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Competent speech requires closure of the velopharyngeal sphincter by dynamic apposition of the velum and posterior and lateral pharyngeal walls. An accurate estimation of lateral pharyngeal wall motion is an important determinant in the planning and the outcome of any operation to correct velopharyngeal insufficiency (VPI). The purpose was to compare the assessment of lateral pharyngeal wall movement by videofluoroscopy (VP) versus nasopharyngoscopy (NP).The authors retrospectively reviewed the charts of 269 consecutive patients in our cleft lip/palate clinic from 1982 to 2008 and culled those treated with a pharyngeal flap for VPI. The authors included patients who were evaluated preoperatively by both VP and NP, and had studies of suitable quality. Percentage of lateral pharyngeal wall motion was estimated with each technique and compared for each patient.The authors identified 25 patients who underwent both VP and NP at the same median age (4.7 years). The estimated percentage of lateral pharyngeal wall motion between the 2 techniques was significantly different ( P0.001). Average lateral pharyngeal wall motion was estimated to be 59±25% (range: 5%-90%) by VP and only 40%±25% (range: 0%-95%) during NP.VP and NP are complementary, but assessment of lateral pharyngeal wall motion can vary between the 2 methods. The surgeon should be aware of the difference in estimated lateral pharyngeal wall movement when planning a procedure to correct VPI.

This report summarizes the recent activity of the International Stem Cell Banking Initiative held at Harvard Stem Cell Institute, Boston, MA, USA, on June 18, 2017. In this meeting, we aimed to find consensus on ongoing issues of quality control (QC), safety, and efficacy of human pluripotent stem cell banks and their derivative cell therapy products for the global harmonization. In particular, assays for the QC testing such as pluripotency assays test and general QC testing criteria were intensively discussed. Moreover, the recent activities of global stem cell banking centers and the regulatory bodies were briefly summarized to provide an overview on global developments and issues. stem cells 2019;37:1130–1135, Photo of the 2017 Boston meeting, celebrating 10 years of International Stem Cell Banking Initiative activities.

Objective: To assess whether children with torticollis have quantifiably greater facial asymmetry than their age-matched controls using 3-dimensional (3D) photogrammetry. Design: We retrospectively analyzed patients diagnosed with torticollis and age-matched volunteers who underwent 3D photogrammetry of their faces. We calculated the root mean square deviation (RMSD) between native and reflected facial images, as a measure of asymmetry. Two observers independently measured RMSD values for all study participants. The Spearman correlation coefficient evaluated interobserver reliability. The Wilcoxon rank-sum test with Bonferroni adjusted P values for multiple comparisons. Setting: Institutional. Participants: Twenty patients diagnosed with torticollis and 12 age-matched volunteers. Patients were analyzed on a computer database and volunteers were selected and consented in the hospital. We excluded patients with a history of facial trauma, facial operations, or other craniofacial diagnoses. Interventions: Facial surface scans were obtained using the Canfield Vectra stereophotogrammetry system. The technology captures surface anatomy without radiation. Main Outcome Measures: RMSD comparisons between patients with torticollis and age-matched controls. Results: Compared to controls, patients with torticollis had statistically significant greater full face, upper third, and middle third facial asymmetry. There was a trend toward greater asymmetry of the lower facial third. Conclusions: We used 3D photogrammetry to quantitate facial asymmetry from torticollis. We found greater asymmetry in patients with torticollis than in their unaffected peers. All areas of the face appeared to be affected, though the asymmetry in the lower facial third just failed to reach significance.

Facial symmetry is a fundamental goal of plastic surgery, yet some asymmetry is inherent in any face. Three-dimensional photogrammetry allows for rapid, reproducible, and quantitative facial measurements. With this tool, the authors investigated the relationship between age and facial symmetry.The authors imaged normal subjects using three-dimensional photogrammetry. Facial symmetry was calculated by identifying the plane of maximum symmetry and the root-mean-square deviation. Regression analysis was used to assess the relationship between age and symmetry. Subgroup analyses were performed among facial thirds.The authors imaged 191 volunteers with an average age of 26.7 ± 22.2 years (range, 0.3 to 88 years). Root-mean-square deviation of facial symmetry clustered between 0.4 and 1.3 mm (mean, 0.8 ± 0.2 mm). The authors found a significant positive correlation between increasing age and asymmetry (p0.001; r = 0.66). The upper, middle, and lower facial third's average root-mean-square deviations were 0.5 ± 0.2 mm (range, 0.2 to 1.2 mm), 0.6 ± 0.2 mm (range, 0.2 to 1.4 mm), and 0.6 ± 0.2 mm (range, 0.2 to 1.2 mm), respectively. Asymmetry also increased with age across all facial thirds (p0.001).Facial asymmetry increases with age in each facial third, with a greater asymmetry and increase in asymmetry in the lower two-thirds. Contributing factors may include asymmetric skeletal remodeling along with differential deflation and descent of the soft tissues. The observed correlation between increasing facial asymmetry and age may be a useful guide in plastic surgery to produce age-matched features.

Objective: To evaluate 3-dimensional (3-D) photogrammetry as a tool for assessing the postoperative head shape of patients who had undergone cranial vault remodeling for metopic synostosis. Design: We prospectively analyzed images of patients with metopic craniosynostosis who had undergone anterior cranial vault remodeling and age-matched controls. To ensure standardized facial orientation, each 3-D image was positioned to “best fit” the preoperative face by aligning 6 soft tissue landmarks. Forehead measurements were taken from a standardized position behind the surface of the face to landmarks placed in a ray configuration across the forehead. Setting: Academic teaching hospital. Patients, Participants: Thirteen pediatric patients with metopic craniosynostosis who had undergone anterior cranial vault remodeling and age-matched controls. Interventions: Images were taken preoperatively, immediately postoperatively, and over 1-year postoperatively. Main Outcome Measures: Forehead contours preoperatively and postoperatively, with statistics performed using a multivariate analysis of variance shape analysis. Results: Mean postoperative follow-up was 1.8 (0.6) years. The average distance from the origin to forehead landmarks was 55.1 (3.4) mm preoperatively, 59.3 (0.7) mm immediate postoperatively, 59.1 (1.0) mm 1-year postoperatively, and 59.4 (0.6) mm in controls. Postoperative metopic forehead contours varied significantly from preoperative contours ( P < .01), while there was no statistical difference between the 2 postoperative time points ( P = .70). One-year postoperative patients were not significantly different from their age-matched controls ( P > .99). Conclusions: Preoperative metopic forehead contours varied significantly from postoperative contours. Cranial reconstructions approximated the foreheads of normal controls, and reconstructions were stable at more than 1-year follow-up.

