Customized bilaminar resorbable mesh with BMP-2 promotes cranial bone defect healing.

BACKGROUND: For repair of cranial vault (skull) defects, alloplastic (methylmethacrylate or titanium mesh) techniques may result in nonhealing or infectious complications and autogenous (split rib or calvarial) techniques may result in excessive blood loss or donor-site morbidity. Osteogenic factors such as bone morphogenetic protein-2 (BMP-2) provide promising alternatives for repairing bone defects. As a new option for this reconstructive challenge, we investigated by using a bilaminar resorbable construct made from computer-aided design and computer-aided manufacturing computed tomographic scan technology with BMP-2 in hopes of providing initial structural support for the skull, followed by bone healing without permanent foreign body problems. METHODS: Outcomes of consecutive adult patients with long-standing critical-sized cranial vault defects who underwent cranial vault reconstruction between 1999 and 2010 were studied (n = 69). Reconstructive options were titanium mesh, cryopreserved bone, patient-specific implants, autogenous (split calvarial), and a new bilaminar resorbable mesh construct sandwiched with BMP-2. These reconstructive options were compared for operating room time, blood loss, complications, reoperations, and bone healing (3-dimensional computed tomographic scans). RESULTS: Defects in the group were similar, 92 cm (60-176 cm). The autogenous bone group had the longest operating room time (1.1 times longer than the BMP-2 construct group) and the greatest blood loss (1.5 times more than the BMP-2 construct group). Perioperative complications and reoperation rates were lower in autogenous bone (5%) and BMP-2 construct groups (14%) when compared with alloplastic groups (22%-36%). Bone healing was superior with BMP-2 construct and autogenous bone (85%; 90%) versus cryopreserved bone (18%) and minimal healing for alloplastic. CONCLUSIONS: In select cases, a customized bilaminar resorbable construct with BMP-2 resulted in improved bone healing with fewer complications than alloplastic options and without the morbidity and blood loss associated with autogenous bone grafting. This allowed critically sized calvarial defects in adults to be successfully corrected with no residual foreign body.

"Strategic sequences" in adipose-derived stem cell nerve regeneration.

BACKGROUND: Peripheral nerve injuries (PNI) are a major source of morbidity worldwide. The development of cellular regenerative therapies has the potential to improve outcomes of nerve injuries. However, an ideal therapy has yet to be found. The purpose of this study is to examine the current literature key points of regenerative techniques using human adipose-derived stem cells (hADSCs) for nerve regeneration and derive a comprehensive approach to hADSC therapy for PNI. METHODS: A literature review was conducted using the electronic database PubMed to search for current experimental approaches to repairing PNI using hADSCs. Key search elements focused on specific components of nerve regeneration paradigms, including (1) support cells, (2) scaffolds, and (3) nerve conduits. RESULTS: Strategic sequences were developed by optimizing the components of different experimental regenerative therapies. These sequences focus on priming hADSCs within a specialized growth medium, a hydrogel matrix base, and a collagen nerve conduit to achieve neuromodulatory nerve regeneration. hADSCs may exert their neuroregenerative influence through paracrine effects on surrounding Schwann cells in addition to physical interactions with injured tissue. CONCLUSIONS: hADSCs may play a key role in nerve regeneration by acting primarily as support for local neurotrophic mediation and modulation of nerve growth rather than that of a primary neuronal differentiation agent.

Long-term effects of breast aging in patients undergoing explantation: analysis of breast aesthetics from before augmentation to after explantation.

