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Introduction: Symptoms, endoscopy and histology have been proposed as therapeutic targets in ulcerative colitis (UC). Observational studies suggest that the achievement of histologic remission may be associated with a lower risk of complications, compared with the achievement of endoscopic remission alone. The actiVE ulcerative colitis, a RanDomIsed Controlled Trial (VERDICT) aims to determine the optimal treatment target in patients with UC., Methods and Analysis: In this multicentre, prospective randomised study, 660 patients with moderate to severe UC (Mayo rectal bleeding subscore [RBS] ≥1; Mayo endoscopic score [MES] ≥2) are randomly assigned to three treatment targets: corticosteroid-free symptomatic remission (Mayo RBS=0) (group 1); corticosteroid-free endoscopic remission (MES ≤1) and symptomatic remission (group 2); or corticosteroid-free histologic remission (Geboes score <2B.0), endoscopic remission and symptomatic remission (group 3). Treatment is escalated using vedolizumab according to a treatment algorithm that is dependent on the patient's baseline UC therapy until the target is achieved at weeks 16, 32 or 48. The primary outcome, the time from target achievement to a UC-related complication, will be compared between groups 1 and 3 using a Cox proportional hazards model., Ethics and Dissemination: The study was approved by ethics committees at the country level or at individual sites as per individual country requirements. A full list of ethics committees is available on request. Study results will be disseminated in peer-reviewed journals and at scientific meetings., Trial Registration Number: EudraCT: 2019-002485-12; NCT04259138., Competing Interests: Competing interests: VJ has received consulting/advisory board fees from AbbVie, Alimentiv Inc (formerly Robarts Clinical Trials), Arena Pharmaceuticals, Asieris, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Reistone Biopharma, Roche, Sandoz, Takeda and Topivert; and speaker’s fees from Abbvie, Ferring, Janssen, Pfizer, Shire and Takeda. GZ has received consulting fees from Alimentiv Inc. ZW is an employee of Alimentiv Inc. SA is an employee of Takeda Pharmaceuticals. JFC reports receiving research grants from AbbVie, Janssen Pharmaceuticals and Takeda; payment for lectures from AbbVie, Amgen, Allergan. Ferring Pharmaceuticals, Shire and Takeda; consulting fees from AbbVie, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, BMS, Celgene Corporation, Eli Lilly, Ferring Pharmaceuticals, Galmed Research, Genentech, Glaxo Smith Kline, Janssen Pharmaceuticals, Kaleido Biosciences, Imedex, Immunic, Iterative Scopes, Merck, Microbia, Novartis, PBM Capital, Pfizer, Protagonist Therapeutics, Sanofi, Takeda, TiGenix, Vifor; and holds stock options in Intestinal Biotech Development. GRD has served as a consultant and/or received speaker fees from Abbvie, Alimentiv, AstraZeneca, Biora (Progenity), Boehringer Ingelheim, Bristol Myers Squibb, Celltrion Healthcare, Cytoki Pharma, Eli Lilly, Ferring, Galapagos, GlaxoSmithKline, Gossamer Bio, Immunic, InDex Pharmaceuticals, Janssen, Johnson & Johnson, Kaleido, Pfizer, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Takeda, Tillotts and Ventyx Biosciences. MF is an employee of Takeda Pharmaceuticals. GWM is a consultant for Alimentiv and in receipt of research funding from AstraZeneca and Johnson and Johnson. LPB has received personal fees from AbbVie, Adacyte, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HAC-Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Nordic Pharma, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Sanofi, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax, Samsung, Ventyx, Roivant and Vectivbio. WJS reports receiving consulting fees from Abbvie, Abivax, Alfasigma, Alimentiv, Beigene, Biora (Progenity), Celltrion, Forbion, Genentech, Gossamer Biosciences, Index Pharmaceuticals, Prometheus Biosciences, Protagonist Therapeutics, Shoreline Biosciences, Vedanta Biosciences, Ventyx Biosciences, Zealand Pharma; and stock or stock options from BeiGene, Gossamer