Low Prevalence of Clinically Significant Hyponatremia following Cranial Vault Reconstruction for Single-Suture Craniosynostosis.

BACKGROUND: Patients are commonly monitored for hyponatremia after intracranial procedures, yet the prevalence of hyponatremia after cranial vault reconstruction (CVR) remains unclear. The purpose of this study is to define the prevalence, risk factors, and complications of hyponatremia after CVR to optimize postoperative sodium surveillance protocols. METHODS: Patients with nonsyndromic, single-suture craniosynostosis who underwent primary CVR between 2009 and 2020 at Michigan Medicine were included (n = 231). Demographic, intraoperative, and postoperative characteristics were compared by postoperative hyponatremia status at P < 0.05 significance. Hyponatremia was defined as mild (<135 mEq/L), moderate (<130 mEq/L), or severe (<125 mEq/L) based on the lowest postoperative laboratory draw. RESULTS: Twenty-three patients (10.0%) developed mild postoperative hyponatremia. No patient developed moderate or severe postoperative hyponatremia. On multivariable regression, decreased preoperative sodium level (P = 0.03) and decreased preoperative weight (P = 0.02) were significantly associated with mild postoperative hyponatremia. No patient developed complications or required hospital readmission because of hyponatremia. CONCLUSIONS: This large retrospective cohort study of patients with nonsyndromic single-suture craniosynostosis demonstrated a 10% prevalence of mild, clinically inconsequential hyponatremia and 0% prevalence of moderate or severe, clinically significant hyponatremia after primary CVR. Patients with low preoperative sodium level or weight were at increased risk for developing mild postoperative hyponatremia. The results suggest that patients with preoperative sodium greater than 140 mEq/L or preoperative weight greater than 10 kg may be candidates for limited postoperative sodium surveillance; however, future prospective studies are warranted before implementation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Reasons for Removal of Rigid Internal Fixation Devices in Craniofacial Surgery: A 20-year Update.

The hardware utilized for rigid internal fixation of the craniofacial skeleton has evolved over time. Thus, the reasons for the unplanned removal of hardware continue to change. The purpose of this study is to compare past (1989-1995) and present (2000-2020) patient cohorts to establish trends related to unplanned removal of craniofacial hardware. A retrospective review study was designed. Data from our institution's original publication describing the unplanned removal of craniofacial hardware (1989-1995) was obtained. Data related to patients who underwent unplanned removal of hardware from 2000 to 2020 was collected from the electronic medical record. A descriptive statistical analysis was performed to compare demographics, reasons for hardware placement, and reasons for unplanned hardware removal between cohorts. This study includes 55 patients treated from 1989 to 1995 and 184 patients treated from 2000 to 2020. The average age at hardware placement decreased from 32 years (1989-1995) to 28 years (2000-2020). The most common reason for hardware placement changed from motor vehicle accident (1989-1995) to congenital deformity (2000-2020). The length of time with hardware in situ increased from 13 months (1989-1995) to 25 months (2000-2020). The most common reason for hardware removal changed from prominent hardware (1989-1995) to hardware exposure (2000-2020). In summary, patients who underwent rigid internal fixation of the craniofacial skeleton from 2000 to 2020 retained their hardware 2 times longer than patients treated from 1989 to 1995. Factors potentially contributing to increased retention include improved surgical technique, decreased profile of hardware, and increased surgeon experience. Further studies are warranted to define preoperative risk factors for unplanned hardware removal.

Flexor Tendon Rupture Secondary to Gout.

Extra-articular deposition of monosodium urate crystals is a widely recognized manifestation of gout. However, gouty infiltration of flexor tendons in the hand resulting in tendon rupture is exceedingly rare. This case report highlights a patient with gouty infiltration of flexor tendons in the right middle finger resulting in rupture of both the flexor digitorum profundus and flexor digitorum superficialis. Given the extent of gouty infiltration and need for pulley reconstruction, the patient was treated with two-stage flexor tendon reconstruction. Febuxostat was prescribed preoperatively to limit further deposition of monosodium urate crystals and continued postoperatively to maximize the potential for long-lasting results. Prednisone was prescribed between the first- and second-stage operations to prevent a gout flare while the silicone rod was in place. In summary, tendon rupture secondary to gouty infiltration is the most likely diagnosis in patients with a history of gout presenting with tendon insufficiency.

Adipose-Derived Stem Cells Enhance Graft Incorporation and Mineralization in a Murine Model of Irradiated Mandibular Nonvascularized Bone Grafting.