PURPOSE: Although most patients with implants have an uneventful course, some will require explantation. Moreover, women's breasts and their perception of their body habitus change with time. This study covering greater than a 32-year period will address the reconstruction options available after breast implant explantation. METHODS: Augmentation mammoplasty was performed on 42 patients who subsequently underwent explantation. The following data were recorded: age at time of implantation and explantation, length of implant, type, reason for explantation, and decision after explantation. Recommendations were made based on patient preferences, degree of ptosis, clinical history, opinions regarding scars, and breast contour. Reconstruction options were categorized into none, mastopexy, capsulectomy and reaugmentation with saline implants, and mastopexy with immediate or delayed augmentation. RESULTS: The average age of patients at implantation was 32.3 years, 46.8 years at explantation, with a length of implantation of 14.4 years. Thirty-six (86%) of 42 patients received explantation for capsular contracture, 7 (17%) for negative publicity of silicone implants, 7 (17%) for change in body habitus and perception of implants, 6 (14%) for rupture, 5 (12%) for ptosis, and 1 (2.4%) each for synmastia, breast cancer, and painful implants. Sixteen (38%) patients underwent mastopexy after explantation, 15 (36%) underwent no reconstruction after explantation, 6 (14%) with mastopexy and reaugmentation (2 immediate and 4 delayed), 4 (9.5%) with implant exchange, and 1 (2.4%) with mastectomy and reconstruction. All patients demonstrated satisfactory to excellent results. CONCLUSIONS: This study provides long-term results of augmentation mammoplasty by a single surgeon (G.P.G.) evaluating available options and reasonable expectations after explantation. Although most of the augmentation patients have a good outcome, some require removal of implants for a variety of reasons and long-term satisfactory options do exist after explantation.

Staged reconstruction of the lower eyelid following tri-lamellar injury: a case series and anatomic study.

PURPOSE: Lower eyelid scaring and malposition following violation of all three lamellae pose a significant ophthalmologic reconstructive challenge. The purpose of our study was to document a staged approach for this problem using: 1) transconjunctival scar release followed by palatal graft below the tarsal plate and subciliary scar release followed by full-thickness skin graft superficial to the tarsal plate and 2) subsequent autologous fat grafting to the lower eyelid. METHODS: Cadaveric anatomic dissections were performed. Post-traumatic and post-surgical lower eyelid deformities requiring reconstruction were reviewed and outcome assessment was based on symptomatic improvement, perioperative complications, reoperations and long-term follow-up (> 1 year). RESULTS: Cadaver dissections demonstrated consistent lower eyelid tarsal plate and lamellar anatomy for the use of palatal graft and skin grafting. Clinically, 75% cases resulted from full thickness traumatic laceration of the lower eyelid or malar region and 25% of cases occurred after transconjunctival incisions were made for zygomatic maxillary repositioning following partial lower eyelid laceration. Preoperative symptoms of: epiphora, tearing, redness, blurry vision and dryness improved in all patients and complete resolution was seen in 63% of patients. Thirty-seven percent of patients had complications: Redundancy of palatal graft, Partial FTSG loss, cellulitis after fat transfer. CONCLUSIONS: We describe an approach for the scarred and displaced lower eyelid following injury to all three lamellae that provided symptomatic improvement after lower lid scar tissue release, lengthening of the contracted septum, support of the posterior lamellae with a palatal graft and a replacement of anterior lamella with full thickness skin graft.

Total upper and lower eyelid reconstruction using an expanded forehead flap.

Surgical modalities have been described with varying success for the correction of eyelid defects. The reconstructive surgeon must choose the procedure on a case-by-case basis taking into consideration the following criteria: mechanism of injury, comorbidities, and goals of surgery. In this study, we describe a unique case of total upper and lower eyelid reconstruction using an expanded forehead flap technique in an adult patient who underwent left eye enucleation and radiation to the orbit for rhabdomyosarcoma in infancy. After this patient reached adulthood, examination revealed a contracted, anophthalmic left orbit with paper-thin upper and lower eyelids adhering to the concave walls of the orbit. There was absence of significant periorbital soft tissue. The expanded forehead flap procedure achieved our aims of providing not only an aesthetic result, but also adequate soft tissue support for placement of an ocular prosthesis.

Current national incidence, trends, and health care resource utilization of cleft lip-cleft palate.

