Citations

Abstract Background We examined real-world utilization of treat-to-target (TTT) strategies and conducted a quality improvement (QI) project to improve uptake of TTT strategies in a learning health system, IBD Qorus. Methods We implemented a structured QI intervention to increase uptake of TTT in 41 gastroenterology practices in the United States, over a 13-month intervention period (November 2020 to November 2021; modified breakthrough series [BTS] collaborative), and a 10-month post-BTS observation period (December 2021 to October 2022). Through encounter-level surveys, we examined providers’ “intention to TTT” based on discussion of TTT with patients, documentation of inflammation, and intention to change therapy to TTT. We examined changes in rates of “intention to TTT,” and whether improvement in intention to TTT influenced site-level rates of remission. Results Over 13 months, there were 7932 patient visits (55% with Crohn’s disease; 47% in clinical remission); patients in 2160 visits (27%) were not in endoscopic remission. Overall, rates of intention to TTT increased from 31% to 54% (P = .06) with considerable site-to-site variability and was maintained at 49% in the post-BTS observation period. The increased rate was attributable to higher rates of testing for inflammation. Despite an increase in the rate of intention to TTT, there was no significant change in site-level achievement of remission over the same time. Conclusions Through a QI initiative in a learning health system, rates of intention to TTT increased significantly over 12-months, though overall rates remained low. Assessing patient-, provider- and practice-level barriers and facilitators for successful implementation of a TTT strategy is warranted to improve clinical outcomes.

Abstract Repetitive head impacts are common in contact and collision sports and are linked to structural brain changes and an elevated risk of neurodegenerative diseases such as Chronic Traumatic Encephalopathy. Identifying early in vivo structural markers remains challenging. Although diagnosis currently requires post-mortem confirmation, clinical symptoms, including cognitive impairment and behavioural changes, are reflected in the diagnosis of Traumatic Encephalopathy Syndrome. These symptoms align with dysfunction in key brain regions—amygdala, hippocampus and thalamus—which support memory, emotion and behaviour and commonly show tau pathology in Chronic Traumatic Encephalopathy. This study uses shape analysis to examine structural differences in these regions between former American football players and unexposed asymptomatic controls and evaluates the influence of age, head impact exposure and clinical diagnosis on brain structure. We analyzed brain morphology in former American football players (n = 163) and unexposed, asymptomatic controls (n = 53). Structural segmentation was performed with FreeSurfer 7.1, and the shape analysis pipeline was used to generate subregional reconstructions. Vertex-level morphometry, based on the logarithm of the Jacobian determinant and radial distance, quantified local surface area dilation and thickness. Group differences were examined with covariate-adjusted linear regression models contrasting football players and controls, as well as participants with and without a Traumatic Encephalopathy Syndrome diagnosis. Partial correlations examined the influence of age, age of first football exposure and cumulative head impact index metrics, including frequency, linear acceleration and rotational force. Models were adjusted accordingly for age, body mass index, education, race, imaging site, apolipoprotein ϵ4 status and total intracranial volume. Former football players exhibited bilateral surface area contractions in the hippocampus and amygdala, along with reduced amygdala thickness, compared to controls. Older age was associated with widespread surface contractions and thinning across all regions, except for preserved thickness in the left hippocampus. An earlier age of first exposure to football correlated with surface contractions in the thalamus and left hippocampus. Greater cumulative linear acceleration was linked to bilateral hippocampal surface contractions and reduced thickness in the left thalamus, while greater rotational force exposure was associated with hippocampal thinning. No significant structural differences were found between players with and without a diagnosis of Traumatic Encephalopathy Syndrome. These findings extend volume-based research by revealing localized alterations in surface area dilation and thickness and emphasize the roles of age and repetitive head impact exposure in long-term brain changes.