Bio, Biora (Progenity), Prometheus Biosciences, Prometheus Laboratories, Shoreline Biosciences, Ventyx Biosciences, Vimalan Biosciences, Vivreon Gastrosciences; he is an employee at Shoreline Biosciences and Ventyx Biosciences. Spouse: Iveric Bio—consultant, stock options; Biora (Progenity)—stock; Prometheus Biosciences—employee, stock, stock options; Prometheus Laboratories—stock, stock options; Ventyx Biosciences—stock, stock options; Vimalan Biosciences—stock, stock options. SS reports research grants from Takeda, Pfizer, Tillotts Pharma, Abbvie and Biogen; and personal fees for speaker role and advisory board meetings from Janssen, Amgen, Tillotts Pharma, Abbvie, Takeda, Celgene, Roche, Pharmacosmos, and Falk Pharma outside the submitted work. ST has received grants/research support from AbbVie, Buhlmann, Celgene, ECCO, Helmsley Trust, IOIBD, Janssen, Lilly, Pfizer, Takeda, UCB, UKIERI, Vifor and Norman Collisson Foundation; consulting fees from Abacus, AbbVie, Actial, ai4gi, Alcimed, Allergan, Amgen, Apexian, Aptel, Arena, Asahi, Aspen, Astellas, Atlantic, AstraZeneca, Barco, Biocare, Biogen, BLPharma, Boehringer Ingelheim, BMS, Buhlmann, Calcico, Celgene, Cellerix, Cerimon, ChemoCentryx, Chiesi, CisBio, ComCast, Coronado, Cosmo, Ducentis, Dynavax, Elan, Enterome, EQrX, Equillium, Falk, Ferring, FPRT Bio, Galapagos, Genentech/Roche, Genzyme, Gilead, Glenmark, Grunenthal, GSK, GW Pharmaceuticals, Immunocore, Immunometabolism, Indigo, Janssen, Lexicon, Lilly, Medarex, Medtrix, Merck, Merrimack, Mestag, Millenium, Neovacs, Novartis, Novo Nordisk, NPS-Nycomed, Ocera, Optima, Origin, Otsuka, Palau, Pentax, Pfizer, Pharmaventure, Phesi, Phillips, P&G, Pronota, Protagonist, Proximagen, Resolute, Robarts, Sandoz, Sanofi, Santarus, Satisfai, Sensyne Health, Shire, SigmoidPharma, Sorriso, Souffinez, Syndermix, Synthon, Takeda, Theravance, Tigenix, Tillotts, Topivert, Trino Therapeutics with Wellcome Trust, TxCell, UCB Pharma, Vertex, VHsquared, Vifor, Warner Chilcott and Zeria; speaker fees from AbbVie, Amgen, Biogen, BMS, Falk, Ferring, Janssen, Lilly, Pfizer, Shire, Takeda and UCB. He has no stocks or share options. SV has received grants from AbbVie, J&J, Pfizer, Takeda and Galapagos; consulting and/or speaking fees from AbbVie, AbolerIS Pharma, AgomAb, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Avaxia, BMS, Boehringer Ingelheim, Celgene, CVasThera, Cytoki Pharma, Dr Falk Pharma, Ferring, Galapagos, Genentech-Roche, Gilead, GSK, Hospira, Imidomics, Janssen, J&J, Lilly, Materia Prima, MiroBio, Morphic, MrMHealth, Mundipharma, MSD, Pentax, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillots Pharma AG and Zealand Pharma. GR is an employee of Alimentiv Inc. JS is an employee of Alimentiv Inc. JH has received consulting fees from Alimentiv Inc.; and speaker’s fees from Abbvie, Janssen and Takeda. CM has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Takeda, Pfizer and Roche; speaker's fees from AbbVie, Amgen, AVIR Pharma, Alimentiv, Ferring, Janssen, Takeda and Pfizer; and research support from Pfizer. RS is an employee of Alimentiv Inc. SCM is an employee of Alimentiv Inc. NA reports no conflicts of interest. MB has received honoraria from Shire, Allergan, Pfizer, and Takeda; advisory board fees from AbbVie, Takeda, Janssen, Lupin, Gilead, Pfizer, and Novo Nordisk; clinical trials: AbbVie, Novo Nordisk, Gilead, Takeda, Boehringer Ingelheim, Janssen, Pfizer, AstraZeneca and Intercept; research publications: AbbVie (2021–letter signed). PB reports receiving research grants from Abbvie, Amgen, Celltrion, Mylan, Pfizer and Takeda; lecture fees from AbbVie, Celltrion, Janssen, Lilly, and Takeda; and consulting fees Abbvie, Arena Pharmaceuticals, BMS, Celltrion, Dr Falk, Galapagos, Janssen, Lilly, Pentax, PSI-CRO, Roche, Takeda, and Tetrameros. DG has received advisory board fees from Takeda, Abbvie, Janssen, Pfizer, Merck, and Freseni Kabi. WH reports no conflicts of interest. MH reports no conflicts of interest. MK has received personal fees from Shire, a Takeda company, during the conduct of the study; personal fees and non-financial