Faculty Bibliography

Peri-implantitis, characterized by inflammation of peri-implant tissues and progressive bone loss, remains a major biological complication affecting long-term implant success. Material composition, surface characteristics and biocompatibility influence microbial colonization, host immune response and implant durability. Therefore, it is of interest to investigate the relationship between different dental implant materials and the incidence of peri-implantitis among patients treated at a tertiary dental center. Clinical parameters including probing depth, bleeding on probing, radiographic bone loss, plaque index and type of implant material were recorded and analyzed. Data shows that surface roughness and alloy composition influence peri-implant tissue response, with implants exhibiting rougher surfaces and greater plaque accumulation showing higher inflammation levels. Thus, we show that appropriate material selection, optimized surface engineering and meticulous maintenance are essential strategies to minimize peri-implantitis risk and ensure long-term implant stability.

PURPOSE/OBJECTIVE:Effective immunotherapy for mismatch repair proficient colorectal cancer (CRC) is lacking. We examined the safety and efficacy of the novel next-generation immune activator/Fc-enhanced CTLA-4 inhibitor botensilimab (BOT) plus PD-1 inhibitor balstilimab (BAL) in the neoadjuvant setting for patients with resectable CRC. PATIENTS AND METHODS/METHODS:Patients 18 years of age or older with non-metastatic CRC awaiting surgical resection were eligible. BOT/BAL was administered followed by surgical resection. In cohort A, patients received BOT 75 mg d1 and BAL 240 mg d1, 15; in cohorts B/C, patients received 2 additional BAL doses (d29, 43). The primary study objectives were safety, feasibility (based on surgery delay), and pathologic response. Exploratory analyses examined changes in the tumor microenvironment. RESULTS:Twenty-four eligible patients (26 tumors, n=22 pMMR; n=4 dMMR) were enrolled (two patients had synchronous primary tumors). Neoadjuvant BOT/BAL was safe and did not delay planned surgery in any patient. The major pathologic response rate was 41% (95% CI, 21%-64%) for pMMR, and 100% (95% CI, 40%-100%) for dMMR CRC. BOT/BAL was associated with significant anti-tumor effects in the tumor microenvironment, with an increase in the density and proportion of CD8+ T cells, a reduction in tumor infiltrating FOXP3+ Tregs, and evidence of increased immune cell-cell interaction in responding patients. CONCLUSIONS:These findings demonstrate safety, feasibility, and encouraging pathological responses for BOT/BAL in both non-metastatic pMMR and dMMR CRC. Tumor microenvironment remodeling suggests a robust anti-tumor immune response induced by immunotherapy. These data support the continued development of BOT/BAL in CRC.

BACKGROUND:Tumour-infiltrating lymphocytes (TILs) are a robust prognostic marker in patients with triple-negative breast cancer. Artificial intelligence (AI)-derived computational tools assessing TILs could improve efficiency, but require independent validation against clinical outcomes. We aimed to compare the prognostic performance of AI-derived TIL scores with pathologist-scored TILs in a large, prospectively collected dataset pooled from randomised controlled trials. METHODS:CATALINA was an independent, external validation study using prospectively collected long-term clinical outcome data pooled from seven randomised clinical trials conducted at multiple sites. We independently evaluated two previously validated AI pipelines that generate five computationally assessed tumour-infiltrating lymphocyte (cTIL) scores by masked, independent deployment of locked models. cTIL scores were correlated with the mean of the pathologist-scored stromal TILs (sTILs) in 220 digitised haematoxylin and eosin whole slide images in a cohort of patients with early-stage triple-negative or HER-2 positive breast cancer, previously scored by trained pathologists in a TIL-reproducibility study. Prognostic performance was assessed in a separate cohort of patients with early triple-negative breast cancer pooled from seven prospective, randomised adjuvant trials. Multivariable Cox regression models adjusted for clinicopathological factors and study heterogeneity assessed associations of cTIL score and sTIL score with invasive disease-free survival, distant disease-free survival, and overall survival. 5-year discrimination was estimated using time-dependent area under the receiver operating characteristic curve (AUC). FINDINGS/RESULTS:Individual data were collated from 1759 patients, of whom 1356 had complete clinicopathological data, pathologist sTIL scores, and cTIL scores available. Modest correlation (r 0·375-0·473) was observed between cTIL scores and the mean pathologist sTIL score. Both sTIL and cTIL were independently associated with 5-year invasive disease-free survival, distant disease-free survival, and overall survival after adjustment for clinicopathological factors (hazard ratio for invasive disease-free survival was 0·73 [95% CI 0·66-0·82]; q<0·0001, distant disease-free survival was 0·70 [0·61-0·79]; q<0·0001, and overall survival was 0·72 [0·63-0·82]; q<0·0001 for sTIL scores and 0·80 [0·73-0·89]; q<0·0001, 0·77 [0·69-0·86]; q<0·0001, and 0·79 [0·70-0·88]; q=0·0002, respectively, for percentage_lymphocyte scores). In models adjusted for clinicopathological variables and sTIL score, cTIL score did not maintain a statistically significant prognostic association. Both sTIL and cTIL scores improved the 5-year AUC over clinicopathological variables alone, while cTIL score did not significantly further improve AUC when combined with clinicopathological variables and sTIL score. INTERPRETATION/CONCLUSIONS:Two cTIL models deployed entirely without retraining or modification provided statistically significant prognostic information and improved risk discrimination compared with clinicopathological variables alone in this large, platform-based, independent validation study. Although cTIL score did not incrementally improve prognostication compared with models combining clinicopathological variables with sTIL score, these findings support the application of cTILs as a reproducible prognostic biomarker, particularly in settings where routine or widespread pathologist assessment is unavailable. FUNDING/BACKGROUND:Breast Cancer Research Foundation (USA).