ObjectiveTo evaluate nasal symmetry using three-dimensional photogrammetry following primary tip rhinoplasty with or without an internal splint in patients with unilateral complete cleft lip/palate.DesignWe captured three-dimensional images of patients with unilateral complete cleft lip/palate who underwent nasolabial repair by rotation-advancement of the lip and primary tip rhinoplasty, either with or without an internal resorbable splint, and normal control subjects. We assessed nasal symmetry by identifying the plane of maximum symmetry and the root-mean-square deviation between native and reflected surfaces.Patients/ParticipantsWe imaged 38 controls and 38 subjects with repaired unilateral complete cleft lip/palate (20 with, 18 without an internal splint).ResultsNasal asymmetry root-mean-square deviation clustered between 0.19 and 0.50 mm (median = 0.24 ± 0.08 mm) for controls; whereas, those with repaired unilateral complete cleft lip/palate ranged from 0.4 to 1.5 mm (median = 0.75 ± 0.40 mm). Although root-mean-square deviation ranges overlapped, patients with repaired unilateral complete cleft lip/palate had significantly greater asymmetry than controls ( P < .001). We found no difference in asymmetry between patients with or without an internal splint ( P = .5).ConclusionsThree-dimensional photogrammetry was used to successfully compare symmetry among different patient and control groups. Although “normal” nasal symmetry was attained in some patients following cleft lip/nasal repair, most had persistent asymmetry compared with normal controls. Placement of a resorbable internal splint did not improve symmetry in patients with unilateral complete cleft lip/palate.

Postadenotonsillectomy velopharyngeal incompetence/insufficiency/dysfunction (VPI) is an uncommon but potentially surgically challenging problem. We report a child without cleft palate who developed severe palatoglossal arch cicatrix and VPI after adenotonsillectomy, and describe bilateral palatoglossal arch z-plasty to restore palatal function and speech.

A study of a 22-year-old male who was assaulted and sustained a left orbital floor blowout fracture was presented in this study. The orbital floor was repaired with a titanium-reinforced porous polyethylene implant. Two years postoperatively, the patient sustained repeated left orbital trauma. The orbital floor implant remained stable while the medial wall blew out.

Langerhans cell histiocytosis (LCH) commonly affects the craniofacial skeleton and prognosis depends on location, extension, and recurrence of the disease. The aim of our study is to better define the treatment of single craniofacial lesions, as to date different treatment modalities have been suggested and recurrence rates for both unifocal and multifocal bony lesion range between 10% and 70%. Between 2000 and 2014, we retrospectively reviewed clinical findings, anatomic location, extent of the disease, therapy, and outcomes in 24 pediatric patients with histologically confirmed LCH. Seventeen patients (67%) had craniofacial involvement, of which 13 had single system involvement and 4 had multisystem involvement. Eight patients (33%) had no craniofacial involvement. Eleven patients affected by unifocal cranial lesions were treated with resection and reconstruction. One patient with a unifocal mastoid lesion was treated with chemotherapy alone (vinblastine and prednisone). Four patients with mandible lesions were treated with curettage alone.There were no recurrences in patients treated with excision alone. One patient (25%) treated with curettage recurred. Two patients with diffuse disease manifested organ dysfunction and diabetes insipidus. Chemotherapy was tolerated in 12 patients treated.Our findings suggest that resection of isolated LCH lesions of the cranium is safe and chemotherapy is effective and well tolerated for nonsurgical cases.

The authors present the case of a 32-year-old patient treated for a left, isolated zygomatic fracture following assault. The injury was reduced without fixation via the Keene approach. The same patient presented to the emergency room 16 months later with a right-sided fracture similar to the previous contralateral injury. This fracture was left untreated. Repeated assaults over a 4-year period provide us with a natural history of both injuries, allowing for comparison between the 2 approaches. The authors found that reduction of the arch without fixation led to an outcome without palpable or visible deformity and no impaired mastication. Additionally, considering etiology of injury, such as alcohol or drug use, treatment may provide an important point of intervention to prevent recurrence.

Traumatic orbital roof fractures are rare and are managed nonoperatively in most cases. They are typically associated with severe mechanisms of injury and may be associated with significant neurologic or ophthalmologic compromise including traumatic brain injury and vision loss. Rarely, traumatic encephalocele or pulsatile exophthalmos may be present at the time of injury or develop in delayed fashion, necessitating close observation of these patients. In this article, we describe two patients with minimally displaced blow-in type orbital roof fractures that were later complicated by orbital encephalocele and pulsatile exophthalmos, prompting urgent surgical intervention. We also suggest a management algorithm for adult patients with orbital roof fractures, emphasizing careful observation and interdisciplinary management involving plastic surgery, neurosurgery, and ophthalmology.