support from Takeda; personal fees and non-financial support from Janssen; personal fees and non-financial support from Ferring, outside the submitted work. RP has received consulting/advisory board fees from AbbVie, Janssen, Pfizer and Allergan. MSS has received consulting, speaker and advisory board fees from Abbvie, Janssen, Pfizer, and Takeda. LW reports no conflicts of interest. BGF is a scientific advisory board member for AbbVie, Allergan, Amgen, AstraZeneca, Avaxia Biologics, Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Elan, Biogen, Ferring, Genentech–Roche, Janssen–Johnson & Johnson, Merck, Millennium, Nestlé, Novo Nordisk, Novartis, Pfizer, Prometheus, Protagonist, Receptos, Salix, Sigmoid Pharma, Takeda, Teva, TiGenix, Tillotts Pharma and UCB Pharma; consulting fees from AbbVie, Actogenix, Akros, Albireo Pharma, Allergan, Amgen, AstraZeneca, Avaxia Biologics, Avir Pharma, Axcan, Baxter Healthcare, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan–Biogen, EnGene, Ferring, Genentech–Roche, GiCare Pharma, Gilead Sciences, Given Imaging, GlaxoSmithKline, Ironwood, Janssen Biotech–Centocor, Janssen–Johnson & Johnson, Kyowa Hakko Kirin, Eli Lilly, Merck, Mesoblast Pharma, Millennium, Nestlé, Novo Nordisk, Novartis, Pfizer, Prometheus, Protagonist, Receptos Salix, Sanofi, Shire, Sigmoid Pharma, Synergy Pharma, Takeda, Teva, TiGenix, Tillotts Pharma, UCB Pharma, Vertex, VHsquared, Wyeth, Zealand and Zygenia; lecture fees from AbbVie, Janssen–Johnson & Johnson, Takeda, and UCB Pharma, and grant support from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Janssen Biotech–Centocor, Janssen–Johnson & Johnson, Pfizer, Receptos, Sanofi, and Takeda and is the Senior Scientific Officer of Alimentiv Inc. Alimentiv Inc is an academic gastrointestinal contract research organisation (CRO), operating under the Alimentiv Health Trust. Alimentiv Inc. provides comprehensive clinical trial services, precision medicine offerings, and centralised imaging solutions for endoscopy, histopathology and other imaging modalities. The beneficiaries of the Alimentiv Health Trust are the employees of the enterprises it holds. BGF, GRD, GZ, VJ and WJS are consultants to Alimentiv Inc. and have a primary academic appointment; they do not hold equity positions or shares in Alimentiv Inc., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: Endoscopic assessment of disease activity is integral for evaluating treatment response in patients with Crohn's disease (CD). We aimed to define appropriate items for evaluating endoscopic activity and conventions for consistent endoscopic scoring rules in CD., Methods: A 2-round modified RAND/University of California at Los Angeles Appropriateness Method study was conducted. A panel of 15 gastroenterologists used a 9-point Likert scale to rate the appropriateness of statements pertaining to the Simple Endoscopic Score for CD, Crohn's Disease Endoscopic Index of Severity, and additional items relevant to endoscopy scoring in CD. Each statement was voted as appropriate, uncertain, or inappropriate based on the median panel rating and presence of disagreement., Results: Panelists voted that it is appropriate for all ulcers to contribute to endoscopic scoring in CD, including aphthous ulcers, ulcerations at a surgical anastomosis, and anal canal ulcers (scored in the rectum). Endoscopic healing should reflect an absence of ulcers. Narrowing should be defined as a clear decrease in luminal diameter; stenosis should be defined by an impassable narrowing, and if occurring at the junction of 2 segments, scored in the distal segment. Scarring and inflammatory polyps were considered inappropriate for including in the affected area score. The optimal method for defining ulcer depth remains uncertain., Conclusions: We outlined scoring conventions for the Simple Endoscopic Score for CD and Crohn's Disease Endoscopic Index of Severity, noting that both scores have limitations. Therefore, we identified priorities for future research and steps for developing and validating a more representative endoscopic index in