Mechanisms of response and resistance to combined decitabine and ipilimumab for advanced myeloid disease.

The challenge of eradicating leukemia in patients with acute myelogenous leukemia (AML) after initial cytoreduction has motivated modern efforts to combine synergistic active modalities including immunotherapy. Recently, the ETCTN/CTEP 10026 study tested the combination of the DNA methyltransferase inhibitor decitabine together with the immune checkpoint inhibitor ipilimumab for AML/myelodysplastic syndrome (MDS) either after allogeneic hematopoietic stem cell transplantation (HSCT) or in the HSCT-naïve setting. Integrative transcriptome-based analysis of 304 961 individual marrow-infiltrating cells for 18 of 48 subjects treated on study revealed the strong association of response with a high baseline ratio of T to AML cells. Clinical responses were predominantly driven by decitabine-induced cytoreduction. Evidence of immune activation was only apparent after ipilimumab exposure, which altered CD4+ T-cell gene expression, in line with ongoing T-cell differentiation and increased frequency of marrow-infiltrating regulatory T cells. For post-HSCT samples, relapse could be attributed to insufficient clearing of malignant clones in progenitor cell populations. In contrast to AML/MDS bone marrow, the transcriptomes of leukemia cutis samples from patients with durable remission after ipilimumab monotherapy showed evidence of increased infiltration with antigen-experienced resident memory T cells and higher expression of CTLA-4 and FOXP3. Altogether, activity of combined decitabine and ipilimumab is impacted by cellular expression states within the microenvironmental niche of leukemic cells. The inadequate elimination of leukemic progenitors mandates urgent development of novel approaches for targeting these cell populations to generate long-lasting responses. This trial was registered at www.clinicaltrials.gov as #NCT02890329.

A low-background, fluorescent assay to evaluate inhibitors of diverse viral proteases.

Multiple coronaviruses (CoVs) can cause respiratory diseases in humans. While prophylactic vaccines designed to prevent infection are available for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), incomplete vaccine efficacy, vaccine hesitancy, and the threat of other pathogenic CoVs for which vaccines do not exist have highlighted the need for effective antiviral therapies. While antiviral compounds targeting the viral polymerase and protease are already in clinical use, their sensitivity to potential resistance mutations as well as their breadth against the full range of human and preemergent CoVs remain incompletely defined. To begin to fill that gap in knowledge, we report here the development of an improved, noninfectious, cell-based fluorescent assay with high sensitivity and low background that reports on the activity of viral proteases, which are key drug targets. We demonstrate that the assay is compatible with not only the SARS-CoV-2 Mpro protein but also orthologues from a range of human and nonhuman CoVs as well as clinically reported SARS-CoV-2 drug-resistant Mpro variants. We then use this assay to define the breadth of activity of two clinically used protease inhibitors, nirmatrelvir and ensitrelvir. Continued use of this assay will help define the strengths and limitations of current therapies and may also facilitate the development of next-generation protease inhibitors that are broadly active against both currently circulating and preemergent CoVs. IMPORTANCE Coronaviruses (CoVs) are important human pathogens with the ability to cause global pandemics. Working in concert with vaccines, antivirals specifically limit viral disease in people who are actively infected. Antiviral compounds that target CoV proteases are already in clinical use; their efficacy against variant proteases and preemergent zoonotic CoVs, however, remains incompletely defined. Here, we report an improved, noninfectious, and highly sensitive fluorescent method of defining the sensitivity of CoV proteases to small molecule inhibitors. We use this approach to assay the activity of current antiviral therapies against clinically reported SARS-CoV-2 protease mutants and a panel of highly diverse CoV proteases. Additionally, we show this system is adaptable to other structurally nonrelated viral proteases. In the future, this assay can be used to not only better define the strengths and limitations of current therapies but also help develop new, broadly acting inhibitors that more broadly target viral families.

Conceptualizing Adult Dysphagia in the United States Within the International Classification of Functioning, Disability and Health (ICF).

Despite the well-documented safety concerns and effect on quality of life, there does not yet exist a wide-reaching framework that links the etiologies of swallowing disorders to the potential short- and long-term outcomes in the context of International Classification of Functioning, Disability and Health (ICF). This paper introduces an expert-reviewed conceptual framework to highlight common etiologies of dysphagia as well as integrate immediate outcomes of dysphagia with long-term outcomes of dysphagia in terms of medical problems, health-related quality of life, functional effect, and psychosocial features. It also outlines the potential cyclical nature of long-term dysphagia outcomes perpetuating the original dysphagia. This framework serves to inform clinicians of important dysphagic outcomes and to bring awareness to long-term outcomes that should be monitored by health care professionals, caregivers, or people with dysphagia.

