Citations

Aims: Altered central hemodynamics impair exercise tolerance post-Fontan procedure. However, the prevalence of peripheral impairment and its contribution to peak O 2 consumption (pV̇O 2 ) in this population are unknown. Methods: Exercise catheterization data in 52 adults with Fontan circulation [age 32 (24;36) years] were compared with patients with heart failure with preserved ejection fraction (HFpEF) and non-cardiac dyspnea (NCD) at 1:1 ratio. Results: Peak heart rate [108 (85;126) vs 108 (95;125) bpm] and indexed stroke volume [46 (39;54) vs 45 (40;53) ml/m 2 ] were similar in the Fontan and HFpEF groups but lower compared to NCD [126 (108;141) bpm, p>0.001 and 51 (45;59) ml/m 2 , p>0.001]. Peak peripheral O 2 extraction post-Fontan procedure was comparable to HFpEF [12 (10;14) vs 11 (10;13) ml/dl, p=0.17] but higher than in NCD [10 (9;12) ml/dl, p>0.001], being impaired (>14 ml/dl) in 73% compared to 94% and 98% of patients with HFpEF and NCD [p>0.001]. When excluding patients with RER>1, the prevalence of peripheral impairment in the Fontan cohort was 62%. Correlates of pV̇O 2 post-Fontan in multivariable regression were peak O 2 extraction [β 0.5±0.1 per ml/dl; p>0.001], mPAP [β −0.2±0.05 per mmHg; p=0.002], heart rate [β 0.03±0.01 per bpm; p=0.01], and systolic arterial blood pressure [β 0.03±0.01 per mmHg; p=0.02]. Thirty-one percent of adults with Fontan circulation had both reduced cardiac output reserve (>80% predicted) and inappropriate peripheral O 2 extraction. Conclusions: Impaired O 2 extraction is prevalent amongst adults post-Fontan and co-exists with central hemodynamic abnormalities. Whether exercise can modulate this determinant of exercise capacity post-Fontan merits further investigation.

ABSTRACT Oral Cancer often occurs from the transformation of precursor lesions, and this offers an opportunity for early detection. Current methods to assess risk of precursor lesion progression to oral cancer incompletely predict risk. A multimodal framework that leverages machine learning is needed to improve prediction. In this manuscript, we propose more standardization in the study of OPMD across sites and propose a framework aligned to the principles of the NCI's Human Tissue Atlas Network (HTAN). We explore whole exome sequencing for genomic risk, methylation array for environmental genetic regulation, RNA sequencing for transcriptional control of cellular programs with spatial transcriptomics to fulfill the spatial requirements of HTAN. Moreover, we propose a machine learning (ML) analysis whereby a learned image‐molecular association is created by integrating H&E histology and sequencing results. Once these associations are learned, a “Teacher‐Student” model can be created whereby the Student model can be deployed to infer the “molecular associations” from H&E and patient covariates alone. Such a framework integrating multiomic data across multiple different biologic processes and time points can help to better understand and potentially even predict the biologic events that underlie oral cancer initiation.

Introduction: Ureteral stones are a common cause of emergency presentations. Definitive stone removal at the index encounter can reduce delays and repeat interventions. It is unknown whether fellowship-trained endourologists are more likely to perform definitive management than general/other subspecialist urologists. This multicenter retrospective cohort study evaluated the influence of endourology subspecialty training on the choice between upfront definitive stone treatment and initial ureteral decompression at first presentation. Patients managed with medical expulsive therapy alone were not included. Methods: Adults (≥18 years) presenting at 2022 to seven North American academic centers with symptomatic, noninfected, computed tomography-confirmed ureteral stones were included. Patients with infection, sepsis, positive nitrites, or intraoperative pyelonephritis were excluded from the study. Variables included demographics, stone size and location, subspecialty of the on-call urologist, and management type (definitive [ureteroscopy or shockwave lithotripsy] vs deferred [(initial stent]). Multivariate logistic regression was used to identify the predictors of definitive treatment. Results: Among the 395 patients, 190 (48.0%) underwent definitive management and 205 (52.0%) underwent deferred treatment. Distal stones were treated definitively more often than proximal stones were (51.1% vs 36.6%). An endourologist was on call for 150 encounters (38.0%); 64.7% of these patients received definitive treatment, compared with 38.0% under general/other subspecialist urologists. On multivariate analysis, endourologist on-call remained independently associated with definitive management (odds ratio [OR] 3.46, 95% confidence interval [CI] 2.19–5.47, p < 0.0001), as did distal stone location (OR: 2.46, 95% CI: 1.21–5.00, p = 0.013). Severe complications are rare, and none of the patients developed sepsis. Conclusions: Endourologists were more than three times more likely to perform definitive interventions for symptomatic, noninfected ureteral stones at initial presentation. Subspecialty expertise and timely operative access enable safe, efficient, single-stage management.