CD., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: End points to determine the efficacy and safety of medical therapies for Crohn's disease (CD) and ulcerative colitis (UC) are evolving. Given the heterogeneity in current outcome measures, harmonizing end points in a core outcome set for randomized controlled trials is a priority for drug development in inflammatory bowel disease., Methods: Candidate outcome domains and outcome measures were generated from systematic literature reviews and patient engagement surveys and interviews. An iterative Delphi process was conducted to establish consensus: panelists anonymously voted on items using a 9-point Likert scale, and feedback was incorporated between rounds to refine statements. Consensus meetings were held to ratify the outcome domains and core outcome measures. Stakeholders were recruited internationally, and included gastroenterologists, colorectal surgeons, methodologists, and clinical trialists., Results: A total of 235 patients and 53 experts participated. Patient-reported outcomes, quality of life, endoscopy, biomarkers, and safety were considered core domains; histopathology was an additional domain for UC. In CD, there was consensus to use the 2-item patient-reported outcome (ie, abdominal pain and stool frequency), Crohn's Disease Activity Index, Simple Endoscopic Score for Crohn's Disease, C-reactive protein, fecal calprotectin, and co-primary end points of symptomatic remission and endoscopic response. In UC, there was consensus to use the 9-point Mayo Clinic Score, fecal urgency, Robarts Histopathology Index or Geboes Score, fecal calprotectin, and a composite primary end point including both symptomatic and endoscopic remission. Safety outcomes should be reported using the Medical Dictionary for Regulatory Activities., Conclusions: This multidisciplinary collaboration involving patients and clinical experts has produced the first core outcome set that can be applied to randomized controlled trials of CD and UC., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Aims: The NASH Clinical Research Network histologic scoring system, the gold-standard NASH histology assessment for clinical trials, has demonstrated intrarater and interrater variability. An expert panel in a previous systematic Research and Development/University of California Los Angeles (RAND/UCLA) study determined that existing histologic scoring systems do not fully capture NASH disease activity and fibrosis, and standardized definitions of histologic features are needed. We evaluated the reliability of existing and alternate histologic measures and their correlations with a disease activity visual analog scale to propose optimal components for an expanded NAFLD activity score (NAS)., Approach and Results: Four liver pathologists who were involved in the prior RAND/UCLA study underwent standardized training and multiple discussions with the goal of improving agreement. They were blinded to clinical information and scored histologic measures twice, ≥2 weeks apart, for 40 liver biopsies representing the full spectrum of NAFLD. Index intraclass correlation coefficient (ICC) estimates demonstrated intrarater (0.80-0.85) and interrater (0.60-0.72) reliability. Hepatocyte ballooning items had similar interrater ICCs (0.68-0.79), including those extending scores from 0-2 to 0-4. Steatosis measures (interrater ICCs, 0.72-0.80) correlated poorly with disease activity. Correlations with disease activity were largest for hepatocyte ballooning and Mallory-Denk bodies (MDBs), with both used to develop the expanded NAS (intrarater ICC, 0.90; interrater ICC, 0.80). Fibrosis measures had ICCs of 0.70-0.87., Conclusions: After extensive preparation among a group of experienced pathologists, we demonstrated improved reliability of multiple existing histologic NAFLD indices and fibrosis staging systems. Hepatocyte ballooning and MDBs most strongly correlated with disease activity and were used for the expanded NAS. Further validation including evaluation of responsiveness is required., (© 2022 American Association for the Study of Liver Diseases.)

