Citations

Introduction Shoulder arthroplasties have been demonstrated to provide reliable pain relief as well as functional benefits. The advent of the reverse shoulder arthroplasty allowed for expanded indications for shoulder replacement. Several studies comparing the outcomes of anatomic and reverse total shoulder arthroplasties have demonstrated decreased range of motion in the reverse arthroplasty cohort, especially in internal rotation. The authors hypothesized that slight modifications to the humeral component of a reverse shoulder arthroplasty could result in increased impingement free range of motion without significant sacrifices to stability. Methods A reverse shoulder arthroplasty model was fashioned to mimic a setting of anterior mechanical impingement after replacement. Sequential resections were taken from the anterior aspect of the polyethylene up to a resection of 10 mm. A solid modeling software was utilized to compare the experimental group to the control group with regard to impingement free motion. Finite element analysis was subsequently utilized to assess stability of the construct in comparison to the nonmodified polyethylene. Results Impingement free internal rotation increased minimally at 3 mm of resection but considerably at each further increase in resection. A resection of 10 mm resulted roughly 30% improvement in impingement free internal rotation. Instability in this model increased with modifications beyond 7 mm. Conclusion Slight alterations to the geometry of the humeral tray and polyethene components can result in improvements in impingement-free internal rotation without substantial increased instability in this model. Further work is needed to determine in vivo implications of modifications to the humeral tray and polyethylene.

AbstractObjectiveTo report on a series of patients with cANCA/PR3‐positive, granulomatosis with polyangiitis (GPA)‐associated subglottic stenosis (SGS) and evaluate response to medical maintenance therapy with rituximab versus other immunosuppressants following initial endoscopic laser excision.Study DesignRetrospective chart review.SettingTertiary academic center.MethodsA retrospective chart review of patients with SGS and cANCA/PR3‐positive GPA who received immunosuppressive maintenance therapy following endoscopic laser excision at our institution from June 1989 to March 2020 was performed. Data pertaining to patient demographics, clinical features, medications, and endoscopic laser procedures were collected.ResultsA total of 27 patients (15 women) with mean age (range) of 40 (19‐59) years and mean (range) follow‐up of 12.6 years (1.5‐28.6) were identified. Sixteen patients (60%) had limited GPA. Six patients (24%) had previously received local intervention with open surgery (n = 1, 4%) or endoscopic techniques (n = 5, 20%). All patients experienced symptom improvement following initial CO2 laser excision at our institution without any procedural complications or adverse events. Following initial laser excision, 15 patients (60%) were treated with rituximab and 10 patients (40%) were treated with nonrituximab immunosuppressive agents. Patients treated with rituximab were less likely to recur (P = 0.040). Limited GPA was associated with an increased incidence of recurrence (P = 0.031). Median time (years) to recurrence (range) was 3.2 (0.3‐19.3) and was not significantly associated with treatment or GPA subtype.ConclusionEndoscopic CO2 laser excision is a safe and effective local intervention for GPA‐associated SGS. Medical maintenance therapy with rituximab reduces risk of recurrence following initial laser excision relative to treatment with non‐rituximab agents.

PURPOSE Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with AML harboring an internal tandem duplication mutation of FLT3 ( FLT3-ITD) AML. These patients are routinely treated with a FLT3 inhibitor after HCT, but there is limited evidence to support this. Accordingly, we conducted a randomized trial of post-HCT maintenance with the FLT3 inhibitor gilteritinib (ClinicalTrials.gov identifier: NCT02997202 ) to determine if all such patients benefit or if detection of measurable residual disease (MRD) could identify those who might benefit. METHODS Adults with FLT3-ITD AML in first remission underwent HCT and were randomly assigned to placebo or 120 mg once daily gilteritinib for 24 months after HCT. The primary end point was relapse-free survival (RFS). Secondary end points included overall survival (OS) and the effect of MRD pre- and post-HCT on RFS and OS. RESULTS Three hundred fifty-six participants were randomly assigned post-HCT to receive gilteritinib or placebo. Although RFS was higher in the gilteritinib arm, the difference was not statistically significant (hazard ratio [HR], 0.679 [95% CI, 0.459 to 1.005]; two-sided P = .0518). However, 50.5% of participants had MRD detectable pre- or post-HCT, and, in a prespecified subgroup analysis, gilteritinib was beneficial in this population (HR, 0.515 [95% CI, 0.316 to 0.838]; P = .0065). Those without detectable MRD showed no benefit (HR, 1.213 [95% CI, 0.616 to 2.387]; P = .575). CONCLUSION Although the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable FLT3-ITD MRD pre- or post-HCT who received gilteritinib treatment. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HCT therapy.

