Faculty Bibliography

PURPOSE/OBJECTIVE:XPO1 functions in key cellular processes, including nucleo-cytoplasmic export and mitosis. The gene is deleted in a subset of patients with the 2p15p16.1 microdeletion syndrome, however no monogenic XPO1-related disorder has been described to date. MATERIALS AND METHODS/METHODS:We collected clinical data of individuals with de novo XPO1 variants through online matchmaking. We employed Drosophila to study XPO1 function in development and habituation learning. RESULTS:A total of 22 individuals met the criteria to be included in the main study cohort. Of these, half have putative loss-of-function variants and half have coding variants (10 missense and 1 in-frame deletion variant). We find an overlapping phenotype, consistent with a monogenic neurodevelopmental disorder (NDD). We demonstrate XPO1 functions in development by ubiquitous and neuron-specific knockdown in Drosophila. GABAergic neuron specific knockdown flies demonstrated impaired habituation. CONCLUSION/CONCLUSIONS:Our results establish XPO1 as a novel dominant monogenic NDD gene and demonstrate a central role for XPO1 in development.

BACKGROUND:This study evaluates the Presurgical Lip, Alveolus, and Nose Approximation (PLANA) technique as a novel alternative to NasoAlveolar molding (NAM). The study hypothesizes that PLANA can achieve comparable Nasolabial outcomes to NAM while addressing its limitations, particularly by reducing the burden of care. METHODS:A retrospective review was conducted on 50 patients with non-syndromic unilateral or bilateral cleft lip and palate (CLP) treated with either NAM (n=28, including 2 treatment discontinuations) or PLANA (n=22). The overall physical burden of care was assessed in the full cohort. A subset of 25 patients with complete unilateral CLP (PLANA n=12; NAM n=13) was further analyzed to assess changes in nasolabial anthropometric ratios between cleft and non-cleft side using standardized 2D photographs taken pre-treatment (T1) and post-treatment (T2). RESULTS:The physical burden of care was significantly lower in the PLANA group, with 61.2 % fewer total office visits (5.2 vs. 13.4; p<0.001). The PLANA group also showed 72.19 % reduction in transient reversible side effects, such as oral, nasal, and cheek irritations (18.18% [n=4] vs. 65.38% [n=17]; p<0.001). PLANA achieved a significantly greater improvement in the columellar length ratio (0.53 vs. 0.37; p = 0.026), while NAM demonstrated a greater increase in the nostril height ratio (0.29 vs. 0.39; p = 0.04). No significant differences were observed in nostril width and alar base width ratios, or columellar deviation angle between the groups. CONCLUSION/CONCLUSIONS:These findings suggest that PLANA significantly reduces the burden of care for patients with cleft lip and palate and may offer comparable nasolabial outcomes to NAM.

Patients with unilateral cleft lip and palate (UCLP) often exhibit asymmetric paranasal flatness of soft tissues. Despite clinical recognition of this asymmetry, skeletal paranasal asymmetry remains poorly quantified. Measuring skeletal landmark asymmetries can aid in planning surgical maxillary yaw corrections that simultaneously enhance paranasal symmetry and maxillary dental midline position. This study aims to quantify skeletal paranasal asymmetry in patients with UCLP. Skeletally mature patients with complete UCLP who were orthodontically prepared for orthognathic surgery between 2014 and 2023 were included in this study. Presurgical CBCTs were analyzed using Dolphin 3D. Anterior-posterior discrepancies between affected and unaffected sides were measured at the most lateral point of piriform aperture (PA) and 15 mm lateral to PA (15PA). A one-sample t test was conducted. Analysis of 30 patients (mean age 18-8 y, 17 male, 13 female, 20 left-sided, 10 right-sided) was completed. On the affected side, PA and 15PA were positioned 3.8 mm (P<0.05) and 2.4 mm (P<0.05) more posteriorly, respectively. These results suggest that skeletal paranasal asymmetry should be assessed during the pretreatment stage, as presurgical orthodontics should maintain a maxillary midline deviation toward the affected side when yaw correction is indicated. This approach facilitates simultaneous correction of piriform projection and midline alignment during surgery and may reduce the need for secondary procedures, such as malar implants or fat injections, which add cost and morbidity. This study confirms skeletal paranasal asymmetry in patients with UCLP and establishes a standardized method for measuring these deficiencies using CBCT-based skeletal landmarks.

