and MDA-MB-468) was determined by means of MTS (percentage cell viability) and tumorsphere (sphere number) analysis. Radiation therapy and deferoxamine were delivered both individually and in combination, and all experiments were completed in triplicate. Intracellular iron, nuclear factor-κB localization, and apoptosis/necrosis assays were performed to delineate mechanism. Analysis of variance statistical analysis was performed using SPSS (p < 0.05).

Results: For both cell lines, percentage viability and sphere number significantly decreased following exposure to 10 Gy of radiation. Surprisingly, the administration of 25 µM deferoxamine also significantly decreased each metric. The administration of deferoxamine (100 µM) in combination with radiation (10 Gy) resulted in significantly reduced percentage viability and sphere number compared with the administration of radiation alone. Deferoxamine treatment decreased intracellular iron, suppressed nuclear factor-κB activation, and induced apoptosis.

Conclusion: Radiation and deferoxamine significantly decrease breast cancer proliferation when delivered independently and in combination, suggesting deferoxamine may be safely used to facilitate improved reconstructive outcomes among triple-negative breast cancer survivors.

Clinical Question/level Of Evidence: Therapeutic, V.
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http://dx.doi.org/10.1097/PRS.0000000000005647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538447PMC
June 2019

Stem Cells for Bone Regeneration: Current State and Future Directions.

J Craniofac Surg 2019 May/Jun;30(3):730-735

Department of Plastic Surgery, Craniofacial Research Laboratory, University of Michigan Health Systems, Ann Arbor, MI.

Mesenchymal stem cells (MSCs) are capable of differentiating into osteoblasts, chondrocytes, and adipocytes, each of which is important for musculoskeletal tissue regeneration and repair. Reconstruction and healing of bony defects remains a major clinical challenge. Even as surgical practices advance, some severe cases of bone loss do not yield optimal recovery results. New techniques involving implantation of stem cells and tissue-engineered scaffolds are being developed to help improve bone and cartilage repair. The invasiveness and low yield of harvesting MSCs from the bone marrow (BMSCs) has led to the investigation of alternatives, including adipose-derived mesenchymal stem cells (ASCs). A review of the literature yielded several studies concerning the use of BMSCs and ASCs for the treatment of bone defects in both in vitro and in vivo models. Although both ASCs and BMSCs have demonstrated bone regenerative capabilities, BMSCs have outperformed ASCs in vitro. Despite these in vitro study findings, in vivo study results remain variable. Analysis of the literature seems to conclude there is no significant difference between bone regeneration using ASCs or BMSCs in vivo. Improved study design and standardization may enhance the application of these studies to patient care in the clinical setting.
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http://dx.doi.org/10.1097/SCS.0000000000005250DOI Listing
July 2019

Short- and Long-Term Outcomes by Procedure Type for Nonsagittal Single-Suture Craniosynostosis.

J Craniofac Surg 2019 Mar/Apr;30(2):458-464

Section of Plastic Surgery, University of Michigan, Ann Arbor, MI.

Background: Minimally invasive approaches for the treatment of single-suture craniosynostosis are sometimes touted as equivalent to cranial vault reconstruction. While techniques for sagittal synostosis have been reviewed previously, evidence regarding open and less invasive surgical techniques for metopic, coronal, and lambdoid synostosis has yet to be reviewed.

Methods: Systematic searches were performed using Embase.com and PubMed. Included studies reported short- or long-term outcomes, compared at least 2 standard techniques, discussed single-suture coronal, metopic, or lambdoid craniosynostosis, and enrolled at least 20 study participants. Two authors screened titles and abstracts, and also performed full text review and data extraction. Given heterogeneous outcomes, qualitative synthesis was performed after data extraction.

Results: The search strategy yielded 2348 articles. Of these, 313 were removed as duplicates, and 1935 were excluded during title/abstract review. After full text review of 100 articles, 19 were selected for data extraction. The heterogeneity of outcomes precluded meta-analysis and required qualitative synthesis. While short-term outcomes indicated decreased morbidity of minimally invasive techniques, only 2 articles presented long-term reoperation rates. One study reported higher reoperation rates in the less invasive technique, and the second reported no reoperations in the median follow-up period of 33 months.

