Faculty Bibliography

External cervical resorption is a disease entity with an idiopathic etiology by which osteoclastic invasion cavitates teeth near the cementoenamel junction. The lesion, if left untreated, has the potential to progress and compromise tooth maintainability. Treatment of these lesions requires access (often surgical), removal of the affected tissue, and placement of a restorative material. This case series documents 10 external cervical resorption lesions that were treated by surgical crown lengthening with concurrent placement of a resin-modified glass-ionomer restoration and followed up for a period ranging from July 2020 to July 2024. This case series offers evidence that external cervical resorption can be treated with a high expectancy of tooth survival. Longer-term follow-ups are needed to see if this treatment remains stable and predictable.

IMPORTANCE/UNASSIGNED:Patients with obstructive hypertrophic cardiomyopathy (oHCM) endure life-altering exercise limitations. Current treatment guidelines recommend β-blockers as first-line therapy primarily based on expert opinion. The Metoprolol vs Aficamten in Patients with Left Ventricular Outflow Tract Obstruction on Exercise Capacity in HCM (MAPLE-HCM) trial characterizes comprehensive exercise response to aficamten monotherapy vs β-blockade (metoprolol). OBJECTIVE/UNASSIGNED:To determine the effect of aficamten compared with metoprolol across all stages of exercise using 16 quantitative measures in individuals with oHCM. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This was a prespecified secondary analysis of the MAPLE-HCM study, a phase 3, randomized, active-control trial conducted from June 2023 to March 2025 with data analyzed between May and July 2025 at 71 sites in North America, South America, Europe, Israel, and China. Patients with symptomatic oHCM with objective evidence of exercise intolerance (peak oxygen uptake [pVO2] <100% of predicted) were included. Those with a history of atrial fibrillation (paroxysmal or persistent), medical indication for β-blockers or calcium channel blockers prohibiting drug discontinuation, or intolerance or medical contraindication to β-blockers were excluded. INTERVENTION/UNASSIGNED:Randomized 1:1 to titrated aficamten (5-20 mg daily) or matching titrated metoprolol (50-200 mg daily) for 24 weeks. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The main outcomes were submaximal exercise minute ventilation (VE)/carbon dioxide output (VCO2) slope and anaerobic threshold; peak exercise duration, workload, heart rate and heart rate reserve; and postexercise oxygen recovery rates; and composite variables, such as circulatory power. RESULTS/UNASSIGNED:Of 175 randomized participants (mean [SD] age, 57.7 [13.2] years; 102 [58.3%] male), 165 (94%) had core laboratory-validated exercise tests at baseline and week 24. Compared with metoprolol, aficamten treatment improved multiple stages of exercise; including submaximal exercise VE/VCO2 slope (-2.8; 95% CI, -4.0 to -1.5; P < .001) and anaerobic threshold (76 mL/min; 95% CI, 41 to 111; P < .001); peak workload (8 watts; 95% CI, 3 to 13; P = .003); the time required for VO2 to recover by 12.5% postexercise (-11 seconds; 95% CI, -16 to -5; P < .001); and circulatory power (819 mm Hg × mL/min per kg; 95% CI, 569 to 1070; P < .001). Large improvements (≥3.0 mL/kg/min) in peak VO2 were more common with aficamten compared with metoprolol (17 [20.5%] vs 3 [3.7%], respectively; odds ratio, 6.8; 95% CI, 2.0 to 22.5; P < .001). In contrast, large reductions in peak VO2 (≥3.0 mL/kg/min) were significantly more common with metoprolol than aficamten (17 [20.7%] vs 2 [2.4%], respectively; odds ratio, 10.6; 95% CI, 2.6 to ∞; P < .001). CONCLUSIONS AND RELEVANCE/UNASSIGNED:This prespecified analysis of MAPLE-HCM demonstrated monotherapy with aficamten was superior to metoprolol in promoting adaptation to multiple phases of exercise in patients with symptomatic oHCM and supports aficamten as first-line therapy for oHCM. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT05767346.