The dorsal cutaneous appendage, or human tail, is a rare congenital anomaly that can span a broad spectrum of tissue and spinal involvement. Associated occult spinal anomalies may not be limited to the lumbar region and can occur at any point along the length of the spinal column. Five cases of human tails are presented with varying degrees of soft tissue anomalies, spinal dysraphism, and neurologic symptoms. Patients range in age from newborn to 22 years. The spectrum of pathology includes those isolated to skin and subcutaneous tissue as well as underlying spinal dysraphism and tethered cord. Surgical treatment ranged from simple tail excisions to microsurgical debulking and spinal cord detethering. The clinical presentation of a lumbosacral appendage should prompt the workup for underlying spinal anomalies at all levels of the spinal cord. Without treatment, the neurologic sequelae of occult spinal dysraphism can be progressive. With proper preoperative evaluation and interdisciplinary treatment, the soft tissue anomaly as well as the spinal dysraphism can be surgically treated to restore function or prevent further neurologic compromise.

Use of clinical-grade human induced pluripotent stem cell (iPSC) lines as a starting material for the generation of cellular therapeutics requires demonstration of comparability of lines derived from different individuals and in different facilities. This requires agreement on the critical quality attributes of such lines and the assays that should be used. Working from established recommendations and guidance from the International Stem Cell Banking Initiative for human embryonic stem cell banking, and concentrating on those issues more relevant to iPSCs, a series of consensus workshops has made initial recommendations on the minimum dataset required to consider an iPSC line of clinical grade, which are outlined in this report. Continued evolution of this field will likely lead to revision of these guidelines on a regular basis.

BACKGROUND Large numbers of international children with cleft lip-cleft palate are adopted in the United States; many underwent their first operation before arrival. METHODS The authors reviewed records of internationally adopted children with cleft lip-cleft palate treated by one surgeon over 25 years. This study focused on anatomical types, frequency/methods of repair, correction of unrepaired deformities, and secondary procedures in this country. RESULTS Of 105 internationally adopted children with cleft lip-cleft palate, 91 percent were Asian; 75 percent had labial or labiopalatal closure in their native country. Of repaired unilateral cleft lips, 43 percent required complete revision, 49 percent required minor revisions, and 8 percent required no revision. All repaired bilateral cleft lips were revised; 90 percent were complete and 10 percent were minor. "Delayed" primary nasal correction was always necessary in both unilateral and bilateral forms. Labial closure was scheduled first in young infants with an unrepaired unilateral defect, whereas palatal closure took precedence in older children. Premaxillary setback and palatoplasty were scheduled first in older children with unrepaired bilateral cleft lip-cleft palate. Of children arriving with repaired palate, 43 percent required a pharyngeal flap. CONCLUSIONS Whenever cleft lip-cleft palate is repaired in another country, revision rates are high for both unilateral and bilateral types. Nevertheless, primary closure in the native country may increase the likelihood for adoption. Traditional surgical protocols often are altered for an adoptee with an unrepaired cleft lip-cleft palate, particularly the sequence of labial and palatal closure, depending on the child's age and type of defect.

The orbital roof forms part of the anterior skull base and is positioned for potential concomitant ophthalmologic and neurologic injury. Despite potential morbidity and mortality, orbital roof fractures have garnered little attention compared with orbital floor fractures. The authors' purpose is to review and describe key points when treating these fractures.The authors reviewed 1171 consecutive patient at a trauma center with orbital or skull base fractures from 2009 to 2011. Patient demographics, mechanism of injury, associated injuries, treatment, outcomes, and complications were recorded.Among the 1171 patients, the authors identified 60 with an orbital roof fracture (5 percent). All were evaluated by plastic surgery, neurosurgery, and ophthalmology. Average age was 38.1 years, and the male-to-female ratio was 4:1. Frequent mechanisms of injury were fall (33 percent), followed by assault (25 percent). Concomitant craniofacial skeletal fractures were common (87 percent), as were ophthalmologic injuries (47 percent), and traumatic brain injury with intracranial hemorrhage (65 percent). Six patients (10 percent) required operative repair of the orbital roof, all of whom had a dural laceration and cerebrospinal fluid leak. Most patients (90 percent) had minimal displacement and no clinically evident cerebrospinal fluid leak and were treated with observation without complications.Orbital roof fractures are a less common but potentially serious craniofacial injury. Most can be safely observed; however, intracranial or intraorbital injury may warrant surgical intervention to remove impinging bony fragments, repair dura, or reconstruct the orbital roof. An interdisciplinary approach with plastic surgery, ophthalmology, and neurosurgery is crucial to providing comprehensive care.Therapeutic, IV.

The natural history of unrepaired craniosynostosis is not well defined. Delayed surgical intervention carries greater risk of postoperative complications and its functional benefits for older patients are poorly characterized. The authors reviewed patients in whom children presented beyond 1 year of age to better understand the natural history of craniosynostosis, and the risk-benefit relationship for delayed reconstruction.After institutional IRB approval the authors conducted a retrospective review of patients who presented after 1 year of age with craniosynostosis. Type of craniosynostosis, age at evaluation, medical history, surgical findings, developmental abnormalities, ophthalmologic findings, and clinical course were reviewed.Ten patients with delayed presentation for craniosynostosis were identified. The mean age at presentation was 6.8 years ± 4.2 years (range, 3-17 years). Seven of 10 patients presented with developmental delay. Five patients presented with debilitating headaches. Five patients presented with comorbid Chiari malformations, 3 of whom required surgical decompression. Two patients had papilledema. Four patients underwent intracranial pressure monitoring, with elevated pressures found in 3 patients. Six patients underwent delayed cranial vault remodeling. There were no peri- or postoperative complications, including infection or residual bony defects, in those undergoing delayed operation.Children who present in a delayed fashion with unrepaired craniosynostosis have high rates of debilitating headaches, developmental delays, head shape anomalies, and Chiari malformation. Five patients reporting preoperative headaches noted subjective improvements in headaches following delayed operation. Cranial reconstruction can be safely performed at an older age and is appropriate to consider in carefully selected patients for aesthetic and/or functional concerns.

