Perioperative Pain Management in Cleft Lip and Palate Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Studies.

BACKGROUND: Developing effective strategies to manage perioperative pain remains a focus of cleft care. The present study's purpose was to systematically review perioperative pain control strategies for cleft lip and palate repair. METHODS: A systematic review and meta-analysis of randomized controlled trials was performed. Primary outcomes included pain scale scores and time to analgesia failure. Cohen d normalized effect size permitted comparison between studies, and a fixed-effects model was used for analysis. I2 and Q-statistic p values were calculated. RESULTS: Twenty-three studies were included: eight of 23 studies provided data for meta-analytic comparison. Meta-analyses evaluated the efficacy of intraoperative nerve blocks on postoperative pain management. Meta-analysis included a total of 475 treatment and control patients. Cleft lip studies demonstrated significantly improved pain control with a nerve block versus placebo by means of pain scale scores ( p < 0.001) and time to analgesia failure ( p < 0.001). Measurement of effect size over time demonstrated statistically significant pain relief with local anesthetic. Palatoplasty studies showed significantly improved time to analgesia failure ( p < 0.005) with maxillary and palatal nerve blocks. Multiple studies demonstrated an opioid-sparing effect with the use of local anesthetics and other nonopioid medications. Techniques for nerve blocks in cleft lip and palate surgery are reviewed. CONCLUSIONS: The present systematic review and meta-analysis of randomized controlled studies demonstrates that intraoperative nerve blocks for cleft lip and palate surgery provide effective pain control. Opioid-sparing effects were appreciated in multiple studies. Intraoperative nerve blocks should be considered in all cases of cleft lip and palate repair to improve postoperative pain management. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Evaluation and treatment of facial feminization surgery: part II. lips, midface, mandible, chin, and laryngeal prominence.

Facial feminization surgery (FFS) refers to a set of procedures aimed at altering the features of a masculine face to achieve a more feminine appearance. In the second part of this twopart series, assessment and operations involving the midface, mandible, and chin, as well as soft tissue modification of the nasolabial complex and chondrolaryngoplasty, are discussed. Finally, we provide a review of the literature on patient-reported outcomes in this population following FFS and suggest a path forward to optimize care for FFS patients.

Early Alveolar Bone Grafting Is Associated with Lower Regraft Rates and Improvements in Long-Term Psychosocial Outcomes.

BACKGROUND: Late childhood (8 to 10 years of age) has emerged as a vulnerable period in children with cleft and craniofacial anomalies such that increased interventions during this period are associated with worse long-term patient-reported anxiety and depressive symptoms. These findings suggest that one possible practice change may be to consider changes in timing for surgical treatment algorithms. In this work, the authors investigated outcomes in altering the timing of the most common operation in late childhood for cleft lip and palate patients, alveolar bone grafting. METHODS: A two-part, multi-institutional cohort study was conducted. To understand the feasibility of changing alveolar bone graft timing with respect to surgical success, reoperation rates were retrospectively compared among patients grafted at different ages (4 to 7, 8 to 10, and 11 to 13 years of age). To understand the long-term effect of changing alveolar bone graft timing on psychosocial outcomes, the psychosocial suite of the Patient-Reported Outcomes Measurement Information System was prospectively administered to teenagers and adults with cleft lip and palate. RESULTS: Among the three age groups, early grafting (4 to 7 years of age) demonstrated the lowest regraft rates compared with the other groups. As these results suggested that early grafting is a viable alternative to standard timing, we next compared the differences in long-term psychosocial outcomes. Patients who were grafted early reported lower levels of anxiety and depressive symptoms as teenagers and adults. CONCLUSION: Altering timing of one stage in cleft lip and palate reconstruction to an earlier age decreases regraft rates and improves long-term patient-reported anxiety and depressive symptoms. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Facial Feminization Surgery under Insurance: The University of California Los Angeles Experience.