BACKGROUND: Nonvascularized bone grafting represents a practical method of mandibular reconstruction. However, the destructive effects of radiotherapy on native bone preclude the use of nonvascularized bone grafts in head and neck cancer patients. Adipose-derived stem cells have been shown to enhance bone healing and regeneration in numerous experimental models. The purpose of this study was to determine the impact of adipose-derived stem cells on nonvascularized bone graft incorporation in a murine model of irradiated mandibular reconstruction. METHODS: Thirty isogenic rats were randomly divided into 3 groups: nonvascularized bone graft (control), radiation with nonvascularized bone graft (XRT), and radiation with nonvascularized bone graft and adipose-derived stem cells (ASC). Excluding the control group, all rats received a human-equivalent dose of radiation. All groups underwent mandibular reconstruction of a critical-sized defect with a nonvascularized bone graft from the contralateral hemimandible. After a 60-day recovery period, graft incorporation and bone mineralization were compared between groups. RESULTS: Compared with the control group, the XRT group demonstrated significantly decreased graft incorporation (P = 0.011), bone mineral density (P = 0.005), and bone volume fraction (P = 0.001). Compared with the XRT group, the ASC group achieved a significantly increased graft incorporation (P = 0.006), bone mineral density (P = 0.005), and bone volume fraction (P = 0.013). No significant differences were identified between the control and ASC groups. CONCLUSIONS: Adipose-derived stem cells enhance nonvascularized bone graft incorporation in the setting of human-equivalent radiation.

Cross-Sectional Analysis of Insurance Coverage for Lymphedema Treatments in the United States.

Importance: Lymphedema is a debilitating condition that affects approximately 1 in 1000 individuals in the United States. Complete decongestive therapy is currently the standard of care, and innovative surgical techniques have demonstrated potential to further improve outcomes. Despite the growing armamentarium of treatment options, a large proportion of patients with lymphedema continue to struggle because of limited access to care. Objective: To define the current state of insurance coverage for lymphedema treatments in the United States. Design, Setting, and Participants: A cross-sectional analysis of insurance reimbursement for lymphedema treatments in 2022 was designed. The top 3 insurance companies per state based on market share and enrollment data maintained by the Kaiser Family Foundation were included. Established medical policies were gathered from insurance company websites and phone interviews, and descriptive statistics were performed. Main Outcomes and Measures: Treatments of interest included nonprogrammable pneumatic compression, programmable pneumatic compression, surgical debulking, and physiologic procedures. Primary outcomes included level of coverage and criteria for coverage. Results: This study included 67 health insurance companies representing 88.7% of the US market share. Most insurance companies offered coverage for nonprogrammable (n = 55, 82.1%) and programmable (n = 53, 79.1%) pneumatic compression. However, few insurance companies offered coverage for debulking (n = 13, 19.4%) or physiologic (n = 5, 7.5%) procedures. Geographically, the lowest rates of coverage were seen in the West, Southwest, and Southeast. Conclusions and Relevance: This study suggests that in the United States, less than 12% of individuals with health insurance, and even fewer patients without health insurance, have access to pneumatic compression and surgical treatments for lymphedema. The stark inadequacy of insurance coverage must be addressed through research and lobbying efforts to mitigate health disparities and promote health equity among patients with lymphedema.

Longitudinal Assessment of Neurodevelopment in Patients With Nonsyndromic Single-Suture Craniosynostosis: A Retrospective Review of 66 Patients.

The neurodevelopmental consequences of nonsyndromic single-suture (NSS) craniosynostosis are the subject of continued debate. Although the predictive validity of the Bayley Scales of Infant and Toddler Development (Third Edition) (BSID-III) have been questioned, this neurodevelopmental testing battery continues to be widely utilized among multidisciplinary craniofacial teams. The purpose of this study is to evaluate the neurodevelopmental functioning of patients with NSS craniosynostosis before and after surgical correction and the impact of surgical correction on neurodevelopmental trajectory based on BSID-III testing. All patients with NSS craniosynostosis who underwent cranial vault remodeling between 2009 and 2020 were considered for inclusion. Patients who failed to complete BSID-III testing within 2 months of surgery preoperatively and 2 years of surgery postoperatively were excluded. A total of 66 patients met criteria for the study. On language testing, both the preoperative mean score ( P =0.007) and postoperative mean score ( P =0.003) were significantly lower than the population norm. Furthermore, on motor testing, both the preoperative mean score ( P =0.005) and postoperative mean score ( P =0.001) were significantly lower than the population norm. Bayley Scales of Infant and Toddler Development (Third Edition) testing revealed no significant change between preoperative and postoperative neurodevelopmental functioning. Overall, this study suggests that patients with NSS craniosynostosis experience modest delays in language and motor development, which are present before and after cranial vault remodeling. In addition, this study provides evidence that cranial vault remodeling does not significantly impact the neurodevelopmental trajectory. Multicenter st udies and refined neurodevelopmental testing methods are necessary to definitively establish the neurodevelopmental implications of NSS craniosynostosis.

