Faculty Bibliography

INTRODUCTION/BACKGROUND:The tear trough is one of the areas that most reflects aging. The anatomy of the preseptal, premaxillary, prezygomatic and deep pyriform spaces are essential for successful planning of filler treatments. MATERIAL AND TECHNIQUE/UNASSIGNED:This work analyzes the anatomic relationship between the origin of the orbital septum and the tear trough/ orbicularis retaining ligaments, and between the anatomical spaces and the cheek fat compartments, to classify patients who undergo a filler treatment for tear trough deformity. Patients are classified in 'innie' or 'outie' and blending technique is described based on this classification. RESULTS:A total of 38 patients were evaluated, comprising 21 females and 17 males, with a mean age of 53 years (range, 31-72 years). The mean follow-up period was 10.4 months (range, 5-22 months). All patients presented with an innie-type tear trough deformity. Prior to treatment, 76.3% of patients (n = 29) were classified as Hirmand Type II, and 23.7% (n = 9) as Type III. Following treatment, 84.2% (n = 32) of patients were rated as "very much improved" (GAIS score of 1), and 15.8% (n = 6) as "much improved" (GAIS score of 2). The mean volume of hyaluronic acid injected per unilateral tear trough was 0.35 cc (range of 0.2-0.5 cc), and for the unilateral midcheek was 0.65 cc (range of 0.5 to 2 cc). No complications were reported. CONCLUSION/CONCLUSIONS:The blending technique is an effective technique to improve the appearance of the lid-cheek junction, correcting the TT deformity and the palpebromalar groove. Patients are classified as innies or outies based on the position of the AM on the orbital bone. Innie patients are more favorable to the injection of HA in the gap between AM and ORL (preseptal space) to correct the TT groove. Outie patients benefit from the volumization and support of the DMCFP, but not from direct injection into the TT and preseptal space. LEVEL OF EVIDENCE V/METHODS:This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

BACKGROUND:Current staging systems for head and neck cutaneous squamous cell carcinoma (HNCSCC), such as AJCC8 and BWH, often fail to adequately stratify high-risk patients, particularly due to the exclusion of important biological and host factors. This study aimed to identify independent prognostic factors for HNCSCC outcomes in the largest multi-institutional retrospective series to date. METHODS:De-identified data from 8,610 primary HNCSCC tumors, treated with curative intent surgery across multiple international centers, were analyzed. Outcomes included local recurrence (LR), locoregional metastasis (LM), distant metastasis (DM), and disease-specific death (DSD). Multivariable Fine-Gray subdistribution hazard regression models with robust standard errors clustered at the patient level were fitted to generate exploratory hypotheses regarding independent hazard determinants. RESULTS:During a median follow-up of 31.4 months (IQR 14.2-52.8), the cumulative incidence was 3.3% for LR, 2.7% for LM, 0.5% for DM, and 1.2% for DSD. Multivariable analysis confirmed that tumor diameter, poor differentiation, deep invasion, and large-caliber perineural invasion (LCPNI) were the strongest predictors, being significantly associated with at least three of the four outcomes. Notably, factors currently excluded from or weighted differently in staging systems also proved critical: Immunosuppression was significantly associated with LR (SHR 2.03) and DSD (SHR 1.70); and lymphovascular invasion (LVI) was independently associated with LM (SHR 3.00). Poor differentiation demonstrated high prognostic impact, being a significant predictor for all four endpoints. CONCLUSION/CONCLUSIONS:Tumor diameter, poor differentiation, deep invasion, LCPNI, immunosuppression status, and LVI are the most critical independent factors for HNCSCC prognosis. Our multi-institutional data provide a robust framework for hypothesis generation, highlighting that incorporating host biological features and non-anatomic variables could significantly refine future staging system discussions.

BACKGROUND/UNASSIGNED:Concomitant ocular and facial trauma (COFT) can result in devastating functional, aesthetic, and psychosocial consequences, including vision loss. Standard reconstructive techniques often fall short in addressing the intricate needs of these injuries, making advanced techniques, such as combined facial transplantation and whole-eye transplantation (FT-WET), promising solutions. This study characterizes COFT patients to define a population that may benefit from FT-WET. METHODS/UNASSIGNED:A retrospective analysis of the National Trauma Data Bank (2018-2022) was conducted to identify COFT patients using International Classification of Diseases, Tenth Revision diagnosis codes. Patients were stratified into surgical and nonsurgical cohorts based on the presence of major surgical interventions targeting the face or eye. Characteristics of each group were compared. RESULTS/UNASSIGNED:< 0.001) were also more common in this group. CONCLUSIONS/UNASSIGNED:Surgical COFT patients represent a younger population with more complex injuries, aligning with favorable characteristics for potential FT-WET candidates. This study identified a distinct population of COFT patients who may benefit from FT-WET, providing critical insights into candidate selection and injury patterns.