BACKGROUND:In patients with hormone receptor (HR)-positive early breast cancer (BC), the POSITIVE trial demonstrated that temporary interruption of adjuvant endocrine therapy (ET) for pregnancy is feasible and safe in early follow-up (median 41 months). In this article, we report updated results from a preplanned analysis with 2.5 years of additional follow-up. PATIENTS AND METHODS/METHODS:POSITIVE, a single-arm prospective trial evaluating temporary interruption of adjuvant ET (after 18-30 months and for up to 2 years) to attempt pregnancy in young patients with BC, enrolled 518 eligible women (≤42 years of age, stage I-III BC, desiring pregnancy) from December 2014 to December 2019. Using the bootstrap-matching method, 5-year breast cancer-free interval (BCFI) and distant recurrence-free interval (DRFI) event rates were compared with those of the SOFT/TEXT trials as external controls. RESULTS:At a median follow-up of 71 months in the POSITIVE cohort and 80 months in the SOFT/TEXT cohort, the 5-year cumulative incidence of BCFI events was 12.3% in POSITIVE and 13.2% in SOFT/TEXT [-0.9% difference, 95% confidence interval (CI) -4.2% to 2.6%]. The 5-year cumulative incidence of DRFI events was 6.2% and 8.3%, respectively (-2.1% difference, 95% CI -4.5% to 0.4%). Among 497 women followed for nondisease outcomes, 377 (76%) had ≥1 documented pregnancy on trial, and 343 of 497 (69%) had ≥1 live birth, totaling 440 offspring. In an unadjusted analysis comparing the 180 women (36%) who had pre-enrollment embryo/oocyte cryopreservation with those who did not, the 5-year cumulative incidence of BCFI events was 14.0% (95% CI 9.6% to 20.2%) and 11.5% (95% CI 8.4% to 15.7%), respectively. CONCLUSION/CONCLUSIONS:Longer-term follow-up of the POSITIVE trial demonstrates that temporary interruption of ET for pregnancy, including use of fertility preservation, does not increase the risk of BC events. Continued follow-up is warranted given the known risk of late recurrence in this population.

BACKGROUND:Effective screening and cohort enrichment remain major challenges in clinical trials for Alzheimer's disease (AD), where traditional diagnostic pathways rely on costly, invasive, and time-consuming procedures. Speech and language analysis has emerged as a scalable, low-burden approach for detecting subtle cognitive-linguistic and motor-speech changes that may appear early in the disease course. SUMMARY/CONCLUSIONS:This review synthesizes current evidence on acoustic, prosodic, lexical, semantic, and syntactic speech features associated with AD and mild cognitive impairment (MCI) and evaluates their reported utility across a range of elicitation tasks including picture description, verbal fluency, narrative recall, spontaneous speech, and reading. Across studies, machine-learning models trained on speech and language features have reported consistent performance, although results vary substantially depending on task design, feature sets, and cohort characteristics. Task-dependent variability is evident, with picture description and verbal fluency tasks capturing lexical-semantic and timing markers, while narrative and spontaneous speech tasks capture impairments in coherence, information content, and prosody. Hybrid approaches integrating hand-crafted and machine-extracted features have also been explored to improve interpretability and model performance. Speech and language analytics may support digital prescreening, cohort enrichment, and quality-assurance monitoring within clinical trials; however, their application depends on methodological considerations and validation across diverse settings. KEY MESSAGES/CONCLUSIONS:Despite encouraging findings, several methodological challenges persist, including interindividual variability, limited dataset sizes, differences in recording conditions, and limitations in automatic speech recognition performance in cognitively impaired populations. Continued development of standardized protocols, disorder-adapted speech models, and multimodal analytic pipelines is needed to support clinical translation. Collectively, current evidence suggests that speech and language features represent candidate digital markers that may improve screening efficiency and support clinical trial enrichment in AD, although further validation is required to establish their reliability and generalizability.