Surgical Timing and Neurocognitive Development among Patients with Craniosynostosis: Analysis of Confounders.

BACKGROUND: In 1988, Renier and Marchac asserted that children with craniosynostosis who undergo cranial vault remodeling (CVR) after 12 months of age experience delayed neurocognitive development compared to children who undergo CVR before 12 months of age. The purpose of this study was to identify factors potentially confounding this cause-and-effect relationship. The authors hypothesize that children with socioeconomic disadvantages or comorbid conditions are more likely to undergo CVR after 12 months and may represent a selection bias toward delayed neurocognitive development. METHODS: Patients with nonsyndromic single-suture craniosynostosis who underwent CVR between 2009 and 2020 at Michigan Medicine were included ( n = 227). Sociodemographic and clinical variables were documented. The sample was dichotomized to compare patients who underwent CVR before (early) and after (late) 12 months of age. Statistical analysis was performed at P < 0.05 significance. RESULTS: The early and late groups contained 157 patients and 70 patients, respectively. Compared to the early group, the late group contained a larger proportion of patients who identified as non-White ( P = 0.03), qualified for need-based financial assistance ( P = 0.03), were born preterm ( P < 0.01), or had a comorbid condition ( P < 0.01). Based on preoperative testing, the late group contained a larger proportion of patients with baseline cognitive ( P < 0.001) and language ( P = 0.008) delays relative to the early group. CONCLUSIONS: This study demonstrates that socioeconomic disadvantages and comorbid conditions are prevalent among patients who undergo delayed CVR and may represent a selection bias toward delayed neurocognitive development. Future studies evaluating the relationship between surgical timing and neurocognitive development must control for these factors. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Therapeutic Efficacy of Adipose-Derived Stem Cells Versus Bone Marrow Stromal Cells for Irradiated Mandibular Fracture Repair.

BACKGROUND: Mesenchymal stem cells have immense potential in applications of bone healing and regeneration. However, few studies have evaluated the therapeutic efficacy of adipose-derived stem cells (ASCs) and bone marrow stromal cells (BMSCs) in irradiated bone. The purpose of this study is to compare the ability of ASCs versus BMSCs to enhance healing outcomes in a murine model of irradiated mandibular fracture repair. METHODS: Forty-eight isogenic male Lewis rats underwent radiation therapy followed by mandibular osteotomy with intraoperative placement of either ASCs or BMSCs. Animals were killed on postoperative day 40. Mandibles were analyzed for union rate, biomechanical strength, vascularity, and mineralization. Groups were compared at P < 0.05 significance. RESULTS: The ASC and BMSC groups demonstrated 92% and 75% union rates. Compared with the BMSC group, the ASC group demonstrated a trending increase in maximum load ( P = 0.095) on biomechanical strength analysis and a significant increase in vessel number ( P = 0.001), vessel thickness ( P = 0.035), and vessel volume fraction ( P = 0.007) on micro-computed tomography angiography analysis. No significant differences in bone mineralization were identified on micro-computed tomography analysis. CONCLUSION: This study demonstrates the superior therapeutic efficacy of ASCs over BMSCs in irradiated fracture healing as evidenced by union rate, vascular morphometry, and a trend in biomechanical strength. We posit that the robust vascular response induced by ASCs better recapitulates the sequence and synchronicity of physiologic bone healing compared with BMSCs, thereby improving the reliability of irradiated fracture repair.

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

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.

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

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

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

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). ß-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.

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

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.

Sociodemographic Factors Associated With Adherence to Referrals From the Pediatric Emergency Department.

