Citations

ObjectivesTo quantify the bias of shear wave speed (SWS) measurements between different commercial ultrasonic shear elasticity systems and a magnetic resonance elastography (MRE) system in elastic and viscoelastic phantoms.MethodsTwo elastic phantoms, representing healthy through fibrotic liver, were measured with 5 different ultrasound platforms, and 3 viscoelastic phantoms, representing healthy through fibrotic liver tissue, were measured with 12 different ultrasound platforms. Measurements were performed with different systems at different sites, at 3 focal depths, and with different appraisers. The SWS bias across the systems was quantified as a function of the system, site, focal depth, and appraiser. A single MRE research system was also used to characterize these phantoms using discrete frequencies from 60 to 500 Hz.ResultsThe SWS from different systems had mean difference 95% confidence intervals of ±0.145 m/s (±9.6%) across both elastic phantoms and ± 0.340 m/s (±15.3%) across the viscoelastic phantoms. The focal depth and appraiser were less significant sources of SWS variability than the system and site. Magnetic resonance elastography best matched the ultrasonic SWS in the viscoelastic phantoms using a 140 Hz source but had a − 0.27 ± 0.027‐m/s (−12.2% ± 1.2%) bias when using the clinically implemented 60‐Hz vibration source.ConclusionsShear wave speed reconstruction across different manufacturer systems is more consistent in elastic than viscoelastic phantoms, with a mean difference bias of < ±10% in all cases. Magnetic resonance elastographic measurements in the elastic and viscoelastic phantoms best match the ultrasound systems with a 140‐Hz excitation but have a significant negative bias operating at 60 Hz. This study establishes a foundation for meaningful comparison of SWS measurements made with different platforms.

Objectives/HypothesisThe purpose of this study is to develop consensus on key points that would support the use of systemic bevacizumab for the treatment of recurrent respiratory papillomatosis (RRP), and to provide preliminary guidance surrounding the use of this treatment modality.Study DesignDelphi method‐based survey series.MethodsA multidisciplinary, multi‐institutional panel of physicians with experience using systemic bevacizumab for the treatment of RRP was established. The Delphi method was used to identify and obtain consensus on characteristics associated with systemic bevacizumab use across five domains: 1) patient characteristics; 2) disease characteristics; 3) treating center characteristics; 4) prior treatment characteristics; and 5) prior work‐up.ResultsThe international panel was composed of 70 experts from 12 countries, representing pediatric and adult otolaryngology, hematology/oncology, infectious diseases, pediatric surgery, family medicine, and epidemiology. A total of 189 items were identified, of which consensus was achieved on Patient Characteristics (9), Disease Characteristics (10), Treatment Center Characteristics (22), and Prior Workup Characteristics (18).ConclusionThis consensus statement provides a useful starting point for clinicians and centers hoping to offer systemic bevacizumab for RRP and may serve as a framework to assess the components of practices and centers currently using this therapy. We hope to provide a strategy to offer the treatment and also to provide a springboard for bevacizumab's use in combination with other RRP treatment protocols. Standardized delivery systems may facilitate research efforts and provide dosing regimens to help shape best‐practice applications of systemic bevacizumab for patients with early‐onset or less‐severe disease phenotypes.Level of Evidence5 Laryngoscope, 131:E1941–E1949, 2021