Absent epiglottic inversion as seen on flexible endoscopic evaluations of swallowing (FEES) is associated with a gestalt reduction in swallowing mechanics.

PURPOSE: Epiglottic inversion, which provides one layer of the requisite protection of the airway during swallowing, is dependent on a number of biomechanical forces. The aim of this study was to examine the association between swallowing mechanics, as visualized during a Modified Barium Swallow (MBS) exam, and the rating of epiglottic inversion as seen on Flexible Endoscopic Evaluation of Swallowing (FEES). METHODS: This study analyzed twenty-five adult outpatients referred for a simultaneous FEES/MBS exams. Each participant swallowed a 5 mL thin liquid bolus, which was the bolus size analyzed for this study's question. Epiglottic inversion, as seen on FEES, was rated by three independent raters. Additionally, twelve swallowing landmarks tracked the shape change of each participant's swallow on the MBS video using a MatLab-specific tracking tool. Analyses were run to determine mean differences in swallowing shape change between the swallows across 3 groups: complete, reduced, and absent epiglottic inversion, as seen on FEES. Using a Computerized Analysis of Swallowing Mechanics (CASM), canonical variate analyses and discriminant function testing were carried out. Other swallowing mechanics were also analyzed for kinematic movements to isolate the function of the hyoid and larynx. A two-sample t-test was conducted to compare mean hyolaryngeal movement between complete and incomplete epiglottic inversion groups. RESULTS: Overall swallowing shape changes were statistically significantly different between the absent, reduced, and complete epiglottic inversion groups on FEES. Canonical variate analyses revealed a significant overall effect of shape change between the groups (eigenvalue = 2.46, p < 0.0001). However, no statistically significant differences were found on hyoid excursion (p = 0.37) and laryngeal elevation (p = 0.06) kinematic measurements between patients with complete and incomplete epiglottic inversion on FEES. CONCLUSION: Epiglottic inversion on FEES is a valuable rating that infers reduced range of motion of structures that cannot be seen on FEES. This small sample of patients suggests that FEES ratings of absent epiglottic inversion may represent gestalt reduction in swallowing mechanics.

Effects of Orthoses on Standing Postural Control and Muscle Activity in Children With Cerebral Palsy.

PURPOSE: This exploratory study assessed postural control and muscle activity in children with cerebral palsy while standing barefoot (BF), in prescribed ankle-foot orthoses (AFOs) and in distal control orthoses (DCOs), which stabilized foot-ankle and deliberately aligned the shank. METHODS: This within-subject study evaluated 10 participants, Gross Motor Functional Classification System level III, across the 3 ankle-foot conditions in: (1) static standing duration and (2) modified Clinical Test of Sensory Interaction on Balance with electromyography (EMG) on 7 muscles. RESULTS: Participants had significantly decreased center of gravity (COG) velocity sway in DCO versus BF and AFO, decreased loss of balance (LOB), and increased standing for DCO versus BF. DCO had minimal effect on EMG activity. CONCLUSIONS: DCO provided significant stabilizing effects on COG sway velocity, standing duration, and LOB. DCO may be effective in balance training. It is unclear whether benefit was derived from stabilization of the ankle joint, the resultant shank alignment, or both.

Residue Ratings on FEES: Trends for Clinical Application of Residue Measurement.

Considering that measurement is a critical part of diagnostic technique for evaluating swallowing dysfunction, there is a need for a better foundational understanding of what influences residue measurement on flexible endoscopic evaluation of swallowing (FEES). This study investigated two factors and their potential influence on trends in residue ratings on FEES: (1) bolus consistency, and (2) residue severity levels on two different types of rating scales. Thirty-three clinicians were asked to rate their overall impressions of pharyngeal residue on 75 FEES videos representing a wide range of residue severities for thin liquid, applesauce, and cracker boluses. Ratings were made on both a visual analog scale (VAS) and a five-point ordinal scale in a randomized fashion across two sessions about two weeks apart. Statistical correlations were determined to assess the association between residue ratings and severity levels and bolus consistency. A total of 2475 VAS ratings and 2473 ordinal ratings were collected. Residue ratings were statistically different depending on severity level (p < 0.0001) and bolus consistency (p < 0.004). Raters appeared to avoid rating at the severe end of the scales, especially on visual analog scales. This study documented the relationship between clinician ratings of pharyngeal residue on FEES and various factors like severity and bolus type. Other findings, such as differences in ratings depending on the type of rating scale and halo effects on the VAS, are valuable for future scale development for understanding perceptual ratings of residue on FEES.