Brain tumor-related epilepsy (BTRE) is a common and debilitating symptom of central nervous system (CNS) tumors. The epileptogenic zone, defined as cortex responsible for seizure generation, is located at the peritumoral region for most tumors, and lower-grade intrinsic brain tumors have the highest seizure incidence. Surgery is often the most effective treatment for the reduction in seizures in BTRE. However, surgical decisions have historically often been made exclusively for oncologic reasons, with less emphasis on seizure control. Surgical approaches for all tumor types are reviewed, highlighting relevant risk factors. Adjunctive tools during surgery, such as intraoperative electrocorticography (ECoG), may help identify and remove surrounding brain areas which are epileptogenic. Minimally invasive surgery is also gaining traction, given its utility in treating seizures deep-seated tumors. This review explores epileptogenic brain tumors, surgery for BTRE, and emerging strategies to better achieve seizure control.

Background: Heart failure (HF) is the leading cause of mortality in adults with congenital heart disease (CHD) after transcatheter pulmonary valve replacement (TPVR), likely due to preexisting myocardial dysfunction and suboptimal reverse remodeling. Left ventricular (LV) diastolic dysfunction, unmasked by an acute increase in preload post-TPVR, may elevate left-sided filling pressures and precipitate pulmonary edema. However, the prognostic implications of elevated left-sided filling pressures prior to TPVR are currently unknown. Objective: To evaluate the prognostic value of pre-TPVR pulmonary artery wedge pressure (PAWP) and the heart failure with preserved ejection fraction – Age, Body mass index (BMI), Atrial fibrillation (HFpEF-ABA) score in patients undergoing TPVR. Methods: Adults with congenital heart disease (CHD) undergoing TPVR were stratified by pre-implant PAWP (<15 vs ≥15 mmHg) and HFpEF-ABA score (low <25%, intermediate 25–75%, high >75%). The composite endpoint was all-cause mortality, heart transplantation, heart failure (HF) hospitalization, or sustained ventricular arrhythmia. Kaplan-Meier and Cox regression analyses assessed associations with clinical outcomes. Results: Out of 150 patients, 37 (24.7%) had PAWP ≥15 mmHg. Elevated PAWP was associated with older age (36 [31;53] vs. 26 [19; 37] years, p<0.01), BMI (27.9 [24.5; 35.1] vs. 24.2 [20.6; 29.7] kg/m 2 , p<0.01), and higher HFpEF-ABA score (42.8 [9.5;63.6] vs. 6.4 [2.5;18.1]%, p<0.001) compared to normal PAWP. Over a median follow-up of 38 [13; 83] months, 26 events (17.3%) occurred. Kaplan-Meier analysis demonstrated a significant difference in event-free survival based on pre-TPVR PAWP categories (log-rank p=0.002) and HFpEF-ABA score categories (log-rank p<0.001). Elevated PAWP was associated with adverse outcomes (hazard ratio [HR] 4.27, 95% CI 1.61–11.31, p=0.003) (Figure 1), but this was no longer significant after age adjustment. HFpEF-ABA ≥25% was associated with adverse outcomes (HR 10.6, 95% CI 3.8–30.0, p<0.001) (Figure 2), independent of N-terminal prohormone of brain natriuretic peptide levels and left ventricular ejection fraction. Conclusion: Albeit confounded by demographics, pre-TPVR PAWP correlated with adverse long-term outcomes, and patients with this hemodynamic profile may require closer post-procedural surveillance. HFpEF-ABA was independently associated with incident events, representing an inexpensive, novel prognostic tool in patients undergoing TPVR.

