Faculty Bibliography

Localized treatment of oligometastatic liver disease can improve both local control and survival. The liver is a frequent site of metastases from colorectal, breast, and lung cancers, but most patients are not eligible for surgical resection due to lesion number, location, or comorbidities. For these patients, non-surgical ablative methods such as radiofrequency ablation (RFA) and stereotactic body radiotherapy (SBRT) and increasingly microwave ablation (MWA) are used. RFA was used as the primary comparator in this review because it represents the most historically established and widely reported ablative modality in the comparative radiotherapy literature. While RFA has been the traditional approach, SBRT is emerging as a promising alternative, offering precise, non-invasive treatment. SBRT may be especially useful for larger lesions or tumors in locations where RFA is difficult to perform. However, high-quality evidence and large-scale trials are still needed to confirm its efficacy and define its role. This review compares the strengths and limitations of both methods and provides practical guidance for clinical decision-making in the treatment of patients with inoperable liver metastases.

Meckel's cartilage is a central structure in mandibular morphogenesis, but how developing muscles establish their attachment to the mandible in relation to Meckel's cartilage remains unclear. In this study, we investigated the fetal development of the mouse mylohyoid attachment site using histological analysis, immunohistochemistry, in situ hybridization, and three-dimensional reconstruction, with particular attention to SOX9 and Scleraxis (Scx), markers associated with cartilage and tendon development. At E13.5, the mylohyoid attachment site was located close to the inferior aspect of Meckel's cartilage, and SOX9-positive mesenchymal cells were observed between the mylohyoid muscle bundle and Meckel's cartilage. During subsequent development, the intramembranous mandibular bone extended into the space between Meckel's cartilage and the mylohyoid attachment site. By E17.5, the mylohyoid attachment site was closely associated with the mandibular bone. SOX9 expression was detected at the developing attachment site from E13.5 to E17.5, whereas Scx mRNA expression was detected transiently and became progressively reduced during this period. Three-dimensional reconstruction further supported the developmental shift in the spatial relationship among Meckel's cartilage, the mandibular bone, and the mylohyoid attachment site. These findings suggest that Meckel's cartilage may serve as a transient anatomical framework associated with early organization of the mylohyoid attachment site before definitive attachment to the mandibular bone is established.

Toxicity of prenatal ethanol leading to fetal alcohol spectrum disorders (FASDs) has been linked to disturbances in retinoic acid (RA) signaling necessary for embryonic development. While ethanol exposure in the postnatal day 7 (P7) mice, which induces immediate neurodegeneration and long-lasting GABAergic cell loss and behavioral deficits, has been used for the third trimester FASD model, involvement of RA signaling in the process has not been well explored. Using RARE-LacZ reporter mice that express β-galactosidase (β-Gal) under the control of retinoic acid response element (RARE), we examined RA signaling activity of the forebrains of P8 and P30 mice with or without P7 ethanol treatment. In all experimental groups, β-Gal was expressed mainly in the hippocampus with the strongest expression in the granule cell layer of dentate gyrus. In addition, β-Gal was expressed in pyramidal neurons and parvalbumin (PV) neurons in CA1-3 pyramidal layer and in astrocytes scattered around the CA1-3 region although PV neurons were only examined at P30 because of the low PV expression at P8. β-Gal was also expressed in the anteroventral/anteromedial (AV/AM) thalamus and the retrosplenial (Rs) and Tbr1-positive (+) layer 6 cortices. β-Gal-expressing PV neurons were also found in the cortex such as Rs, while β-Gal was barely detected in somatostatin neurons in any brain regions examined. Such region and cell specific β-Gal expression was significantly higher in P8 brains than P30 brains in various brain regions. P7 ethanol reduced β-Gal expression in the CA1-3 pyramidal layer, Tbr1 + cortical layer 6, and the AV/AM thalamus at P8 or P30 or both. Although P7 ethanol decreased PV cells in CA2-3 pyramidal layers as reported, it decreased β-Gal+ PV cells more drastically. The active RA signaling found in PV neurons and the effects of P7 ethanol on the signaling suggest that reduced RA signaling by P7 ethanol may disturb PV cell maturation and enhance long-lasting brain abnormalities.