Background The authors' purpose was to document speech outcome after cleft palate repair in patients with syndromic versus nonsyndromic Robin sequence. Results of secondary correction of velopharyngeal insufficiency using a superiorly based pharyngeal flap or double-opposing Z-palatoplasty are also reported. Methods Charts of patients with Robin sequence and cleft palate between 1980 and 2007 were reviewed. Data collected included date of birth, sex, syndrome/association, cleft palatal type (Veau I or II), age at palatoplasty, incidence of palatal fistula, postoperative speech assessment, videofluoroscopic results, need for secondary operation for velopharyngeal insufficiency, and type of secondary operation (pharyngeal flap or double-opposing Z-palatoplasty). Results The authors identified 140 patients with Robin sequence who had palatal closure. Postoperative speech evaluation was available for 96 patients (69 percent). A syndrome or association was identified in 42 patients (30 percent). Primary palatoplasty was successful in 74 patients (77 percent); speech was characterized as competent and competent to borderline competent. The authors found a significantly higher incidence of velopharyngeal insufficiency following palatal repair for syndromic (38 percent) than nonsyndromic Robin sequence (16 percent). (p = 0.039). In patients with velopharyngeal insufficiency, competent or borderline competent speech was determined after double-opposing Z-palatoplasty (two of five patients) or pharyngeal flap (eight of 10 patients). Conclusions The rate of velopharyngeal insufficiency in syndromic Robin sequence is significantly greater than in nonsyndromic Robin sequence. The authors prefer pharyngeal flap for velopharyngeal insufficiency in patients with Robin sequence, whether syndromic or nonsyndromic, without retrognathism or signs/symptoms of obstructive sleep apnea.

The World Health Organization estimates that the burden of surgical disease due to war, self-inflicted injuries, and road traffic incidents will rise dramatically by 2020. During the 2009 Harvard Humanitarian Initiative's Humanitarian Action Summit (HHI/HAS), members of the Burden of Surgical Disease Working Group met to review the state of surgical epidemiology, the unmet global surgical need, and the role international organizations play in filling the surgical gap during humanitarian crises, conflict, and war. An outline of the group's findings and recommendations is provided.

The neuropeptide, substance P (SP), up-regulates nitric oxide production (NO). The purpose of this study was to determine whether SP enhances response to cutaneous injury in nitric oxide synthase knockout (NOS null) mice.We studied mice with targeted deletions of the 3 NOS genes, neuronal NOS, inducible NOS, or endothelial NOS. Full thickness dorsal wounds were treated daily (d 0-6) with topical SP or normal saline (NaCl). Wounds were analyzed by flow cytometry for macrophage, leukocyte, endothelial, and dendritic cells. Healing time and wound epithelialization were compared using analysis of variance.Wound closure in the 3 NOS null mice was slower than the control mice (P0.05). SP treatment enhanced wound closure in NOS null mice (P0.02). NOS null wounds exhibited reduced inflammation. SP increased macrophage, leukocyte, and dendritic cell densities at d 3 and d 7 (P0.05) in all NOS null mice. SP increased endothelial cell number in neuronal NOS and inducible NOS null mice, but not in endothelial NOS null mice (P0.05).SP ameliorated the impaired wound healing response observed in NOS null mice by enhancing wound closure kinetics and epithelialization. SP increased inflammatory cell density in the wounds supporting the essential role of inflammatory cells, especially macrophages, in wound repair.

The primary objective of cleft palate repair is velopharyngeal competence without fistula. The reported incidence of fistula and velopharyngeal insufficiency (VPI) is variable. Our purpose was to assess the senior surgeon's 29-year palatoplasty experience with respect to incidence of fistula and VPI. Our hypotheses were that VPI is related to (1) age at palatoplasty, (2) cleft palate type, and (3) VPI and palatal fistula incidence decrease with the surgeon's experience. We reviewed the records of all children with cleft palate treated by the senior author between 1976 and 2004. Cleft palate was categorized according to Veau. Palatoplasty was performed on 449 patients, using a 2-flap technique with muscular retropositioning. The mean age at palatoplasty was 11.6 +/- 4.9 months (range, 7.0-46.4 months). The incidence of palatal fistula was 2.9%, and velopharyngeal sufficiency was found in 85.1% of patients. We found a significant association between age at palatoplasty and VPI (P = 0.009, odds ratio, 1.06 [95% confidence interval, 1.02-1.10]). Velopharyngeal insufficiency was also associated with the Veau hierarchy (P = 0.001). Incidence of VPI was independent of surgeon experience (P = 0.2). In conclusion, the incidence of palatal fistula was low. Velopharyngeal insufficiency was associated with increasing age at palatoplasty and with the Veau hierarchy.

Improved self-image and psychological well-being after breast reconstruction are well documented. To determine methods that optimized results with minimal morbidity, the authors examined their results and complications based on reconstruction method and timing.The authors reviewed all breast reconstructions after mastectomy for breast cancer performed under the supervision of a single surgeon over a 6-year period at a tertiary referral center. Reconstruction method and timing, patient characteristics, and complication rates were reviewed.Reconstruction was performed on 240 consecutive women (94 bilateral and 146 unilateral; 334 total reconstructions). Reconstruction timing was evenly split between immediate (n = 167) and delayed (n = 167). Autologous tissue (n = 192) was more common than tissue expander/implant reconstruction (n = 142), and the free deep inferior epigastric perforator was the most common free flap (n = 124). The authors found no difference in the complication incidence with autologous reconstruction, whether performed immediately or delayed. However, there was a significantly higher complication rate following immediate placement of a tissue expander when compared with delayed reconstruction (p = 0.008). Capsular contracture was a significantly more common late complication following immediate (40.4 percent) versus delayed (17.0 percent) reconstruction (p0.001; odds ratio, 5.2; 95 percent confidence interval, 2.3 to 11.6).Autologous reconstruction can be performed immediately or delayed, with optimal aesthetic outcome and low flap loss risk. However, the overall complication and capsular contracture incidence following immediate tissue expander/implant reconstruction was much higher than when performed delayed. Thus, tissue expander placement at the time of mastectomy may not necessarily save the patient an extra operation and may compromise the final aesthetic outcome.