BACKGROUND: Outpatient referrals constitute a critical component of emergency medical care. However, barriers to care after emergency department (ED) visits have not been investigated thoroughly. OBJECTIVE: The purpose of this study was to determine the impact of sociodemographic variables on referral attendance after ED visits. METHODS: A retrospective cohort study was designed. Patients aged 0-17 years who visited the C.S. Mott Children's Hospital ED in 2016 and received a referral were included. Multiple referrals for 1 patient were counted as independent encounters for statistical analysis. RESULTS: Chart review was performed on 6120 pediatric ED encounters, producing a total of 822 referrals to University of Michigan Health System outpatient clinics. Referral attendance did not differ by race, ethnicity, language, or religion. Older age was associated with decreased attendance at referrals (p = 0.043). Patients who were black and female (p = 0.019), patients with public health insurance (p = 0.004), and patients residing in areas with either high rates of unemployment (p = 0.003), or lower high school education rates (p = 0.006) demonstrated decreased attendance. Patients referred to pediatric neurology had lower attendance rates (p < 0.001), and those referred to pediatric orthopedic surgery attended referrals more often (p = 0.006). CONCLUSIONS: This study provides an overview of the impact of sociodemographic and departmental factors on attendance at outpatient follow-up referrals. Significant disparities exist with respect to referral attendance after emergency medical care. Informed resource allocation may be utilized to improve care for these at-risk patient populations.

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

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.

Abdominoplasty in the Overweight and Obese Population: Outcomes and Patient Satisfaction.

BACKGROUND: Abdominoplasty is a safe, efficacious body contouring procedure commonly performed on patients after massive weight loss or pregnancy, or because of general aging. However, complication rates and patient satisfaction levels remain largely unexplored for the overweight and obese patient population. The purpose of this study was twofold: to determine the complication rate and to gauge the psychological impact of abdominoplasty in the overweight or obese patient. METHODS: A retrospective review was conducted of consecutive overweight and obese patients undergoing abdominoplasty or panniculectomy over a 12-year period from January of 2004 to December of 2016. Patient medical records were reviewed to identify patient demographics and comorbidities, operative details, and postoperative course. A patient survey was used to assess satisfaction, personal experience with complications, and the recovery process. RESULTS: Forty-six total patients underwent abdominoplasty or panniculectomy during the 12-year period and met the criterion of body mass index greater than or equal to 25 kg/m. The average patient body mass index was 32.0 kg/m, with the majority of the patients categorized as overweight. The average abdominal resection weight was 4834.9 g. Major complications, defined as complications requiring return to the operating room, occurred in four patients (8.7 percent). Minor complications, defined as complications that could be handled in an office setting, occurred in 18 patients (39.1 percent). Thirty-six patients (78.3 percent) responded to the survey. The overwhelming majority of patients who responded to the survey [n = 35 (97.2 percent)] stated that they were satisfied with the final outcome and would choose to have the procedure again. CONCLUSION: Abdominoplasty and panniculectomy in overweight and obese patients are associated with an elevated complication rate, yet patient satisfaction is overwhelmingly high, suggesting the viability of body contouring procedures in this patient population. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

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

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.

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

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.

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

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.

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

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.

Novel Formulation Strategy to Improve the Feasibility of Amifostine Administration.

PURPOSE: Amifostine (AMF), a radioprotectant, is FDA-approved for intravenous administration in cancer patients receiving radiation therapy (XRT). Unfortunately, it remains clinically underutilized due to adverse side effects. The purpose of this study is to define the pharmacokinetic profile of an oral AMF formulation potentially capable of reducing side effects and increasing clinical feasibility. METHODS: Calvarial osteoblasts were radiated under three conditions: no drug, AMF, and WR-1065 (active metabolite). Osteogenic potential of cells was measured using alkaline phosphatase staining. Next, rats were given AMF intravenously or directly into the jejunum, and pharmacokinetic profiles were evaluated. Finally, rats were given AMF orally or subcutaneously, and blood samples were analyzed for pharmacokinetics. RESULTS: WR-1065 preserved osteogenic potential of calvarial osteoblasts after XRT to a greater degree than AMF. Direct jejunal AMF administration incurred a systemic bioavailability of 61.5%. Subcutaneously administrated AMF yielded higher systemic levels, a more rapid peak exposure (0.438 vs. 0.875 h), and greater total systemic exposure of WR-1065 (116,756 vs. 16,874 ng*hr/ml) compared to orally administered AMF. CONCLUSIONS: Orally administered AMF achieves a similar systemic bioavailability and decreased peak plasma level of WR-1065 compared to intravenously administered AMF, suggesting oral AMF formulations maintain radioprotective efficacy without causing onerous side effects, and are clinically feasible.