BACKGROUND:Identifying oral potentially malignant disorders and oral cavity cancer early can lead to better patient outcomes. The guideline panel evaluated the usefulness of light-based adjuncts for screening adults without mucosal abnormalities and for determining the need for biopsy among adults with mucosal abnormalities in the oral cavity or on the lip. TYPES OF STUDIES REVIEWED/METHODS:The authors conducted a living systematic review to evaluate evidence on the benefits and harms of light-based adjuncts and a scoping review to assess people and clinician values and preferences regarding the use of light-based adjuncts and biopsy of mucosal abnormalities. The guideline panel used this evidence to formulate recommendations according to the Grading of Recommendations Assessment, Development and Evaluation Evidence to Decision framework. The framework also guided the panel's consideration of required resources, equity, acceptability, and feasibility in shaping the final recommendations. RESULTS:The guideline panel formulated 2 recommendations and 2 good practice statements. For adults with and without mucosal abnormalities, they formulated conditional recommendations against the use of light-based adjuncts on the basis of very low certainty evidence. The good practice statements urge clinicians to perform a clinical oral examination in all adult patients. CONCLUSIONS AND PRACTICAL IMPLICATIONS/CONCLUSIONS:Biopsy remains the reference standard for establishing a definitive diagnosis of an oral potentially malignant disorder and oral squamous cell carcinoma. All adults should undergo a clinical oral examination in primary care settings. When implementing or adapting these recommendations, local contexts should be considered to promote equitable access to early detection.

BackgroundPostoperative care following endoscopic sinus surgery (ESS) aims to optimize mucosal healing, reduce inflammation, and minimize infectious complications. Although saline irrigation is considered standard of care, the potential benefit of adding topical antibiotics, such as mupirocin, during the early postoperative period remains uncertain.ObjectiveTo evaluate whether short-term postoperative mupirocin nasal irrigation improves clinical, endoscopic, and microbiological outcomes compared with saline irrigation alone following ESS.MethodsThis prospective, randomized, double-blinded, placebo-controlled trial included adults with chronic rhinosinusitis undergoing ESS. Patients were randomized to receive either mupirocin (0.05%) nasal irrigation or placebo saline irrigation twice daily for 21 days postoperatively. Outcomes assessed within the first 3 months included patient-reported symptoms using the sinonasal outcomes test (SNOT-22) and visual analog scale (VAS), endoscopic findings (mucosal edema, polyp formation, crusting, granulation tissue, and purulence), postoperative sinus culture results, and need for systemic antibiotics.ResultsSixty-eight patients were enrolled, and 56 completed follow-up. Both groups demonstrated significant postoperative improvement in SNOT-22 and VAS scores compared with preoperative baseline, without significant between-group differences. However, the mupirocin group showed significantly lower rates of endoscopic mucosal edema and polyp formation at 1 month postoperatively. Negative postoperative cultures were also more frequent in the mupirocin group, with reduced need for systemic oral antibiotics. No significant differences were observed in crusting, granulation tissue, purulence, steroid use, or pain medication requirements.ConclusionShort-term prophylactic postoperative mupirocin nasal irrigation after ESS does not confer additional improvement in patient-reported quality-of-life outcomes compared with saline alone but appears to reduce early inflammatory endoscopic changes, bacterial culture positivity, and need for systemic antibiotics. Larger studies with longer follow-up are needed to confirm these findings.

Acute coronary syndrome (ACS) requires prompt treatment, yet management delays are difficult to identify. In this study, we developed a large language model (LLM) system to identify ACS management delays and characterized delay cases. Admissions to internal medicine residents at NYU July 2022-June 2025 (n=4,642) were included. Prompts were validated to determine if the resident admission note documented initiation of ACS management and if the initial cardiology consult note documented initiation of ACS management (ground truth) (n=161 for each). Discordant cases were reviewed by three physicians using a validated tool to confirm management delays. Demographics and key clinical findings of patients with and without delays were compared. The LLM identified management delays with a 52% positive predictive value (n=35/67). Patients who were older, females, and with preferred language other than English or Spanish were more likely to have a management delay (73.4 ± 15.3 vs 68.5 ± 12.6 years-old, p=0.036, 56.8% vs 34% females, p=0.014, and 27.0% vs 15.5% other preferred language, p=0.046, in management delay vs non-management delay cases). The management delay group had longer average time in hours to receiving heparin, aspirin, and cardiac catheterization (56.91 ± 56.78 vs 18.97 ± 13.76, p<0.001, 13.94 ± 16.64 vs 8.23 ± 9.82, p=0.005, and 65.12 ± 51.65 vs 39.51 ± 44.19, p=0.006, respectively in management delay vs non-management delay cases). In conclusion, the LLM-based system we developed to identify ACS management delays can detect cases at scale to inform individual and systems-level interventions to improve quality of ACS care.

