Faculty Bibliography

OBJECTIVE:Study the prevalence of otologic disease in a pediatric post-palatoplasty population with no prior ear tube placement in resource-deprived countries and assess patient characteristics associated with these abnormal results. DESIGN/METHODS:Retrospective data review. PARTICIPANTS/METHODS:Ecuadorian and Chinese children identified during humanitarian cleft lip and palate repair trips with cleft palates undergoing palatoplasty from 2007 to 2010. INTERVENTIONS/METHODS:Tympanometry and otoacoustic emission (OAE) testing performed following palatoplasty. Patients' parents administered surveys regarding perceived hearing deficits. MAIN OUTCOME MEASURES/METHODS:Age, gender, Veau classification, follow-up time, laterality, and country of origin were evaluated for possible association with type B tympanogram, "Refer" Otoacoustic results, and presence of hearing difficulty as identified by a parent. Significant predictors were further evaluated with multivariate analysis. RESULTS:The cohorts included 237 patients (129 Ecuadorian, 108 Chinese); mean age: 3.9 years; mean follow-up: 4.2 years. Thirty-nine percent scored type B, 38% failed OAE testing, and 8% of parents noted hearing deficits. The country of origin and a younger age were identified as predictive variables regarding type B tympanogram. Follow-up time, country of origin, and bilateral OAE "Refer" results all significantly predicted parental questionnaire results. Subsequent multivariable analysis further demonstrated effect modification between the 2 variables of age at palatoplasty and country of origin when predicting type B vs type A tympanometry. CONCLUSION/CONCLUSIONS:Without otologic intervention, cleft palate children in resource-deprived settings suffer type B tympanometry and failed OAE results with similar to increased incidences to other studied cleft palate populations with otologic interventions available.

While many of the basic tenants of upper lid blepharoplasty remain constant regardless of skin type, the thick-skinned eyelid patient requires special consideration. The brow may be naturally lower in the thick-skinned patient. These patients are more prone to having the brow pulled downward while attempting to remove redundant skin. There may also be more fat in the medial and central compartments. There may be fat in a lateral compartment overlying the lacrimal gland. Patient's expectations for a deep lid sulcus and complete excision of redundant skin may not be possible. They are more prone to an observable scar, a small dog ear at the lateral wound edge, and prolonged postoperative lid edema. Patients with lifelong upper lid fullness must get some input from significant others because their upper face aesthetic will change. In these patients, the eyelid surgery is not a rejuvenation, but a creation.

Mandibular reconstruction presents unique functional and aesthetic challenges to the reconstructive surgeon. This review will cover current techniques for mandibular reconstruction, including the various plating strategies for rigid fixation, the choice of osseous donor site, and the concurrent reconstruction of associated soft tissue defects. Recent developments and future horizons in mandibular reconstruction including the use of virtual surgical planning and tissue engineering will also be addressed.

Programmed cell death-1 (PD-1) is an essential inhibitory receptor in T cells. Antibodies targeting PD-1 elicit durable clinical responses in patients with multiple tumor indications. Nevertheless, a significant proportion of patients do not respond to anti-PD-1 treatment, and a better understanding of the signaling pathways downstream of PD-1 could provide biomarkers for those whose tumors respond and new therapeutic approaches for those whose tumors do not. We used affinity purification mass spectrometry to uncover multiple proteins associated with PD-1. Among these proteins, signaling lymphocytic activation molecule-associated protein (SAP) was functionally and mechanistically analyzed for its contribution to PD-1 inhibitory responses. Silencing of SAP augmented and overexpression blocked PD-1 function. T cells from patients with X-linked lymphoproliferative disease (XLP), who lack functional SAP, were hyperresponsive to PD-1 signaling, confirming its inhibitory role downstream of PD-1. Strikingly, signaling downstream of PD-1 in purified T cell subsets did not correlate with PD-1 surface expression but was inversely correlated with intracellular SAP levels. Mechanistically, SAP opposed PD-1 function by acting as a molecular shield of key tyrosine residues that are targets for the tyrosine phosphatase SHP2, which mediates PD-1 inhibitory properties. Our results identify SAP as an inhibitor of PD-1 function and SHP2 as a potential therapeutic target in patients with XLP.

LINE-1/L1 retrotransposon sequences comprise 17% of the human genome. Among the many classes of mobile genetic elements, L1 is the only autonomous retrotransposon that still drives human genomic plasticity today. Through its co-evolution with the human genome, L1 has intertwined itself with host cell biology. However, a clear understanding of L1's lifecycle and the processes involved in restricting its insertion and intragenomic spread remains elusive. Here we identify modes of L1 proteins' entrance into the nucleus, a necessary step for L1 proliferation. Using functional, biochemical, and imaging approaches, we also show a clear cell cycle bias for L1 retrotransposition that peaks during the S phase. Our observations provide a basis for novel interpretations about the nature of nuclear and cytoplasmic L1 ribonucleoproteins (RNPs) and the potential role of DNA replication in L1 retrotransposition.