Conclusion: Studies comparing long-term outcomes between different surgical techniques for single-suture craniosynostosis remain deficient. The development of standardized outcome measures is essential, and prospective, multicenter studies are necessary to assess the long-term efficacy of these procedures.
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http://dx.doi.org/10.1097/SCS.0000000000005129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541498PMC
August 2019

Debunking a Surgical Myth: Do Not Touch the Temporalis.

J Craniofac Surg 2019 Mar/Apr;30(2):429-432

Section of Plastic Surgery, University of Michigan.

Background: A longstanding dictum exists to avoid surgical manipulation of the temporalis muscle out of concern for an exceedingly high rate of muscle atrophy and recurrent temporal hollowing. The authors challenge this surgical myth, considering such advice to be erroneous. The authors hypothesize that elevation of the temporalis muscle, if performed using standard muscle flap principles, will demonstrate excellent results.

Methods: To assess temporalis response to surgical manipulation, the authors reviewed patients who underwent calvarial vault remodeling by the senior author for craniosynostosis between 1988 and 2011. Nonsyndromic patients with single-suture synostosis and 5 years of follow-up were eligible for inclusion. The medical record was used to measure rates of reoperation, recurrent temporal hollowing, and persistent temporalis overcorrection.

Results: Of the cohort reviewed, 196 patients met inclusion criteria. Ten patients (5.1%) exhibited recurrent bitemporal constriction. One patient (0.5%) underwent a revision temporalis turnover flap, and 2 patients (1.0%) underwent soft tissue augmentation. The overall reoperation rate was 1.5%. Temporalis overcorrection, in an attempt to prophylactically rectify the expected atrophy after temporalis manipulation, persisted in 11 patients (5.6%). Three of these patients required treatment with steroid injections, Botox injections, or operative muscle debulking. The overall reoperation rate for temporalis overcorrection was 1.5%.

Conclusions: The authors' low reoperation rates for recurrent deformity, in combination with persistent temporalis overcorrection in 5.6% of patients, should dispel the myth that manipulation of the temporalis invariably results in atrophy. The muscle may be surgically manipulated, as long as plastic surgery principles are followed.
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http://dx.doi.org/10.1097/SCS.0000000000005106DOI Listing
August 2019

Nonvascularized Bone Graft Reconstruction of the Irradiated Murine Mandible: An Analogue of Clinical Head and Neck Cancer Treatment.

J Craniofac Surg 2019 Mar/Apr;30(2):611-617

Section of Plastic and Reconstructive Surgery, Michigan Medicine, Ann Arbor, MI.

Nonvascularized bone grafts (NBGs) represent a practical method of mandibular reconstruction that is precluded in head and neck cancer patients by the destructive effects of radiotherapy. Advances in tissue-engineering may restore NBGs as a viable surgical technique, but expeditious translation demands a small-animal model that approximates clinical practice. This study establishes a murine model of irradiated mandibular reconstruction using a segmental iliac crest NBG for the investigation of imperative bone healing strategies. Twenty-seven male isogenic Lewis rats were divided into 2 groups; control bone graft and irradiated bone graft (XBG). Additional Lewis rats served as graft donors. The XBG group was administered a fractionated dose of 35Gy. All rats underwent reconstruction of a segmental, critical-sized defect of the left hemi-mandible with a 5 mm NBG from the iliac crest, secured by a custom radiolucent plate. Following a 60-day recovery period, hemi-mandibles were evaluated for bony union, bone mineralization, and biomechanical strength (P < 0.05). Bony union rates were significantly reduced in the XBG group (42%) compared with controls (80%). Mandibles in the XBG group further demonstrated substantial radiation injury through significant reductions in all metrics of bone mineralization and biomechanical strength. These observations are consistent with the clinical sequelae of radiotherapy that limit NBGs to nonirradiated patients. This investigation provides a clinically relevant, quantitative model in which innovations in tissue engineering may be evaluated in the setting of radiotherapy to ultimately provide the advantages of NBGs to head and neck cancer patients and reconstructive surgeons.
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http://dx.doi.org/10.1097/SCS.0000000000005032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541514PMC
August 2019

Caregiver-Reported Outcomes and Barriers to Care among Patients with Cleft Lip and Palate.

