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Supplemental material, sj-docx-1-cpc-10.1177_10556656231169479 for Characterizing Cleft Rhinoplasty Across Skeletal Maturity: A Systematic Review of Terminology and Surgical Techniques by Jenn J. Park, Matteo Laspro, Fernando D. Arias, Ricardo Rodriguez Colon, Bachar F. Chaya, Danielle H. Rochlin, David A. Staffenberg and Roberto L. Flores in The Cleft Palate Craniofacial Journal

Background Many cleft centers incorporate NasoAlveolar Molding (NAM) into their presurgical treatment protocols. However, there are limited data on eligible patients who do not receive or complete NAM. This study characterizes the demographics associated with non-utilization or completion of NAM. Methods A single-institution retrospective review was performed of all patients with cleft lip and alveolus undergoing primary unilateral and bilateral cleft lip repair from 2012-2020. Patients were grouped based on utilization or non-utilization of NAM. Demographic and treatment data were collected, including documented reasons for not pursuing or completing NAM. Results Of 230 eligible patients, 61 patients (27%) did not undergo or complete NAM (no-NAM). In this group, 37 (60.7%) received no presurgical intervention, 12 (19.7%) received presurgical nostril retainers, 3 (4.9%) received lip taping, 1 (1.6%) received a combination of taping/nostril retainers, and 8 (13.1%) discontinued NAM. The most common reasons for not receiving NAM were sufficiently aligned cleft alveolus (21.3%), medical complexity (16.4%), late presentation (16.4%), and alveolar notching (18%). Compared to the NAM group, the no-NAM group had significantly lower rates of prenatal cleft diagnosis/consult, and significantly higher proportion of non-married and non-English speaking caregivers. Multivariable analysis controlling for insurance type, primary language, prenatal consult, marital status, and age at first appointment found that age at first appointment is the only statistically significant predictor of NAM utilization ( P Conclusions Common reasons for non-utilization of NAM include well-aligned cleft alveolus, medical complexity, and late presentation. Early presentation is an important modifiable factor affecting rates of NAM utilization.

BACKGROUND Skin color matching is an essential factor in achieving optimal aesthetic outcome in partial facial transplantation. However, there is no published literature evaluating the success of color matching to date. Furthermore, a medical professional's perception of an optimal color match may not necessarily translate to that of the general public. The purpose of our study was to evaluate skin color matching between the donor allograft and recipient native tissue in partial facial transplantations to determine the level of success perceived by the general public and medical professionals. METHODS Published photographs of partial face transplant recipients were used to create a survey where recipient native and donor allograft skin samples were juxtaposed. Thirty-three members of the general public and 30 medical professionals were asked to rate skin color match on a scale from "excellent match" to "not a match." RESULTS Overall, 47% of given ratings were positive, indicating an "excellent" or "good match," and 53% of ratings were negative, indicating a "poor match" or "lack of match" between the skin sample pairings shown. Of the 19 partial face transplant patients who were rated, 9 patients received >50% positive ratings, and 10 patients received

Objectives Cleft lip repair has traditionally been performed as an inpatient procedure. There has been an interest toward outpatient cleft lip repair to reduce healthcare costs and avoid unnecessary hospital stay. We report surgical outcomes following implementation of an ambulatory cleft lip repair protocol and hypothesize that an ambulatory repair results in comparable safety outcomes to inpatient repair. Design/Setting This is a single-institution, retrospective study. Patients/Participants Patients undergoing primary unilateral (UCL) and bilateral (BCL) cleft lip repair from 2012 to 2021 with a minimum 30-day follow-up. A total of 226 patients with UCL and 58 patients with BCL were included. Intervention Ambulatory surgery protocol in 2016. Outcome Measures Variables include demographics and surgical data including 30-day readmission, 30-day reoperation, and postoperative complications. Results There were no differences in rates of 30-day readmission, reoperation, wound complications, or postoperative complications between the pre- and post-protocol groups. Following ambulatory protocol implementation, 80% of the UCL group and 56% of the BCL group received ambulatory surgery. Average length of stay dropped from 24 h pre-protocol to 8 h post-protocol. The 20% of the UCL group and 44% of the BCL group chosen for overnight stay had a significantly higher proportion of congenital abnormalities and higher American Society of Anesthesiology (ASA) class. Reasons for overnight stay included cardiac/airway monitoring, prematurity, and monitoring of comorbidities. There were no differences in surgical outcomes between the ambulatory and overnight stay groups. Conclusions An ambulatory cleft lip repair protocol can significantly reduce average length of stay without adversely affecting surgical outcomes.