BACKGROUND/UNASSIGNED:The potential of methadone maintenance treatment (MMT) to address the opioid crisis has been limited by restrictive federal and local policies that require frequent clinic visits for medication. Unprecedented federal regulatory changes started in early COVID-19 and were made permanent in 2024, allowing clinics increased flexibility in granting take-home medication to patients. Medicaid payment policies can profoundly shape provider behaviors but may not align with regulatory changes. METHODS/UNASSIGNED:We conducted a systematic synthesis of Medicaid MMT payment and billing policies among 40 states over March 2020-July 2025. RESULTS/UNASSIGNED:More than half of the states continued to adopt a per-dose or per-diem approach to paying for methadone dosing and a per-service approach to paying for addiction counseling, thus tying Medicaid revenue closely to clinic visits. More than one-quarter maintained a flat bundled payment dating back to prepandemic era that provided little incentive for granting patients more than 1 week of take-home medication. Adoption of a 2-tiered bundled payment modeled after Medicare's payment increased over time but remained limited. CONCLUSION/UNASSIGNED:Medicaid payment policies for MMT saw limited changes over the 5 years following initial federal regulatory changes. Practice changes toward more flexible and patient-centered care may be hindered without compatible changes in payment approaches.

BACKGROUND:Non-English-speaking individuals have noted disparities in health outcomes in the United States, but the role of language in obstetric settings is not well characterized. OBJECTIVE:We examined the association between primary spoken (preferred) language and the risk of nulliparous, term, singleton vertex cesarean delivery. STUDY DESIGN/METHODS:We conducted a retrospective cohort study of nulliparous, term, singleton vertex deliveries in California (2016-2021) using birth certificates linked to hospital discharge records. The primary outcome was the risk of cesarean delivery. Poisson log-linear regression was used to estimate the association between preferred language and cesarean delivery overall, adjusted for demographic, hospital, and obstetric factors. Analyses were stratified by labor type (pre-labor versus intrapartum), risk characteristics (standard versus high risk), and hospital characteristics (hospital type [academic versus nonacademic], setting [urban versus non-urban], and annual hospital cesarean delivery volume by sample tertiles). RESULTS:Among 721,263 birthing people in California, 87,538 (12.1%) indicated that their preferred language was not English and 359,988 (49.9%) had no measured medical comorbidities (termed standard risk). Non-English speaking patients had a decreased risk of cesarean delivery (adjusted relative risk 0.94, 95% confidence interval 0.92-0.96), including among Chinese- (adjusted relative risk 0.83, 95% confidence interval 0.79-0.86) and Spanish-speaking patients (adjusted relative risk 0.94, 95% confidence interval 0.93-0.97), although non-English speaking birthing people who preferred languages other than Spanish or Chinese had slightly higher risk of cesarean delivery (adjusted relative risk 1.06, 95% confidence interval 1.02-1.10). There was a decreased cesarean risk among non-English speaking patients across labor types (spontaneous labor or prelabor rupture of membranes: adjusted relative risk 0.94, 95% confidence interval 0.89-1.00; induced labor: adjusted relative risk 0.90, 95% confidence interval 0.87-0.93; no indication of either: adjusted relative risk 0.97, 95% confidence interval 0.95-1.00), among standard risk patients (adjusted relative risk 0.95, 95% confidence interval 0.92-0.97), and across hospital type, setting, and annual cesarean delivery volume tertile. A small decrease in cesarean risk was also observed in teaching (adjusted relative risk 0.93, 95% confidence interval 0.91-0.96) and non-teaching hospitals (adjusted relative risk 0.95, 95% confidence interval 0.92-0.97), urban settings (adjusted relative risk 0.93, 95% confidence interval 0.92-0.95), and highest volume tertile (adjusted relative risk 0.93, 95% confidence interval 0.91-0.95), though there was no increase risk in non-urban settings (adjusted relative risk 1.02, 95% confidence interval 0.95-1.11) and across lowest and middle volume tertiles (adjusted relative risk 1.01, 95% confidence interval 0.92-1.11; and adjusted relative risk 0.95, 95% confidence interval 0.91-0.98, respectively). CONCLUSION/CONCLUSIONS:Non-English language preference was associated with a slight decreased risk for cesarean delivery among nulliparous, term, singleton, and vertex presenting patients, and an increased risk among people who spoke other languages (i.e., not Chinese or Spanish). Our findings suggest that populations that speak less common non-English languages in California may be at elevated risk of disparate cesarean delivery outcomes.

