Lisa Gfrerer

Distinct requirements for wnt9a and irf6 in extension and integration mechanisms during zebrafish palate morphogenesis

Development of the palate in vertebrates involves cranial neural crest migration, convergence of facial prominences and extension of the cartilaginous framework. Dysregulation of palatogenesis results in orofacial clefts, which represent the most common structural birth defects. Detailed analysis of zebrafish palatogenesis revealed distinct mechanisms of palatal morphogenesis: extension, proliferation and integration. We show that wnt9a is required for palatal extension, wherein the chondrocytes form a proliferative front, undergo morphological change and intercalate to form the ethmoid plate. Meanwhile, irf6 is required specifically for integration of facial prominences along a V-shaped seam. This work presents a mechanistic analysis of palate morphogenesis in a clinically relevant context.

Assessment of Patient Factors, Surgeons, and Surgeon Teams in Immediate Implant-based Breast Reconstruction Outcomes

Background: Outcome studies of immediate implant-based breast reconstruction have focused largely on patient factors, whereas the relative impact of the surgeon as a contributing variable is not known. As the procedure requires collaboration of both a surgical oncologist and a plastic surgeon, the effect of the surgeon team interaction can have a significant impact on outcome. This study examines outcomes in implant-based breast reconstruction and the association with patient characteristics, surgeon, and surgeon team familiarity. Methods: A retrospective review of 3142 consecutive implant-based breast reconstruction mastectomy procedures at one institution was performed. Infection and skin necrosis rates were measured. Predictors of outcomes were identified by unadjusted logistic regression followed by multivariate logistic regression. Surgeon teams were grouped according to number of cases performed together. Results: Patient characteristics remain the most important predictors for outcomes in implant-based breast reconstruction, with odds ratios above those of surgeon variables. The authors observed significant differences in the rate of skin necrosis between surgical oncologists with an approximately two-fold difference between surgeons with the highest and lowest rates. Surgeon teams that worked together on fewer than 150 procedures had higher rates of infection. Conclusions: Patient characteristics are the most important predictors for surgical outcomes in implant-based breast reconstruction, but surgeons and surgeon teams are also important variables. High-volume surgeon teams achieve lower rates of infection. This study highlights the need to examine modifiable risk factors associated with optimum implant-based breast reconstruction outcomes, which include patient and provider characteristics and the surgical team treating the patient. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Nonendoscopic deactivation of nerve triggers in migraine headache patients: surgical technique and outcomes.

Background: Low efficacy, significant side effects, and refractory patients often limit the medical treatment of migraine headache. However, new surgical options have emerged. Dr. Bahman Guyuron and others report response rates between 68 and 95 percent after surgical deactivation of migraine trigger sites in select patients. In an effort to replicate and expand migraine trigger-site deactivation surgery as a treatment option, the authors’ group and others have developed nonendoscopic algorithms. The exclusion of endoscopic techniques may be useful for surgeons with little experience or limited access to the endoscope and in patients with challenging anatomy. Methods: Forty-three consecutive trigger deactivation procedures in 35 patients were performed. Preoperative and 12-month postoperative migraine questionnaires and patient charts were reviewed. Response to surgery in terms of migraine symptom relief and adverse events were evaluated. Results: The overall positive response rate was 90.7 percent. Total elimination of migraine headaches was reported in 51.3 percent of those with a positive response, greater than 80 percent resolution of symptoms was reported in 20.5 percent, and 28.2 percent had resolution between 50 and 80 percent. No significant effect was reported following 9.3 percent of procedures. There were no major adverse events. Conclusions: Nonendoscopic trigger deactivation is a safe and effective treatment in select migraine headache patients. Although surgical techniques and understanding of the mechanisms of relief are evolving, results continue to be promising. This series confirms that excellent results can be attained without the endoscope. The authors continue to study these patients prospectively to improve patient selection and refine the protocol. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Functional Analysis of SPECC1L in Craniofacial Development and Oblique Facial Cleft Pathogenesis