Despite improved insurance coverage for gender confirmation surgeries in the United States, coverage for facial feminization surgery (FFS) continues to be difficult. Here, we describe our institutional experience on navigation, time, and costs of the FFS insurance authorization process. METHODS: FFS consults (n = 40) at the University of California, Los Angeles (2018-2020) were reviewed for time and cost to definitive insurance authorization decision. Patients were stratified into 3 groups based on authorization process: Group A (standard approval, n = 26, 65.0%) including public and private insurances; Group B (extended approval, n = 10, 25.0%) consisting of private insurance plans that initially denied and required multi-level appeals for denial overturn; and Group C (denial, n = 4, 10.0%), including private insurance plans that denied even after multi-level appeals. RESULTS: An estimated 90% of all patient consults were approved for FFS under insurance. Group A averaged 1.1 months for approval, requiring 1.4 hours of administrative time translating to $38.18 per patient. The addition of multi-level appeals in Groups B and C increased the total time for a definitive decision (7.0 and 5.1 months, respectively) and required both surgeon and administrative time to navigate the process (10.8 and 12.0 hours, respectively). The time spent on the presurgical authorization process for Groups B and C translated to an over 20-fold increase in cost ($855.00 and $988.38, respectively) compared with Group A. CONCLUSION: Navigation of the insurance process for FFS is challenging and time-consuming; however, coverage is a reality in California provided that multi-level appeals are exhausted.

Velopharyngeal Insufficiency in Craniofacial Microsomia: Prevalence, Diagnosis, and Treatment.

ABSTRACT: The purpose of this study was to analyze the prevalence, diagnosis, and management of velopharyngeal insufficiency (VPI) in patients with craniofacial microsomia (CFM).Craniofacial microsomia patients 13 years of age and above treated at 2 centers from 1997 to 2019 were reviewed retrospectively for demographics, prevalence of VPI, and management of VPI. Patients with isolated microtia were excluded. Comparisons were made between patients with and without VPI using chi-square and independent samples t tests.Among 68 patients with CFM (63.2% male, mean 20.7 years of age), VPI was diagnosed in 19 patients (27.9%) at an average age of 7.2 years old. Among the total cohort, 61 patients had isolated CFM, of which 12 (19.6%) were diagnosed with VPI. Of the patients with isolated CFM and VPI, 8 patients (66.7%) were recommended for nasoendoscopy, of which only 2 patients completed. Seven isolated CFM patients (58.3%) underwent speech therapy, whereas none received VPI surgery. In contrast, 7 patients were diagnosed with both CFM and cleft lip and/or palate (CL/P), all of whom had VPI and were recommended for nasoendoscopy, with 5 (71.4%) completing nasoendoscopy, 6 (85.7%) undergoing speech therapy, and 6 (85.7%) undergoing corrective VPI surgery. Overall, we demonstrated that VPI was present in 27.9% of all CFM patients. On subset analysis, VPI was diagnosed in 20% of patients with isolated CFM and 100% of patients with CFM and CL/P. In addition, despite clinical diagnosis of VPI, a sizeable proportion of isolated CFM patients did not undergo therapy or surgical interventions.

Evaluation and treatment of facial feminization surgery: part I. forehead, orbits, eyebrows, eyes, and nose.

Facial feminization surgery (FFS) incorporates aesthetic and craniofacial surgical principles and techniques to feminize masculine facial features and facilitate gender transitioning. A detailed understanding of the defining male and female facial characteristics is essential for success. In this first part of a two-part series, we discuss key aspects of the general preoperative consultation that should be considered when evaluating the prospective facial feminization patient. Assessment of the forehead, orbits, hairline, eyebrows, eyes, and nose and the associated procedures, including scalp advancement, supraorbital rim reduction, setback of the anterior table of the frontal sinus, rhinoplasty, and soft tissue modifications of the upper and midface are discussed. In the second part of this series, bony manipulation of the midface, mandible, and chin, as well as soft tissue modification of the nasolabial complex and chondrolaryngoplasty are discussed. Finally, a review of the literature on patient-reported outcomes in this population following FFS is provided.

Component Restoration in the Bilateral Intermediate Cleft Tip Rhinoplasty.