To identify clinical characteristics of burn patients requiring emergent orbital decompression for vision-threatening orbital compartment syndrome.A retrospective review of 28 burn patients at a trauma center provided data regarding demographics, physical examination findings, and resuscitation fluid volumes. Patients requiring orbital decompression were compared with those who did not, using t tests and Fisher exact test. Linear regression was used to test for an association between peak intraocular pressure and fluid volume. Logistic regression was used to assess associations between need for orbital decompression and fluid volume.Eight of 28 patients required emergent orbital decompression, which immediately reduced intraocular pressure from 59.4 +/- 15.9 mm Hg to 28.6 +/- 8.2 mm Hg (p0.001). There was a positive relationship between fluid volume in the first 24 hours and peak intraocular pressure (p0.001). Patients who were treated with orbital decompression were resuscitated with a higher fluid volume in the first 24 hours than those who were not (37,218 +/- 14,405 ml versus 24,649 +/- 12,339 ml, p = 0.015). This was no longer statistically significant when adjusted for periocular burns. The relative risk for undergoing orbital decompression in patients receivingor =8.6 ml/kg/% total body surface area burned in the first 24 hours was 4.4 (p = 0.03).Risk factors for vision-threatening orbital compartment syndrome include fluid volume and periocular burns. Signs of vision-threatening orbital compartment syndrome should be addressed early with orbital decompression.

Nuclear reprogramming is the process by which a differentiated somatic nucleus has developmental potential restored to it. It involves heritable changes in gene expression as well as structural and functional changes to chromatin structure. This process is naturally induced immediately after fertilization, but can also be artificially induced by nuclear transfer, cell fusion and also now by viral transduction with four stem cell genes. However, the frequency of successful reprogramming is low in each system. The highest success rates, those using nuclear transfer, are only of the order of 2-5%. This article briefly reviews these three methods and proposes a synergistic approach where conditions that facilitate reprogramming in one system are transposed to the others. This might increase the incidence of successful reprogramming and identify common steps necessary for the reacquisition of developmental potential.

Background Fascial closure after damage control or decompression laparotomy is not always possible. The result is a ventral hernia covered with skin grafts. Massive hernias impair bowel, bladder, and respiratory function and are displeasing aesthetically. Most repair methods provide inadequate closure of large full-thickness abdominal wall defects. We describe our method of repair using bilateral anterior abdominal bipedicle flaps over permanent mesh. Methods We reviewed 6 patients who underwent this repair method. This staged repair first involves flap elevation followed by delay. In the next stage, the hernia skin graft is excised, mesh is placed, and flaps are advanced to midline to cover the mesh. Results The average hernia size was 885 ± 274 cm2 (28-cm wide × 31-cm vertical), with a range of up to 37-cm wide. An average of 3 surgeries were required for closure, with a mean hospital stay of 22 days. No patients developed hernia recurrence with a mean follow-up period of 23 months. Conclusions This method provides successful and durable closure of massive skin-grafted hernias.

Breast cancer chest wall recurrence is often treated with chemotherapy, radical surgery, and radiation. Extensive chest wall resection requires soft-tissue reconstruction with tissue that provides chest wall stability and durability for additional radiation. Local and regional muscle and musculocutaneous flaps are often used for reconstruction. Free flaps, such as the transverse rectus abdominis musculocutaneous flap, are used for large defects, although donor site morbidity can result. The free deep inferior epigastric perforator (DIEP) flap provides coverage for large defects and may have less donor site morbidity. We describe the use of the free DIEP flap to reconstruct large chest wall defects (mean, 501 cm2 defects) after the resection of recurrent breast cancer in two patients. One patient had 2% flap loss. No donor site morbidity occurred. The free DIEP flap is a durable and reliable flap that provided immediate and complete coverage of these large chest wall defects with no donor site morbidity and did not delay the administration of adjuvant therapy.

BACKGROUND Orbital reconstruction requires knowledge of orbital depth in order to prevent optic nerve injury. Numerous analyses of adult orbital dimensions have been undertaken previously in order to characterize this measurement, including skull specimen and computerized tomography studies. However, there is a paucity of information regarding the pediatric orbit. METHODS The authors used pediatric magnetic resonance imaging (MRI) studies in order to quantify the change in orbital depth in relationship to patient age, and to develop methods to estimate and calculate orbital depth for individual pediatric patients. MRIs of the head in normal pediatric patients were reviewed retrospectively. Orbital depths were measured and correlated with age and cephalometric dimensions. In a randomly selected subgroup of patients, measurements were repeated by an independent investigator to determine interobserver reliability. RESULTS Measurements were obtained in 72 patients ranging from 3 months to 18 years of age (mean=7.8 years). There was a significant exponential relationship between orbital depth and patient age (r=0.81, F(2,69)=143.97, P

Objective To examine the impact of dentofacial infant orthopedic treatment (DFIO) on facial growth in preadolescent children with unilateral complete cleft lip and palate (UCCLP) and bilateral complete cleft lip and palate (BCCLP). Methods This is a retrospective study of patients with UCCLP and BCCLP treated at a single center. The treatment group had DFIO, and the control group did not have DFIO. Regression models were used to compare outcomes between the study and control groups. Results The study sample comprised 81 patients (54 had DFIO and 27 did not have DFIO). Among those with UCCLP, those who had DFIO had a shorter maxillary length (−2.12 mm; P = .04) and shorter lower anterior facial height (−2.77 mm; P = .04) compared with controls. Among those with BCCLP, there were no significant differences between the treatment and control groups. Conclusions DFIO treatment could result in shorter maxillary length and lower anterior facial height in those with UCCLP.