BACKGROUND:Effect of junctional reflux on the venous clinical severity score in patients with insufficiency of the great saphenous vein (JURY) study proved that venous clinical severity scores (VCSS) are similar in patients with great saphenous vein (GSV) reflux, with or without saphenofemoral junction (SFJ) reflux. Most studies testing the efficacy of endovenous ablation have simply required the presence of truncal reflux for inclusion, and limited data exist on whether junctional reflux impacts benefit. JURY-2 hypothesizes that patients with GSV reflux, with or without SFJ reflux, will derive similar benefit from endovenous ablation. METHODS:JURY-2 was a prospective longitudinal multicenter study of patients undergoing GSV ablation. INCLUSION CRITERIA/METHODS:18 to 80 years age, reflux of ≥0.5 seconds in ≥2 contiguous segments of the GSV above the knee, and C2 or C3 disease. EXCLUSION CRITERIA/METHODS:prior deep vein thrombosis; prior vein ablation on the index leg; concomitant obstruction of the iliocaval system; or known renal, hepatic, or cardiac failure. The primary outcome, sample size, and analytic plan were determined pre hoc. The primary outcome was the 3-month postprocedural change in VCSS. The outcome in patients with isolated GSV reflux vs combined GSV and SFJ reflux was considered equivalent if the difference in VCSS change-scores was within the minimum detectable change of ±1.4 points. Change scores were also compared between groups. The multivariable regression model adjusted for baseline VCSS, demographic, clinical, and therapeutic covariates. Statistical analyses were two-tailed, and P < .05 was considered significant. RESULTS:A total of 252 patients were enrolled; most were female (75.00%) and White (78.57%). Of them, 207 patients (82.14%) had combined SFJ+GSV reflux, whereas 45 (17.86%) had isolated GSV reflux. Thermal ablation was used predominantly in both groups, but more so in the SFJ+GSV reflux group (77.78% vs 57.78%). GSV ablation was successful in nearly all cases (99.51% in the SFJ+GSV reflux group; 100% in the isolated GSV reflux group) with no complications. Both groups demonstrated a significant reduction in postprocedural VCSS (6.17 ± 2.20 to 1.86 ± 2.04). The change score in the SFJ+GSV reflux group was equivalent to the GSV group 3 months after endovenous ablation (a difference of -0.54 between groups, 95% confidence interval: -1.36, +0.27). There was no statistical difference in the VCSS change-scores between the two groups (P = .12). CONCLUSIONS:In this prospective multicenter study with full accounting of important clinical covariates, patients with isolated GSV reflux derived equivalent benefit after endovenous ablation compared with those with combined GSV+SFJ reflux. These data support the clinical recommendation that venous ablation must be guided by symptomatic severity rather than the presence or absence of junctional reflux.

Chronic kidney disease (CKD) is closely intertwined with obesity, diabetes, hypertension, dyslipidemia, and cardiovascular disease. In 2023, the American Heart Association formally recognized these interconnections as a unified entity, the cardiovascular-kidney-metabolic (CKM) syndrome. The CKM syndrome brings renewed attention to the importance of CKD in cardiovascular disease and reinforces the need for effective, evidence-based, interdisciplinary approaches to diagnose and prevent its intersecting components. The Kidney Disease: Improving Global Outcomes (KDIGO) organization has long led efforts to synthesize knowledge and translate evidence to practice in this area through the lens of the kidney. This review highlights KDIGO clinical practice guidelines and controversies conference publications that directly address the CKM syndrome. These include guidelines addressing CKD, blood pressure, diabetes, and lipids; an upcoming guideline addressing heart failure in CKD; and controversies conference reports addressing obesity and CKD prevention. Overarching themes include the importance of early detection and intervention; comprehensive, personalized management of kidney and cardiovascular risk; and multidisciplinary care. Through integrated, evidence-based, disease-specific guidelines and reports, KDIGO has established a robust framework for the management of people at risk for or with CKM syndrome as well as priorities for ongoing research.

INTRODUCTION/BACKGROUND:Durvalumab consolidation after concurrent chemoradiotherapy (cCRT) is standard for unresectable stage III NSCLC; however, radiation pneumonitis (RP) remains a major treatment-limiting toxicity. Lung dosimetry incompletely explains the risk of toxicity. Recent studies have established radiographic thymic health as clinically relevant in cancer, but its relationship to treatment-related toxicity remains unclear. We evaluated whether percent thymic tissue (pTT), an interpretable CT-derived measure of residual thymic tissue, is associated with severe pneumonitis after cCRT in NSCLC. METHODS:We analyzed patients with locally advanced NSCLC treated with cCRT with or without durvalumab in RTOG 0617 (n = 453) and at the Memorial Sloan Kettering Cancer Center (MSKCC, n = 230). pTT was derived from pretreatment CT using autosegmentation and Gaussian mixture modeling. Logistic regression with restricted cubic splines assessed the associations of pTT, mean radiation dose to the thymic region, and volume of lungs receiving more than or equal to 20 Gy (lung V20) with high-grade (≥3) pneumonitis. RESULTS:Higher pTT was associated with lower severe pneumonitis rates, independent of lung V20. Grade 3+ pneumonitis occurred in 8.0% versus 3.1% of low- versus high-pTT patients in RTOG 0617 (p = 0.03) and in 13.9% versus 5.2% at the MSKCC (p = 0.04). Patients with both low pTT and high lung V20 had the highest severe pneumonitis rates. Mean radiation dose to the thymic region revealed a weaker, nonlinear relationship with pneumonitis risk. CONCLUSIONS:pTT is an interpretable, host-specific radiographic biomarker associated with severe pneumonitis after cCRT in NSCLC. Incorporating pTT into risk stratification may improve individualized treatment planning and support the safer delivery of curative-intent therapy in locally advanced NSCLC.