Faculty Bibliography

All life-stages of Atlantic tomcod from the Hudson River (HR) estuary, New York, are highly resistant to toxicity from coplanar PCBs and TCDD, and this resistance results from a six-base-pair deletion in the Aryl hydrocarbon receptor 2 (ahr2) gene. Tomcod in the HR estuary are also exposed to high levels of PAHs; however, their sensitivity to toxicity from a suite of PAHs has yet to be evaluated. Based on preliminary studies, we hypothesized that HR tomcod are also resistant to PAH toxicity, but not as strongly as to PCBs and TCDD, and that the magnitude of resistance will vary among structurally diverse PAHs. In this study, tomcod adults were collected from the HR and tributaries of Cobscook Bay in Downeast Maine, bred, their embryos exposed for 48 h to graded doses of PCB126 and four structurally diverse PAHs (BaA, BaP, BkF, and DMBA), and the responses of young life-stages were compared at a variety of toxic endpoints that are likely mediated by ahr2 and are representative of adult fitness. HR tomcod embryos were highly resistant, by at least 100-fold to toxicity from PCB126 at all endpoints investigated. They also exhibited resistance to all four PAHs, although the strength of the resistance phenotype varied among the different toxic endpoints. We also found that the resistance phenotype varied among the four PAHs with it being strongest for BaA and BkF. We conclude that HR tomcod are resistant to PAHs, but the magnitude of the resistance phenotype is significantly less than for PCBs.

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:In principle, whole-genome sequencing of Staphylococcus aureus in hospitals is most effective when used prospectively, but its practical limits are unclear. METHODS:We performed large-scale genomic surveillance across two interconnected hospitals, sequencing 4,779 S. aureus isolates from admission screening and clinical cultures. Integration of genomic and epidemiologic data identified 361 transmission events undetected by standard surveillance. RESULTS:Despite dense sampling, most events (90%) were detected only at readmission, indicating that transmission escapes recognition during the index hospitalization. Serial or discharge screening is likely required to capture transmission. Detection depended on sampling: clinical isolates alone were insufficient, and nearly all events required screening and repeated sampling. CONCLUSIONS:Because such approaches are unlikely to scale if applied universally, surveillance must be targeted. Transmission concentrated in methicillin-resistant strains, and it increased when healthcare exposure coincided with hospital-associated strain lineage. These findings help define the limits of prospective genomic surveillance and provide a framework for targeted detection.

Scans constitute an important role in cancer management. "Scanxiety", or scan-associated anxiety, is commonly experienced by patients undergoing cancer-related scans. Although more patients are turning to the internet and social media platforms such as YouTube for health information, few studies have evaluated the scanxiety content presented in these online resources. This study aims to evaluate YouTube videos and webpages available to patients relating to scanxiety. YouTube was searched using pre-defined scanxiety search terms and a Google search analysis for the term scanxiety was carried out and results from the first two pages were collected in August 2024. YouTube videos and webpages were evaluated using the validated DISCERN quality criteria for consumer health information and the Agency for Healthcare Research and Quality Patient Education Materials Assessment Tool (PEMAT). To assess accessibility of reading content, the Flesch-Kincaid reading level was determined for each webpage. Three independent reviewers performed video and webpage analysis. There were 82 videos and 18 webpages included in the analysis. Videos had a mean independent-reviewer rated quality DISCERN score of 1.8 out of 5, which was between low and moderate quality. Websites showed a higher mean quality DISCERN score of 2.7 out of 5. Despite better quality of information, websites were written at a higher reading level than that of the general population, limiting accessibility. Both videos and webpages had low actionability as patient education materials. Efforts are needed to improve scanxiety-related patient education as the number of patients living with cancer and requiring cancer-related scans has significantly increased.