Hypomethylating agents (HMA) and allogeneic hematopoietic stem cell transplantation (alloHSCT) have both demonstrated remissions in VEXAS; however, comparative data is lacking. We conducted a multicenter, retrospective analysis of 66 patients diagnosed with VEXAS syndrome treated with HMA (n = 35) or alloHSCT (n = 31). Baseline characteristics such as genetics, co-morbidities, and performance status were balanced between the groups, except older age in the HMA group. Median follow-up from therapy initiation was 18 months (95% CI: 11-26), and 14 (21%) deaths were reported (alloHSCT n = 3; HMA n = 11). Among all evaluable patients within the alloHSCT cohort, all patients achieved molecular remission, and a substantial proportion of patients discontinued glucocorticoids (58%). In contrast, HMA therapy was associated with lower but meaningful rates of molecular remission (22%) and glucocorticoid discontinuation (6%). In a real-world setting, HMA therapy was associated with a high discontinuation rate related to toxicity or lack of response. On multivariable analysis adjusted for age and Charlson Comorbidity Index, alloHSCT was associated with improved overall survival (HR = 0.20, 95% CI: 0.05-0.81; p = 0.024). This association remained consistent across multiple ancillary sensitivity analyses, including restriction to transplant-eligible patients, patients aged ≤ 75 years, 1:1 matching, and propensity score-based weighted analyses. Although limited by retrospective design, these findings suggest that alloHSCT remains an attractive and potentially curative strategy in selected patients with VEXAS. Prospective validation of these findings is warranted.

PURPOSE/OBJECTIVE:This narrative review summarizes an artificial intelligence (AI)-integrated digital workflow that enables a seamless, multidisciplinary approach to dental diagnosis and treatment planning, aiming to improve diagnostic coordination, efficiency, and interdisciplinary communication. STUDY SELECTION/METHODS:All studies selected for this narrative review were extracted from the PubMed database. Forty studies were selected, of which 24 were used for general information and 16 were used for the statistical analysis of accuracy of AI software within data acquisition, treatment planning, and clinical implementation. RESULTS:The digital workflow was divided into three phases: data acquisition, treatment planning, and AI data analysis for decision support. Six articles reported the accuracy outcomes for AI-integrated data acquisition tools, such as intraoral scanners (IOS), cone-beam computed tomography (CBCT), facial scanners (FS), and jaw motion trackers (JMT); seven reported AI performance in assisting treatment planning; and three assessed the clinician acceptance rate of AI-supported decisions. IOS, CBCT, FS, and JMT achieved 88-97% overall accuracies. The integrated convolutional neural network and recurrent neural network models obtained 87-98% overall accuracy for treatment planning. Finally, the AI-generated treatment plan obtained 75-95% clinician acceptance rate. CONCLUSIONS:By integrating the IOS, CBCT, FS, and JMT, a comprehensive virtual patient can be created to facilitate seamless communication and effective treatment planning. This AI-integrated workflow may enhance interdisciplinary coordination and treatment planning. However, prospective clinical studies are required to validate their effects on patient outcomes and satisfaction.

Cocaine produces widely recognized rewarding effects, but also produces aversive effects that occur several minutes after rewarding effects dissipate. Prior work shows these aversive effects are particularly strong in some animals, in whom they produce conditioned avoidance effects that reduce overall cocaine-seeking. The sources of these individual variations are largely unknown, but we found evidence for contributions from heritable influences. Using outbred male and female Sprague-Dawley (SD) and Heterogeneous Stock (HS) rats, we found that offspring of individuals expressing higher versus lower levels of conditioned avoidance to cocaine on a runway operant task are themselves higher or lower in this trait. These results did not differ between sexes, and are consistent with a heritable influence driving conditioned avoidance of cocaine, which could either be genetic or non-genetic. Runway latency to obtain cocaine also differed markedly between seven inbred rat strains (tested in males only), again consistent with a heritable influence. Several control tasks showed that variations in cocaine avoidance were not explained by differences in exploratory locomotion, overall motivation, or resistance of food-seeking to footshock punishment. Notably, the latter punishment resistance task has been linked to addiction-like behaviors in its own right, and performance on this task also varied considerably between inbred strains, but did so independently of cocaine avoidance. Hence, punishment resistance and cocaine avoidance may be influenced by independent heritable factors.Significance statement Cocaine's strong rewarding effects critically drive drug intake, but this intake can be reduced by cocaine's aversive effects, which occur a few minutes after rewarding effects dissipate, and whose intensity varies considerably between animals. Using inbred rat strains and selective breeding we show that conditioned avoidance to cocaine may have a substantial heritable component, which could be either genetic or non-genetic. We also show that aversive effects of cocaine vary independently of other aversive tasks, including resistance to punishment.