The T-lymphocyte-mediated inflammation in Crohn's disease can be assessed by quantifying CD3-positive T-lymphocyte counts in colonic sections. We developed and validated a process to reliably quantify immunohistochemical marker-positive cells in a high-throughput setting using whole slide images (WSIs) of CD3-immunostained colonic and ileal tissue sections. In regions of interest (ROIs) and/or whole tissue sections of 40 WSIs from 36 patients with Crohn's disease, CD3-positive cells were quantified by an expert gastrointestinal pathologist (gold standard) and by image analysis algorithms developed with software from 3 independent vendors. Semiautomated quantification of CD3-positive cell counts estimated in 1 ROI per section were accurate when compared with manual analysis (Pearson correlation coefficient, 0.877 to 0.925). Biological variability was acceptable in digitally determined CD3-positive cell measures between 2 to 5 ROIs annotated on the same tissue section (coefficient of variation <25%). Results from computer-aided analysis of CD3-positive T lymphocytes in a whole tissue section and the average of results from 2 to 5 ROIs per tissue section lacked reliability (overestimation or underestimation and systematic bias), suggesting that absolute quantification of CD3-positive T lymphocytes in a whole tissue section may be more accurate. Semiautomated image analysis in WSIs demonstrated reproducible CD3-positive cell measures across 3 independent algorithms. A computer-aided digital image analysis method was developed and validated to quantify CD3-positive T lymphocytes in colonic and ileal biopsy sections from patients with Crohn's disease. Results support consideration of this digital analysis method for use in future Crohn's disease clinical studies., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Immune checkpoint inhibitor-associated colitis (ICIC) affects approximately 15% of cancer patients treated with immunotherapy. Although histological evaluation is potentially valuable for both the diagnosis of ICIC and evaluation of disease activity, use in clinical practice is heterogeneous. We aimed to develop expert recommendations to standardize histological assessment of disease activity in patients with ICIC. Using the modified Research and Development/University of California Los Angeles (RAND/UCLA) appropriateness methodology, an international panel of 11 pathologists rated the appropriateness of 99 statements on a 9-point Likert scale during two rounds of anonymous voting. Results were discussed between rounds using moderated videoconferences. There are currently no disease-specific instruments for assessing histological features of ICIC. The panel considered that colonoscopy with at least three biopsies per segment from a total of at least five segments, including both endoscopically normal and inflamed areas, was appropriate for tissue acquisition. They agreed that biopsies should be oriented such that the long axis of the colonic crypts is visualized and should be stained with hematoxylin and eosin. Histological items that the panel voted were appropriate to evaluate in ICIC included the degree of structural/architectural change, chronic inflammatory infiltrate, lamina propria and intraepithelial neutrophils, crypt abscesses and destruction, erosions/ulcerations, apoptosis, surface intraepithelial lymphocytosis, and subepithelial collagen thickness. The appropriateness of routine immunohistochemistry was uncertain. These expert recommendations will help standardize assessment of histological activity in patients with ICIC. The panel also identified the development and validation of an ICIC-specific histological index as a research priority., Competing Interests: Competing interests: CM has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Takeda, Pfizer, Roche; speaker's fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Ferring, Janssen, Takeda, and Pfizer; research support from Pfizer. RiKP has received consulting fees from AbbVie, Eli Lilly, Allergan, Genentech, and Alimentiv. DFS has received