BACKGROUND: Available reports on the epidemiology of cleft lip, cleft palate, and cleft lip-cleft palate have been numerous yet inconsistent, and have originated only from institutional or regional studies. The need for current national data and the recognition of recent trends exists. METHODS: The authors examined the Kids' Inpatient Database to obtain national information on pediatric orofacial cleft discharges from 1997 to 2007. The authors examined patient and hospital characteristics to discern differences in use of care, hospital charges, type of hospital, untoward events, and other variables among various groups. A detailed investigation searching for significant trends during the 6-year study period was also conducted. RESULTS: Trends appreciated from 1997 to 2007 included (1) an increase in cleft operations performed at teaching hospitals compared with nonteaching hospitals (teaching increased 13.4 percent and nonteaching decreased 15.8 percent); (2) an increase in the mean overall charges (74.5 percent increase; p < 0.001) and a rate of rise higher than that of aggregate charges (60 percent; p < 0.001); and (3) a lower rate of perioperative complications in teaching hospitals from 2000 to 2007, ranging from 14 to 27 percent less than in nonteaching hospitals. CONCLUSIONS: The authors' data show that there is a current trend of cleft patients receiving treatment at teaching hospitals, with higher costs and decreasing complications. An understanding of such trends and disparities in resource use among various patient, hospital, and geographic settings is important for physicians and policy makers.

Economic advantages to a distraction decision tree model for management of neonatal upper airway obstruction.

BACKGROUND: Neonatal upper airway obstruction demands urgent attention. Tracheostomy can prove to be lifesaving but has morbidities. Recently, the authors found reduced morbidity/mortality when using a distraction decision tree model compared with conventional "case-by-case" management. In this current study, the authors assess the long-term costs of (1) a decision tree model versus conventional treatment and (2) tracheostomy versus distraction osteogenesis. METHODS: An inpatient cost-matrix analysis study on neonates with upper airway obstruction and micrognathia was performed (n=149). In Part I, conventionally treated neonates managed on a case-by-case basis received home monitoring or a tracheostomy. Decision tree model-managed newborns had specialist consultations and diagnostic testing to determine whether home monitoring, tracheostomy, or distraction osteogenesis would be implemented. In Part II, tracheostomy treatment was compared directly to distraction osteogenesis. RESULTS: In Part I (conventional versus decision tree model), taking into account the costs of the distraction, tracheostomy, hospital stay, diagnostic studies, physician fees, and emergency department visits, the total per patient treatment cost was 1.5 greater in the conventional treatment group ($332,673) compared with the decision tree model ($225,998) (p<0.05). In Part II (tracheostomy versus distraction osteogenesis), the total per-patient treatment cost in the tracheostomy group was two times greater than in the distraction group ($382,246 versus $193,128) (p<0.05). CONCLUSIONS: In treating newborns with micrognathia and upper airway obstruction, a decision tree model with mandibular distraction decreases long-term health care costs compared with conventional treatment. Furthermore, when comparing distraction to tracheostomy, similar decreases in long-term health care costs occurred.

Reconstruction of the irradiated orbit with autogenous fat grafting for improved ocular implant.

BACKGROUND: Soft-tissue augmentation of irradiated sites has posed numerous challenges to craniofacial reconstructive surgeons. Irradiated and enucleated orbits are challenging, especially when attempting to prime the orbit for a future prosthesis. The authors document a series of successful autologous fat injections in irradiated orbits of patients with primary tumors of the orbit, using the Coleman fat grafting technique. METHODS: Six patients underwent serial autologous fat grafting after irradiation to the orbit and enucleation. The amount of fat transferred to the periorbita was measured. For measuring fat retention, the authors used surface area analysis of the images and three-dimensional photography. Outcomes were measured by physicians and patients on a scale of 0 to 4. Also, fat retention in these irradiated patients was compared with that of nonirradiated patients who had malar fat injections for cosmetic purposes. RESULTS: Patients had a mean of three fat injection procedures with a mean of 24 cc per injection. After serial fat grafting, four of the six patients were successfully fitted for orbital prostheses. Outcomes measured by physicians and patients were a mean of 3.1 and 3.3, respectively. Retention in the postoperative period was initially similar between the nonirradiated orbit (81 percent retention) and the irradiated orbit (78 percent retention) but differed at long-term follow-up (72 percent versus 38 percent). CONCLUSION: Autologous fat grafting may be used for improved ocular implantation to the irradiated enucleated orbit.