OBJECTIVES/OBJECTIVE:To examine the feasibility of outpatient alveolar bone grafting (ABG) using Exparel (bupivacaine liposome injectable suspension) for donor site analgesia. DESIGN/METHODS:Retrospective, observational study. SETTING/METHODS:Single institution, 39-month retrospective review. PATIENTS/PARTICIPANTS/METHODS:In total, 21 patients with cleft alveolus were included in this study. INTERVENTION/METHODS:In autologous outpatient ABG procedures using a mixed open harvest and Acumed trephine method to retrieve corticocancellous bone from the iliac crest, Exparel was injected in the donor site fascia. MAIN OUTCOME MEASUREMENTS/METHODS:Postoperative data including length of stay, post anesthesia care unit narcotics delivered, and maximum pain scores were recorded. Successful outcomes were assessed by exploring 30-day complications, 30-day emergency department visits, 30-day readmissions, and ambulation at follow-up. RESULTS:The average hospital length of stay was 360.8 min. Four patients required overnight stay secondary to pain. The average doses of pain medications administered postoperatively were 198.4 mg acetaminophen, 9.3 mg ketorolac, 3.0 µg fentanyl, and 1.5 mg oxycodone. No patient reported 30-day complications secondary to donor site pain, 30-day emergency department visits, or 30-day readmissions, and there was only one case of wound dehiscence. All patients exhibited proper ambulation at follow-up and healed well from ABG. CONCLUSIONS:The use of Exparel for donor site analgesia in outpatient ABG procedures using corticocancellous grafts can result in adequate pain management and ambulation without an increased risk of complications and readmissions.

IMPORTANCE/UNASSIGNED:Catastrophic facial injury with globe loss remains a formidable clinical problem with no previous reports of reconstruction by whole eye or combined whole eye and facial transplant. OBJECTIVE/UNASSIGNED:To develop a microsurgical strategy for combined whole eye and facial transplant and describe the clinical findings during the first year following transplant. DESIGN, SETTING, AND PARTICIPANT/UNASSIGNED:A 46-year-old man who sustained a high-voltage electrical injury with catastrophic tissue loss to his face and left globe underwent combined whole eye and face transplant using personalized surgical devices and a novel microsurgical strategy at a specialized center for vascularized composite allotransplantation. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Reperfusion and viability of the whole eye and facial allografts, retinal function, and incidence of acute rejection. RESULTS/UNASSIGNED:The patient underwent a combined whole eye and face transplant from an immunologically compatible donor with primary optic nerve coaptation and conventional postoperative immunosuppression. Globe and retinal perfusion were maintained throughout the immediate postoperative period, evidenced by fluorescein angiography. Optical coherence tomography demonstrated atrophy of inner retinal layers and attenuation and disruption of the ellipsoid zone. Serial electroretinography confirmed retinal responses to light in the transplanted eye. Using structural and functional magnetic resonance imaging, the integrity of the transplanted visual pathways and potential occipital cortical response to light stimulation of the transplanted eye was demonstrated. At 1 year post transplant (postoperative day 366), there was no perception of light in the transplanted eye. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This is the first report of whole eye transplant combined with facial transplant, demonstrating allograft survival including rejection-free graft survival and electroretinographic measurements indicating retinal response to light stimuli. These data highlight the potential for clinical allotransplantation for globe loss.

