Faculty Bibliography

BACKGROUND:The widespread use of next-generation sequencing has allowed refinement of the classification and diagnosis of salivary gland neoplasms, leading to identification of recurrent gene fusions in a majority of salivary gland carcinoma types, and characterization of several novel entities. A small proportion of salivary gland carcinomas do not meet the diagnostic criteria for any known tumor type and are therefore classified as "salivary gland carcinoma, not otherwise specified". Given the ever-growing arsenal of tools to classify these lesions, the number of cases diagnosed as such is expected to continue decreasing. CASE PRESENTATION/METHODS:In this article we describe a novel DLG1::BRAF fusion in a high grade salivary gland carcinoma arising in the tongue of a 78 year-old woman. This tumor had solid and cribriform architectural features and was composed of a dual population of abluminal and mucinous cells. Immunohistochemically, it had variable SOX10 expression, variable and strong MUC4 reactivity and expression of p63 and p40 (delta Np63) in the abluminal cell population. The gene fusion retained the kinase domain of BRAF, without the self-inhibitory CR1 domain, which is expected to lead to upregulation of BRAF protein. The patient had a complete resection of her tumor, without evidence of local recurrence or metastasis 10 months after diagnosis. CONCLUSION/CONCLUSIONS:These findings may represent a previously undescribed type of salivary gland tumor. However, additional reports of similar lesions are necessary for definitive characterization.

BACKGROUND:Population-based studies have linked progestin exposure to increased meningioma risk. However, the molecular basis of meningiomas associated with depot medroxyprogesterone acetate (DMPA) - a common injectable contraceptive-remains undefined. METHODS:We performed an integrated clinicopathologic and genomic analysis of meningiomas from 10 women with long-term DMPA exposure. Tumors underwent histopathological analysis, targeted sequencing, and DNA methylation profiling. Data were integrated with reference cohorts (Baylor and Heidelberg) and analyzed through classifier assignment, consensus clustering, copy number analysis, differential methylation testing, and dimensionality reduction. RESULTS:DMPA-associated meningiomas were all newly diagnosed, WHO grade 1 tumors with a predilection for the anterior and central skull base (n = 6). Nine patients harbored multiple meningiomas. Four experienced regression of untreated meningiomas following DMPA cessation, while five demonstrated stabilization. Histopathology demonstrated relative overrepresentation of metaplastic morphology, an uncommon meningioma subtype. All DMPA-associated meningiomas mapped to benign molecular groups, and most exhibited low copy number alteration burden. Targeted sequencing revealed enrichment for TRAF7 mutations (n = 5), with no NF2 mutations detected. Eight tumors shared consensus cluster identity, with cohesive grouping on principal component analysis and t-distributed stochastic neighbor embedding. No differential methylation was identified at the progesterone receptor locus. CONCLUSIONS:DMPA-associated meningiomas represent a recognizable phenotype within the broader NF2-wildtype/TRAF7-enriched spectrum of benign meningiomas, characterized by chromosomal stability, a shared methylation profile, tumor multiplicity, and regression or stabilization following DMPA cessation. While derived from a small single-institution cohort, these findings provide a molecular framework for understanding progestin-associated meningioma biology, re-interpreting epidemiologic literature, and informing population-level risk stratification.

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.

BACKGROUND:Early detection of oral potentially malignant disorders (OPMDs) and oral cavity cancer can improve patient prognosis. In this guideline, the authors address the use of vital staining, specifically toluidine blue, as an adjunct to screen adults without mucosal abnormalities and to determine the need for biopsy among adults with mucosal abnormalities in the oral cavity. TYPES OF STUDIES REVIEWED/METHODS:The authors conducted systematic searches to identify evidence on the benefits and harms of using vital staining as an adjunct as well as patient and clinician values and preferences regarding the use of this adjunct. The guideline panel used the Grading of Recommendations Assessment, Development and Evaluation Evidence to Decision framework to formulate recommendations. As part of the framework, the panel also considered the resources required, equity, acceptability, and feasibility when formulating recommendations. RESULTS:The panel formulated 2 recommendations and 2 good practice statements. For adults with and without mucosal abnormalities, the panel recommend against the use of vital staining as an adjunct (conditional recommendation, very low certainty). The good practice statements encourage clinicians to perform a clinical oral examination in all adult patients. CONCLUSIONS AND PRACTICAL IMPLICATIONS/CONCLUSIONS:Biopsy remains the first choice for obtaining a definitive diagnosis of an OPMD and oral squamous cell carcinoma. Clinical oral examination should be performed in all asymptomatic adults with no clinically evident mucosal abnormality. When implementing or adapting these recommendations, local contexts should be taken into account to ensure equitable access to early detection.