SUMMARY: The intermediate cleft tip rhinoplasty is frequently performed during childhood to address nasal tip anomalies in cleft patients before the most critical period of psychosocial development. The authors previously described the component restoration intermediate cleft tip rhinoplasty technique for the unilateral cleft nose, which was developed to systematically address the lining deficiency, cleft lower lateral cartilage malpositioning, and cleft lateral cartilage weakness using a combination of lower lateral cartilage release, lateral cartilage repositioning, and placement of an auricular composite chondrocutaneous graft. In this work, the authors evaluate the utility of this technique to the bilateral cleft nose. Preoperative and postoperative (mean ± SD, 18.6 ± 10.8 months) photographs of bilateral cleft patients treated with the component restoration intermediate cleft tip rhinoplasty (n = 7) were evaluated using photogrammetric measurements and aesthetic assessments. From preoperatively to postoperatively, the columella length-to-alar width ratio on basal photographs increased (0.19 ± 0.05 versus 0.28 ± 0.05; p = 0.001). On lateral view, the columella-labial angle decreased from preoperatively to postoperatively [138 degrees (interquartile range, 132 to 144 degrees) versus 123 degrees (interquartile range, 122 to 139 degrees); p = 0.04]. Aesthetic ratings performed by four blinded observers also improved from preoperatively to postoperatively (1.6 ± 0.8 versus 2.4 ± 0.7; p = 0.004). As a comparison, bilateral cleft nose patients who did not undergo intermediate cleft tip rhinoplasty (n = 3) of similar ages were subjected to the same photogrammetric and aesthetic analyses, which showed no differences from preoperatively to postoperatively. In combination, the current work suggests that the component restoration technique in the bilateral intermediate cleft tip rhinoplasty improves nasal tip support and aesthetic outcomes.

The Effect of Functional Nasal Surgery on Olfactory Function.

BACKGROUND: Functional and aesthetic nasal operations are some of the most common plastic surgery procedures performed in the United States. The purpose of the study was to evaluate the effects of septoplasty, septorhinoplasty, and rhinoplasty procedures on postoperative olfactory function and their relationship to nasal airflow and quality of life. METHODS: A systematic review and meta-analysis was performed evaluating olfactory function following nasal surgery. Preoperative and postoperative values for olfaction, nasal airflow, and quality of life/nasal symptoms were analyzed. The effect size was calculated from each study and used for meta-analysis. As studies evaluated patients at different points in the postoperative period, the latest time point reported by each study was used in the meta-analysis. The 95 percent confidence interval of the effect size was calculated for each study. Study quality was assessed using the Jadad and Methodological Index for Nonrandomized Studies instruments. All included studies were Level of Evidence II. RESULTS: There were 25 included studies. Following nasal surgery, patients experienced significant improvements in olfaction (p < 0.001), nasal airflow (p < 0.001), and quality of life/nasal symptoms (p < 0.001). Patients often experienced a transient decrease in olfaction immediately after surgery, followed by improvement postoperatively. Preoperative olfactory dysfunction rates were low and postoperative dysfunction was equally low. Olfaction improvement was directly correlated with improvement in nasal airflow and quality of life. CONCLUSIONS: Functional and aesthetic nasal operations appear to significantly improve olfaction, which is directly correlated with nasal airflow. Some studies report a transient worsening of these measures in the immediate postoperative period, which subsequently improved at later time points.

Planning and Osteotomy Designs in the Correction of Single-Suture Craniosynostosis.