Hybrid embryonic stem (ES)-like clones were generated by fusion of murine ES cells with somatic cells that carried a neo resistance gene under the transcriptional control of the Oct-4 promoter. The Oct-4 promoter was reactivated in hybrid ES cells formed by fusion with fetal fibroblasts, and all hybrid colonies were of ES rather than fibroblast phenotype, suggesting efficient reprogramming of fibroblast chromosomes. Like normal diploid murine ES cells, hybrid lines expressed alkaline phosphatase activity and formed differentiated cells derived from the three embryonic germ layers both in vitro and in vivo. Treatments thought to affect nuclear transfer efficiency (ES cell confluence and serum starvation of primary embryonic fibroblasts) were investigated to determine whether they had an effect on reprogramming in cell hybrids. Serum starvation of primary embryonic fibroblasts increased hybrid colony number 50-fold. ES cells were most effective at reprogramming when they contained a high proportion of cells in the S and G2/M phases of the cell cycle. These data suggest that nuclear reprogramming requires an initial round of somatic DNA replication of quiescent chromatin in the presence of ES-derived factors produced during S and G2/M phases.

The pedicled reverse-flow lateral arm flap has been described primarily for the reconstruction of nontraumatic elbow wounds. We describe our experience using this flap in staged operations for soft tissue coverage after elbow trauma, including acute coverage of open fractures and salvage of infected hardware.Review of patients who underwent staged pedicled reverse-flow lateral arm flap transfer for coverage of traumatic elbow defects.Three patients were identified; all underwent 2-stage repair with flap delay for coverage of traumatic elbow injuries. Each patient had stable wound coverage with this flap. The only complication was 5% distal flap necrosis in 1 patient.The pedicled reverse-flow lateral arm flap provides reliable soft tissue coverage of traumatic elbow defects with minimal donor-site morbidity.

Reconstructive goals for orbitozygomaticomaxillary complex fractures include restoration of orbital volume, facial projection, and facial width. Delayed reconstruction is made more difficult by malunion, nonunion, bony absorption, loss of the soft tissue envelope, and scar. Three-dimensional intraoperative navigation, widely used in neurosurgery and sinus surgery, can improve the accuracy with which bony reduction is performed. This is particularly useful in the setting of bony absorption and comminution. We report a case of delayed reconstruction of an orbitozygomaticomaxillary complex fracture using intraoperative navigation and review this technology's utility in this setting.

Recent studies have shown that burn patients receive larger volumes of fluids than predicted by the Baxter formula and the reason for this is unclear. One potential reason is that increased analgesics are used which could blunt the response to fluid resuscitation. The purpose of this study was to compare the administration of opioid agonists in patients treated at a single burn center in the 1970s and in the year 2000. We performed a retrospective chart review comparing two matched cohorts. Group I consisted of 11 patients admitted between 1975 and 1978. Group II consisted of 11 patients admitted in 2000 matched for age, sex and %TBSA. Patients in Group II received a significantly higher mean opioid equivalent than those in Group I (26.5 +/- 12.3 versus 3.9 +/- 2.2 in the first 24h, P < 0.001). In addition, in Group II, a larger variety and combination of opioid agonists were used. This review demonstrates a significant increase from the 1970s to 2000 in the type, dose prescribed and dose delivered of opioid agonists. Along with "fluid creep", we have also increased our use of opioid agonists or "opioid creep". Higher doses of opioid agonists may have hemodynamic consequences, which may contribute to the increased fluid volumes.

In this paper, the authors present two case reports with patients who presented at different institutions for traumatic aneurysmal dilation of temporal vessels. The first case is a 18-year-old male who presented to plastic surgery following attempted excision by an outside provider after a fist fight. The second case is a 22-year-old male who presented to plastic surgery while inpatient after gunshot wound to the face. The differences in the cases are highlighted by the different approaches to the management of the lesions with direct incision and embolization respectively.

Large numbers of international children with cleft lip-cleft palate are adopted in the United States; many underwent their first operation before arrival.The authors reviewed records of internationally adopted children with cleft lip-cleft palate treated by one surgeon over 25 years. This study focused on anatomical types, frequency/methods of repair, correction of unrepaired deformities, and secondary procedures in this country.Of 105 internationally adopted children with cleft lip-cleft palate, 91 percent were Asian; 75 percent had labial or labiopalatal closure in their native country. Of repaired unilateral cleft lips, 43 percent required complete revision, 49 percent required minor revisions, and 8 percent required no revision. All repaired bilateral cleft lips were revised; 90 percent were complete and 10 percent were minor. "Delayed" primary nasal correction was always necessary in both unilateral and bilateral forms. Labial closure was scheduled first in young infants with an unrepaired unilateral defect, whereas palatal closure took precedence in older children. Premaxillary setback and palatoplasty were scheduled first in older children with unrepaired bilateral cleft lip-cleft palate. Of children arriving with repaired palate, 43 percent required a pharyngeal flap.Whenever cleft lip-cleft palate is repaired in another country, revision rates are high for both unilateral and bilateral types. Nevertheless, primary closure in the native country may increase the likelihood for adoption. Traditional surgical protocols often are altered for an adoptee with an unrepaired cleft lip-cleft palate, particularly the sequence of labial and palatal closure, depending on the child's age and type of defect.