The Cattell-Imanaga reconstruction (CIR) is considered a more physiologic reconstruction after pancreaticoduodenectomy, as it promotes a more physiological mixing of alimentary and biliopancreatic secretions and facilitates endoscopic access to the anastomoses compared with traditional techniques. However, its application after total pancreatectomy (TP) has not previously been reported. This study describes the surgical technique and institutional experience with CIR, named modified CIR (mCIR), in patients undergoing open TP at a high-volume pancreatic surgery center. The mCIR positions the gastro-/duodeno-jejunostomy (G/DJ) proximally and the hepatico-jejunostomy (HJ) distally on a single transmesocolic limb. 89 patients underwent open TP with mCIR. Both en bloc and stepwise TP were performed; stepwise was mainly used for positive frozen margins (51.7%), high POPF risk (34.8%), or need for vascular resection to reduce POPF-related vascular complications (12.4%). Grade B-C biliary fistula occurred in 6.7% of patients, cholangitis secondary to hepatico-jejunostomy (HJ) stricture in 2.2%, delayed gastric emptying (DGE) in 11%, and duodeno-jejunostomy (DJ) leakage in 1.1%. An endoscopic interventional approach was generally preferred for the management of HJ complications. Major morbidity and 90-day mortality were 23.6% and 3.4%, respectively. The readmission rate was 9.7%, mainly due to infected or symptomatic collections. This is the first study to describe mCIR following TP and to report postoperative outcomes in line with previously reported results for traditional reconstruction techniques.

Many individuals hospitalized due to severe viral infections develop mental and physical sequelae, which could potentially be prevented by targeted interventions for those at risk. Our goal was to develop and externally validate an algorithm for predicting mental and physical symptoms after SARS-CoV-2 hospitalization utilizing routinely collected clinical data. Participants were included from two independent samples of the German National Pandemic Cohort Network (NAPKON): a model development sample (SUEP; N = 451; mean age: 55.6 ± 15.3; 36.2% female) and an external validation sample (HAP: N = 158; mean age: 55.1 ± 12.1; 39.9% female). Machine learning models leveraging demographic, clinical and biological variables collected at the time of admission were employed to predict Patient-Reported Outcomes Measurement Information System scores (PROMIS) across 7 domains (physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles and activities, and pain) three months after SARS-CoV-2 hospitalization. Shapley Additive exPlanation values were used to provide interpretable information about key predictive factors. Approximately 15-20% of participants reported moderate to severe impairment in at least one PROMIS domain three months after hospitalization. For the mental health composite score, the best-performing model achieved RMSE = 1.833 ± 0.341 and R² = 0.927 ± 0.031 in SUEP and RMSE = 3.131 and R² = 0.893 in HAP. For the physical health composite, the best-performing model achieved RMSE = 2.908 ± 0.703 and R² = 0.824 ± 0.052 in SUEP and RMSE = 3.019 and R² = 0.850 in HAP. Furthermore, the models achieved high predictive performance across all individual PROMIS domain scores in both samples. We provide an externally validated methodology for accurately predicting mental and physical symptomatology following hospitalization due to a severe viral infection. This approach may facilitate the development of a brief risk stratification tool at the point of hospitalization, enabling early identification of at-risk patients, improving the prediction accuracy of subsequent psychological and physical sequelae, and supporting timely preventive interventions.

Although mandibular implant-supported overdentures demonstrate high survival rates, uncertainty remains regarding their long-term biologic stability and maintenance burden, particularly across different attachment systems. Sixty edentulous patients were fitted with two-implant mandibular overdentures either by locator-type or ball retainers and followed up to a 5 years. At last follow-up, the survival rate of implants was 98.3% and 93.3% in terms of prostheses success; mean change of marginal bone was low. Maintenance requirements were frequent and mostly minor including insert/ matrix replacement and relines. Hence, long-term success is to be measured not just by survival.

The mammalian interstitium is a body-wide network of fluid-filled, prelymphatic spaces. Recent studies demonstrate that it exists at three scales in continuity both within and between organs, comprising intercellular, pericapillary, and large (or fascial) interstitial spaces, the latter including fascia, dermis, organ submucosae and capsules, vascular adventitia, and perineurium. Hyaluronic acid fills all interstitial spaces, but large interstitial spaces also contain additional structurally complex and varied extracellular matrices that support soluble factor, mechanical, and potentially electrical signaling. Here we review areas where the new anatomic concept of the interstitium has led to the re-examination of previous findings, including data on interstitial matrix composition and cell trafficking. We also identify new questions arising specifically from the finding that the interstitium is multiscale and body-wide, including questions about the characteristics and drivers of interstitial fluid flow and the role of the interstitium as a rich and active basolateral signaling compartment.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic caused significant global harm. Seroprevalence studies detected antibody increases from SARS-CoV-2 infection, assessing transmission and risk from infection. These studies and epidemiological modeling informed public health policy and behavior. Biases in early seroprevalence analyses caused underestimation of fatality risk, including the risk posed to pediatric populations and to those in lower-income nations. The scope of the pandemic was clarified by seroprevalence studies that better assessed at-risk groups and by adjustment of seroprevalence data for known data biases. Reassessment of seroprevalence data confirms the accuracy of early modeling. Public health authorities should inform the public of this modeling success and of the limitations of early seroprevalence analyses. This will prepare the public to better assess global health risk during future pandemics.