Successful staged correction of transsphenoidal encephaloceles.

BACKGROUND: Transsphenoidal encephaloceles are rare cystic herniations of meninges, cerebrospinal fluid, and/or brain matter resulting from incomplete closure of the cranial base and may be associated with midfacial, central nervous system, and endocrine anomalies. Although some centers choose not to operate because of risks, the authors document their staged operative approach to avoid recurrent meningitis, progressive neurologic decline, and other symptoms. METHODS: Patients with symptomatic transsphenoidal encephaloceles who underwent staged treatment with intracranial and transpalatal cyst correction, facial bipartition, and cleft palate repair were studied (n = 4). Outcome measures included perioperative complications, recurrence, interdacyron distance comparison, and speech and developmental assessments. RESULTS: The authors' staged correction of transsphenoidal encephaloceles as detailed in this article proved successful in all four patients, with no recurrence of meningitis, no cerebrospinal fluid leakage, alleviation of headaches, aesthetic improvement, and no encephalocele relapse. Skeletal correction by computed tomographic scan showed correction of interdacyron distance with a mean 22-mm reduction (56 percent). After the initial procedure of encephalocele correction, speech scores fell from 2.2 (borderline incompetent) to 7.9 (incompetent) but improved after the cleft palate repair and speech therapy to 1.4 (borderline competent). Follow-up developmental tests showed normal global evaluations in memory and attention skills in all but one patient (who had persistent deficiencies consistent with preoperative evaluations). CONCLUSION: A staged operative treatment for symptomatic transsphenoidal encephaloceles offers functional and morphologic correction.

Correction of hydrocephalic macrocephaly with total cranial vault remodeling and molding helmet therapy.

BACKGROUND: Hydrocephalic macrocephaly is a rare problem that may result in cranial vault instability, difficulties with posture and movement, and hindrance in neurological development. The authors studied the outcomes of hydrocephalic macrocephalic cases in which patients underwent single-stage total cranial vault remodeling and postoperative helmet therapy. METHODS: Consecutive patients with hydrocephalic macrocephaly treated at University of California, Los Angeles from 2000 to 2007 were studied (n = 8). Perioperative examinations (head circumference), lateral cranial radiographs (anteroposterior, lateral, and cranial height measurements) and three-dimensional computed tomography scans (cranial volume) were used to access cranial reduction. Developmental testing, physician evaluations (Whitaker score), and parental surveys were used. RESULTS: Improvements in mean head circumference (from 58.8 cm to 48.9 cm, or 17 percent reduction), and cranial volume measurements (from 1924 cc to 1212 cc, or 35 percent reduction) were seen in patients after the procedure. In addition, developmental testing scores improved in half, or four of eight patients. Whitaker score was 1.9 with only one case requiring revision but five needing subsequent shunts. Surveys showed a high satisfaction rate with final appearance and ease of childcare. CONCLUSION: For the rare patient with hydrocephalic macrocephaly, treatment with total cranial vault remodeling with postoperative helmet therapy may be successful, but follow-up monitoring and subsequent ventriculoperitoneal shunting may be necessary.

Duodenal bulb mucosa with hypertrophic gastric oxyntic heterotopia in patients with zollinger ellison syndrome.