Plast Reconstr Surg 2018 12;142(6):884e-891e

From the Section of Plastic Surgery, Department of Surgery, University of Michigan.

Background: For children with cleft lip and/or palate, access to care is vital for optimizing speech, appearance, and psychosocial outcomes. The authors posited that inadequate access to care negatively impacts outcomes in this population.

Methods: Sixty caregivers of children with cleft lip and palate were surveyed to assess perceived barriers using the validated Barriers to Care questionnaire. The questionnaire includes 39 items divided into five subscales, with higher scores indicating fewer barriers. Caregiver-reported outcomes were assessed using the Cleft Evaluation Profile, which captures cleft-specific appearance- and speech-related outcomes. Higher scores correspond to less satisfactory outcomes. Desire for revision surgery was assessed as a binary outcome among caregivers. Multivariable regression was used to evaluate the relationship of barriers to care, caregiver-reported outcomes, and desire for revision, adjusting for clinical and demographic covariates.

Results: Sixty percent of caregivers perceived barriers to care, and caregivers who reported poorer access to care described poorer cleft-related outcomes (r = 0.19, p = 0.024). Caregivers with poorer skills (r = 0.17, p = 0.037), expectations (r = 0.17, p = 0.045), and pragmatics (r = 0.18, p = 0.026) subscale scores were associated with worse Cleft Evaluation Profile scores. Barriers were also negatively associated with aesthetic item scores (r = 0.11, p = 0.025). Finally, caregivers reporting fewer barriers were 21.2 percent less likely to express interest in revision surgery.

Conclusions: Barriers to care were associated with poorer appearance-related outcomes and increased interest in revision among caregivers of cleft patients. Enhancing access to care is critical in order to effectively meet goals of care for these families.
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http://dx.doi.org/10.1097/PRS.0000000000004987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282168PMC
December 2018

The Ethical and Professional Use of Social Media in Surgery: A Systematic Review of the Literature.

Plast Reconstr Surg 2018 09;142(3):388e-398e

From the Section of Plastic Surgery, Department of Surgery, and the Taubman Health Sciences Library, University of Michigan; the Division of Plastic Surgery, Department of Surgery, Columbia University; and the Division of Medical Ethics, Department of Medicine, Weill Medical College of Cornell University.

Although certain medical societies have released guidelines on the use of social media, plastic surgery, with its inherent visual nature and potential for sensationalism, could benefit from increasing direction regarding the ethical use of social media. The authors hypothesized that although general platitudes for use exist in the literature, guidelines articulating the boundaries of professional use are nonspecific. Systematic searches of MEDLINE, Embase.com, and Cochrane Central Register of Controlled Trials were completed on January 18, 2017. Searches consisted of a combination of Medical Subject Headings terms and title and abstract keywords for social media and professionalism concepts. In addition, the authors manually searched the three highest impact plastic surgery journals (ending in October of 2017). Two authors screened all titles and abstracts. Studies related to clinical medicine, patient care, and the physician-patient relationship were included for full-text review. Articles related to surgery merited final inclusion. The initial search strategy yielded 954 articles, with 28 selected for inclusion after final review. The authors' manual search yielded nine articles. Of the articles from the search strategy, 10 were published in the urology literature, eight were published in general surgery, six were published in plastic surgery, three were published in orthopedic surgery, and one was published in vascular surgery. Key ethical themes emerged across specialties, although practical recommendations for professional social media behavior were notably absent. In conclusion, social media continue to be a domain with potential professional pitfalls. Appropriate use of social media must extend beyond obtaining consent, and plastic surgeons must adhere to a standard of professionalism far surpassing that of today's media culture.
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http://dx.doi.org/10.1097/PRS.0000000000004692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6112181PMC
September 2018

Topical Deferoxamine Alleviates Skin Injury and Normalizes Atomic Force Microscopy Patterns Following Radiation in a Murine Breast Reconstruction Model.