Rethinking Residue: Determining the Perceptual Continuum of Residue on FEES to Enable Better Measurement.

The goal of this work was to better understand perceptual judgments of pharyngeal residue on flexible endoscopic evaluation of swallowing (FEES) and the influence of a visual analog scale (VAS) versus an ordinal scale on clinician ratings. The intent was to determine if perceptual judgments of residue were more accurately described by equal or unequal intervals. Thirty-three speech language pathologists rated pharyngeal residue from 75 FEES videos representing a wide range of residue severities for thin liquid, applesauce, and cracker boluses. Clinicians rated their impression of the overall residue amount in each video on a VAS and, in a different session, on a five-point ordinal scale. Residue ratings were made in two separate sessions separated by several weeks. Statistical correlations of the two rating methods were carried out and best-fit models were determined for each bolus type. A total of 2475 VAS ratings and 2473 ordinal ratings were collected. Residue ratings from both methods (VAS and ordinal) were strongly correlated for all bolus types. The best fit for the data was a quadratic model representing unequal intervals, which significantly improved the r 2 values for each bolus type (cracker r 2 = 0.98, applesauce r 2 = 0.99, thin liquid r 2 = 0.98, all p < 0.0001). Perceptual ratings of pharyngeal residue demonstrated a statistical relationship consistent with unequal intervals. The present findings support the use of a VAS to rate residue on FEES, allowing for greater precision as compared to traditional ordinal rating scales. Perceptual judgments of pharyngeal residue reflected unequal intervals, an important concept that should be considered in future rating scales.

Reliability of Untrained and Experienced Raters on FEES: Rating Overall Residue is a Simple Task.

The purpose of this study was to investigate the reliability of residue ratings on Fiberoptic Endoscopic Evaluation of Swallowing (FEES). We also examined rating differences based on experience to determine if years of experience influenced residue ratings. A group of 44 raters watched 81 FEES videos representing a wide range of residue severities for thin liquid, applesauce, and cracker boluses. Raters were untrained on the rating scales and simply rated their overall impression of residue amount on a visual analog scale (VAS) and a five-point ordinal scale in a randomized fashion across two sessions. Intra-class correlation coefficients, kappa coefficients, and ANOVAs were used to analyze agreement and differences in ratings. Residue ratings on both the VAS and ordinal scales had acceptable inter- and intra-rater reliability. Inter-rater agreement was acceptable (ICC > 0.7) for all comparisons. Intra-rater agreement was excellent on the VAS scale (rc = 0.9) and good on the ordinal scale (k = 0.78). There was no significant difference between expert ratings and other raters based on years of experience for cracker ratings (p = 0.2119) and applesauce ratings (p = 0.2899), but there was a significant difference between clinicians on thin liquid ratings (p = 0.0005). Without any specific training, raters demonstrated high reliability when rating the overall amount of residue on FEES. Years of experience with FEES did not influence residue ratings, suggesting that expert ratings of overall residue amount are not unique or specialized. Rating the overall amount of residue on FEES appears to be a simple visual-perceptual task for puree and cracker boluses.

2014 section on pediatrics knowledge translation lecture: clinicians and researchers on the same path toward facilitating family goals for mobility and participation.

BACKGROUND: The knowledge translation (KT) lecture at the Combined Sections Meeting 2014 was a personal perspective from a researcher who had been a therapist and a longtime clinician, now a PhD candidate. OBJECTIVE: To better integrate research and clinical care, KT is a seamless rather than separate process. KEY POINTS: Knowledge translation can be enhanced by improved receptivity to evidence, and increasing use of research designs that encourage and even require clinician involvement, from single-subject designs to large-scale pragmatic trials. Clinical practice databases and hiring therapists to provide intervention in research efforts also serve to integrate research and clinical care. Limitations of applying mean group research results to an individual patient were also discussed and suggest an important unanswered topic for future research. CONCLUSION: We all need to assume responsibility for the researcher-clinician partnership, making our jobs more joyful and fulfilling, and hopefully the biggest beneficiaries will be our current and future patients.