OBJECTIVES/OBJECTIVE:To assess surgical instrument usage in cleft lip (CL) and cleft palate (CP) surgery and create an optimized surgical tray with an associated cost-savings analysis. DESIGN/METHODS:Prospective, observational study. SETTING/METHODS:Single institution, 6-month prospective review. PATIENTS/PARTICIPANTS/METHODS:A total of 10 primary CL surgeries and 10 primary CP surgeries were included in this study. INTERVENTION/METHODS:Complete lists of surgical instruments utilized in CL and CP surgeries were collected. UNLABELLED:Utilization fractions (UFs) were calculated as the percentages of average used instruments to averaged opened instruments per case. New optimized CL and CP surgical trays were idealized by removing instruments not used in at least 20% of cases, and a cost analysis was performed to identify potential savings. Calculation of annual potential savings was also conducted based on institutional caseload. RESULTS:The average instrument UFs were 26.0% for CL and 22.6% for CP. The estimated costs were $33.15 to $290.29 for the original CL surgical tray and $10.20 to $63.80 for the optimized tray. For CP, the original tray's cost was estimated at $38.25 to $319.00, and the optimized tray at $9.18 to $57.42. This demonstrates a cost reduction of $22.95 to $226.49 for CL and $29.07 to 261.58 for CP. CONCLUSIONS:The idealized surgical instrument tray could contribute to reducing healthcare expenditures and promoting operating room efficiency, patient safety, and environmentally friendlier operating theaters.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Inherent complex angioarchitecture associated with ethmoidal dural arteriovenous fistulas (dAVFs) can make endovascular treatment methods challenging. Many surgical approaches are accompanied by unfavorable cosmetic results such as facial scarring. Blepharoplasty incision of the eyelid offers a minimal, well-hidden scar compared with other incision sites while offering the surgeon optimal visualization of pathogenic structures. This case series aims to report an initial assessment of the safety and efficacy of supraorbital craniotomy by blepharoplasty transpalpebral (eyelid) incision for surgical disconnection of ethmoidal dAVFs. METHODS:Retrospective chart review was conducted for all patients who underwent blepharoplasty incision and craniotomy for disconnection of ethmoidal dAVFs at our institution between October 2011 and February 2023. Patient charts and follow-up imaging were reviewed to report clinical and angiographic outcomes as well as periprocedural and follow-up complications. RESULTS:Complete obliteration and disconnection of ethmoidal dAVF was achieved in all 6 (100%) patients as confirmed by intraoperative angiogram with no resulting morbidity or mortality. Periprocedural complications included one case of transient nasal cerebrospinal fluid leak that was self-limiting and resolved before discharge without intervention. CONCLUSION/CONCLUSIONS:Surgical treatment for ethmoidal dAVFs, specifically by transpalpebral incision and supraorbital craniotomy, is a safe and effective treatment option and affords the surgeon greater access to the floor of the anterior fossa when necessary. In addition, blepharoplasty incision addressed patient concerns for facial scarring compared with other incision sites by creating a more well-hidden, minimal scar in the natural folds of the eyelid for patients with an eyelid crease.

Patients with cleft lip and palate (CLP) characteristically present with maxillary hypoplasia and class III malocclusion. Protraction headgear (PHG) is a commonly used treatment for this type of malocclusion, with the goal of reducing future surgical needs. The purpose of this study was to evaluate the long-term effects of PHG treatment and determine the pretreatment predictors of long-term PHG success in patients with CLP. Twenty-nine patients with CLP who had undergone PHG treatment from 2012 to 2017 at a single institution were retrospectively analyzed. Patients were included if they had a lateral cephalogram or CBCT before, immediately after, and at least 5 years after their PHG treatment. Patients were divided into surgery and nonsurgery groups based on their 5-year follow-up clinical presentation. Student t tests, Wilcoxon signed-rank test, and a multivariate logistic regression model were used to compare pretreatment and post-treatment changes in both groups. Immediately post-treatment, the maxilla advanced 2.6 mm, the maxillary dentition advanced 4.7 mm, and the mandible rotated downward 5.0 mm and backward 2.6 mm. At long-term follow up the maxilla advanced 0.0 mm while the mandible advanced an additional 7.5 mm. Thus, PHG treatment is effective at improving class III malocclusion in the short term, but may not prevent future surgical need for patients with more severe skeletal discrepancies. Variables predictive of future surgical need include ANB, anterior facial height, overjet, and starting age of treatment, with ANB as the most reliable early predictor.