Objective The purpose of this study is to assess cleft rhinoplasty terminology across phases of growth. Design/Setting: A systematic review was performed on cleft rhinoplasty publications over 20 years. Interventions: Studies were categorized by age at surgical intervention: infant (15 years). Main Outcome Measures: Collected data included terminology used and surgical techniques. Results The 288 studies included demonstrated a wide range of terminology. In the infant group, 51/54 studies used the term “primary.” In the immature group, 7/18 studies used the term “primary,” 3/18 used “secondary.” In the mature group, 2/33 studies used the term “primary,” 16/33 used “secondary,” 2/33 used “definitive,” 5/33 used terms such as “mature,” “adult,” and “late,” and 8/33 did not use terminology. Surgical technique assessment demonstrated: cleft rhinoplasty at infancy used nostril rim or no nasal incision, immature rhinoplasty used closed and open rhinoplasty incisions; and mature rhinoplasty used a majority of open rhinoplasty. Infant and immature cleft rhinoplasty incorporated septal harvest or spur removal in Conclusions Current terminology for cleft rhinoplasty is varied and inconsistently applied across stages of facial development. However, cleft rhinoplasty performed at infancy, childhood, and facial maturity are surgically distinct procedures. The authors recommend the terminology “infant,” “immature,” and “mature” cleft rhinoplasty to accurately describe this procedure within the context of skeletal growth.

Supplemental material, sj-docx-1-cpc-10.1177_10556656221113997 for “Septoplasty” Performed at Primary Cleft Rhinoplasty: A Systematic Review of Techniques and Call for Accurate Terminology by Jenn J. Park, Ricardo Rodriguez Colon and Fernando D. Arias, Matteo Laspro, Bachar F. Chaya, Danielle H. Rochlin, David A. Staffenberg, Roberto L. Flores in The Cleft Palate-Craniofacial Journal

Matrix metalloproteinase-9 (MMP-9) is a secreted endopeptidase targeting extracellular matrix proteins, creating permissive environments for neuronal development and plasticity. Developmental dysregulation of MMP-9 may also lead to neurodevelopmental disorders (ND). Here, we test the hypothesis that chronically elevated MMP-9 activity during early neurodevelopment is responsible for neural circuit hyperconnectivity observed in Xenopus tadpoles after early exposure to valproic acid (VPA), a known teratogen associated with ND in humans. In Xenopus tadpoles, VPA exposure results in excess local synaptic connectivity, disrupted social behavior and increased seizure susceptibility. We found that overexpressing MMP-9 in the brain copies effects of VPA on synaptic connectivity, and blocking MMP-9 activity pharmacologically or genetically reverses effects of VPA on physiology and behavior. We further show that during normal neurodevelopment MMP-9 levels are tightly regulated by neuronal activity and required for structural plasticity. These studies show a critical role for MMP-9 in both normal and abnormal development.

ObjectivePrimary cleft nasal repair can include septal reconstruction. We hypothesize that primary cleft septoplasty and adult septoplasty have fundamental differences that render these procedures as distinct surgical entities.DesignSystematic review of the PubMed, Cochrane, and Embase databases performed on pediatric cleft and general adult septoplasty techniques through December 2021. (PROSPERO ID CRD42022295763)Main Outcome MeasuresCollected data included information on septal dissection, septal detachment, and management of the bony and cartilaginous septum.ResultsTwenty-eight pediatric cleft septoplasty and 229 adult septoplasty studies were included. Dissection in primary cleft septoplasty was limited to the anterocaudal septum, while secondary cleft septoplasty and adult septoplasty techniques entailed wide exposures of the cartilaginous septum with or without exposure of the perpendicular plate of the ethmoid. In primary cleft septoplasty, detachment of the septum was mostly limited to the nasal spine and anterior base of the cartilaginous septum, while secondary cleft septoplasty and adult septoplasty included detachment from the vomer, and ethmoid. In the few reports of cartilage excision during primary cleft septoplasty, removal was limited to the anterior inferior border of the septum, while secondary cleft septoplasty and adult septoplasty included excision of the cartilaginous and bony septum.ConclusionPrimary cleft septoplasty is distinct from septoplasty performed on facially mature patients. More specifically, septal dissection and detachment are limited to the anterior caudal area during primary lip repair, with rare removal of cartilage or bone. Given these differences, the authors suggest the term “septal reset” to describe septoplasty performed during primary cleft nasal repair.