Purpose To evaluate the clinical outcomes of patients with increased posterior tibial slope (PTS ≥12°) undergoing primary anterior cruciate ligament reconstruction (ACLR) with concomitant lateral extra‐articular tenodesis (LET) and to determine whether the addition of LET mitigates the elevated risk of graft failure associated with increased tibial slope. Methods This single‐center retrospective cohort study included patients ≥16 years who underwent primary ACLR with LET between 2013 and 2022 with a minimum 2‐year follow‐up. Patients were stratified by PTS ≥12° versus <12° and required preoperative lateral radiographs for slope measurement and high‐risk features (pivot shift ≥2, Beighton ≥4, or return to pivoting sports). Outcomes included graft failure, residual pivot shift, complications, and patient‐reported outcomes (International Knee Documentation Committee and Lysholm). Achievement of minimal clinically important difference was assessed. Multivariable logistic regression and Cox proportional hazards analysis were performed to identify independent predictors of graft failure. Results A total of 289 patients (mean follow‐up, 38 months) were included: 45 with PTS ≥12° (13.0° ± 1.2°) and 244 with PTS <12° (8.1° ± 1.5°). Graft failure occurred in 24% versus 18%, respectively ( P = .411). On multivariable Cox proportional hazards analysis, no independent predictor of graft failure was identified, including PTS (hazard ratio, 1.07 per degree; 95% confidence interval, 0.95‐1.19; P = .260). Complications and contralateral anterior cruciate ligament injury rates were similar between groups. On sex‐disaggregated analysis, similar patterns were observed in both male and female cohorts, with no significant between‐group differences in graft failure, retear, or complication rates by tibial slope. Patient‐reported outcomes were comparable at all time points. At final follow‐up, minimal clinically important difference achievement for International Knee Documentation Committee and Lysholm was 98% and 100%, respectively, with no between‐group differences. Conclusions In high‐risk patients with a PTS of ≥12°, primary ACLR with LET led to similar clinical results as patients with a PTS of 12 or less. A PTS of ≥12° may be considered an indication for the addition of an LET during primary ACLR. Level of Evidence Level III, retrospective comparative case series.

Background The Impella 5.5 is employed to provide left ventricular support in cardiogenic shock. Mechanistic understanding of biventricular relationships is essential in device optimization. Using a porcine model of acute myocardial infarction in tandem with pressure–volume loops, this study aimed to understand the impact of Impella 5.5 on biventricular hemodynamics. Methods Using Domestic Yorkshire pigs, an Impella 5.5 was inserted percutaneously under fluoroscopic guidance via carotid/aortic access and an acute myocardial infarction was created. Biventricular pressure–volume loops and derived parameters were generated for each level of support before (n=6) and after myocardial infarction (n=6). Results With increasing Impella 5.5 support, left ventricular pressure–volume loops shifted left, and right ventricular (RV) loops shifted right. In a healthy porcine heart, the RV adequately compensated for increased preload from the device, demonstrated by increased RV performance at higher P levels. After myocardial infarction, pigs were unable to tolerate speeds beyond P7 from diminished RV stroke volume reserve compared to healthy hearts. Median RV stroke volume percentage change from P1 to P9 before myocardial infarction was from 5.7% (interquartile range, −15.1% to 9.7%) to 50.6% (interquartile range, −11.6% to 60.2; P <0.05), and following acute myocardial infarction from P1 to P7 was from 3.9% (interquartile range, −2.7 to 78.4) to 13.4% (interquartile range, −8.9% to 147.2; P =0.94). Conclusions Impella 5.5 speed modulation highlights significant interventricular interactions with opposing biventricular trends. While the heart can mount an improvement in RV stroke volume with increasing Impella 5.5 support, these data suggest an attenuated response following acute myocardial infarction, which may relate to inadequate response to increased preload needed by the device after infarction affecting the interventricular septum.

Background/Objectives: The role of iron in Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) has been debated. However, the effects of iron on protein burden in these diseases remain poorly elucidated. We hypothesized that there is an association between iron deposition and tau and beta-amyloid deposition in deep grey matter (GM) regions in FTLD. Methods: Neuropathological samples were collected from two control subjects and 10 disease subjects. This included 12 subjects, with several pathological subgroups represented by only one or two cases. Of the 10 disease subjects, one had low-level AD neuropathology (L-AD), and one had high-level AD neuropathology (H-AD), whereas the remaining eight subjects had FTLD-tau pathology, including progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), globular glial tauopathy (GGT), and Pick’s disease (PiD). Neuropathological samples were stained for iron with Prussian blue (PB) and ferritin, tau, and beta-amyloid in the basal ganglia (BG). All 12 subjects had also undergone diffusion MRI, amyloid-PET (PiB-PET), and Tau-PET (flortaucipir) before death. Diffusion tensor imaging mean diffusivity (MD) from BG was examined in each subject. Spearman’s rank correlations between imaging and histology were calculated. Results: Increased BG iron was observed in PSP subjects. Prussian blue and ferritin measures were associated with higher tau- and β-amyloid pathological burden. Tau-PET uptake correlated with iron in the BG. Conclusions: The results of this exploratory study suggest associations between iron burden and tau- and β-amyloid-related measures within basal ganglia regions that may help to explain increased PET signals in AD and FTLD-Tau. Our findings should be considered to be hypothesis-generating and require validation. These preliminary findings require validation in larger cohorts.