Objective Pediatric traumas are high-stakes yet relatively low-frequency events, limiting resident exposure and learning. We developed a low-cost, accessible virtual reality (VR) experience using 360-degree video to supplement pediatric trauma education and explored resident perceptions of its usability, relevance, and educational value. Methods We performed a mixed-methods descriptive study at an academic pediatric emergency department. Residents used VR headsets to experience a simulated pediatric blunt abdominal trauma resuscitation which was created with 360-degree video equipment. Interactive access points embedded within the video allowed for review of pediatric-specific considerations and Advanced Trauma Life Support concepts. Pediatric and Emergency Medicine residents provided feedback via anonymous survey with five-point Likert items assessing comfort, ease of use, usefulness, applicability, and interest in curricular integrations. Free-text responses and semi-structured interviews underwent qualitative analysis to extract themes. Results Forty-two residents completed the surveys. Most reported the experience was comfortable (n=40, 95.2%) and easy to use (n=42, 100%). Participants rated VR as useful compared with traditional resources (n=42, 100%) and applicable to clinical care (n=41, 97.6%). The majority supported incorporation of VR into the curriculum (n=38, 90.5%) and 69.0% (n=29) would use headsets for independent learning. Qualitative themes highlighted realism, improved appreciation of team dynamics, and the ability to pause for reflection. Learners requested greater interactivity and embedded knowledge checks. Conclusion A 360-degree video VR experience was a feasible and positively perceived supplementary educational modality for pediatric trauma training. Learners valued its immersive and flexible format. Our findings reflect learner perceptions rather than objective educational outcomes. Future studies should evaluate effects on knowledge acquisition, behavioral performance, long-term retention, and patient-centered clinical outcomes.

BACKGROUND:Glioblastoma (GBM) is the most aggressive primary malignant brain tumor in adults and demonstrates substantial transcriptomic heterogeneity associated with patient survival. High-dimensional genomic datasets present statistical challenges because the number of measured molecular features often exceeds the number of available patient samples. Penalized regression methods such as Least Absolute Shrinkage and Selection Operator (LASSO) regression enable simultaneous feature selection and survival modeling in these settings. METHODS:Transcriptomic expression and survival data from The Cancer Genome Atlas (TCGA) GBM cohort were analyzed using LASSO-regularized Cox proportional hazards regression implemented through the glmnet package in R. After preprocessing and sample matching, 518 tumor samples and 12,042 transcriptomic features were retained for analysis. Patients were randomly divided into training (n=414) and test (n=104) cohorts. Ten-fold cross-validation using Harrell's concordance index (C-index) was performed to identify optimal regularization parameters. Kaplan-Meier survival analysis was used to evaluate risk stratification performance, and receiver operating characteristic (ROC) analysis was performed for selected candidate genes. RESULTS:Cross-validation identified a maximum C-index of 0.583 at the optimal lambda.min regularization parameter. The final LASSO-Cox model retained 74 genes with nonzero coefficients. Two identified genes, CLEC5A and RANBP17, overlapped with previously reported GBM prognostic genes from an independent study. Kaplan-Meier analysis demonstrated significant survival separation between predicted high-risk and low-risk groups in both the training cohort (log-rank p < 0.0001) and the held-out test cohort (log-rank p < 0.05). ROC analysis of selected candidate genes demonstrated moderate discriminatory performance, with area under the curve values ranging from 0.604 to 0.701. CONCLUSIONS:LASSO-regularized Cox regression identified sparse transcriptomic features associated with survival in TCGA GBM patients. Survival stratification performance persisted in a held-out test dataset, supporting the reproducibility of the derived transcriptomic risk model. These findings demonstrate the applicability of penalized survival modeling approaches to high-dimensional cancer transcriptomic datasets and support further investigation of transcriptomic biomarkers in GBM prognosis.