Background Since the 1990s, the field of vascularized composite allotransplantation has gained momentum, offering unprecedented solutions for patients with defects not amenable to autologous reconstruction. As with solid organ donation, the vascularized composite allotransplant donor pool remains limited. This systematic review identifies past successes and failures in organ donation campaigns to guide future strategies for expanding vascularized composite allotransplant donation. Methods A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Three databases (PubMed/MEDLINE, PsycINFO, and Embase) were searched through July 31, 2019. The study compiled solid organ and vascularized composite allotransplant campaigns that aimed to increase donor registration. Articles depicting the current state of vascularized composite allotransplant donation were also assessed. Results Of an initial 3318 articles identified, 40 were included. Six articles described direct mail or print interventions, 10 depicted Web-based interventions, 13 dealt with interpersonal interventions, and seven used multimodal interventions. Four articles described the current state of vascularized composite allotransplant donation. A qualitative synthesis was conducted. The authors found that social media campaigns can have a robust but fleeting effect on registration trends and that interpersonal interventions are effective at increasing registration rates. In addition, the opportunity for participants to immediately register as organ donors, by means of either return mail, in-person, or online, is vital to campaign success. Conclusions Public organ donation campaigns have had success in increasing organ donor registration rates, particularly through the use of social media and interpersonal interventions that allow for immediate registration. Synthesizing this information, we propose a multimodal campaign to expand the vascularized composite allotransplant donor pool.

BACKGROUND Cross-sex vascularized composite allotransplantation has been performed in cadaveric facial transplantation and clinical extremity transplantation. Understanding the challenge of appropriate donor-recipient matching, this study sought to characterize the public's perception of cross-sex vascularized composite allotransplantation. METHODS Participants were surveyed in New York City. Data collected included demographics and willingness to donate vascularized composite allografts (VCAs) of various types. Similar questions were asked in the context of same-sex and cross-sex donation. RESULTS A total of 101 participants (male: 56.4%; age ≤35 years: 62.4%) were surveyed. The majority expressed willingness to donate to recipients of a different sex (hand: 78.2%, face: 56.4%, penis or uterus: 69.3%, lower limb: 81.2%, abdominal wall: 80.2%, larynx: 81.2%, and solid organs: 85.2%). Among VCAs, willingness to donate facial allografts was significantly different in same-sex versus cross-sex contexts (64.4% vs 56.4%; P = 0.008). Participants were also significantly more likely to donate VCAs to same-sex recipients on behalf of themselves versus loved ones (P < 0.05). There was significantly lower willingness to receive cross-sex versus same-sex facial (P = 0.022) and genital allografts (P = 0.022). Education on the preservation of recipient masculinity or femininity in cross-sex facial transplantation increased participants' willingness to receive a cross-sex face transplant from 56.4% to 71.3% (P = 0.001). CONCLUSIONS This study highlights the urban public's acceptance of VCA donation or reception regardless of sex mismatch. There is increased willingness to receive a cross-sex face transplant after education, highlighting opportunities for future focused interventions to increase public awareness and ultimately the donor pool.

Matrix metalloproteinase-9 (MMP-9) is a secreted endopeptidase targeting extracellular matrix proteins, creating permissive environments for neuronal development and plasticity. Developmental dysregulation of MMP-9 is also associated with neurodevelopmental disorders (ND). Here we test the hypothesis that chronically elevated MMP-9 activity during early neurodevelopment is responsible for neural circuit hyperconnectivity observed after early exposure to valproic acid (VPA), a known teratogen associated with autism spectrum disorder in humans. In Xenopus tadpoles, VPA exposure results in excess local synaptic connectivity, disrupted social behavior and increased seizure susceptibility. We found that overexpressing MMP-9 in the brain copies effects of VPA on synaptic connectivity, and blocking MMP-9 activity pharmacologically or genetically reverses effects of VPA on physiology and behavior. We further show that during normal neurodevelopment MMP-9 levels are tightly regulated by neuronal activity and required for structural plasticity. These studies show a critical role for MMP-9 in both normal and abnormal development.