Ann Plast Surg 2018 11;81(5):604-608

Department of Chemistry, University of Michigan, Ann Arbor, MI.

Background: Breast cancer is most commonly managed with a combination of tumor ablation, radiation, and/or chemotherapy. Despite the oncologic benefit of these treatments, the detrimental effect of radiation on surrounding tissue challenges the attainment of ideal breast reconstruction outcomes. The purpose of this study was to determine the ability of topical deferoxamine (DFO) to reduce cutaneous ulceration and collagen disorganization following radiotherapy in a murine model of expander-based breast reconstruction.

Methods: Female Sprague-Dawley rats (n = 15) were divided into 3 groups: control (expander), XRT (expander + radiation), and DFO (expander + radiation + deferoxamine [DFO]). Expanders were placed in a submusculocutaneous plane in the right upper back and ultimately filled to 15 mL. Radiation was administered via a fractionated dose of 28 Gy. Deferoxamine was delivered topically for 10 days following radiation. After a 20-day recovery period, skin ulceration and dermal type I collagen organization were analyzed.

Results: Compared with control, the XRT group demonstrated a significant increase in skin ulceration (3.7% vs 43.3%, P = 0.00) and collagen fibril disorganization (26.3% vs 81.8%, P = 0.00). Compared with the XRT group, treatment with topical DFO resulted in a significant reduction in ulceration (43.3% vs 7.0%, P = 0.00) and fibril disorganization (81.8% vs 15.3%, P = 0.00). There were no statistical differences between the control and DFO groups in skin ulceration or collagen disorganization.

Conclusions: This study suggests topical DFO is capable of reducing skin ulceration and type I collagen fibril disorganization following radiotherapy. This novel application of DFO has potential to enhance expander-based breast reconstruction outcomes and improve quality of life for women suffering the devastating effects of breast cancer.
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http://dx.doi.org/10.1097/SAP.0000000000001592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179919PMC
November 2018

Persistent Opioid Use Among Children, Adolescents, and Young Adults After Common Cleft Operations.

J Craniofac Surg 2018 Oct;29(7):1697-1701

Section of Plastic Surgery.

Background: Surgical care represents an important source of opioid prescribing and chronic use, but rates of prolonged opioid use following pediatric procedures remain unclear. The authors describe the rates and risk factors for new persistent opioid use in patients after common cleft operations.

Methods: The authors examined claims from the Truven Marketscan databases from January 1, 2010 to December 31, 2014. The authors included opioid-naive patients ages 8 to 25, who underwent 1 of 10 cleft-related procedures. Patients were considered opioid-naïve if they had no opioid prescription fills in the 11 months prior to the perioperative period. The authors obtained a random sample of age-matched, nonsurgical patients from the same dataset to be used as a control group. Included cleft patients had no procedural codes in the 6 months following surgery. All included patients filled an opioid prescription during the perioperative period, defined as 30 days before and 14 days after surgery. The primary outcome was new persistent opioid use, which is defined as continued opioid prescription fills between 90 and 180 days after the procedure.

Results: This cohort included 2039 cleft patients and 2100 control patients. The incidence of new persistent opioid use following surgery was 4.4% and 0.1% in the control group. Higher odds of opioid use 3 months beyond surgery were associated with distractor placement (OR 5.34, CI 2.00-14.24, P = 0.001). Increasing age (OR 1.11, CI 1.04-1.17, P = 0.001) and presence of a gastrointestinal comorbidity (OR 7.37, CI 1.49-36.54, P = 0.014) were also associated with new persistent use.

Conclusions: New persistent opioid use occurs after cleft-related procedures and could lead to chronic use in children, adolescents, and young adults.
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http://dx.doi.org/10.1097/SCS.0000000000004762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173989PMC
October 2018

Histologic Improvements in Irradiated Bone Through Pharmaceutical Intervention in Mandibular Distraction Osteogenesis.