Objectives. Zollinger-Ellison Syndrome (ZES) results in hypersecretion of gastric acid (via gastrinoma) leading to peptic ulcers, diarrhea, and abdominal pain. We describe the novel discovery of hypertrophic, heterotopic gastric mucosa in the proximal duodenal bulb in patients with ZES, which we hypothesize results in an increased incidence of postbulbar ulcers in patients with ZES (a mechanism previously unreported). We determined the incidence of the novel finding of duodenal gastric oxyntic hypertrophic heterotopia (GOH) in patients with ZES. Methods. Seven patients with ZES were enrolled. The diagnosis of ZES was established by hypergastrinemia, gastric acid hypersecretion, and a positive secretin test or based on biopsy specimens (evaluated via tissue staining). Basal acid output (BAO) and baseline gastrin secretion were determined by established methods. Endoscopic examinations with methylene blue staining and biopsy of the gastric and duodenal mucosa were conducted in all patients every 3-6 months for an average of 5 years. Results. The duodenal mucosa demonstrated hypertrophic GOH in 5 out of 7 patients with ZES and an intact stomach and duodenum. Biopsies from the bowel mucosa demonstrated patchy replacement of surface epithelium by gastric-type epithelium with hypertrophic oxyntic glands in the lamina propria in 5 patients. Two of the patients had no evidence of GOH in the duodenal bulb. Patients with GOH had an average serum gastrin level of 1245 pg/mL and BAO of 2.92 mEq/hr versus 724 pg/mL and 0.8 mEq/hr in patients without GOH. Conclusions. This study demonstrated the presence of duodenal mucosa with GOH in 5 out of 7 patients with ZES and an intact stomach and duodenum. The presence of hypertrophic and heterotopic gastric mucosa is proposed to result from increased gastrin levels and may contribute to the increased incidence of postbulbar ulcers in these patients.

The relationship between preoperative cervical alignment and postoperative spinal cord drift after decompressive laminectomy and arthrodesis for cervical spondylotic myelopathy.

BACKGROUND: Cervical spondylotic myelopathy represents a debilitating disorder, often resulting in significant neurological impairment over time. Cervical laminectomy has enjoyed a successful track record in the surgical management of these patients. Little is understood regarding the significance of postdecompressive migration of the spinal cord in relation to patient outcome. METHODS: Preoperative and postoperative cervical spine MRIs of 28 patients who underwent cervical laminectomy and fusion for the treatment of CSM were reviewed. Radiographic parameters including preoperative cervical alignment, LDI, space available at the level cepahlad/caudad to the decompression, percent spinal cord expansion at the radiographically most compressed level, and spinal cord drift to the midpoint of the spinal cord were measured and subsequently analyzed for statistical correlation. The recovery rate based on the mJOA score was calculated for each patient and analyzed for correlation with spinal cord drift. RESULTS: The Cobb angle C2-7, cervical spinal angle, and CCI represented tightly correlated measures of cervical alignment. The preoperative cervical alignment did not statistically correlate with postoperative spinal cord drift. No statistical correlation was revealed between postdecompressive spinal cord drift and recovery rate. CONCLUSIONS: Preoperative cervical alignment does not statistically correlate with postoperative spinal cord drift in patients undergoing multisegmental decompressive laminectomy and fusion for CSM. The observation of significant posterior shifting of the spinal cord in the context of straight or kyphotic preoperative alignment suggests that posterior decompression and arthrodesis represent a viable option in the surgical management of patients with CSM with nonlordotic preoperative alignment.

Pfeiffer syndrome twins: despite improved correction in one twin, growth disturbance results in similar need for subsequent monobloc advancement.