The current standard of care for an alveolar cleft defect is an autogenous bone graft, typically from the iliac crest. Given the limitations of alveolar bone graft surgery, such as limited supply, donor site morbidity, graft failure, and need for secondary surgery, there has been growing interest in regenerative medicine strategies to supplement and replace traditional alveolar bone grafts. Though there have been preliminary clinical studies investigating bone tissue engineering methods in human subjects, lack of consistent results as well as limitations in study design make it difficult to determine the efficacy of these interventions. As the field of bone tissue engineering is rapidly advancing, reconstructive surgeons should be aware of the preclinical studies informing these regenerative strategies. We review preclinical studies investigating bone tissue engineering strategies in large animal maxillary or mandibular defects and provide an overview of scaffolds, stem cells, and osteogenic agents applicable to tissue engineering of the alveolar cleft. An electronic search conducted in the PubMed database up to December 2021 resulted in 35 studies for inclusion in our review. Most studies showed increased bone growth with a tissue engineering construct compared to negative control. However, heterogeneity in the length of follow up, method of bone growth analysis, and inconsistent use of positive control groups make comparisons across studies difficult. Future studies should incorporate a pediatric study model specific to alveolar cleft with long-term follow up to fully characterize volumetric defect filling, cellular ingrowth, bone strength, tooth movement, and implant support.

Summary: Skin color matching in vascularized composite allotransplantation (VCA) is an important determinant of aesthetic outcomes. The process of color matching is infrequently described in the literature. The Pantone SkinTone Guide (PSTG) is a handheld tool comprised of realistic skin tone swatches with a corresponding virtual swatch system. A color match acceptability threshold (AT) is defined as the point beyond which >50% of observers deem a given skin tone pairing as unacceptable. In this study, color match acceptability thresholds were developed using the PSTG to help standardize donor-recipient color matching. Four representative colors were chosen across the skin tone spectrum. These standard colors were used to develop a survey asking participants to determine the acceptability of color pairings. Using survey results, ATs were determined for changes in lightness, undertone, and lightness and undertone combined for each of the standard colors. Inter- and intra-rater reliability were determined using Fleiss’s Kappa. Participants were more critical of skin tone pairings on the darker versus the lighter end of the spectrum, as evidenced by higher thresholds observed for lighter sample pairs. Additionally, observers were more critical of differences in skin lightness compared with differences in undertone. Intra-rater reliability was fair to substantial, and inter-rater reliability was fair to moderate. The PSTG can be used as a clinical tool to improve the aesthetic outcomes of skin-containing vascularized composite allotransplantation procedures by optimizing donor-recipient skin color matching. This can allow clinicians to complement visual judgment with quantitative reference.

Although selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for prenatal depression, there exists controversy over the adverse effects of SSRI use on fetal development. Few studies have adequately isolated outcomes due to SSRI exposure and those due to maternal psychiatric conditions. Here, we directly investigated the outcomes of exposure to widely-used SSRIs fluoxetine and citalopram on the developing nervous system of Xenopus laevis tadpoles, using an integrative experimental approach. We exposed tadpoles to low doses of citalopram and fluoxetine during a critical developmental period and found that the different groups of tadpoles displayed opposing behavioral effects. While both groups showed reduced schooling behavior, the fluoxetine group showed increased seizure susceptibility and reduced startle habituation. In contrast, the citalopram treated tadpoles had decreased seizure susceptibility and increased habituation. Both groups had abnormal dendritic morphology in the optic tectum, a brain area important for all three behaviors tested. Whole-cell electrophysiological recordings of tectal neurons showed no differences in synaptic function across groups; however, tectal cells from fluoxetine-treated tadpoles had decreased voltage gated K+ currents while cells in the citalopram group had increased K+ currents. Both the behavior and electrophysiological findings indicate that cells and circuits in the fluoxetine treated optic tecta are hyperexcitable, while the citalopram group exhibits decreased excitability. Taken all together, these results show that early developmental exposure to SSRIs is sufficient to induce neurodevelopmental effects, however these effects can be complex and vary depending on the SSRI used. This may explain some of the discrepancies across human studies, and further underscores the importance of serotonergic signaling for the developing nervous system.