IMPORTANCE/UNASSIGNED:Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) lacks proven relapse-preventive therapies. While clinical trials are ongoing, safety data may be limited and approved drugs are costly. Studies of interleukin 6 receptor blocker (IL-6RB) in MOGAD are limited by small numbers and no comparative studies, contributing to low use. OBJECTIVE/UNASSIGNED:To evaluate the impact of IL-6RB therapy on relapse rates in MOGAD and compare relapse frequency with intravenous immunoglobulin (IVIG). DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This international, multicenter, retrospective cohort study (January 1, 2015, through December 31, 2025) included a historical IVIG-treated cohort of varying doses. The study took place across sites in North and South America (US, Canada, Mexico, Argentina, Brazil, Chile, Colombia, and Peru). Patients with MOGAD (n = 116, no excluded patients) who received at least 1 dose of an IL-6RB were included. These data were analyzed in January 2026. EXPOSURES/UNASSIGNED:Tocilizumab or satralizumab. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Annualized relapse rate (ARR) during IL-6RB therapy, time to next relapse after treatment initiation, and adverse events. Outcomes were compared with the IVIG cohort using inverse probability of treatment weighting (IPTW) adjusted for age, sex, prior ARR, and concomitant therapies. RESULTS/UNASSIGNED:A total of 116 patients with MOGAD (89% relapsing) receiving IL-6RB (tocilizumab, 104 [90%] and satralizumab, 12 [10%]) were included; overall, 60.3% were female, 39.7% were male, and 18% were younger than 18 years. The median (IQR) IL-6RB treatment follow-up was 1.4 (0.7-2.5) years and 23 relapses occurred during 241.8 person-years of IL-6RB therapy. The ARR decreased from 0.64 (95% CI, 0.58-0.70) for relapsing MOGAD before IL-6RB to 0.09 (95% CI, 0.06-0.14) during IL-6RB treatment (incidence rate ratio, 0.08; 95% CI, 0.04-0.16). Adverse events occurred in 58 patients (50%), most commonly mild infections, although 10 (9%) had severe infections. In the IVIG cohort (n = 59), 30 relapses occurred over 133.8 person-years (ARR, 0.22; 95% CI, 0.15-0.32). After IPTW, IL-6RB was associated with a lower hazard ratio (HR) than the group who underwent IVIG therapy less than 1 g/kg every 4 weeks (HR, 4.5; 95% CI, 2.0-9.8), with no significant difference vs the group who underwent IVIG 1 g/kg or more every 4 weeks (HR, 2.0; 95% CI, 0.8-4.5). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this multicenter observational cohort, IL-6RB use in MOGAD was associated with low relapse rates and a favorable safety profile, though severe infections occurred occasionally. Relapse rates were lower than the group who underwent IVIG less than 1 g/kg every 4 weeks but not significantly different from the group who underwent IVIG 1 g/kg or more every 4 weeks. This supports IL-6RB as a potential relapse-prevention therapy in MOGAD; the wide availability and relative affordability of tocilizumab may enable broad global use.

PURPOSE/OBJECTIVE:To assess whether adding fluoropyrimidine sensitized radiotherapy (CXRT) to adjuvant chemotherapy improves overall survival (OS) after curative intent resection of the pancreatic head. METHODS:This was a multicenter, randomized phase III, two step trial. Step 1: gemcitabine versus gemcitabine + erlotinib (previously reported). Step 2: random assignment to sixth chemotherapy cycle ± CXRT after five cycles of step 1 chemotherapy without progression. Outcomes of step 2 random assignment are reported here. Assuming 17 months median OS (chemotherapy alone), the sample size was 354 patients (hazard ratio [HR], 0.76, 80% power, one-sided α = .05, 316 OS events). OS/disease-free survival (DFS) were estimated by Kaplan-Meier and arms compared using the log-rank test. RESULTS:= .014) in node-negative patients. CONCLUSION/CONCLUSIONS:Overall, the addition of adjuvant CXRT to adjuvant gemcitabine did not statistically significantly improve OS, DFS, or increase grade 4/5 toxicity. For node-negative patients, CXRT improved OS and DFS. These results, if confirmed in studies with current or future systemic therapies, would support the use of adjuvant/neoadjuvant CXRT for node-negative patients.

INTRODUCTION/BACKGROUND:This study examined risk factors for schizophrenia spectrum disorder (SSD)-related hospitalization among children, adolescents, and transitional-age-youth (TAY). METHODS:A cross-sectional analysis of the nationwide inpatient sample included 618,495 inpatients aged 6-24, divided into SSD and other psychiatric illness cohorts. RESULTS:SSD accounted for 15% of psychiatric hospitalizations. Most SSD inpatients were ages 18-24 (91%), male (68.9%), and identified as Caucasian (37.7%) or African American (35.8%). Higher odds of SSD hospitalization were seen in TAY (OR=17.2), males (OR=2.5), African American (OR=2.8), and Hispanic (OR=2.06) individuals. Stimulant-related disorders (OR=1.36) and epilepsy (OR=1.24) increased risk, especially in children 6-11. Adolescents 12-17, cannabis-related disorders increased SSD hospitalization odds (OR=1.21). CONCLUSIONS:Children under 11 are more likely to be hospitalized for SSD due to stimulant-related disorders and epilepsy, while adolescents face higher risks linked to cannabis-related disorders, highlighting the need for targeted inpatient treatment.