BACKGROUND: Craniosynostosis is among the abnormalities that are more commonly encountered by craniofacial surgeons. Although the overall concepts for cranial vault remodeling are relatively simple, osteotomy designs and methods for calvarial rearrangement are highly varied. In this work, we present a summary of the known designs for correction of single-suture craniosynostosis. METHODS: A review of the literature was performed of the more frequently used osteotomy designs for single-suture craniosynostosis, as well as their reported results and outcomes. Also reviewed are some of the current available approaches for the diagnosis and surgical planning for single-suture craniosynostosis. RESULTS: There remains a diversity of techniques available for the reconstruction of each fused cranial suture. Certain osteotomy designs are reported in the literature and are used by craniofacial surgeons more frequently. Each has its own benefits and disadvantages, and there is a growing body of outcome data available to guide surgical decision-making. Regarding diagnosis and surgical planning, computed tomography with 3-dimensional reconstruction remains the diagnostic standard of care, and efforts are ongoing to develop and implement new diagnostic modalities like Black Bone MRI to reduce radiation exposure. CONCLUSIONS: There has been ongoing evolution of the surgical techniques available to reconstruct single-suture craniosynostosis, leading to ever-improving patient outcomes.

The Development and Commercialization of Medical Technologies.

It is not uncommon for physicians to think of ways to improve the delivery of care, which may take the form of a new medical device, drug, test, or service. In recent years, structured approaches to the identification of unmet needs and the development of solutions have been introduced to the medical community. Yet, due to gaps in exposure and training, there remains an opportunity to improve the level of understanding within the medical community regarding how to develop an innovation, once conceived, to the point of commercialization. The purpose of this article, therefore, is to provide an overview of some of the relevant considerations and requirements when bringing an idea for a new medical technology to market.

Cadaveric Costal Cartilage Grafts in Rhinoplasty and Septorhinoplasty: A Systematic Review and Meta-Analysis of Patient-Reported Functional Outcomes and Complications.

ABSTRACT: Irradiated cadaveric costal cartilage (CC) has been utilized as an alternative to autologous cartilage (AC) in functional and aesthetic nasal surgery. The impact of graft choice between AC and CC on functional outcomes in rhinoplasty has yet to be studied. A systematic review was performed in PubMed, Embase, and Cochrane databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify comparative studies evaluating the efficacy and safety of CC in nasal surgery. Functional and aesthetic outcomes and complications were reviewed and compared between AC and CC. Meta-analytic comparisons were performed when appropriate using data from comparative studies using a random-effects model. Four studies met inclusion criteria. The indication for surgery was functional in the majority of cases, and 34.6% of cases were revision rhino- or septorhinoplasties. Disparate data across studies prevented meta-analysis on functional outcomes; however, qualitative review of function outcomes demonstrated comparable outcomes between the CC and AC groups. No differences in graft infection, warping, and resorption rates were detected. Analysis of all graft-related complications was higher in the CC group (P = 0.02); however, when AC donor site-related complications were included, no significance between the two groups was observed. In conclusion, limited, high quality data was available for analysis. Of the available studies, this systematic review suggest that the use of AC or CC may lead to comparable results in terms of functional outcomes. More long-term studies directly comparing AC and CC functional outcomes would be welcomed.

Stiffness of Nanoparticulate Mineralized Collagen Scaffolds Triggers Osteogenesis via Mechanotransduction and Canonical Wnt Signaling.

The ability of the extracellular matrix (ECM) to instruct progenitor cell differentiation has generated excitement for the development of materials-based regenerative solutions. Described a nanoparticulate mineralized collagen glycosaminoglycan (MC-GAG) material capable of inducing in vivo skull regeneration without exogenous growth factors or ex vivo progenitor cell-priming is described previously. Here, the contribution of titrating stiffness to osteogenicity is evaluated by comparing noncrosslinked (NX-MC) and crosslinked (MC) forms of MC-GAG. While both materials are osteogenic, MC demonstrates an increased expression of osteogenic markers and mineralization compared to NX-MC. Both materials are capable of autogenously activating the canonical BMPR signaling pathway with phosphorylation of Smad1/5. However, unlike NX-MC, human mesenchymal stem cells cultured on MC demonstrate significant elevations in the major mechanotransduction mediators YAP and TAZ expression, coincident with ß-catenin activation in the canonical Wnt signaling pathway. Inhibition of YAP/TAZ activation reduces osteogenic expression, mineralization, and ß-catenin activation in MC, with less of an effect on NX-MC. YAP/TAZ inhibition also results in a reciprocal increase in Smad1/5 phosphorylation and BMP2 expression. The results indicate that increasing MC-GAG stiffness induces osteogenic differentiation via the mechanotransduction mediators YAP/TAZ and the canonical Wnt signaling pathway, whereas the canonical BMPR signaling pathway is activated independent of stiffness.

