Faculty Bibliography

This study evaluates the repeatability of a 3D simultaneous

BACKGROUND:Transcatheter aortic valve replacement (TAVR) is an alternative to surgical aortic valve replacement for patients with symptomatic severe aortic stenosis. However, long-term outcomes data are lacking for TAVR, particularly with newer-generation transcatheter heart valves. OBJECTIVES/OBJECTIVE:The purpose of this study was to compare 10-year outcomes of intermediate-risk patients who underwent TAVR with the third-generation, balloon-expandable SAPIEN 3 valve in the PARTNER 2 SAPIEN 3 Intermediate-risk Registry (P2S3i) with those who underwent surgery in the PARTNER 2A (P2A) randomized trial. METHODS:Intermediate-risk patients were enrolled in the P2A trial from 2011 through 2013 and in the P2S3i registry in 2014. These prospective, multicenter studies used the same eligibility criteria and stratified patients based on suitability for transfemoral or transthoracic (transapical/transaortic) access. Ten-year outcomes were evaluated, including all-cause mortality, aortic valve reintervention, and core laboratory-adjudicated echocardiographic outcomes. Patient reconsent was required at 5 years for extended 10-year follow-up, and vital status sweeps were implemented to improve data completeness for all-cause mortality. To account for potential baseline differences and reduce confounding, P2S3i TAVR patients were propensity score-matched 1:1 to P2A surgical patients. RESULTS:Among 2,005 patients who received a valve, 1,069 underwent TAVR in P2S3i and 936 underwent surgery in P2A. After propensity score matching (N = 783 patients in each group), baseline characteristics were similar between groups: mean age was approximately 82 years, 43% were female, and mean Society of Thoracic Surgeons score was 5.5%. At 10 years, all-cause mortality rate was 83.4% after TAVR and 82.3% after surgery, respectively (HR: 1.01 [95% CI: 0.91-1.13]; P = 0.82). Aortic valve reintervention rates adjusted for competing mortality were 2.0% for TAVR and 1.9% for surgery (P = 0.47). Among 32 TAVR and 30 surgical patients with available echocardiographic data at 10 years, mean gradients were 11.0 mm Hg and 12.6 mm Hg, respectively. CONCLUSIONS:At 10 years, TAVR with the SAPIEN 3 valve and surgery resulted in similar rates of mortality and aortic valve reintervention, and similar hemodynamics in intermediate-risk patients with symptomatic severe aortic stenosis. This analysis highlights challenges associated with extended long-term follow-up of clinical trials, including differential loss to follow-up and the competing risk of mortality in elderly populations. (PARTNER 2A Trial; NCT01314313; PARTNER 2 SAPIEN 3 Intermediate-Risk Registry; NCT03222128).

Poly(A) tails are present on most cellular and viral mRNAs, providing a platform for poly(A)-binding proteins that stimulate translation and regulate the deadenylation and stability of transcripts in the cytoplasm. Here we leverage nanopore direct RNA sequencing to analyse the distribution of poly(A) tail lengths on cellular and viral mRNAs across Herpesviridae and other DNA and RNA virus infections. We find that herpesvirus mRNA poly(A) tails are consistently longer than those on cellular and other viral transcripts, presenting a previously unrecognized yet widespread mechanism to potentially advantage herpesviral gene expression. This contrasts with the templated poly(A) tails on coronavirus RNAs and those on cytoplasmically transcribed poxviral mRNAs, which are more similar in length to those on host mRNAs. Herpesviral noncoding RNAs display differential poly(A) tailing patterns while individual herpesviral mRNAs also show variation in the extent to which their poly(A) tail lengths change during the virus lifecycle, suggestive of additional uncharacterised layers of poly(A) tail length regulation. Importantly, while we detect non-adenosine nucleotides within herpesviral poly(A) tails, which are known to oppose deadenylase activity, this "mixed tailing" is not at sufficient frequency to explain the widespread extended tails of herpesvirus mRNAs.

[This corrects the article DOI: 10.1016/j.waojou.2021.100613.].