Abstract Purpose: Epithelioid hemangioendothelioma (EHE) is a rare vascular cancer with pathogenic TAZ–CAMTA1 (calmodulinbinding transcription activator 1) operating as an oncogenic driver through activation of the MAPK pathway. Trametinib is an inhibitor of MEK, a critical kinase in the MAPK pathway. We sought to evaluate the effect of trametinib in patients with EHE. Patients and Methods: A phase 2 trial of trametinib was conducted in patients with locally advanced or metastatic EHE. Eligibility requirements included evidence of tumor progression or presence of EHE-related pain requiring opiates for management before enrollment. The primary endpoint was objective response rate (ORR) as per RECIST1.1 in cases with TAZ– CAMTA1 confirmed by fusion-FISH. Secondary objectives were to estimate ORR for all patients, median progression-free survival (PFS), 2-year overall survival (OS) rate, patient safety, and change in patient-reported global health and pain scores per PROMIS questionnaires. Results: 44 patients enrolled and 42 started trametinib. TAZ– CAMTA1 was detected in 27 tumor samples. TheORRwas 3.7%[95% confidence interval (CI), 0.094–19.0], median PFS was 10.4 months (95%CI, 7.1–NA), and 2-year OS rate was 33.3%(95%CI, 19.1–58.2) in the target population. Median pain intensity and interference scores improved significantly after 4 weeks of trametinib in patients using opiates. Common adverse events related to trametinib were rash, fatigue, nausea/vomiting, diarrhea/constipation, alopecia, and edema; one grade 5 ARDS/pneumonitis was related to trametinib. Conclusions: Trametinib was associated with reduction in EHE-related pain and median PFS of more than 6 months, providing palliative benefit in patients with advanced EHE, but the trial did not meet the ORR goal. See related commentary by Van Tine and Haarberg, p. 4552

Introduction: The vascular contribution to Alzheimer’s disease (AD) and AD-related dementias is increasingly recognized. Scanning laser ophthalmoscopy (SLO) visualizes two important markers of cognitive dysfunction in the retina, vascular changes and amyloid plaque deposition. The relationship between retinal vascular changes and peri-vascular amyloid deposition in the continuum of neurodegeneration is imperfectly understood. In this exploratory topographic analysis of a cohort of subjects with normal and impaired cognition that underwent SLO, we investigated the retinal vascular-adjacent (para-vascular) amyloid plaque distribution and its correlation with cognitive measures. Methods: 34 subjects with cognitive decline underwent retinal SLO, brain magnetic resonance imaging and standard neuropsychometric testing. Retinal para-arteriolar and para-venular curcumin positive amyloid plaques were quantified in the supero-temporal retinal quadrant, in the first-, second- and third-order retinal vascular branches. The para-venous and para-arteriolar amyloid count were compared between patients with normal and impaired cognition, and their correlation with brain volumes and white matter hyperintensities was determined. Results: We analyzed retinal para-venous and para-arteriolar amyloid and vascular-structural parameters derived from 29 subjects, mean (SD) age 65(7), 48% female. Para-arteriolar plaque was higher than para-venular plaque in the entire cohort (p<0.0001). Secondary branch para-venular amyloid plaque count was higher in patients with impaired cognition, CDR ≥1 and MOCA ≤26. The para-arterial plaque count in the secondary branches significantly correlated with hippocampal volume and white matter hyperintensities scores. Conclusion: Our topographic analysis of the amyloid plaque distribution in retinal para-vascular regions shows higher amyloid accumulation in the para-arteriolar regions overall, and specifically in the secondary para-venular branches in patients with impaired cognition. Larger longitudinal studies are needed to study the temporal and spatial relationship between vascular dysfunction and para-vascular amyloid deposition in AD.