Review of Outcomes in Prepectoral Prosthetic Breast Reconstruction with and without Surgical Mesh Assistance.

BACKGROUND: In the past decade, surgeons have increasingly advocated for a return to prepectoral breast reconstruction with claims that surgical mesh (including acellular dermal matrix) can reduce complication rates. However, numerous surgical and implant advancements have occurred in the decades since the initial prepectoral studies, and it is unclear whether mesh is solely responsible for the touted benefits. METHODS: The authors conducted a systematic review of all English language articles reporting original data for prepectoral implant-based breast reconstruction. Articles presenting duplicate data were excluded. Complications were recorded and calculated on a per-breast basis and separated as mesh-assisted, no-mesh prior to 2006, and no-mesh after 2006 (date of first silicone gel-filled breast implant approval). Capsular contracture comparisons were adjusted for duration of follow-up. RESULTS: A total of 58 articles were included encompassing 3120 patients from 1966 to 2019. The majority of the included studies were retrospective case series. Reported complication outcomes were variable, with no significant difference between groups in hematoma, infection, or explantation rates. Capsular contracture rates were higher in historical no-mesh cohorts, whereas seroma rates were higher in contemporary no-mesh cohorts. CONCLUSIONS: Limited data exist to understand the benefits of surgical mesh devices in prepectoral breast reconstruction. Level I studies with an appropriate control group are needed to better understand the specific role of mesh for these procedures. Existing data are inconclusive but suggest that prepectoral breast reconstruction can be safely performed without surgical mesh.

The Intersection of Mechanotransduction and Regenerative Osteogenic Materials.

Mechanical signals play a central role in cell fate determination and differentiation in both physiologic and pathologic circumstances. Such signals may be delivered using materials to generate discrete microenvironments for the purposes of tissue regeneration and have garnered increasing attention in recent years. Unlike the addition of progenitor cells or growth factors, delivery of a microenvironment is particularly attractive in that it may reduce the known untoward consequences of the former two strategies, such as excessive proliferation and potential malignant transformation. Additionally, the ability to spatially modulate the fabrication of materials allows for the creation of multiple microenvironments, particularly attractive for regenerating complex tissues. While many regenerative materials have been developed and tested for augmentation of specific cellular responses, the intersection between cell biology and material interactions have been difficult to dissect due to the complexity of both physical and chemical interactions. Specifically, modulating materials to target individual signaling pathways is an avenue of interdisciplinary research that may lead to a more effective method of optimizing regenerative materials. In this work, the aim is to summarize the major mechanotransduction pathways for osteogenic differentiation and to consolidate the known materials and material properties that activate such pathways.

Long-Term Effect of Multiple Operations on Psychosocial Function in Teenage Cleft Lip and Palate Patients.

BACKGROUND: Cleft lip and palate patients undergo a significant number of interventions during their childhood and adolescence. Although the intention of such interventions is to improve psychosocial functioning, there exists a paucity of data on the psychosocial outcomes of the burden of care on cleft children. In this work, the long-term effects of quantity and timing of childhood operations on teenagers with cleft lip and palate were evaluated. METHODS: Cleft lip and palate patients (aged 14 to 17 years; n = 55) and an age-matched unaffected cohort (n = 14) prospectively enrolled from two institutions were administered the anger, anxiety, and depressive symptoms instruments from the Pediatric Patient-Reported Outcomes Measurement Information System. Total number of operations and operations stratified by age groups (0 to 7, 8 to 10, 11 to 13, and 14 to 17 years) were evaluated in relationship to instrument scores. Descriptive statistics, independent t tests, Pearson correlations, and multiple linear regression analyses were conducted. RESULTS: No differences in overall psychosocial functioning were found between the cleft lip and palate and comparison groups. Total quantity of childhood operations did not correlate to psychosocial functioning of cleft lip and palate teenagers. However, multiple linear regression analyses demonstrated that increased number of operations in the 8- to 10-year-old age range predicted increased anxiety and depressive symptoms in teenagers (ß = 0.38, p = 0.009; and ß = 0.29, p = 0.03, respectively). CONCLUSIONS: It was previously reported by the authors' group that the 8- to 10-year-old age range is an at-risk period for psychosocial distress in children with craniofacial anomalies. Their current work demonstrates that increased number of operations during this time frame may result in long-term consequences in anxiety and depression in cleft lip and palate patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Simplifying Facial Feminization Surgery Using Virtual Modeling on the Female Skull.