BACKGROUND: Twins with Pfeiffer syndrome (or acrocephalosyndactyly) had a similar phenotypic appearance with findings of classic or type 1 Pfeiffer syndrome, including bicoronal and sagittal craniosynostoses, midface hypoplasia, and broad thumbs/toes. We document their treatment with 2 monobloc advancements and discuss growth disturbances in craniofacial dysostosis. METHODS: At 6 months, both twins underwent release of multisuture (bilateral coronal and sagittal) fusions for improvement of scaphocephalic shape and multisuture release; however, one twin had a more aggressive procedure with advancement of the frontal-orbital region. Despite improved initial correction by one twin, at 5 years of age, both twins presented with midface hypoplasia and exorbitism and underwent a monobloc distraction procedure with similar 20-mm advancements. Comparative analysis by our craniofacial multidisciplinary team included perioperative reports, computed tomographic scans, cephalograms, parent questionnaires, and physician surveys. RESULTS: Both twins had an improved confidence interval scores from 84 to 68 and 82 to 69 postoperatively. In 6-month follow-up, the Whitaker score of the first twin was 2.8, whereas that for the second twin with the frontal-orbital advancement was 1.2. Preschool expressive and receptive tests yielded 97 and 95, and 97 and 98, and developmental testing was similar between the twins. Global evaluations were equivalent to age-matched controls, and memory and attention skills were within normal limits. Parental surveys showed a high level of satisfaction after all procedures in both twins. CONCLUSIONS: Our study demonstrates that the phenotypic outcome for both twins remained unchanged when comparing a more aggressive surgery to less aggressive surgery as an infant. The genetic mutation may have overridden the different surgical interventions. Both twins ultimately required 2 subsequent monobloc corrections.

The effect of age on osteogenic, adipogenic and proliferative potential of female adipose-derived stem cells.

Human adipose tissue is an ideal source of autologous cells that is both plentiful and easily obtainable in large quantities through the simple surgical procedure of liposuction. The stromal vascular fraction of adipose tissue contains a stem cell population, adipose-derived stem cells (ASCs), capable of adipogenic, osteogenic, myogenic and chondrogenic differentiation. These cells have already been recognized to possess great therapeutic potential in tissue engineering and regeneration. In this study, we sought to determine the effect of donor age on the growth kinetics and differentiation potential of ASCs. For this, ASCs were isolated from liposuctioned adipose tissue obtained from female patients in the age range 20-58 years. Population doubling time was calculated over 2 weeks and differentiation potential was determined by assaying for adipogenesis and osteogenesis. ASCs obtained from older donors appeared to have a slower rate of proliferation, but this relationship was not significant. While adipogenic potential was unrelated to donor age, a distinct relationship between donor age and osteogenic potential was observed. The aetiology of this age-dependent change in osteogenic potential was not due to any changes in the number of precursors with osteogenic capacity in the adipose sample. These findings have important implications for emerging cell-based therapeutic strategies, such as tissue engineering, in addition to treatment of various metabolic bone disorders including osteoporosis.

Sagittal synostotic twins: reverse pi procedure for scaphocephaly correction gives superior result compared to endoscopic repair followed by helmet therapy.

A unique situation of twins with similar sagittal synostosis pathology who underwent different surgical corrective procedures allowed us an opportunity to compare an endoscopic technique to the more traditional technique of a modified cranial vault remodeling (CVR). At 4 months of age, 1 twin underwent an endoscopic-assisted extended strip craniectomy with postoperative helmet therapy for 12 months, and the other underwent a reverse pi CVR procedure. Cephalic index, the Whitaker Aesthetic score, and developmental tests were used for comparison during a 6-year follow-up. The modified CVR had a superior outcome compared to the endoscopic procedure with regard to cephalic index measurements (CVR = 77; endoscopic = 63; P < 0.05) and the Whitaker score (CVR = 1 or no revisions necessary; endoscopic = 2.3 or minor to major bony work required for correction). Patients had similar intelligence quotient test scores; however, the endoscopic patient had lower scores in both preschool tests and global evaluations compared with the normal scores of the CVR patient. The modified CVR procedure was superior to the endoscopic procedure, at least in these twins with sagittal synostosis.

Genomewide clonal analysis of lethal mutations in the Drosophila melanogaster eye: comparison of the X chromosome and autosomes.

Using a large consortium of undergraduate students in an organized program at the University of California, Los Angeles (UCLA), we have undertaken a functional genomic screen in the Drosophila eye. In addition to the educational value of discovery-based learning, this article presents the first comprehensive genomewide analysis of essential genes involved in eye development. The data reveal the surprising result that the X chromosome has almost twice the frequency of essential genes involved in eye development as that found on the autosomes.