Abstract Background Community-acquired pneumonia (CAP) in children is usually treated with 10 days of antibiotics. Shorter antibiotic courses may be beneficial if proven effective, with potentially fewer antibiotic adverse effects and decreased antibiotic exposure. Methods This randomized, double-blind, placebo-controlled superiority trial (NCT02891915) compared a strategy of short vs standard course ß-lactam therapy for outpatient CAP in children ages 6–71 months. Children demonstrating clinical improvement by day 3–5 of initial therapy were considered for enrollment. Enrolled children were randomized 1:1 to receive either 5 additional days of the originally prescribed antibiotic (standard) or matching placebo (short). The Desirability of Outcome Ranking (DOOR; PMID: 26113652) was the primary outcome, and was defined by classifying the global experience of children into an ordinal clinical response (OCR) that combined the response to CAP treatment and antibiotic adverse effects 11–15 days after the start of therapy. For those subjects with equivalent OCR, documented days of antibiotic administration was used to further rank the desirability of the outcome with the a priori assumption that shorter antibiotic exposure was more desirable. The OCR was a secondary outcome. The intention to treat population was used to estimate the probability of a more desirable outcome for the strategy of short vs. standard course therapy for both outcomes. Results 385 children were enrolled; 380 had complete data for analysis. Baseline characteristics were similar between the two strategies. In both strategies, &gt; 90% of children had an adequate response to CAP treatment and most antibiotic adverse effects were minor (Table). In the OCR analysis, short course therapy had a 48% probability (95% CI: 42%-53%) of a more desirable outcome. In the DOOR analysis, short course therapy was superior to standard therapy with a 69% probability (95% CI: 63%-72%; p&lt; 0.001) of a more desirable outcome. Conclusion Among children with CAP demonstrating initial clinical improvement with outpatient therapy, both strategies had a similar response to CAP treatment and antibiotic adverse effects, but short course therapy was superior in our a priori defined outcome that incorporated decreased antibiotic exposure. Disclosures Emmanuel B. Walter, MD, MPH, Moderna (Grant/Research Support)Pfizer (Grant/Research Support) Jason Newland, MD, MEd, FPIDS, Merck (Grant/Research Support)Pfizer (Other Financial or Material Support, Industry funded clinical trial) Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Actavis (Grant/Research Support)Advanced Liquid Logics (Grant/Research Support)Affinergy (Consultant, Research Grant or Support)Affinium (Consultant)Allergan (Grant/Research Support)Ampliphi Biosciences (Consultant)Basilea (Consultant, Research Grant or Support)Bayer (Consultant)C3J (Consultant)Cerexa (Consultant, Research Grant or Support)Contrafect (Consultant, Research Grant or Support)Cubist (Grant/Research Support)Debiopharm (Consultant)Destiny (Consultant)Durata (Consultant)Forest (Grant/Research Support)Genentech (Consultant, Research Grant or Support)Integrated Biotherapeutics (Consultant)Janssen (Consultant, Research Grant or Support)Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)Medimmune (Consultant, Research Grant or Support)Merck (Consultant, Research Grant or Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis (Consultant, Research Grant or Support)Pfizer (Grant/Research Support)Regeneron (Consultant, Research Grant or Support)Tetraphase (Consultant)Theravance (Consultant, Research Grant or Support)Trius (Consultant)xBiotech (Consultant) W. Charles Huskins, MD, MSc, ADMA Biologics (Consultant)Pfizer, Inc (Consultant)

Abstract Background Plastic surgery faculty, residencies, and institutions are frequently judged on the quantity and quality of their research output. Some of the most impressive individuals in the specialty receive financial support in the form of grants and payments to help with research ideas. Objectives The authors sought to discern if funding directly correlates to greater impact in the top plastic surgery journals as measured by citations. Methods Using the Web of Science database, the authors identified the 50 most-cited articles in each of the top plastic surgery journals from January 1975 to August 2020. The articles were scanned for funding sources and categorized as industry, federal, foundational, and institutional, while stratifying by decade. Results Between 16 journals, 13.3% of the most-cited articles received funding, 2.6% of which came from industry, 5.4% from government, 4.4% from foundations, and 0.86% from institutions. The percentage of most-cited articles and the proportion that received funding were both correlated with decade (P = 0.0017 and P = 0.043, respectively). However, only the percentage of articles was found to significantly increase over time (P = 0.0068). Conclusions Although funding leads to meaningful publications, this study showed that financial support is not required to have an influence in plastic surgery research.

Metabolic dysfunction underlies several chronic diseases, many of which are exacerbated by obesity. Dietary interventions can reverse metabolic declines and slow aging, although compliance issues remain paramount. 17α-estradiol treatment improves metabolic parameters and slows aging in male mice. The mechanisms by which 17α-estradiol elicits these benefits remain unresolved. Herein, we show that 17α-estradiol elicits similar genomic binding and transcriptional activation through estrogen receptor α (ERα) to that of 17β-estradiol. In addition, we show that the ablation of ERα completely attenuates the beneficial metabolic effects of 17α-E2 in male mice. Our findings suggest that 17α-E2 may act through the liver and hypothalamus to improve metabolic parameters in male mice. Lastly, we also determined that 17α-E2 improves metabolic parameters in male rats, thereby proving that the beneficial effects of 17α-E2 are not limited to mice. Collectively, these studies suggest ERα may be a drug target for mitigating chronic diseases in male mammals.