BACKGROUND:Gastroparesis is a chronic disorder characterized by delayed gastric emptying without mechanical obstruction, significantly impacting patient quality of life. Management of refractory gastroparesis remains challenging, with both gastric electrical stimulation (GES) and prokinetic medications used as treatment options. This systematic review synthesizes the available evidence on GES clinical outcomes, the role of continued prokinetic therapy after GES, and indirect comparative data relevant to symptom management in adult patients with refractory gastroparesis. METHODS:A comprehensive systematic review was conducted following PRISMA guidelines. Multiple databases were searched for studies published between 2000 and 2011 focusing on GES for gastroparesis. This window was selected to capture the period from initial FDA Humanitarian Device Exemption approval of the Enterra system (2000) through publication of cohorts with mature, multi-year follow-up (up to 10 years), maximizing the durability evidence available for analysis. Inclusion criteria required adult patients with refractory gastroparesis, GES as primary intervention, symptom-related outcomes, and minimum 6-week follow-up. Eight studies met eligibility criteria with follow-up periods ranging from 6 weeks to 10 years. Quality assessment utilized the Newcastle-Ottawa Scale for cohort studies and Cochrane risk-of-bias tools for controlled trials. RESULTS:Gastric electrical stimulation (GES) demonstrated significant symptom improvement in patients with treatment-resistant gastroparesis. Controlled studies showed vomiting frequency reduction of 57% at 6 weeks, improving to 67.8% after one year (p < 0.001). Long-term data revealed ≥ 50% reduction in Total Symptom Scores in 58% of diabetic gastroparesis patients, 53% of post-surgical cases, and 48% of idiopathic gastroparesis patients (p < 0.05) (Fig. 3; Table 2). Combination therapy (GES plus prokinetics) yielded significantly better symptom scores (1.35) compared to GES alone (2.20, p = 0.02). Device-related infection requiring removal occurred in approximately 7% of cases. No direct head-to-head comparisons between GES and prokinetic medications alone were identified. CONCLUSION/CONCLUSIONS:GES provides substantial symptom relief for treatment-resistant gastroparesis, particularly in diabetic gastroparesis. Combination therapy with GES plus prokinetics appears superior to GES monotherapy. However, the absence of direct comparative studies limits definitive conclusions regarding relative effectiveness versus prokinetic medications alone. Future randomized controlled trials are needed to establish optimal treatment protocols and patient selection criteria along with the role of other surgical approaches. Planned next steps include direct comparisons of GES with pyloric-directed interventions - namely gastric per-oral endoscopic myotomy (G-POEM) and surgical pyloroplasty - to clarify the optimal positioning of GES within the contemporary treatment algorithm for refractory gastroparesis.

BACKGROUND/UNASSIGNED:Frontline (1L) treatment for transplant-eligible (TE) newly diagnosed multiple myeloma (NDMM) has shifted from triplet (e.g. bortezomib [V], lenalidomide [R], dexamethasone [d]) to quadruplet (e.g. daratumumab with VRd [DVRd]) regimens, based on improved efficacy demonstrated in pivotal trials. This real-world study compared progression-free survival (PFS) in TE patients with NDMM treated with DVRd plus DR or R maintenance (DVRd-DR/R) versus VRd plus R maintenance (VRd-R). METHODS/UNASSIGNED:Adult TE patients with NDMM who initiated DVRd-DR/R or VRd-R between 1 January 2020 and 30 June 2022 were identified through a retrospective chart review at 10 US sites. PFS was assessed using Kaplan-Meier analyses and propensity score-weighted hazard ratios (HR) were estimated using Cox regression. RESULTS/UNASSIGNED:= 0.006). CONCLUSION/UNASSIGNED:Findings aligned with pivotal trials, demonstrating the significant PFS benefit of 1L DVRd over VRd and supporting its real-world use for TE NDMM.