consulting fees from Merck, Diaceutics, Pfizer, Allakos, and Alimentiv; stock ownership in Satisfai Health. JK has received advisory fees from Clovis Oncology, AstraZeneca, and Tesaro. LG is an employee of Alimentiv. SCM is an employee of Alimentiv. JKM is an employee of Alimentiv. RMF receives consulting fees from Alimentiv and has received fees from Bristol Myers Squibb, Janssen, and Takeda. RK has received consulting fees from Alimentiv. GYL has received consulting fees from Alimentiv. ReKP has received consulting fees from Alimentiv. CR has received consulting fees from Alimentiv. BGF is a scientific advisory board member for AbbVie, Allergan, Amgen, AstraZeneca, Avaxia Biologics Inc., Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Elan, Biogen, Ferring, Genentech–Roche, Janssen–Johnson & Johnson, Merck, Millennium, Nestlé, Novo Nordisk, Novartis, Pfizer, Prometheus, Protagonist, Receptos, Salix, Sigmoid Pharma, Takeda, Teva, TiGenix, Tillotts Pharma, and UCB Pharma; consulting fees from AbbVie, Actogenix, Akros, Albireo Pharma, Allergan, Amgen, AstraZeneca, Avaxia Biologics, Avir Pharma, Axcan, Baxter Healthcare, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan–Biogen, EnGene, Ferring, Genentech–Roche, GiCare Pharma, Gilead Sciences, Given Imaging, GlaxoSmithKline, Ironwood, Janssen Biotech–Centocor, Janssen–Johnson & Johnson, Kyowa Hakko Kirin, Eli Lilly, Merck, Mesoblast Pharma, Millennium, Nestlé, Novo Nordisk, Novartis, Pfizer, Prometheus, Protagonist, Receptos Salix, Sanofi, Shire, Sigmoid Pharma, Synergy Pharma, Takeda, Teva, TiGenix, Tillotts Pharma, UCB Pharma, Vertex, VHsquared, Wyeth, Zealand, and Zygenia; lecture fees from AbbVie, Janssen–Johnson & Johnson, Takeda, and UCB Pharma, and grant support from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Janssen Biotech–Centocor, Janssen–Johnson & Johnson, Pfizer, Receptos, Sanofi, and Takeda, and is the Senior Scientific Officer of Alimentiv Inc. VJ has received has received consulting/advisory board fees from AbbVie, Alimentiv (formerly Robarts Clinical Trials), Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Reistone Biopharma, Roche, Sandoz, Second Genome, Takeda, Teva, Topivert; speaker’s fees from, Abbvie, Ferring, Galapagos, Janssen Pfizer Shire, Takeda., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The optimal instrument for assessing histologic disease activity in patients with eosinophilic esophagitis (EoE) is unclear. We assessed the responsiveness of the EoE Histologic Scoring System (EoE-HSS) when compared with that of the peak eosinophil count (PEC)., Methods: Histopathology slides were obtained from patients with EoE at baseline and after 8 weeks of treatment with swallowed topical budesonide or elimination diet. Two blinded gastrointestinal pathologists scored biopsies on the EoE-HSS, PEC, and 100-mm visual analog scale (VAS) of overall histologic severity. Change was defined as an improvement by ≥0.5 SD in baseline VAS. Responsiveness was quantified using the standardized effect size (SES) and the probability that the index distinguishes a patient with improvement from a patient without improvement, which is the area under the receiver operating characteristic curve (AUC). Longitudinal validity was assessed using Pearson correlations between changes in EoE-HSS and both PEC and VAS., Results: The EoE-HSS grade (SES 2.18 [95% confidence interval, CI: 1.46-2.88]; AUC 0.73 [95% CI: 0.57-0.84]) and stage (SES 2.07 [95% CI: 1.37-2.77]; AUC 0.73 [95% CI: 0.58-0.84]) were highly responsive, similar to PEC (SES 1.44 [95% CI: 0.80-2.07]; AUC 0.73 [95% CI: 0.58-0.84]). The EoE-HSS grade and stage were more highly correlated with changes in VAS (grade 0.92 [95% CI: 0.86-0.95]; stage 0.89 [95% CI: 0.81-0.94]) than with changes in PEC (grade 0.74 [95% CI: 0.58-0.85]; stage 0.66 [95% CI: 0.47-0.80])., Discussion: The EoE-HSS is highly responsive, performs similarly to PEC, and is better correlated with changes in overall histologic activity in patients with EoE., (Copyright © 2021 by The American College of Gastroenterology.)