Osseous work in facial feminization has been largely developed by comparing the qualitative and quantitative anthropometric differences between male and female cadaveric skulls. While virtual surgical planning has allowed for improved accuracy and ease in osteotomies and recontouring procedures in facial feminization, ultimately, a subjective decision-making process is still required. In this work, we describe a novel method of simplifying facial feminization by virtually modeling all osseous surgical maneuvers for facial feminization with a reference female skull.

The Effect of Multiple Surgeries on Psychosocial Outcomes in Pediatric Patients: A Scoping Review.

BACKGROUND: Birth defects affect 3% of all babies born in the United States each year. Unlike reconstruction for many acquired deformities, one hallmark of reconstruction for complex congenital conditions is the requirement of multiple surgeries, procedures, and therapies from birth to maturity. These interventions often result in significant medical burden on children during development with potential long-term psychosocial consequences. The aim of this study was therefore to better define the psychosocial impact of repetitive operations on the pediatric patient. METHODS: A scoping review was performed under the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Review guidelines. We searched the PubMed, Cochrane Library, Science Direct, and Web of Science databases using key words "number of surgeries," "psychosocial," "pediatric," and related terms. Primary articles published in English describing psychosocial outcomes in pediatric patients who underwent more than one procedure or surgery were included (n = 25). The Newcastle-Ottawa Scale was used to assess the quality of each study. RESULTS: We included 25 articles published between 1995 and 2019, which included 6520 patients. The most common diagnosis across all studies was congenital heart disease (CHD) (n = 4169, 63.9%), followed by cleft lip and palate (n = 1196, 18.3%). The average number of operations and procedures was 3.4 (range = 1-18) and 32.1 (range = 6-89), respectively. The association between repetitive surgeries and poorer psychosocial outcomes was demonstrated in children with early-onset scoliosis, CHD, hydrocephalus, bladder exstrophy, posterior urethral rupture, anorectal anomalies, and conditions requiring numerous nonsurgical procedures. There were also a few CHD, cleft lip and/or palate, and hydrocephalus studies that did not find a significant correlation. CONCLUSIONS: The studies here suggest that certain pediatric patient populations are at risk for impaired psychosocial functioning as a result of repetitive procedures. However, it is important to differentiate whether the association with poorer psychosocial outcomes is from the number of surgical procedures or whether the number if just a surrogate for increased disease complexity. Standardized psychosocial outcomes measures and future prospective, long-term, randomized clinical trials are also warranted.

Consolidation Time and Relapse: A Systematic Review of Outcomes in Internal versus External Midface Distraction for Syndromic Craniosynostosis.