Background: Randomized clinical trials have demonstrated that catheter ablation for atrial fibrillation in patients with heart failure with reduced ejection fraction may improve survival and other cardiovascular outcomes. Methods: We constructed a decision-analytic Markov model to estimate the costs and benefits of catheter ablation and medical management in patients with symptomatic heart failure with reduced ejection fraction (left ventricular ejection fraction ≤35%) and atrial fibrillation over a lifetime horizon. Evidence from the published literature informed the model inputs, including clinical effectiveness data from meta-analyses. Probabilistic and deterministic sensitivity analyses were performed. A 3% discount rate was applied to both future costs and benefits. The primary outcome was the incremental cost-effectiveness ratio assessed from the US health care sector perspective. Results: Catheter ablation was associated with 6.47 (95% CI, 5.89–6.93) quality-adjusted life years (QALYs) and a total cost of $105 657 (95% CI, $55 311–$191 934; 2018 US dollars), compared with 5.30 (95% CI, 5.20–5.39) QALYs and $63 040 (95% CI, $37 624–$102 260) for medical management. The incremental cost-effectiveness ratio for catheter ablation compared with medical management was $38 496 (95% CI, $5583–$117 510) per QALY gained. Model inputs with the greatest variation on incremental cost-effectiveness ratio estimates were the cost of ablation and the effect of catheter ablation on mortality reduction. When assuming a more conservative estimate of the treatment effect of catheter ablation on mortality (hazard ratio of 0.86), the estimated incremental cost-effectiveness ratio was $74 403 per QALY gained. At a willingness-to-pay threshold of $100 000 per QALY gained, atrial fibrillation ablation was found to be economically favorable compared with medical management in 95% of simulations. Conclusions: Catheter ablation in patients with heart failure with reduced ejection fraction patients and atrial fibrillation may be considered economically attractive at current benchmarks for societal willingness-to-pay in the United States.

Objective Previous studies have explored the restricted nasopharyngeal airway in Apert syndrome patients. This study aims to investigate the segmented airway volume changes with age and directly analyze their correlations with subcranial dimensions and angulations. Methods Ninety-seven preoperative computed tomography scans (Apert, n = 44; control, n = 53) were included in this study, and divided into 5 age-related subgroups. Computed tomography scans were measured using Mimics and 3-matics software. Results Before 6 months of age, the nasal cavity in Apert syndrome is reduced by 47% (P = 0.002), which gradually approximates normal thereafter; however, there remained a 30% reduction, compared with controls. It is highly correlated with the anteroposterior length of subcranial space, and the position of maxilla and palate. The pharyngeal airway volume in Apert syndrome patients, younger than 6 months, was larger than normal by 129% (P = 0.013). However, between 2 and 6 years of age, the pharyngeal airway becomes smaller than normal, with a 57% (P = 0.010) reduction in childhood and 52% (P = 0.005) in adolescence. It is closely correlated with the intercondylar and intergonial widths. Conclusions Airway compromise in Apert syndrome patients is attributable more to the nasal cavity in infants, but in the older child, it is the pharyngeal region. The restricted nasal airway in Apert syndrome is correlated with the subcranial space length and width, but independent of cranial base flexion. The pharyngeal airway volume in Apert syndrome is not as highly correlated with craniofacial morphology. Rather, it is impacted by the growth of mandible, which often requires surgical intervention later in childhood.

Abstract PURPOSE By reducing dose to normal brain tissue, proton radiotherapy (PRT) may lessen neurocognitive risk traditionally associated with photon radiotherapy (XRT). We examined change in neurocognitive scores over time in pediatric medulloblastoma patients treated with PRT versus XRT. METHODS Neurocognitive scores from 79 patients (37 PRT, 42 XRT) were examined. Patients were treated between 2007–2018 on the same treatment protocols that differed only by craniospinal modality (PRT versus XRT). Change in scores over time since diagnosis were compared between groups. RESULTS Groups were similar on most demographic/clinical variables: sex (67.1% male), age at diagnosis (mean 8.6 years), CSI dose (median 23.4 Gy), length of follow-up (mean 4.3 years), and parental education (mean 14.3 years). Boost dose (p&lt;0.001) and margin (p=0.001) differed between groups. Adjusting for covariates, the PRT group exhibited superior outcomes in global IQ, perceptual reasoning, and working memory versus the XRT group (all p&lt;0.05). The XRT group exhibited significant decline in global IQ, working memory, and processing speed (all p&lt;0.05). The PRT group exhibited stable scores in all domains except processing speed (p=0.003). Posterior fossa syndrome imparted risk independent of modality. CONCLUSION This is the first study comparing neurocognitive trajectories between pediatric patients treated for medulloblastoma with PRT versus XRT on comparable, contemporary protocols. PRT was associated with more favorable neurocognitive outcomes in most domains compared to XRT, although processing speed emerged as vulnerable in both groups. This is the strongest evidence to date of an intellectual sparing advantage with PRT in the treatment of pediatric medulloblastoma.