Background: Oblique facial clefts, also known as Tessier clefts, are severe orofacial clefts, the genetic basis of which is poorly understood. Human genetics studies revealed that disruption in SPECC1L resulted in oblique facial clefts, demonstrating that oblique facial cleft malformation has a genetic basis. An important step toward innovation in treatment of oblique facial clefts would be improved understanding of its genetic pathogenesis. The authors exploit the zebrafish model to elucidate the function of SPECC1L by studying its homolog, specc1lb. Methods: Gene and protein expression analysis was carried out by reverse-transcriptase polymerase chain reaction and immunohistochemistry staining. Morpholino knockdown, mRNA rescue, lineage tracing and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assays were performed for functional analysis. Results: Expression of specc1lb was detected in epithelia juxtaposed to chondrocytes. Knockdown of specc1lb resulted in bilateral clefts between median and lateral elements of the ethmoid plate, structures analogous to the frontonasal process and the paired maxillary processes. Lineage tracing analysis revealed that cranial neural crest cells contributing to the frontonasal prominence failed to integrate with the maxillary prominence populations. Cells contributing to lower jaw structures were able to migrate to their destined pharyngeal segment but failed to converge to form mandibular elements. Conclusions: These results demonstrate that specc1lb is required for integration of frontonasal and maxillary elements and convergence of mandibular prominences. The authors confirm the role of SPECC1L in orofacial cleft pathogenesis in the first animal model of Tessier cleft, providing morphogenetic insight into the mechanisms of normal craniofacial development and oblique facial cleft pathogenesis.

Prevention of vein graft intimal hyperplasia with photochemical tissue passivation.

Objective: Saphenous vein is the conduit of choice for bypass grafting. Saphenous vein grafts have poor long‐term patency rates because of intimal hyperplasia (IH) and subsequent accelerated atherosclerosis. One of the primary triggers of IH is endothelial injury resulting from excessive dilation of the vein after exposure to arterial pressures. Photochemical tissue passivation (PTP) is a technology that cross‐links adventitial collagen by a light‐activated process, which limits dilation by improving vessel compliance. The objective of this study was to investigate whether PTP limits the development of IH in a rodent venous interposition graft model. Methods: PTP is accomplished by coating venous adventitia with a photosensitizing dye and exposing it to light. To assess the degree of collagen cross‐linking after PTP treatment, a biodegradation assay was performed. Venous interposition grafts were placed in the femoral artery of Sprague‐Dawley rats. Rats were euthanized after 4 weeks, and intimal thickness was measured histologically. Vein dilation at the time of the initial procedure was also measured. Results: Time to digestion was 63 ± 7 minutes for controls, 101 ± 2.4 minutes for rose bengal (RB), and 300 ± 0 minutes for PTP (P < .001 PTP vs control). A total of 37 animals underwent the procedure: 12 PTP, 12 RB only, and 13 untreated controls. Dilation of the graft after clamp release was 99% for control, 65% for RB only, and 19% for PTP‐treated (P < .001 PTP vs control). Intimal thickness was 77 ± 59 &mgr;m in controls, 60 ± 27 &mgr;m in RB only, and 33 ± 28 &mgr;m in PTP‐treated grafts. There was a statistically significant 57% reduction in intimal thickness after treatment with PTP compared with untreated controls (P = .03). Conclusions: PTP treatment of venous interposition grafts in a rat model resulted in significant collagen cross‐linking, decreased vessel compliance, and significant reduction in IH. Clinical Relevance: Long‐term patency rates are poor after coronary or lower extremity bypass with autologous vein. This is largely due to intimal hyperplasia (IH), superimposed accelerated atherosclerosis, and graft thrombosis. A key inciting event is graft overdistention and endothelial denudation after exposure to arterial pressure. Limiting overdistention by external mechanical support has been shown to reduce IH. Photochemical tissue passivation involves cross‐linking adventitial collagen, a novel approach to limit overdistention of the vein without an external prosthesis. Photochemical tissue passivation resulted in a 57% reduction of IH. Minimizing vein graft IH would greatly improve long‐term outcomes after arterial bypass.

Interface Between Cosmetic and Migraine Surgery

AbstractThis article describes connections between migraine surgery and cosmetic surgery including technical overlap, benefits for patients, and why every plastic surgeon may consider screening cosmetic surgery patients for migraine headache (MH). Contemporary migraine surgery began by an observation made following forehead rejuvenation, and the connection has continued. The prevalence of MH among females in the USA is 26%, and females account for 91% of cosmetic surgery procedures and 81–91% of migraine surgery procedures, which suggests substantial overlap between both patient populations. At the same time, recent reports show an overall increase in cosmetic facial procedures. Surgical techniques between some of the most commonly performed facial surgeries and migraine surgery overlap, creating opportunity for consolidation. In particular, forehead lift, blepharoplasty, septo-rhinoplasty, and rhytidectomy can easily be part of the migraine surgery, depending on the migraine trigger sites. Patients could benefit from simultaneous improvement in MH symptoms and rejuvenation of the face. Simple tools such as the Migraine Headache Index could be used to screen cosmetic surgery patients for MH. Similarity between patient populations, demand for both facial and MH procedures, and technical overlap suggest great incentive for plastic surgeons to combine both. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Ability to Cope with Pain Puts Migraine Surgery Patients in Perspective