The effects of vocal loudness on measures of nasalance was evaluated. Subjects were 30 young adult females with no history of communication disorder who spoke two stimulus passages at three levels of vocal loudness. One passage contained no nasal consonants (Zoo Passage) and the other contained about 35% nasal consonants (Nasal Sentences). The results indicate that there was no significant difference in nasalance measures across the three levels of vocal loudness for either passage. However, when the nasalance measures for the three conditions of vocal loudness were ranked from low to high for each subject, there was an interesting tendency for a subject's lowest nasalance score to occur in the loudest vocal condition on the Nasal Sentences but not for the non-nasal speech material of the Zoo Passage. The implications of these findings with regard to velopharyngeal function are discussed.

This study correlated measures of nasalance computed by the Nasometer with listener judgments of nasality. The subjects were 25 children with craniofacial disorders who spoke three passages, each containing a different proportion of nasal consonants. The results showed a significant but modest correlation between nasalance and nasality when nasal consonants (/m, n, eta/) were not included in the speech passage. When nasal consonants were included in the passage nasalance was unrelated to judgments of hypernasality.

The purpose of this study was to take a critical look at a voice therapy technique known as the yawn-sigh. The voiced sigh as an approach in voice therapy has had increased use in recent years, particularly with problems of vocal hyperfunction. In this study, the physiology of the yawn-sigh was studied with video nasoendoscopy in eight normal subjects; their taped voices were also studied acoustically for possible fundamental frequency and format changes in producing selected vowels under normal and sigh conditions. Although each subject was given a model by the examiner of a yawn-sigh, one of the eight subjects could not produce a true yawn-sigh. Endoscopic findings for seven of the eight subjects performing the yawn-sigh demonstrated retracted elevation of the tongue, a lower positioning of the larynx, and a widened pharynx. Acoustic analyses for the seven subjects producing the sigh found a marked lowering of the second and third formants. Implications for using the yawn-sigh in voice therapy are given, such as using a modified "silent" yawn-sigh, as an easy method for producing greater vocal tract relaxation.

This study compared the vibratory characteristics of normal vocal folds, Teflon-injected paralyzed vocal folds, and noninjected paralyzed vocal folds. Laryngeal videostroboscopy under eight phonatory conditions showed that the Teflon-injected vocal folds were adynamic. The noninjected vocal folds, however, vibrated during each of the phonatory conditions although not necessarily like a normal vocal fold. In terms of vocal fold physiology, it appeared that the noninjected paralyzed vocal folds were too compliant, whereas the Teflon-injected vocal folds were too stiff. Because vocal fold paralysis is often treated in voice therapy with "digital manipulation" and "head turning," the effect of these techniques on vocal fold vibration was also studied. The results showed that digital manipulation was superior to head turning for improving glottal closure but that neither technique appeared to influence the periodicity, amplitude, or extent of vocal fold vibration for either the injected or noninjected vocal folds.

The purpose of this study was to determine whether stutters and nonstutterers differed in latency of vocalization onset as a function of auditory and visual stimulus presentations. Twelve adult stutterers and 12 adult nonstutterers were compared for phonation onset latency under conditions of visual, right ear auditory, and left ear auditory cueing. Analysis of the data indicated that (a) overall phonation onset time did not differ significantly between the groups, (b) no significant differences were found for phonation onset time under conditions of combined auditory cueing, (c) stutterers were significantly slower for /pae/when auditory cueing was presented to either the left or right ear, (d) stutters were significantly slower for /pae/ and /bae/ when the values were combined for the left ear, and (e) there were not significant differences between stutterers' and non nonstutterers' phonation onset times under visual cueing. The results are interpreted to implicate a possible role of auditory system functioning in stutterers' motor control for speech tasks such as phonation onset.

Neural response time (NRT) was compared for 12 adult stutterers and 12 matched normal speakers on two verbal tasks (production of /pae/ and /bae/) and one oral, nonverbal task (lip closure) in response to visual and auditory stimulation. The auditory response stimulus was presented separately to the left and right ears, and the visual stimulus to both eyes. NRT was defined as the time interval between stimulus offset and the onset of electromyographic (EMG) activity from orbicularis oris superior muscle. Results show, in general, that stutterers are slower in NRT for all response tasks in both stimulus modes. Significant differences were found, however, for only the auditory mode. Analyses of the differences between and within groups for response tasks and stimulus modes are discussed in terms of recent research in and theory of timing disturbances in stuttering.