Importance: Otoplasty is performed to correct prominauris, one of the most common head and neck congenital deformities. Advances in combination hybrid approaches enable surgeons to achieve greater precision and accuracy. Objective: To describe a hybrid cartilage-modifying approach and evaluate the procedure's effectiveness and safety. Design, Setting, and Participants: Medical record review including patients undergoing otoplasty by the present technique from January 2006 to December 2016 as performed by the senior author at a tertiary academic referral center. Twenty-three patients underwent 24 total procedures including both bilateral (n = 17) and unilateral (n = 7) procedures. Two procedures were revisions. Interventions: Hybrid cartilage-modifying otoplasty procedure. Main Outcomes and Measures: Preoperative and postoperative measurements were recorded. Paired sample t testing was performed to assess changes between preoperative superior, middle, and inferior helical measurements and corresponding postoperative measurements for all operated ears. Two-tailed, independent sample t testing was performed to compare postoperative differences between right and left ears within separate superior, middle, and inferior measurements in patients undergoing bilateral otoplasty. Results: Twenty-four surgeries were performed on 23 patients. The mean (SD) age at surgery was 16.3 (13.6) years with 13 patients (58%) between the ages of 4 and 10 years. Preoperatively, the mean (SD) superior, middle, and inferior helical rim-to-mastoid distance of the 41 discrete ears measured 16.5 (3.1) mm, 24.1 (3.8) mm, and 19.3 (4.4) mm, respectively. Mean (SD) postoperative measurements were 12.1 (2.4) mm, 14.7 (2.5) mm, and 14.0 (2.8) mm, respectively, for mean (SD) decreases of 4.4 (2.7) mm, 9.4 (3.4) mm, and 5.3 (3.6) mm. For the 17 bilateral procedures, the mean (standard error) postoperative scores between ears measured 0.7 (0.9) mm for the superior, 0.5 (0.9) mm for the middle, and 0.2 (1.0) mm for the inferior. The unaffected ear was measured in 4 of 7 (57%) of patients undergoing unilateral otoplasty, and the mean (SD) postoperative differences between left and right ears were 1.3 (0.8) mm, 3.0 (1.2) mm, and 1.0 (0.7) mm for the superior, middle, and inferior, respectively. Preoperative-to-postoperative differences for all ears (n = 41) were significant (P < .001 for all) for superior, middle, and inferior measurements. There were no significant absolute differences identified for superior (P = .41), middle (P = .58), and inferior (P = .88) measurements regarding left vs right postoperative comparisons for bilateral otoplasties. One patient undergoing bilateral repair required subsequent revision surgery of 1 ear. Two patients developed chronic suture site irritation, and 1 patient developed a hematoma. Conclusions and Relevance: The present technique allows multiple opportunities to adjust the auricular parameters. The results indicate a low revision rate and high degree of symmetry. Level of Evidence: 4.

Importance: Severe anterior septal deviation and resultant nasal obstruction represent a difficult surgical task to correct. The goal of surgery is to straighten the anterior dorsal and caudal struts, while maintaining nasal tip and midvault support. This study presents a novel extracorporeal septoplasty technique to straighten the crooked anterior septum. Objective: To describe the novel anterior septal transplant technique, which consists of complete resection of the caudal septum and reconstruction with extended spreader grafts and a columellar strut, without a separate caudal septal replacement graft. Design, Setting, and Participants: This study was a retrospective case series at a tertiary academic referral center. Participants were sequential adult patients undergoing anterior septal transplant from January 1, 2008, to December 31, 2015. Main Outcomes and Measures: Patient-reported nasal obstruction using Nasal Obstruction Symptom Evaluation (NOSE) scores and objective photographic analysis. Nasal tip deviation, projection, and rotation were measured. Preoperative and postoperative outcomes were compared. Complications are reported. Results: Seventy-one patients (mean age, 46 years [age range, 16-72 years]; 48 [67.6%] female and 23 [32.4%] male) were included in the case series. Postoperative NOSE scores (mean [SD], 24.00 [24.58]) were significantly better than preoperative NOSE scores (mean [SD], 72.25 [14.55]) (P < .001). A separate cohort of 32 patients (mean age, 42 years [age range, 13-72 years]; 23 [71.9%] female and 9 [28.1%] male) had photographs available for analysis. In the frontal view, nasal deviation improved from a mean (SD) of 2.9 (2.0) degrees before surgery to a mean (SD) of 1.4 (1.7) degrees after surgery (P = .004). In the base view, the deviation was corrected from a mean (SD) of 4.9 (2.8) degrees to a mean (SD) of 1.7 (1.2) degrees (P < .001). Tip rotation and projection were unchanged after surgery. Four patients had mild dorsal irregularities after surgery. Conclusions and Relevance: Anterior septal transplant by the described technique is a safe and effective treatment option for severe anterior septal deviation. Level of Evidence: 4.