INTRODUCTION/BACKGROUND:We hypothesized that, in patients at high risk for RE, giving sucralfate prophylactically would reduce the need for opioid pain medication. METHODS AND MATERIALS/METHODS:Patients were enrolled from January 2023 to April 2025 at a single tertiary care center. Patients were randomized to receive 1 gram twice a day within the first five fractions of radiotherapy (RT), with frequency increased during RT at clinician discretion, or standard supportive care. The proportion of patients who took any opioids over the previous 24 hours at the end of the treatment course was compared between groups using logistic regression with the stratification variables and concurrent chemotherapy status as covariates. RESULTS:The trial was closed early due to lack of differences between arms with 117 patients randomized (n=56 in the experimental arm). Rates of opioid use were 30% in both groups (absolute adjusted decrease in the prophylactic sucralfate arm -0.4%; 95% CI -14%, 13%, p>0.9). Rates of grade 2 - 3 RE were non-significantly lower in the prophylactic sucralfate arm (59% vs 69%, absolute adjusted risk decrease 11%; 95% CI -7.2%, 28%; p=0.2). In patients receiving very high esophageal dose (V60 Gy ≥15%), all controls (n=4) experienced grade 2-3 RE compared to only half of those in the experimental arm (6 of 12) (Fisher's exact test p=0.2). CONCLUSIONS:We did not find evidence to support early use of sucralfate in patients at high risk of radiation esophagitis. Limited medical options for the management of RE warrant the continued need to explore further avenues to combat this painful condition.

INTRODUCTION/BACKGROUND:Essential tremor is a common movement disorder that can cause substantial functional disability when symptoms become medically refractory. Stereotactic radiosurgery (SRS) is a minimal access treatment strategy for tremor control, but multicenter outcome data remain limited. METHODS:We performed a retrospective multi-institutional cohort study of 232 stereotactic radiosurgical thalamotomy procedures for medically refractory essential tremor. The median age at treatment was 76.0 years, median tremor duration was 17.0 years, median margin dose was 70.0 Gy, and median maximum dose was 140.0 Gy. The primary endpoint was clinically meaningful tremor improvement. Secondary endpoints included tremor arrest, recurrence, adverse radiation effects (AREs), and change in Fahn-Tolosa-Marín (FTM) scores. Logistic regression was used to evaluate outcome predictors. RESULTS:Significant tremor improvement was observed in 92.1% of patients, with a median time to improvement of 4.0 months. Complete tremor relief occurred in 26.1%. Symptomatic AREs occurred in 4.3%. Tremor recurrence was noted in 12.4% at median follow-up of 2 years. Among procedures, mean unilateral hand FTM score improved from 12.53 to 5.07, corresponding to a mean improvement of 7.46 points (p < 0.001). Significant improvement was also observed across tremor, writing, drawing, and drinking sub scores (all p < 0.001). On multivariable analysis, a maximum lesion dose ≥ 140 Gy was independently associated with greater odds of clinical benefit (OR 3.44, p = 0.019). CONCLUSION/CONCLUSIONS:In this multi-institutional cohort, SRS was associated with high rates of clinically meaningful tremor improvement, significant functional improvement, and durable tremor control in medically refractory essential tremor.