Background: Candidates for migraine surgery are chronic pain patients with significant disability. Currently, migraine-specific questionnaires are used to evaluate these patients. Analysis tools widely used in evaluation of better understood pain conditions are not typically applied. This is the first study to include a commonly used pain questionnaire, the Pain Self-Efficacy Questionnaire (PSEQ) that is used to determine patients’ pain coping abilities and function. It is an important predictor of pain intensity/disability in patients with musculoskeletal pain, as low scores have been associated with poor outcome. Methods: Ninety patients were enrolled prospectively and completed the Migraine Headache Index and PSEQ preoperatively and at 12 months postoperatively. Scores were evaluated using paired t tests and Pearson correlation. Representative PSEQ scores for other pain conditions were chosen for score comparison. Results: All scores improved significantly from baseline (p < 0.01). Mean preoperative pain coping score (PSEQ) was 18.2 ± 11.7, which is extremely poor compared with scores reported for other pain conditions. Improvement of PSEQ score after migraine surgery was higher than seen in other pain conditions after treatment (112 percent). Preoperative PSEQ scores did not influence postoperative outcome. Conclusions: The PSEQ successfully demonstrates the extent of debility in migraine surgery patients by putting migraine pain in perspective with other known pain conditions. It further evaluates functional status, rather than improvement in migraine characteristics, which significantly adds to our understanding of outcome. Poor preoperative PSEQ scores do not influence outcome and should not be used to determine eligibility for migraine surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Functional and subjective assessment of burn contracture release in a mission setting

OBJECTIVE Burns and subsequent contractures are common in developing nations. Contracture release is performed to treat such patients with functional limitations. The aim of this study is to evaluate post-operative functional and psychosocial outcomes following contracture release in a mission setting. METHODS During a surgical mission in Mumbai, India, 39 patients burn contractures underwent surgical release. A total of 31 patients (64% female, mean age 27 years) chose to participate in the study. Patients were scored preoperatively and postoperatively using a SF-36 validated survey and AMA impairment guideline assessment. RESULTS Thirty-one patients completed questionnaires pre-operative and 6-weeks post operatively. Twenty-four patients completed a survey 3-months post operatively (77.4%). Among those enrolled, 67% were women with the majority sustaining <20% total body surface area burns (70.7%) but had multiple contractures (80.6%). SF-36 physical component score increased from a mean score of 49.8 preoperatively to 55.6 by 3 months following contracture release (P<0.001). The SF-36 mental component score similarly increased from 38.8 to 51.1 by 3 months (P<0.001). AMA Whole Person Impairment (WPI) scores improved from 40.3% impairment pre-operative to 26.6% at 6-weeks post-operative (P<0.001). CONCLUSIONS Patients SF-36 and WPI scores improved following burn contracture release, confirming both functional and psychologic improvement following surgery. During the acute post-operative period, this study suggests that contracture release in a mission setting is of benefit to patients.

Abstract 14: requirement of specc1lb in facial prominence integration and formation of the lower jaw.

PurPose: The genetic basis of the rare oblique facial cleft (ObFC) has been unknown until the identification of SPECC1L from human translocation analysis. SPECC1L is a novel scaffolding protein where its molecular function in craniofacial morphogenesis is unknown. We explore the function of SPECC1L in craniofacial development by studying its homologs in zebrafish, where specc1lb is the ortholog.

Impact of Surgeon and Surgical Team on Outcomes in Immediate Implant Based Breast Reconstruction

Background Outcome studies of immediate implant based breast reconstruction (IBR) have largely focused on patient factors, while the relative impact of the surgeon as a contributing variable is not known. In particular, when the procedure requires collaboration of both a surgical oncologist and plastic surgeon, the effect of the surgeon team interaction can have significant impact on outcome. This study examines outcomes in IBR and the association with patient characteristics, surgeon, and surgeon team familiarity. Methods A retrospective review of 3,142 consecutive IBR mastectomy procedures at one institution was performed. Infection rate, skin necrosis and local recurrence were measured. Predictors of outcomes were identified by unadjusted logistic regression followed by multivariate logistic regression. Surgeon teams (oncologic plus reconstructive surgeon) were grouped according to number of cases performed together. Results Patient characteristics remain the most important predictors for outcomes in IBR, with odds ratios above that of surgeon variables. We observed significant differences in rate of skin necrosis between surgical oncologists with approximately two-fold difference between surgeons with the highest and lowest rates (see Table 1). Surgeon teams that worked together on less than 150 procedures had higher rates of infection (OR=2.48, p<0.05) (see Table 2). Conclusion Patient characteristics are the most important predictors for surgical outcomes in IBR, but surgeons and surgeon teams are also important variables. High-volume surgeon teams achieve lower rates of infection. This study highlights the need to examine modifiable risk factors associated with optimum IBR outcomes, which include patient and provider characteristics as well as the surgical team treating the patient.