Faculty Bibliography

BACKGROUND/UNASSIGNED:Neonatal varicella is a rare but potentially life-threatening condition, particularly in preterm infants. Although secondary bacterial infections are common complications, deep organ involvement such as lung abscess formation is exceedingly rare. Reports describing neonatal varicella complicated by Staphylococcus aureus lung abscess are scarce. CASE PRESENTATION/UNASSIGNED:confirming secondary bacterial infection. Initial antibiotic therapy with vancomycin was selected because of severe pulmonary infection and the local prevalence of oxacillin-resistant Staphylococcus aureus. However, subtherapeutic trough concentrations and limited clinical response prompted a switch to linezolid. Following treatment adjustment, the infant showed gradual clinical and radiographic improvement and was discharged in stable condition. Follow-up imaging confirmed complete resolution of the lung abscess. CONCLUSIONS/UNASSIGNED:lung abscess in a preterm infant. It highlights that apparent resolution of cutaneous lesions does not exclude ongoing deep-seated bacterial infection and that persistent respiratory abnormalities should prompt early imaging evaluation, even in the absence of typical respiratory signs. In culture-negative cases, mNGS may facilitate pathogen identification and guide targeted antimicrobial therapy. Early recognition, individualized antimicrobial management, and therapeutic drug monitoring are important for optimizing outcomes in high-risk neonates. This case also underscores the importance of timely post-exposure prophylaxis and the limited availability of varicella-zoster immune globulin (VZIG) in some regions.

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.

Chronic psychological stress is increasingly recognized as an important host-related determinant of cancer progression, yet how stress-associated neuroendocrine signaling reshapes the metastatic immune microenvironment remains incompletely understood. Here, using male mouse models of chronic restraint stress and chronic unpredictable mild stress, together with transcriptomic profiling, flow cytometry, functional assays, and a prospective clinical cohort, we investigated whether chronic stress promotes gastric cancer liver metastasis through glucocorticoid-associated neutrophil reprogramming, neutrophil extracellular trap (NET) formation, and hepatic immune remodeling. Chronic stress induced robust behavioral stress phenotypes, elevated corticosterone levels, and increased hepatic metastatic burden. Immune profiling revealed a myeloid-skewed and immunosuppressive hepatic niche characterized by neutrophil accumulation, impaired CD8⁺ T-cell effector function, and enhanced T-cell exhaustion. Mechanistically, glucocorticoids activated neutrophils through glucocorticoid receptor signaling, increased reactive oxygen species, and promoted NET formation, whereas pharmacological inhibition of glucocorticoid receptor signaling, degradation of NETs, or antibody-mediated neutrophil depletion attenuated stress-associated metastatic progression in vivo. In parallel, glucocorticoid stimulation increased hepatic lipocalin 2 (LCN2) expression and secretion, and conditioned medium from glucocorticoid-treated hepatocytes enhanced neutrophil migration, an effect attenuated by pharmacological LCN2 inhibition. In vivo, LCN2 blockade reduced circulating LCN2 levels and alleviated hepatic metastatic burden. In patients with gastric cancer liver metastasis, higher stress burden was associated with elevated cortisol and circulating myeloperoxidase-DNA levels and with shorter progression-free survival. Multivariable Cox regression further supported an association between Perceived Stress Scale-defined stress burden and shorter progression-free survival. Together, these findings support a stress-associated glucocorticoid-neutrophil-hepatic niche axis linking chronic stress to metastatic progression.

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.

Challenges in orthodontic management for patients with cleft lip and palate (CLP) center on facial growth deficiencies and oral health. Patients with complete CLP exhibit maxillary arch constriction from an early age, typically more severe in the canine region than in the molar region. Transverse management centers on the maxillary arch and types of expansion. The ability to provide targeted anterior expansion while simultaneously addressing posterior crossbites is crucial for correcting arch constriction in patients with cleft lip and palate. Maxillary constrictions are usually addressed immediately prior to the secondary alveolar bone graft procedure. The instability of maxillary expansion in CLP patients is one reason why expansion is often performed early. Anteroposterior (sagittal) orthopedic management of maxillary deficiencies in patients with CLP still remains a challenge, with decisions on treatment based on timing, indications, and severity. A protocol is presented with favorable results for complicated cases. Early correction of the hypoplastic maxilla in patients with CLP is notoriously followed by substantial skeletal relapse; consequently, protraction undertaken in the deciduous or early-mixed dentition should be reserved for cases in which marked functional impairment, such as hipoacusia, is present. Conversely, when the same orthopedic stimulus is applied in proximity to the pubertal growth spurt, the skeletal correction tends to be considerably more stable. Challenges in pediatric dentistry persist with poor oral hygiene and caries. Without a foundation for stable dentition, the best of orthodontic treatment planning can be compromised. Despite awareness on importance of oral health as it relates to systemic conditions and the additional factors faced with CLP patients, more follow-up is needed. Prevention and frequent follow-up with the pediatric dentist are key.

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.

Rubusoside is the major sweet bioactive compound in Rubus chingii var. suavissimus (S.K.Lee) L.T.Lu, characterized by high sweetness, low caloric value, and favorable safety, with potential applications as a natural sweeteners and in functional foods. However, efficient green extraction technologies and their mechanisms remain insufficiently explored. Here, a microwave-assisted deep eutectic solvent (DES) system was developed for rubusoside recovery. The ternary DES composed of choline chloride, 1,2-propylene glycol, and 1,3-butanediol (1:2:2) showed the best performance and outperformed microwave-assisted water extraction. Response surface methodology identified optimal conditions of 33% moisture content, a liquid-solid ratio of 21 mL/g, 6 min, and 320 W, yielding 7.89 ± 0.25% rubusoside. Fourier-transform infrared spectroscopy, electrostatic potential, atoms-in-molecules theory, and independent gradient modelling based on Hirshfeld partition analyses revealed significant non-covalent interactions between the ternary DES and rubusoside. Scanning electron microscopy showed that DES and microwave treatment synergistically disrupted plant tissues and enhanced mass transfer. LX-28 macroporous resin enabled rubusoside separation, and the recovered DES retained stable performance after five reuse cycles. These results demonstrate a green, efficient, and recyclable strategy driven by cooperative hydrogen bonding and van der Waals interactions between the ternary DES and the rubusoside glycosyl moiety, together with DES-microwave-induced tissue disruption and mass-transfer enhancement.