Objectives The aim of the study was to identify trends in postoperative management of persons undergoing surgery for Zenker diverticula (ZD) by evaluating length of stay (LOS), diet on discharge, and imaging with or without surgical complication. Methods Prospectively enrolled adult patients with cricopharyngeal muscle dysfunction with diverticula undergoing surgery from August 1, 2017 to February 1, 2023 were included. Data were extracted from a multi‐institutional REDCap database, summarizing means, medians, percentages, and frequencies. Fisher's exact or chi squared analyses were utilized, as appropriate, to compare subsets of data. Descriptive analysis assessed differences in clinical course and the relationship to postoperative management. Results There were 298 patients with a mean (standard deviation) age of 71.8 (11.2) years and 60% male. Endoscopic surgery was performed in 79.5% (237/298) of patients versus 20.5% (61/298) open surgery. Sixty patients (20.1%) received postoperative imaging, with four leaks identified. Complications were identified in 9.4% of cases ( n = 29 complications in 28 patients), more commonly in open surgery. Most (81.2%) patients were discharged within 23 h. About half of patients (49%) were discharged from the hospital on a pureed/liquid diet; 36% had been advanced to a soft diet. In patients without complications, LOS was significantly longer following open cases ( p = 0.002); postoperative diet was not different between open and endoscopic ( p = 0.26). Conclusions Overall, most patients are discharged within 23 h without imaging. However, LOS was affected by surgical approach. Postoperative complications are different in endoscopic versus open surgery. Complications with either approach were associated with prolonged LOS, need for imaging, and diet restriction. Level of Evidence Level III Laryngoscope , 134:2678–2683, 2024

AbstractObjectivesSingle‐use rhinolaryngoscopes were brought to market in 2019 as an alternative to traditional reusable scopes and have garnered interest across settings given portability and potential cost advantages. While single‐use was previously evaluated compared to traditional devices, the overall impact to the consult experience for both users and patients has not been captured.MethodsEighteen residents performed consults with both single‐use and reusable rhinolaryngoscope systems on alternating weeks. A five‐question cumulative survey administered across three assessment points over a 12‐week period using a five‐point rating system to rate favorability. Residents and patients also completed four‐point scale surveys following procedure(s) to capture the consult experience. Statistical analyses were performed to measure significance differences between survey responses between the two systems.ResultsSingle‐use rhinolaryngoscopes received higher overall ratings compared with reusables across each metric captured including overall consult time (4.3 vs. 2.2, p < .001), multiscope consults (4.4 vs. 3.1, p < .001), patient communication (4.6 vs. 2.1, p < .001), teaching opportunities (4.6 vs. 2.1, p < .001), and overall ease of use (4.7 vs. 2.6, p < .001). Residents rated single‐use higher than reusable after each procedure in terms of ease of use (1.07 vs. 2.68, p < .001) and visual clarity (1.27 vs. 1.89, p = .003), while patients rated single‐use higher for understanding of illness (3.9 vs. 3.1, p < .001) and understanding of treatment rationale (3.9 vs. 3.1, p < .001).ConclusionResident and patient experience feedback favored single‐use rhinolaryngoscopes compared to reusable scope technology across multiple surveyed measurables. Single‐use rhinolaryngoscopes provide a viable tool for otorhinolaryngologist and other clinicians to perform rhinolaryngoscopy consults.Level of Evidence4.

PURPOSE There is strong evidence that leisure-time physical activity is protective against postmenopausal breast cancer risk but the association with premenopausal breast cancer is less clear. The purpose of this study was to examine the association of physical activity with the risk of developing premenopausal breast cancer. METHODS We pooled individual-level data on self-reported leisure-time physical activity across 19 cohort studies comprising 547,601 premenopausal women, with 10,231 incident cases of breast cancer. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% CIs for associations of leisure-time physical activity with breast cancer incidence. HRs for high versus low levels of activity were based on a comparison of risk at the 90th versus 10th percentiles of activity. We assessed the linearity of the relationship and examined subtype-specific associations and effect modification across strata of breast cancer risk factors, including adiposity. RESULTS Over a median 11.5 years of follow-up (IQR, 8.0-16.1 years), high versus low levels of leisure-time physical activity were associated with a 6% (HR, 0.94 [95% CI, 0.89 to 0.99]) and a 10% (HR, 0.90 [95% CI, 0.85 to 0.95]) reduction in breast cancer risk, before and after adjustment for BMI, respectively. Tests of nonlinearity suggested an approximately linear relationship ( Pnonlinearity = .94). The inverse association was particularly strong for human epidermal growth factor receptor 2–enriched breast cancer (HR, 0.57 [95% CI, 0.39 to 0.84]; Phet = .07). Associations did not vary significantly across strata of breast cancer risk factors, including subgroups of adiposity. CONCLUSION This large, pooled analysis of cohort studies adds to evidence that engagement in higher levels of leisure-time physical activity may lead to reduced premenopausal breast cancer risk.