J Oral Maxillofac Surg 2018 12 19;76(12):2660-2668. Epub 2018 May 19.

Professor of Plastic Surgery, Chief of Pediatric Plastic Surgery, and Director, Craniofacial Abnormalities Program, Michigan Medicine, Ann Arbor, MI. Electronic address:

Purpose: Despite the relative surgical ease and reduced donor-site morbidity of distraction osteogenesis (DO) in comparison with free tissue transfer, DO is currently precluded as a reconstructive option for head and neck cancer (HNC) patients because of the destructive effects of radiotherapy (XRT). This study investigates the ability of a novel combined therapy (CT) of radioprotective amifostine (AMF) and angiogenic deferoxamine (DFO) to mitigate XRT-induced bone injury in a murine model of DO.

Materials And Methods: Thirty male Sprague-Dawley rats were divided into 5 groups: DO (primary control), XRT (secondary control), AMF, DFO, and CT. With the exclusion of the DO group, all rats were administered a fractionated, human-equivalent XRT dose of 35 Gy, comparable with 70 Gy administered to HNC patients clinically. All groups underwent mandibular osteotomy and distraction to 5.1 mm. After euthanasia administration on postoperative day 40, the mandibles were sectioned and stained with Gomori trichrome. Osteocyte number, bone volume, and osteoid volume were compared between all groups by analysis of variance (P < .05).

Results: All rats survived and were included in the final analysis. The XRT group exhibited substantial bone injury, evidenced by a decreased osteocyte number and bone volume, as well as an increase in immature osteoid volume, compared with DO controls. The AMF, DFO, and CT groups showed significant increases in osteocyte proliferation compared with the XRT group and were not statistically different from the DO group. Notably, the CT group showed remediation of XRT-induced impairment of bone maturation and exhibited significantly greater bone volume and reduced osteoid volume in comparison with all groups.

Conclusions: Combined AMF and DFO treatment showed the capacity to remediate the deleterious effects of XRT, restore cellularity to nonirradiated levels, and surpass all groups in mature bone formation. Although further investigations of AMF and DFO are warranted, this study provides preliminary support for the potential use of DO in HNC patients through pharmaceutical facilitation of irradiated bone healing.
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http://dx.doi.org/10.1016/j.joms.2018.05.013DOI Listing
December 2018

Sociodemographic Predictors of Missed Appointments Among Patients With Cleft Lip and Palate.

Cleft Palate Craniofac J 2018 11 23;55(10):1440-1446. Epub 2018 Mar 23.

4 Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.

Objective: To identify disparities in compliance of and care for patients with cleft lip and/or palate (CL/P) by determining the impact of sociodemographic variables on the rate of missed appointments and Child Protective Services (CPS) involvement.

Design: A retrospective, noninterventional quality assessment and quality improvement study were designed.

Setting: This institutional study was performed at the University of Michigan in Ann Arbor, Michigan.

Patients: All patients born between January 1, 2011, and December 31, 2014, who underwent surgical CL/P repair, excluding those with fewer than 5 appointments (n = 178).

Main Outcome Measure: The rate of missed appointments, calculated as the total number of no-show appointments divided by the total number of scheduled appointments. All appointments from CL/P diagnosis to data collection were considered, including those outside of plastic surgery.

Results: The average patient was 4.5 years of age and had 49 total scheduled appointments. The overall rate of missed appointments was 9.6%, with 66.8% of patients missing at least 1 scheduled visit. Patients who were black ( P = .04), not affiliated with a religion ( P = .01), Medicaid users ( P = .01), from an unstable social background ( P = .01), or received need-based financial assistance ( P = .00) were significantly more likely to miss appointments. Child Protective Services was involved with 3.9% of patients.

Conclusions: Disparities exist in attendance rates among patients with CL/P, and at-risk patient populations have been identified. The allocation of cleft care resources must be efficiently planned in order to enhance the quality of care for at-risk individuals.
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http://dx.doi.org/10.1177/1055665618764739DOI Listing
November 2018