Introduction: Acute respiratory distress syndrome (ARDS) is characterized by pulmonary edema, hypoxia and systemic inflammation. The presence and clinical implications of a high cardiac output state in patients with ARDS remain unknown given the lack of invasive hemodynamic monitoring in most patients with ARDS. Hypothesis: A subset of patients with ARDS will have high output heart failure with high cardiac output and elevated pulmonary capillary wedge pressure (PAWP) representing a unique subphenotype of ARDS. Methods: Patients from the Comparison of Two Fluid-Management Strategies in Acute Lung Injury (FACTT) Trial were stratified according to baseline cardiac output states and filling pressures: HOLHF (high-output with left heart failure) was defined as cardiac index (CI) ≥ 4 L/min/m 2 and PAWP ≥ 15 mmHg; HOnoLHF (high-output without left heart failure) as CI ≥ 4 L/min/m 2 and PAWP < 15 mmHg; and NOHO (non-high-output) as CI < 4 L/min/m 2 . Hemodynamics, oxygenation, metabolic demand (VO 2 ) and clinical outcomes were compared across groups. Results: Of the 399 patients included, high-output states were present in 52% of all patients (Figure 1). High-output cohorts demonstrated higher myocardial workload, lower systemic vascular resistance (SVR), lower pulsatile arterial load, higher VO 2 and more impaired systemic O 2 utilization despite the highest peripheral O 2 delivery compared to NOHO (Table). Among the high-output cohorts, the HOLHF cohort demonstrated higher right ventricular stroke work (25.2 ± 12.1 vs. 20.3 ± 12.3, P<0.001), worse A-a gradient (326.0 ± 136.5 vs. 276.1 ± 114.7, P=0.048) and higher VO 2 (382.3 ± 234.2 vs. 289.8 ± 171.7, P<0.001) compared to HOnoLHF. Increasing cardiac output was individually related to decreasing SVR (r=-0.742, P<0.001) and increasing VO 2 (r=0.565, P<0.001) (Figure 2). When adjusted, both variables remained strongly related to increasing cardiac output (P<0.001). There were no significant differences among the cohorts with respect to refractory hypoxia and mortality. Conclusions: High-output states in ARDS are prevalent and underrecognized. Such states appear to be driven by arterial vasodilatation and heightened VO 2 with additional manifestations of increased myocardial workload and inefficient peripheral utilization with impaired systemic O 2 utilization. Whether specific strategies to mitigate the high output state might improve gas exchange, hypoxia and outcomes in patients with HOLHF and ARDS requires further study.

Objective This survey study assessed trainee attitudes and perceptions of the longitudinal public speaking curriculum at Mayo Clinic Pediatric and Adolescent Residency Program. Methods This 3-part survey of Mayo Clinic pediatric residents was conducted from 2013 to 2017 and utilized yes/no questions, Likert scales, and open-ended questions. Code book content analysis was used to analyze open-ended questions. Results A total of 121 participants (96.8%, n = 121/125) completed the survey. Most respondents (93.3%, n = 111/119) either agreed or strongly agreed that the public speaking requirement enabled them to be more effective in delivering information to large groups. Most respondents (89.2%, n = 107/120) agreed or strongly agreed that they incorporated feedback from previous public speaking feedback sessions into subsequent presentations. The 2 activities that respondents found most useful for preparing later presentations were setting goals for future presentations in a feedback session and discussing performance in a feedback session. Conclusions There was a perceived effectiveness of a longitudinal public speaking curriculum among pediatric residents at our program. Multidimensional feedback seems to be a critical aspect of a public speaking curriculum in graduate medical education.

Abstract Background In the current clinical workflow of radiation oncology, therapists manually summarize the physician‐issued Computed Tomography (CT) simulation orders to prepare patients' CT simulations. This process increases the workload, introduces variability in documentation quality, and is prone to human errors. Purpose This study aims to address these challenges using a large language model (LLM) to automate the generation of summaries from the CT simulation orders and evaluate its performance. Methods A total of 607 CT simulation orders were collected from the Aria database at our institution. A locally hosted LLaMa 3.1 405B model, accessed via the Application Programming Interface (API) service, was used to extract keywords from the CT simulation orders and generate summaries. The downloaded CT simulation orders were categorized into seven groups based on treatment modalities and disease sites. For each group, a customized instruction prompt was developed collaboratively with therapists to guide the LLaMa 3.1 405B model in generating summaries. The ground truth for the corresponding summaries was manually derived by carefully reviewing each CT simulation order and subsequently verified by therapists. The accuracy of the LLM‐generated summaries was evaluated by therapists using the ground truth. Results Over 98% of the LLM‐generated summaries aligned with the ground truth in terms of accuracy. Our evaluations showed an improved consistency in format and enhanced readability from the LLM‐generated summaries compared to the corresponding therapist‐generated summaries. This automated approach demonstrated consistent performance across all groups, regardless of treatment modality or disease site. Conclusions This study demonstrated the high precision and consistency of the LLaMa 3.1 405B model in extracting keywords and summarizing CT simulation orders, suggesting that LLMs have great potential to assist in this task, reduce the workload of CT simulation therapists and improve radiation oncology workflow efficiency.