STUDY OBJECTIVE/OBJECTIVE:Emergency department (ED) visits among older adults represent critical transition points in health care, often resulting in substantial downstream utilization. We aimed to quantify health care contact days in the 30 days following a treat-and-release ED visit among older adults and examine associations with demographic and clinical characteristics. METHODS:We conducted a pooled cross-sectional analysis of 2016-2021 Medicare Current Beneficiary Survey data. The sample included treat-and-release ED visits among beneficiaries ≥ 65 years. Health care contact days were categorized as institutional (ED, hospital, skilled nursing facility, hospice) and ambulatory (outpatient visits, labs, imaging, procedures, or treatments). We applied zero-inflated Poisson regression to estimate the likelihood and intensity of health care contact. RESULTS:The analytic sample comprised 10,964 treat-and-release ED visits. Within 30 days, 22.5% of visits resulted in institutional contact and 84.4% in ambulatory contact. On average, each ED visit was followed by 4.3 total contact days (3.0 ambulatory, 1.3 institutional) within 30 days. Having ≥ 2 chronic conditions was associated with greater odds of both institutional (OR: 1.46, 95% CI: 1.28-1.66) and ambulatory contact (OR: 1.44, 95% CI: 1.25-1.66). Dementia was associated with reduced odds of ambulatory contact (OR: 0.51, 95% CI: 0.37-0.72). CONCLUSIONS:Older adults experience frequent and sustained health care contact following treat-and-release ED visits, with particularly high intensity among those with multi-morbidity. Reduced ambulatory follow-up among patients with dementia highlights a potential gap in care coordination after ED discharge.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Pediatric large-volume brain arteriovenous malformations (AVMs) carry a substantial lifelong hemorrhage risk, neurological symptoms, and treatment morbidity. Single-session stereotactic radiosurgery (SRS) is often unsuitable due to constraints on dose-volume toxicity. Volume-staged SRS (VS-SRS) enables sequential dosing of large nidus volumes, potentially enhancing safety while maintaining efficacy. Evidence in children remains limited. We aimed to evaluate outcomes of VS-SRS for large AVMs in pediatric patients. METHODS:A multicenter retrospective cohort was assembled from 21 centers, including patients aged younger than 21 years treated with VS-SRS for AVMs >10 cm3. Clinical and radiological end points included obliteration, hemorrhage, and permanent symptomatic radiation-induced changes (RIC). RESULTS:A total of 103 patients were included (median age 14 years; IQR, 12-17). The median nidus volume at first stage was 18.2 cm3 (IQR, 12.3-25.6). Median prescription dose per stage was 17 Gy (IQR, 16-18). The median clinical follow-up from the first stage was 57.5 months (IQR, 25-138). Obliteration occurred in 42 of 103 patients (40.8%), with actuarial rates of 6.9% (95% CI: 2.8-14) at 3 years and 29% (95% CI: 20-39) at 5 years. Hemorrhage occurred in 17 of 103 patients (16.5%) during follow-up, and permanent RIC was observed in 9 of 103 patients (8.7%). CONCLUSION/CONCLUSIONS:VS-SRS is a reasonably safe, selected option for pediatric large-volume AVMs when microsurgical or endovascular cure is not feasible or prudent. Delivering ≥17 Gy per stage while limiting each treatment volume to <15 cm3 supports durable nidus control with acceptable toxicity. VS-SRS represents a key modality in multidisciplinary management of this historically difficult-to-treat population.

PURPOSE/UNASSIGNED:Orbital fractures are a major reason for ophthalmologic consultation in the emergency department. In this study, we studied ocular signs associated with intervention and compared 4 previously published protocols to identify which best identified higher risk patients in need of consultation. METHODS/UNASSIGNED:We performed a retrospective cross-sectional study of patients from the BALCITE (BALtimore Consultation, Inpatient, and Trauma of the Eye) database who received ophthalmologic consultation. Our primary outcomes were the ocular and orbital signs associated with receiving intervention. Our secondary outcome identified the most sensitive and specific screening algorithm for orbital fractures by comparing four existing protocols (HOPE+CT, STOP, MEE, and UTH) to our large independent cohort. RESULTS/UNASSIGNED: < 0.001). The STOP tool had the highest sensitivity of 96.3%, demonstrating a potential 29% reduction in hospital fracture consults, followed by MEE, with a sensitivity of 93.1%. The HOPE+CT tool had the highest specificity of 95.6%. CONCLUSION/UNASSIGNED:The presence of an APD and periorbital laceration are strong indicators of urgent ophthalmologic treatment in the setting of acute orbital fractures. Supportive implementation of the STOP and MEE algorithms can effectively screen orbital fracture patients to help triage in the acute setting, improve resource utilization, and reduce healthcare costs.

Recent clinical trials have suggested the safety and efficacy of psychedelic therapy for treatment-resistant depression, posttraumatic stress disorder, addiction, and end-of-life distress. While neurobiological mechanisms such as 5-HT2A receptor activation, increased neural entropy, and default mode network modulation have been well-characterized, significantly less attention has been given to the emergence of unconscious material within psychedelic states. This article introduces a psychodynamically informed framework for understanding and working with such material in clinical contexts. Drawing on psychoanalytic theory, we explore how psychedelic compounds may facilitate access to preverbal, dissociated, and developmentally embedded psychic content, often expressed through somatic experience, symbolic imagery, and unconstrained affect. Using the four standard phases of psychedelic screening, preparation, psychedelic treatment session, and follow-up or integration, we present a structured psychodynamic lens, integrating conceptual theory with illustrative clinical vignettes. These fictional composites, informed by publicly funded clinical research programs, highlight how unspoken experience, affective intensity, and shifts in psychic structure may unfold within the psychedelic experience. We argue that consideration of unconscious communication, symbolic processes, and defensive functioning can foster greater clinical depth. This article advances the position that psychoanalytic models, though underrepresented in current psychedelic research, offer valuable tools for conceptualizing mechanisms of change beyond symptom reduction. As psychedelic treatments approach regulatory approval and broader clinical use, such perspectives may play an important role in future research, training, supervision, and individualized care models.