Cutaneous sensory nerves mediate inflammation and wound healing by releasing neuropeptides, such as substance P, which stimulates pro-inflammatory responses by keratinocytes, fibroblasts, and endothelial cells. The cell surface enzyme, neutral endopeptidase, degrades substance P, thereby regulating its biologic actions. We hypothesized that neutral endopeptidase enzymatic activity is increased in chronic wounds and skin from subjects with diabetes. We compared cutaneous neutral endopeptidase expression and enzymatic activity between normal controls and diabetic subjects with neuropathy and chronic wounds. Skin samples from subjects with diabetes were taken at the time of amputation for nonhealing ulcers. Skin taken from the ulcer margin, 1 cm from the ulcer (adjacent), and from the most proximal region of the amputated leg were studied. Skin biopsies from the leg of healthy control subjects were also studied. Neutral endopeptidase was localized by immunohistochemistry in all tissue sections. Neutral endopeptidase activity was measured using a fluorimetric assay. The median neutral endopeptidase activity of the ulcer margin was 1.21×higher (p>0.2) than adjacent skin, 5.26×higher (p

UNLABELLED Craniosynostosis is typically treated in the first year of life, when osteogenic potential is high and residual obligate skull defects heal. Delayed reconstruction can result in persistent skull defects because of diminished osteogenic potential. Adequately expanding the cranium yet minimizing residual skull defects in older patients presents a conundrum. Although secondary cranioplasty can be performed, primary cortical bone coverage is preferred. The authors present a technique of cranial expansion by sliding stairstep osteotomies, thus preventing residual skull defects when treating craniosynostosis at an advanced age. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, IV.

The primary goals in repairing complex craniofacial fractures are restoration of occlusion and mastication, and anatomic reconstruction of a symmetric facial skeleton. Failure to accomplish these goals may result in the need for secondary operations. Recognition of malreduction may not be appreciated until review of a postoperative computed tomographic (CT) scan. Intraoperative CT scanning enables immediate on-table assessment of reduction and fixation, allowing alteration of the surgical plan as needed. We report using intraoperative CT scanning while repairing a panfacial injury in which malreduction was appreciated intraoperatively and corrected. Intraoperative CT can be used to improve outcomes and quality of complex facial fracture repair.

Last year a paper appeared in Cell that caused a great degree of excitement in the scientific community. Takahashi and Yamanaka (2006) described a system where murine fibroblasts, virally transduced with as few as four stem cell factors (Oct3/4, Sox2, c-Myc, and Klf4), reverted to an embryonic stem (ES) cell-like phenotype when placed in selective culture conditions. Last month, the same team extended this work, this time showing transduced cells selected for reactivation of the homeoprotein Nanog were even more similar to ES cells than before, and capable of germline transmission (Okita et al., 2007). Two other teams, those of Konrad Hochedlinger (Maherali et al., 2007) and Rudolf Jaenisch (Wernig et al., 2007), concurrently demonstrated the remarkable capacity of this new approach. Figure 1 illustrates the general experimental design used by all of these reports. Fig. 1 Reprogramming the differentiated state by viral transduction. The approach initially outlined by Takahashi and Yamananaka (2006) involves the transduction of fibroblast populations (both embryonic and adult) with four pluripotent stem cell factors Klf4 ... Taken together, the data presented by these four papers show the transduced cells display characteristics strikingly similar to ES cells in every assay to which they were subjected. Table 1 highlights the analyses used in each study. These cells reactivate pluripotency genes and present gene expression profiles strikingly similar to bona fide ES cells. Furthermore, epigenetic analysis showed the cells to have DNA methylation and histone modification patterns virtually indistinguishable from ES cells, both globally and at loci associated with pluripotency. Importantly, this also includes analysis at imprinted loci, suggesting that the cells being reprogrammed are not contaminating germ cells. Perhaps most significantly all three groups have subjected their cells to a battery of functional assays for developmental potential. These include formation of the three germ layers in embryoid bodies and teratomas, high chimeric contribution, and, crucially, germ line transmission, including live, fertile mice obtained by Yamanaka's group. Two additional experiments bolster this evidence of pluripotency: first, Hochedlinger's group has shown cells have the capacity to reprogram somatic cells by cell fusion, and second, Jaenisch's group presented evidence of mid-gestation tetraploid complementation embryos derived from these cells, and hence were named ‘induced Pluripotent Stem (iPS) cells’. Table 1 Summary of published iPS papers While the result presented by Hochedlinger's group that iPS cells generated from adult cells can contribute to a chimera's germline is compelling in contrast with the germline-competent reprogramming of embryonic fibroblasts shown by other groups, these adult tail-tip fibroblasts are nonetheless a very heterogeneous population and it remains to be demonstrated whether terminally differentiated cells can be reprogrammed in this fashion, as has been demonstrated with other reprogramming technologies (Tada et al., 2001; Hochedlinger and Jaenisch, 2002; Eggan et al., 2004; Inoue et al., 2005). Furthermore, the continued presence of transgenes encoding oncogenic factors and delivered by oncogenic retroviruses (Hochedlinger et al., 2005; Yamanaka, 2007) raises concerns about the long-term capacity of these cells to support normal development. Notably, of the only live F1 mice from germline iPS chimeras reported in these studies, approximately one-fifth developed tumors, likely due to reactivation of the c-Myc retrovirus (Okita et al., 2007). Perhaps this problem could be addressed by removal of the transgenes after reprogramming or by an inducible system for all four factors, as was carried out by Hochedlinger with Oct3/4 alone. This second concern is particularly crucial to surmount if this system is to be of use clinically. While the recapitulation of this technology in human cells could address two important challenges currently faced by the stem cell field, the need to avoid immune rejection by creating pluripotent cells genetically identical to a patient and objections of some to the use of surplus preimplantation human embryos, this demonstrated connection to oncogenesis presents for now a significant barrier to such application. Likewise, identifying the appropriate factors and selection regime to produce human iPS cells may require an extensive amount of new work and insight. New methodologies to either deliver or activate these genes will also need to be developed, as suggested by both Yamanaka and Jaenisch, in order to avoid the use of potentially cancer-causing retroviruses. In addition to describing a new system for generating pluripotent cells, which may be clinically relevant, this work provides major insights into how nuclear reprogramming itself proceeds and as such may be able to inform us about fundamental mechanisms of cellular identity. How amenable is cell identity to being altered in this fashion? Can this approach be generalized to reprogram a variety of different cell types? And, further, can it be used to identify various factors or regiments to regress differentiated states in a stepwise fashion, hence generating progenitors and precursors as well as fully pluripotent cells? Certainly the advances reported in these studies create a myriad of opportunities for new directions in controlling and manipulating differentiation. It will be interesting to see how this field progresses.