Background Immune-related adverse events (irAEs) remain largely unpredictable, potentially affecting multiple organ systems and occurring at almost any point during and even occasionally after immune checkpoint inhibitor (ICI) treatment. To identify populations at risk for these immune-mediated toxicities, we analyzed genetic characteristics and immune markers associated with clinically significant irAEs. Methods We carried out a genome-wide association study on 373 white patients receiving ICI treatment. We identified single nucleotide polymorphisms associated with irAEs. Blood cytokine profiling and peripheral blood mononuclear cell RNA sequencing were performed at pretreatment baseline and 6–8 weeks after ICI initiation. Findings were validated in two external cohorts. Results We identified genetic haplotypes in VWA8 (Von Willebrand Factor A Domain Containing 8) , OSBPL6 (Oxysterol Binding Protein Like 6), and ADAMTS9-AS2 (ADAM Metallopeptidase With Thrombospondin Type 1 Motif 9 Antisense RNA 2) associated with grade ≥2 irAEs. Patients carrying risk haplotypes for one or more genes exhibited significantly greater rates of grade ≥2 (OR 3.02; 95% CI 1.83 to 5.02; p<0.001), grade ≥3 (OR 3.59; 95% CI 1.93 to 6.64; p<0.001), and multiple type irAE (OR 2.60; 95% CI 1.53 to 4.39; p<0.001). Serum CCL3 levels were significantly elevated in individuals carrying risk haplotypes (p=0.03). Gene expression analysis demonstrated activated autoimmune and inflammatory pathways in the genetic risk group. Conclusions Novel polymorphisms in VWA8, OSBPL6, and ADAMTS9-AS2 may impact immune pathways, promote inflammation, potentiate autoimmune phenotypes, and convey risk of irAE in ICI-treated patients.

BACKGROUND: The current study aims to describe outcomes after transcatheter valve replacement in adults with congenital heart disease. METHODS: Retrospective study of adults with congenital heart disease who underwent transcatheter valve replacement and had a 1-year follow-up postintervention at Mayo Clinic (2010–2024). The study period was divided into early (2010–2014), mid (2015–2019), and late (2020–2024) eras. The primary outcome was valve reintervention. The secondary outcomes were all-cause mortality and temporal change in prosthetic valve gradient and clinical indices of disease severity. RESULTS: Overall, 341 patients (age 38±17 years; 175 [51%] men) received 346 prostheses (pulmonary [N=236, 68%], tricuspid [N=75, 22%], aortic [N=22, 8%], and mitral [N=7, 2%]). The prostheses were Sapien (N=181, 52%), Melody (N=142, 41%), and Harmony prostheses (N=23, 7%). The number of transcatheter valve implantations increased from the early era (N=75), mid era (N=109), to the late era (N=162). The 10-year incidence of valve reintervention was 35%, and was similar between Sapien versus Melody prosthesis (41% versus 33%; P =0.11). The 10-year incidence of all-cause mortality was 13%. There was a temporal increase in prosthetic valve Doppler mean gradient (baseline versus 10 years) for pulmonary (12±5 versus 28±11 mmHg; P <0.001), tricuspid (3±1 versus 8±3 mmHg; P <0.001), and aortic prosthesis (13±5 versus 26±12 mmHg; P <0.001). There was a temporal increase in predicted peak oxygen consumption (absolute ∆, 9% [95% CI, 4–13]; P =0.006) and a decrease in NT-proBNP (N-terminal pro-B-type natriuretic peptide) level (absolute ∆, −138 pg/mL [95% CI, −209 to −64]; P <0.001) at 1-year postintervention. CONCLUSIONS: There has been a temporal increase in the number of transcatheter valve implantations over time. Transcatheter valve replacement was associated with clinical improvement across multiple domains. However, there was a significant increase in prosthetic valve gradient within 10 years of follow-up, suggesting limited prosthesis longevity. There is a need for strategies to improve prosthetic valve longevity, which in turn may improve outcomes in this population.