A Novel Quantitative Measure of Pharyngeal Shortening.

BACKGROUND: Little is known about pharyngeal shortening (PShort) during swallowing. This observational study measured PShort during swallowing in healthy adults and compared it to patients with swallowing impairments of different aetiologies. METHODS: 275 healthy volunteers (19-99 years) and 75 dysphagic patients (25 with head and neck cancer, 25 with Parkinson's, 25 with stroke) underwent videofluoroscopy. A novel quantitative measure of PShort for 1, 3, and 20 mL thin liquid barium and 3 mL paste boli was determined and compared across age, sex, bolus type and patient cohort. RESULTS: PShort ranged from 1.05 to 4.41 cm across bolus types with larger displacements for 20 mL (M: 2.52 cm) and paste (M: 2.43 cm) compared with 1 mL (M: 2.36 cm) and 3 mL (M: 2.41 cm). PShort correlated with sex, height, and cohort but not age. Inter-rater reliability for three raters was substantial (intraclass correlation >0.80). CONCLUSIONS: This novel fluoroscopic measure of PShort is reliable and demonstrates quantitative changes in vertical pharyngeal displacement in healthy and swallow-impaired adults related to sex, size, and bolus type. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2121-2126, 2024.

Phase 1b trial of tagraxofusp in combination with azacitidine with or without venetoclax in acute myeloid leukemia.

ABSTRACT: CD123, a subunit of the interleukin-3 receptor, is expressed on ∼80% of acute myeloid leukemias (AMLs). Tagraxofusp (TAG), recombinant interleukin-3 fused to a truncated diphtheria toxin payload, is a first-in-class drug targeting CD123 approved for treatment of blastic plasmacytoid dendritic cell neoplasm. We previously found that AMLs with acquired resistance to TAG were re-sensitized by the DNA hypomethylating agent azacitidine (AZA) and that TAG-exposed cells became more dependent on the antiapoptotic molecule BCL-2. Here, we report a phase 1b study in 56 adults with CD123-positive AML or high-risk myelodysplastic syndrome (MDS), first combining TAG with AZA in AML/MDS, and subsequently TAG, AZA, and the BCL-2 inhibitor venetoclax (VEN) in AML. Adverse events with 3-day TAG dosing were as expected, without indication of increased toxicity of TAG or AZA+/-VEN in combination. The recommended phase 2 dose of TAG was 12 µg/kg/day for 3 days, with 7-day AZA +/- 21-day VEN. In an expansion cohort of 26 patients (median age 71) with previously untreated European LeukemiaNet adverse-risk AML (50% TP53 mutated), triplet TAG-AZA-VEN induced response in 69% (n=18/26; 39% complete remission [CR], 19% complete remission with incomplete count recovery [CRi], 12% morphologic leukemia-free state [MLFS]). Among 13 patients with TP53 mutations, 7/13 (54%) achieved CR/CRi/MLFS (CR = 4, CRi = 2, MLFS = 1). Twelve of 17 (71%) tested responders had no flow measurable residual disease. Median overall survival and progression-free survival were 14 months (95% CI, 9.5-NA) and 8.5 months (95% CI, 5.1-NA), respectively. In summary, TAG-AZA-VEN shows encouraging safety and activity in high-risk AML, including TP53-mutated disease, supporting further clinical development of TAG combinations. The study was registered on ClinicalTrials.gov as #NCT03113643.

Dysphagia and dementia: a 'double dilemma'.

PURPOSE OF REVIEW: Dementia and its variants, including Alzheimer's disease, become more prevalent with age. Dysphagia, that is, difficulty swallowing, also occurs with aging, and is often associated with dementia. Currently, there is no cure for dementia, and dysphagia, unrecognized or untreated, can have life-altering, even fatal consequences. Prolonged ability to eat safely and effectively could contribute to improved quality of life in a fragile population. In this review, difficulties associated with the management of dysphagia in individuals with dementia, as well as promising possibilities for continued investigation, will be discussed. RECENT FINDINGS: Recent reports point to unique problems related to understanding the comorbidities of dysphagia and dementia. These include delays in identifying dysphagia in affected individuals, as well as a lack of prevalence data for dysphagia in types and stages of dementia, or according to setting, for example, residential center, hospital. Emphasis on new tools, and new applications of existing tools, are needed. SUMMARY: New evidence not only underscores complexities and shortcomings of our understanding of dysphagia in dementia but also points to existing applications with potential for improving the situation, and new investigational directions that may elaborate our further understanding of these comorbidities.