Background Although symmetry is hailed as a fundamental goal of aesthetic and reconstructive surgery, our tools for measuring this outcome have been limited and subjective. With the advent of three-dimensional photogrammetry, surface geometry can be captured, manipulated, and measured quantitatively. Until now, few normative data existed with regard to facial surface symmetry. Here, we present a method for reproducibly calculating overall facial symmetry and present normative data on 100 subjects. Methods We enrolled 100 volunteers who underwent three-dimensional photogrammetry of their faces in repose. We collected demographic data on age, sex, and race and subjectively scored facial symmetry. We calculated the root mean square deviation (RMSD) between the native and reflected faces, reflecting about a plane of maximum symmetry. We analyzed the interobserver reliability of the subjective assessment of facial asymmetry and the quantitative measurements and compared the subjective and objective values. We also classified areas of greatest asymmetry as localized to the upper, middle, or lower facial thirds. This cluster of normative data was compared with a group of patients with subtle but increasing amounts of facial asymmetry. Results We imaged 100 subjects by three-dimensional photogrammetry. There was a poor interobserver correlation between subjective assessments of asymmetry (r = 0.56). There was a high interobserver reliability for quantitative measurements of facial symmetry RMSD calculations (r = 0.91-0.95). The mean RMSD for this normative population was found to be 0.80 ± 0.24 mm. Areas of greatest asymmetry were distributed as follows: 10% upper facial third, 49% central facial third, and 41% lower facial third. Precise measurement permitted discrimination of subtle facial asymmetry within this normative group and distinguished norms from patients with subtle facial asymmetry, with placement of RMSDs along an asymmetry ruler. Conclusions Facial surface symmetry, which is poorly assessed subjectively, can be easily and reproducibly measured using three-dimensional photogrammetry. The RMSD for facial asymmetry of healthy volunteers clusters at approximately 0.80 ± 0.24 mm. Patients with facial asymmetry due to a pathologic process can be differentiated from normative facial asymmetry based on their RMSDs.

Objective: Posterior vault remodeling by distraction osteogenesis is a relatively new technique used for initial correction of turribrachycephaly in children with bicoronal craniosynostosis. We present a new potential complication from this procedure; a case of pan-suture synostosis subsequent to posterior vault distraction. Methods: We report an infant girl who presented with bicoronal synostosis in the setting of Saethre-Chotzen syndrome. She underwent posterior vault distraction and was distracted a total of 34 millimeters, with successful osteogenesis at the site. Results: One year postoperatively, the patient was found to have incidental, asymptomatic pan-suture synostosis on computed tomography. Conclusions: To our knowledge, this is the first reported case of delayed craniosynostosis after posterior vault distraction in the literature. The possible pathogenesis and significance of this case are discussed with a review of the current literature.

Baxter described the use of 4 cm 3 /kg/%TBSA as a guideline for fluid resuscitation after burns. However, recent studies have shown that, at the present time, patients generally receive greater than the “Baxter” formula. Pruitt has called this phenomenon “fluid creep,” and it has the potential for significant consequences including abdominal and extremity compartment syndromes and severe pulmonary insults. The purpose of this paper is to determine if this supra-Baxter resuscitation is a new phenomenon. We performed a retrospective chart review with two cohorts of patients. Group 1 consisted of 11 patients admitted between 1975 and 1978 to our burn center. Group 2 consisted of 11 patients admitted to our burn center in 2000 who were matched for age, sex, and percent total body surface area burned. Group 1 received 3.6±1.1 cm 3 /kg/% TBSA of fluid in the first 24 h. Group 2 received 8.0±2.5 cm 3 /kg/% TBSA, which is 100% more than the Baxter formula. There was no difference in the median age, weight, or 24-h urine output between the two groups. Our data demonstrate that the “fluid creep” phenomenon is relatively new.

Little is known about pediatric surgical disease in resource-poor countries. This study documents the surgical care of children in central Haiti and demonstrates the influence of the 2010 earthquake on pediatric surgical delivery. METHODS: We conducted a retrospective review of operations performed at Partners in Health/Zanmi Lasante hospitals in central Haiti. RESULTS: Of 2,057 operations performed prior to the earthquake, 423 were pediatric (20.6%). Congenital anomalies were the most common operative indication (159/423 operations; 33.5%). Pediatric surgical volume increased significantly after the earthquake, with 670 operations performed (23.0% post-earthquake v. 20.6% pre-earthquake, p=.03). Trauma and burns became the most common surgical diagnoses after the disaster, and operations for non-traumatic conditions decreased significantly (p

Velocardiofacial syndrome is the most common defined disorder associated with palatal insufficiency. The authors' purpose is to evaluate one surgeon's experience with correction of velopharyngeal insufficiency in velocardiofacial syndrome using a tailored pharyngeal flap.The authors reviewed the records of all children with velocardiofacial syndrome and velopharyngeal insufficiency who were managed with a pharyngeal flap between 1983 and 2009. Data collected included age at operation, preoperative videofluoroscopic findings, speech outcomes, complications, and need for a secondary operation.The authors identified 33 patients with velocardiofacial syndrome and velopharyngeal insufficiency who had postoperative speech evaluations. Velopharyngeal insufficiency was diagnosed at a median age of 5 years. Palatal findings were: Veau type I (n = 4), overt submucous (n = 6), or occult submucous (n = 23). Median preoperative lateral pharyngeal wall movement was 22 percent (range, 0 to 90 percent). Successful correction of velopharyngeal insufficiency was achieved in 29 of 33 patients (88 percent). One patient had a medially displaced right internal carotid artery, and evidenced intraoperative bleeding and required a blood transfusion. One patient developed obstructive sleep apnea.A tailored pharyngeal flap is highly effective for correction of velopharyngeal insufficiency in velocardiofacial syndrome with few complications.