PurposeTo investigate the molecular basis of posterior polymorphous corneal dystrophy (PPCD) by examining the PPCD transcriptome and the effect of decreased ZEB1 expression on corneal endothelial cell (CEnC) gene expression.MethodsNext-generation RNA sequencing (RNA-seq) analyses of corneal endothelium from two PPCD-affected individuals (one with PPCD3 and one of unknown genetic cause) compared with two age-matched controls, and primary human CEnC (pHCEnC) transfected with siRNA-mediated ZEB1 knockdown. The expression of selected differentially expressed genes was validated by quantitative polymerase chain reaction (qPCR) and/or assessed by in situ hybridization in the corneal endothelium of four independent cases of PPCD (one with PPCD3 and three of unknown genetic cause).ResultsExpression of 16% and 46% of the 104 protein-coding genes specific to ex vivo corneal endothelium was lost in the endothelium of two individuals with PPCD. Thirty-two genes associated with ZEB1 and 3 genes (BMP4, CCND1, ZEB1) associated with OVOL2 were differentially expressed in the same direction in both individuals with PPCD. Immunohistochemistry staining and RNA-seq analyses demonstrated variable expression of type IV collagens in PPCD corneas. Decreasing ZEB1 expression in pHCEnC altered expression of 711 protein-coding genes, many of which are associated with canonical pathways regulating various cellular processes.ConclusionsIdentification of the altered transcriptome in PPCD and in a cell-based model of PPCD provided insight into the molecular alterations characterizing PPCD. Further study of the differentially expressed genes associated with ZEB1 and OVOL2 is expected to identify candidate genes for individuals with PPCD and without a ZEB1 or OVOL2 mutation.

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Purpose Fibula free flaps (FFF) are the gold standard tissue for reconstruction of segmental mandibular defects. A comparison of mini-plate (MP) and reconstruction bar (RB)-based fixation of FFFs has been previously described in a systematic review. Long-term studies comparing the two plating methods are lacking. The authors aim to examine the complication profile between MPs and RBs at a single tertiary cancer center. We hypothesized that increased components and a lack of rigid fixation inherent to MPs would lead to higher rates of hardware exposure/failure. Methods A retrospective review was performed from a prospectively maintained database at Memorial Sloan Kettering Cancer Center. Patients who underwent FFF-based reconstruction of mandibular defects between 2015-2021 were included. Data on patient demographics, risk factors, operative indications, and chemoradiation was collected. Primary outcomes of interest were perioperative flap-related complications, union rates, osteoradionecrosis (ORN), return to the operating room (OR), and hardware exposure/failure. Recipient site complications were stratified into two groups: early (<90 days) and late (>90 days). Results 96 patients met inclusion criteria (RB=63, MP=33). Patients in were similar with respect to age, comorbidities, smoking history, and operative characteristics. The mean follow-up period was 17.24 months. There were no differences in rates of hardware failure overall; however, in patients with an initial complication after 90 days, MPs had significantly higher rates of hardware exposure (3 vs. 0, p=0.046).  Conclusions MPs were found to have a higher risk of exposed hardware in patients with a late initial recipient site complication. It is possible that improved fixation with highly adaptive RBs designed by computer-aided design/manufacturing (CAD/CAM) technology explains these results. Future studies are needed to assess the effects of rigid mandibular fixation on patient reported outcome measures in this unique population.

Supplement, 100th Annual Meeting Display EPosterslip repair between 2012-2021 comparing surgical outcomes before and after protocol implementation in 2016. The ambulatory protocol selected non-syndromic patients without airway or cardiac abnormalities and involved morning surgery, long-lasting local anesthesia, and parental education with direct access to the clinical team. Variables included patient demographics, operative details, length of stay, and surgical outcomes including 30-day readmission and 30-day reoperation.RESULTS: 261 patients met study criteria. The pre-protocol and post-protocol groups contained 99 and 162 patients, respectively, with no differences in rates of 30-day readmission, reoperation, or wound complications. Following protocol implementation, 130 (80%) patients underwent ambulatory surgery, and average length of stay decreased from 24 to 8 hours (p<0.05). The 32 patients staying overnight had higher rates of other congenital abnormalities (40.6%) than the ambulatory group (8.6%), with higher ASA class (p<0.05). Ambulatory and overnight stay patients had no differences in surgical outcomes.CONCLUSION: An ambulatory cleft lip repair protocol incorporating morning surgery, patient stratification, and parental education allows for safe ambulatory surgery, reducing length of stay without adversely affecting surgical outcomes.