Bolus Clearance Ratio Elevated in Patients With Neurogenic Dysphagia Compared With Healthy Adults: A Measure of Pharyngeal Efficiency.

PURPOSE: Postswallow pharyngeal residue is a risk factor for aspiration, implies swallowing inefficiency, and increases the work of eating. The Bolus Clearance Ratio (BCR) is a derived metric that relates quantities of bolus material observed in the pharynx at two different points: before and after a swallow. The ratio provides a percentage estimate of bolus clearance. In healthy adults, mean BCR is < .05; that is, less than 5% of an ingested bolus is retained in the pharynx. The aim of this study was to compare BCR measures from patients referred for videofluoroscopic swallow studies with concerns related to stroke (n = 100) or other neurological conditions (n = 131, including Parkinson's disease and dementia) with BCRs for 139 healthy adults across the age range. METHOD: BCR for a 20 ml of thin liquid barium bolus was measured. Additional metrics included age, penetration-aspiration scale (PAS) score, and quantitative measures of timing and displacement. Correlations were explored between BCR and pharyngeal constriction ratio (PCR), pharyngoesophageal segment opening (PESmax), maximum hyoid displacement (HMax), and total pharyngeal transit time (TPT). RESULTS: BCR values for patients with stroke (Mdn = 9%, interquartile range [IQR]: 19%, range: 0%-73%) and other neurological conditions (Mdn = 9%, IQR: 16%, range: 0%-96%) were significantly higher than in healthy norms (Mdn = 2%, IQR: 4%, range: 0%-16%, p < .001). BCR was significantly correlated with age (R s = .23, p < .01), TPT (R s = .20, p < .01), PCR (R s = .55, p < .01), PESmax (R s = -.17, p < .01), HMax (R s = -.16, p < .01), and PAS (R s = .38, p < .01). CONCLUSIONS: BCR was elevated in patients with neurogenic dysphagia in comparison with healthy norms and was significantly associated with increased aspiration severity (i.e., PAS). BCR was also correlated with pharyngeal timing and displacement parameters, with the strongest correlation with pharyngeal constriction-a measure of pharyngeal strength. The BCR offers clinicians a simple, quantitative measure of bolus residue and, therefore, pharyngeal efficiency and may be used to assess change in patients over time and with treatment.

Segmented, Negative-Sense RNA Viruses of Humans: Genetic Systems and Experimental Uses of Reporter Strains.

Negative-stranded RNA viruses are a large group of viruses that encode their genomes in RNA across multiple segments in an orientation antisense to messenger RNA. Their members infect broad ranges of hosts, and there are a number of notable human pathogens. Here, we examine the development of reverse genetic systems as applied to these virus families, emphasizing conserved approaches illustrated by some of the prominent members that cause significant human disease. We also describe the utility of their genetic systems in the development of reporter strains of the viruses and some biological insights made possible by their use. To conclude the review, we highlight some possible future uses of reporter viruses that not only will increase our basic understanding of how these viruses replicate and cause disease but also could inform the development of new approaches to therapeutically intervene.

Pixel-Based Swallow Measurements: Correcting Nonsquare Pixels.

PURPOSE: This research note illustrates the effects of video data with nonsquare pixels on the pixel-based measures obtained from videofluoroscopic swallow studies (VFSS). METHOD: Six pixel-based distance and area measures were obtained from two different videoflouroscopic study units; both yielding videos with nonsquare pixels with different pixel aspect ratios (PARs). The swallowing measures were obtained from the original VFSS videos and from the videos after their pixels were squared. RESULTS: The results demonstrated significant multivariate effects both in video type (original vs. squared) and in the interaction between video type and sample (two video recordings of different patients, different PARs, and opposing tilt angles of the external reference). A wide range of variabilities was observed on the pixel-based measures between original and squared videos with the percent deviation ranging from 0.1% to 9.1% with the maximum effect size of 7.43. CONCLUSIONS: This research note demonstrates the effect of disregarding PAR to distance and area pixel-based parameters. In addition, we present a multilevel roadmap to prevent possible measurement errors that could occur. At the planning stage, the PAR of video source should be identified, and, at the analyses stage, video data should be prescaled prior to analysis with PAR-unaware software. No methodology in prior absolute or relative pixel-based studies reports adjustment to the PAR prior to measurements nor identify the PAR as a possible source of variation within the literature. Addressing PAR will improve the precision and stability of pixel-based VFSS findings and improve comparability within and across clinical and research settings. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21957134.