BACKGROUND/UNASSIGNED:Solid organ transplant (SOT) recipients undergoing total joint arthroplasty (TJA) may face elevated perioperative risk because of chronic immunosuppression, medical comorbidity, and organ-specific physiologic considerations. Although intravenous tranexamic acid (TXA) is widely used during TJA to reduce perioperative blood loss, evidence regarding outcomes among SOT recipients receiving TXA remains limited. METHODS/UNASSIGNED:A retrospective review was performed of 29,240 consecutive primary TJA patients who all received intraoperative intravenous TXA between June 2011 and March 2025. Patients undergoing unicompartmental knee arthroplasty, hemiarthroplasty, TJA for fracture, bilateral procedures, revision procedures, or those with less than 90 days of postoperative follow-up were excluded. SOT history was identified using diagnosis and procedural codes and verified by manual review. Outcomes included 90-day deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI), operative time, and hospital length of stay (LOS). RESULTS/UNASSIGNED:Sixty-six patients with verified SOT were identified. The most common transplant types were kidney (59%), liver (24%), and heart (9%). One SOT patient experienced a 90-day VTE event compared with 95 control patients (1.5% versus 0.3%, P = 0.20). There were no PEs or MIs in the SOT cohort, compared with PE and MI rates of 0.2% and 0.01% in controls, respectively (P > 0.05 for both). Operative times were similar between groups (100.8 versus 108.5 min, P = 0.11), while LOS was significantly longer among SOT recipients (86.2 versus 43.8 h, P < 0.001). CONCLUSION/UNASSIGNED:In this retrospective cohort of primary TJA patients who all received intraoperative intravenous TXA, SOT recipients had low observed rates of VTE, PE, and MI. Because all patients received TXA and the SOT cohort was small, these findings should be interpreted as comparative observational safety data rather than evidence that TXA independently increases or does not increase thromboembolic risk in this population.

PURPOSE/OBJECTIVE:To evaluate the impact of high oxygen concentration using a novel oxygen chamber on epi-off corneal cross-linking (CXL) efficacy and patients' perceived pain during the procedure. SETTING/METHODS:Farabi Eye Hospital, Tehran, Iran. DESIGN/METHODS:Interventional randomized clinical trial. METHODS:Forty-eight eyes with progressive keratoconus were enrolled. The high-oxygen group (24 eyes) underwent accelerated epi-off CXL (9 mW/cm 2 UV-A, 5.4 J/cm 2 for 10 minutes) in a controlled high-oxygen environment (∼60%) using a novel oxygen chamber, while the control group (24 eyes) underwent the same protocol under ambient air oxygen (∼21%). Visual acuity, manifest refraction, and keratometry values were measured at baseline, 1 month, and 12 months post-CXL. Demarcation line depth and endothelial cell density were recorded at 1 month postoperatively. Pain was assessed intraoperatively using the Wong-Baker FACES scale (WBF). RESULTS:The high-oxygen group demonstrated significantly deeper demarcation line depth (307 ± 14 µm vs 279 ± 23 µm, p<0.001) and greater reductions in keratometry values (K1 and K2) at 12 months (p=0.04 and p=0.02, respectively). Compared to baseline, significant improvements in K1 (p=0.02), K2 (p=0.02), and Kmax (p<0.01) were observed in the high-oxygen group, whereas only K1 showed a significant improvement in the ambient oxygen group (p=0.02). Endothelial cell count remained stable in both groups. Patient reported intraoperative pain scores were significantly lower in the high-oxygen group (Wong-Baker FACES scale (2.4 ± 0.9 vs 3.4 ± 0.7, p=0.003). CONCLUSION/CONCLUSIONS:Use of the oxygen chamber to create a high-oxygen environment during accelerated epi-off CXL was associated with deeper stromal demarcation and improved keratometric outcomes, while also reducing intraoperative pain. This approach may improve clinical outcomes and patient experience during CXL.