BACKGROUND: The choice between internal and external distraction osteogenesis for midface advancement in patients with syndromic craniosynostosis is based primarily on surgeon preference and expertise. However, differences in outcomes between the two techniques have been sparingly compared. In this work, the authors performed a systematic review to compare outcomes between internal versus external midface distraction. METHODS: A systematic review was performed of studies published between 1998 and 2018 (61 studies included; n = 689 patients). Operative characteristics, early reoperations, complications, and relapse rates were extracted. Bias evaluation was performed using the Newcastle-Ottawa instrument. Statistical analyses were performed with independent samples t tests and linear regression analyses (p < 0.05 considered significant). RESULTS: The authors found that external distraction was associated with more Le Fort III osteotomies and hardware adjustments (p = 0.023), whereas internal distraction was associated with more monobloc osteotomies and longer consolidation times (p = 0.008). No significant differences in the distance of midface advancement, reoperations, complications, or relapse rates were noted between internal versus external distraction, although external distraction trended toward a slightly higher relapse rate. Regardless of distraction protocol, consolidation time was found to be a strong negative predictor for relapse (beta = -0.792; p = 0.02). CONCLUSIONS: No significant differences were demonstrated in advancement distance, reoperative rates, complication rates, or relapse rates for internal versus external distraction for midface advancement. Regardless of distraction type, consolidation time was strongly inversely associated with relapse rates. The trend toward higher relapse in external distraction is potentially explained by the significantly lower consolidation times.

Changing attitudes toward hand allotransplantation among North American hand surgeons.

OBJECTIVES: Although more than 70 hand transplants have been performed worldwide, the appropriate clinical indications for this operation are still being determined. Cost and patient exposure to the challenges of lifelong immunosuppression for what is a quality of life-improving (but not life-saving) operation are the focus of the ongoing discussion. A study performed in 2007 showed that surgeons' opinions on the issue varied widely. Recently, more information has been made available regarding long-term patient outcomes, and significant improvements in immunotherapy protocols have been reported. In light of this, we sought to examine changing attitudes regarding hand allotransplantation and its indications by surveying hand surgeons. METHODS: An email-based survey was sent to members of the American Society for Surgery of the Hand. Demographic information and practice profiles were identified, followed by their risk assessment of hand allotransplants and endorsement of performing the operation in different clinical scenarios. Additional questions focused on the appropriate indications for hand allotransplantation, as well as the procedure's associated ethical and financial implications. RESULTS: A total of 385 surgeons responded to the survey (14% response rate). The majority (82%) considered hand transplantation to be a high-risk operation (as opposed to 27% in hand replantation), with 78% citing lifelong immunosuppression as the primary factor impacting their overall risk assessment. The most commonly accepted indication for hand vascularized composite allotransplantation was loss of bilateral hands (80% in favor). Dominant hand loss (with an intact contralateral hand) was a far less frequently accepted indication (36% in favor). Patient adherence to immunosuppressive regimens (51%) and expectations of functional/aesthetic outcome (38%) were the most frequently chosen top psychosocial issues that must be addressed by the surgical/medical teams involved in the operation. CONCLUSIONS: Our study's results demonstrate increasing overall support for hand allotransplantation and increasing acceptance of today's immunosuppressive regimens compared to prior literature. Bilateral hand loss remains the primary agreed-upon indication for transplantation. Despite increasing acceptance in the surgical community, the dangers of chronic immunosuppression, cost and patient adherence continue to be the primary concerns hindering its broader acceptance.

Derivation of injury-responsive dendritic cells for acute brain targeting and therapeutic protein delivery in the stroke-injured rat.

Research with experimental stroke models has identified a wide range of therapeutic proteins that can prevent the brain damage caused by this form of acute neurological injury. Despite this, we do not yet have safe and effective ways to deliver therapeutic proteins to the injured brain, and this remains a major obstacle for clinical translation. Current targeted strategies typically involve invasive neurosurgery, whereas systemic approaches produce the undesirable outcome of non-specific protein delivery to the entire brain, rather than solely to the injury site. As a potential way to address this, we developed a protein delivery system modeled after the endogenous immune cell response to brain injury. Using ex-vivo-engineered dendritic cells (DCs), we find that these cells can transiently home to brain injury in a rat model of stroke with both temporal and spatial selectivity. We present a standardized method to derive injury-responsive DCs from bone marrow and show that injury targeting is dependent on culture conditions that maintain an immature DC phenotype. Further, we find evidence that when loaded with therapeutic cargo, cultured DCs can suppress initial neuron death caused by an ischemic injury. These results demonstrate a non-invasive method to target ischemic brain injury and may ultimately provide a way to selectively deliver therapeutic compounds to the injured brain.