Targeting MET and FGFR in Relapsed or Refractory Acute Myeloid Leukemia: Preclinical and Clinical Findings, and Signal Transduction Correlates.

PURPOSE: Patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) have poor outcomes and require new therapies. In AML, autocrine production of hepatocyte growth factor (HGF) drives MET signaling that promotes myeloblast growth and survival, making MET an attractive therapeutic target. MET inhibition exhibits activity in AML preclinical studies, but HGF upregulation by the FGFR pathway is a common mechanism of resistance. PATIENTS AND METHODS: We performed preclinical studies followed by a Phase I trial to investigate the safety and biological activity of the MET inhibitor merestinib in combination with the FGFR inhibitor LY2874455 for patients with R/R AML. Study Cohort 1 underwent a safety lead-in to determine a tolerable dose of single-agent merestinib. In Cohort 2, dose-escalation of merestinib and LY2874455 was performed following a 3+3 design. Correlative studies were conducted. RESULTS: The primary dose-limiting toxicity (DLT) observed for merestinib alone or with LY2874455 was reversible grade 3 transaminase elevation, occurring in 2 of 16 patients. Eight patients had stable disease and one achieved complete remission (CR) without measurable residual disease. Although the MTD of combination therapy could not be determined due to drug supply discontinuation, single-agent merestinib administered at 80 mg daily was safe and biologically active. Correlative studies showed therapeutic plasma levels of merestinib, on-target attenuation of MET signaling in leukemic blood, and increased HGF expression in bone marrow aspirate samples of refractory disease. CONCLUSIONS: We provide prospective, preliminary evidence that MET and FGFR are biologically active and safely targetable pathways in AML.

Fluoroscopic surrogate for pharyngeal strength: the pharyngeal constriction ratio (PCR).

The pharyngeal constriction ratio (PCR), derived directly from videofluoroscopy without the need for manometry, requires validation as a surrogate for pharyngeal strength. A correlation of -0.70 was previously identified between PCR and pharyngeal clearing pressures (PP) on separate fluoroscopic and manometric studies. As PP increases, PCR decreases. The objective of the current study was to evaluate the correlation between PCR and PP in 25 patients undergoing simultaneous fluoroscopy and pharyngeal manometry. The effect of the manometric catheter on PCR was also investigated. The correlation between the PCR and averaged pharyngeal clearing pressures was -0.72 (p<0.001). All patients with a PCR>0.25 had a P <60 mmHg. PCR did not differ significantly as a consequence of the manometric catheter. Results suggest the utility of an objective fluoroscopic measure in assessing pharyngeal strength when manometry may not be available or possible.

Posterior cricoid region fluoroscopic findings: the posterior cricoid plication.

The region posterior to the cricoid cartilage is challenging to assess fluoroscopically. The purpose of this investigation is to critically evaluate the posterior cricoid (PC) region on fluoroscopy and describe patterns of common findings. This was a case control study. All fluoroscopic swallowing studies performed between June 16, 2009, and February 9, 2010, were reviewed for features seen in the PC region. These findings were categorized into distinct patterns and compared to fluoroscopic studies performed in a cohort of normal volunteers. Two hundred patient studies and 149 healthy volunteer studies were reviewed. The mean age of the referred patient cohort and the volunteer cohort was 57 years (±19) and 61 years (±16), respectively (p > 0.05). The patient cohort was 53% male and the control cohort was 56% female (p > 0.05). Four groups were identified. Pharyngoesophageal webs were seen in 7% (10/149) of controls and 14% (28/200) of patients (p = 0.03). A PC arch impression was seen in 16% of patients (32/200) and controls (24/149) (p = 1). A PC plication was demonstrated in 23% (34/149) of controls and 30% (60/200) of patients (p = 0.13). No distinctive PC region findings were seen in 54% (81/149) of controls and 42% (84/200) of referred patients (p = 0.02). Four patients (2%) had both a web and a PC plication. Four categories of PC region findings were identified (unremarkable PC region, web, PC arch impression, and PC plication). Both patients referred for swallowing studies and healthy volunteers demonstrated esophageal webs, PC arch impressions, and PC plications. Only webs were more common in patients than in control subjects (p = 0.03). The PC impression and PC plication are likely to represent normal variants that may be identified on fluoroscopic swallow studies.