BACKGROUND/UNASSIGNED:During the last 20 years, the novel and highly visible nature of facial transplantation (FT) has posed a dual and potentially conflicting obligation for FT programs: to disseminate findings for scientific advancement while respecting recipients' preferences for privacy, given the significant public and media attention. The individually identifying nature of FT is not present in other forms of vascularized composite allotransplantation, making it unique. Despite extensive ethical discourse on FT, implications for privacy are largely absent from ethical analyses. METHODS/UNASSIGNED:This conceptual analysis assesses the complex ethical implications associated with privacy in FT and offers guidance to FT programs for navigating concerns related to donors, recipients, and their families. A literature review was performed and supplemented by our institutional experience. RESULTS/UNASSIGNED:Ethical approaches to privacy require balancing the conflicting ethical principles at the center of this dual obligation. Patient-centered strategies should include comprehensive psychological screening to understand patients' goals for care, informed consent that clearly addresses the dissemination of information and media involvement, and control of media coverage until the recipient is ready and willing. Public relations support for recipients has been helpful in our institution's experience. Additional community-based strategies include educational outreach interventions to satisfy public curiosity. CONCLUSIONS/UNASSIGNED:Findings from published reports alongside our institution's experience suggest that a nuanced, multifaceted approach is essential to navigate the ethical complexities of privacy in FT. Aligning key stakeholders to support FT recipients' well-being while maintaining scientific integrity reflects the ethical tension between duties to patients and obligations to advance transplant science.

IMPORTANCE/UNASSIGNED:In vivo biomarkers for detecting neuropathologies from repetitive head impacts (RHI), including chronic traumatic encephalopathy (CTE), are needed. OBJECTIVE/UNASSIGNED:To evaluate the utility of plasma phosphorylated tau 217 (p-tau217), assess its performance as a beta-amyloid (Aβ) biomarker in participants with RHI exposure at risk for CTE, and explore concordance with CTE neuropathology in a postmortem subsample. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This longitudinal, multicenter, case-control study used data from the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of CTE (DIAGNOSE CTE) Research Project, collected from September 2016 to October 2023. Participants were former American football players (case participants) and asymptomatic men unexposed to RHI (control participants). A subsample had available neuropathologic data. EXPOSURES/UNASSIGNED:RHI, traumatic encephalopathy syndrome (TES) diagnoses, and levels of CTE certainty. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Plasma p-tau217 (classified as positive [≥0.63 pg/mL], intermediate [0.40-0.62 pg/mL], and negative [<0.40 pg/mL]), Aβ-positron emission tomography (PET; 18F-florbetapir; with Aβ-positive defined as a standardized uptake value ratio [SUVR] ≥1.10), and tau-PET (18F-flortaucipir). TES diagnoses were assigned by multidisciplinary consensus conference. Analyses of postmortem brains controlled for age, race, and APOE ε4 status. RESULTS/UNASSIGNED:Among 231 participants (mean [SD] age, 57.75 [8.25] years), 177 were former football players (117 professional and 60 college) and 54 were unexposed participants. Former football players had higher baseline mean (SD) p-tau217 concentrations than unexposed participants (0.35 [0.26] pg/mL vs 0.27 [0.14] pg/mL; P = .008), although this was driven by a higher proportion of Aβ-PET-positive participants among former players. Plasma p-tau217 increased over time across the sample (B = 0.207 [95% CI, 0.117-0.298]; P < .001), with no significant time × exposure group interactions. Among football players, p-tau217 showed no time × group interactions with TES diagnosis, TES-CTE certainty, or RHI metrics. Higher p-tau217 concentration correlated with higher global Aβ-PET SUVR (B = 0.058 [95% CI, 0.053-3.501; P = .01), with a few discordant cases (5 participants were p-tau217-negative and Aβ-PET-positive; 7 participants were p-tau217-positive and Aβ-PET-negative). P-tau217 had similar areas under the curve for projecting Aβ-PET positivity as cerebrospinal fluid (CSF) p-tau181/Aβ42 and CSF Aβ40/42 measures (p-tau217: AUC, 0.88 [95% CI, 0.80-0.96]; CSF p-tau181/Aβ42: AUC, 0.89 [95% CI, 0.79-1.00]; CSF Aβ40/42: AUC, 0.85 [95% CI, 0.72-0.98]). Among 9 brain donors, 6 had CTE (stages II-IV; none with Alzheimer disease). Seven had negative or intermediate p-tau217, concordant with Aβ-PET. Two p-tau217 outliers with stage III CTE had normal concentrations upon additional testing. CONCLUSIONS AND RELEVANCE/UNASSIGNED:The findings of this study suggest that plasma p-tau217 concentration is unlikely to be useful for the detection of CTE, but it does show utility for ruling out Aβ pathology in participants at risk for CTE.