Search

Objective: We sought to explore whether nausea and vomiting are predictive of entrapment. Study design and setting We retrospectively evaluated the data regarding orbital floor fractures in children younger than 19-years-old presenting at a tertiary care center from 1990 to 2001. Zygomatic, naso-orbital ethmoid, and displaced orbital rim fractures were excluded from our analysis. Data on the fracture type, signs and symptoms, ocular motility, surgical repair, and resolution of diplopia were also collected.Results: Twenty-nine orbital floor fractures were identified. One fourth of the children had nausea/vomiting, and half had trapdoor fractures. Seventeen percent of patients had entrapment of the inferior rectus. The positive predictive value of nausea/vomiting with a trapdoor fracture for entrapment was 83.3% (P = 0.002, Fisher exact test). Half the patients required surgical intervention, most commonly for diplopia or gaze restriction. Gaze impairment did not resolve in 2 patients.Conclusion: Patients with trapdoor fractures who present with nausea/vomiting are at a high risk of inferior rectus entrapment and poor outcome. [ABSTRACT FROM AUTHOR]

Objectives: This study investigated the effectiveness of a specialized manual physical therapy (PT) program at improving voice among patients diagnosed with concomitant muscle tension dysphonia (MTD) and cervicalgia at a tertiary care voice center., Materials and Methods: Cervicalgia was determined by palpation of the anterior neck. Both voice therapy (VT) and PT was recommended for all patients diagnosed with MTD and cervicalgia. PT included full-body manual physical therapy with myofascial release. Patients underwent: 1) VT alone, 2) concurrent PT and VT (PT with VT), 3) PT alone, 4) VT, but did not have PT ordered by treating clinician (VT without PT order) or 5) VT followed by PT (VT then PT). The pairwise difference in post-Voice Handicap Index-10 (VHI-10) controlling for baseline variables was calculated with a linear regression model., Results: 178 patients met criteria. All groups showed improvement with treatment. The covariate-adjusted differences in mean post-VHI-10 improvement comparing the VT alone group as a reference were as follows: PT with VT 9.95 (95% confidence interval 7.70, 12.20); PT alone 8.31 (6.16, 10.45); VT without PT order 8.51 (5.55, 11.47); VT then PT 5.47 (2.51, 8.42)., Conclusion: Among patients diagnosed with MTD with cervicalgia, treatment with a specialized PT program was associated with improvement in VHI-10 scores regardless of whether they had VT. While VT is the standard of care for MTD, PT may also offer benefit for MTD patients with cervicalgia., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The Physical Therapy intervention in this study is a copyrighted program. Vanderbilt University Medical Center, 2013 with revisions 2019: All Rights Reserved. Created by co-author Carey A. Tomlinson, Physical Therapist for the Vanderbilt Dayani Center. All necessary permission was obtained for use of this program in this study.

Background: Fcγ-receptor (FcγR)-independent enhancement of SARS-CoV-2 infection mediated by N-terminal domain (NTD)-binding monoclonal antibodies (mAbs) has been observed in vitro , but the functional significance of these antibodies in vivo is less clear., Methods: We characterized 1,213 SARS-CoV-2 spike (S)-binding mAbs derived from COVID-19 convalescent patients for binding specificity to the SARS-CoV-2 S protein, VH germ-line usage, and affinity maturation. Infection enhancement in a vesicular stomatitis virus (VSV)-SARS-CoV-2 S pseudovirus (PV) assay was characterized in respiratory and intestinal epithelial cell lines, and against SARS-CoV-2 variants of concern (VOC). Proteomic deconvolution of the serum antibody repertoire was used to determine functional attributes of secreted NTD-binding mAbs., Results: We identified 72/1213 (5.9%) mAbs that enhanced SARS-CoV-2 infection in a PV assay. The majority (68%) of these mAbs recognized the NTD, were identified in patients with mild and severe disease, and persisted for at least 5 months post-infection. Infection enhancement by NTD-binding mAbs was not observed in intestinal and respiratory epithelial cell lines and was diminished or lost against SARS-CoV-2 VOC. Proteomic deconvolution of the serum antibody repertoire from 2 of the convalescent patients identified, for the first time, NTD-binding, infection-enhancing mAbs among the circulating immunoglobulins directly isolated from serum. Functional analysis of these mAbs demonstrated robust activation of FcγRIIIa associated with antibody binding to recombinant S proteins., Conclusions: Functionally active NTD-specific mAbs arise frequently during natural infection and can last as major serum clonotypes during convalescence. These antibodies display functional attributes that include FcγR activation, and may be selected against by mutations in NTD associated with SARS-CoV-2 VOC., Competing Interests: Laura M. Walker, Mrunal Sakharkar, and C. Garrett Rappazzo are current or former employees of Adimab, LLC and may hold shares in Adimab, LLC. Laura M. Walker is a former employee and holds shares in Invivyd Inc. The remaining authors declare no competing interests., (Copyright © 2024 Pathogens and Immunity.)

Interleukin 22 (IL-22) has a non-redundant role in immune defence of the intestinal barrier 1-3 . T cells, but not innate lymphoid cells, have an indispensable role in sustaining the IL-22 signalling that is required for the protection of colonic crypts against invasion during infection by the enteropathogen Citrobacter rodentium 4 (Cr). However, the intestinal epithelial cell (IEC) subsets targeted by T cell-derived IL-22, and how T cell-derived IL-22 sustains activation in IECs, remain undefined. Here we identify a subset of absorptive IECs in the mid-distal colon that are specifically targeted by Cr and are differentially responsive to IL-22 signalling. Major histocompatibility complex class II (MHCII) expression by these colonocytes was required to elicit sustained IL-22 signalling from Cr-specific T cells, which was required to restrain Cr invasion. Our findings explain the basis for the regionalization of the host response to Cr and demonstrate that epithelial cells must elicit MHCII-dependent help from IL-22-producing T cells to orchestrate immune protection in the intestine., (© 2024. The Author(s).)

Objective: To analyze the effects of lingual frenotomy on adults with restrictive ankyloglossia and difficult direct laryngoscopy exposure. Methods: A case series study was conducted. Restriction of tongue protrusion due to ankyloglossia was identified in 2 patients who had a history of suboptimal true vocal fold (TVF) exposure on direct laryngoscopy for phonomicrosurgery. Inadequate exposure of the vocal folds was achieved on direct laryngoscopy attempts with manual tongue protrusion. Mandibular tori were not present in these patients. An intraoperative lingual frenotomy was performed in both patients. Results: After frenotomy and with manual tongue protrusion, direct laryngoscopy exposure was substantially improved allowing for considerably more visualization of the anterior TVFs. Conclusion: Lingual frenulum procedures with manual tongue protrusion should be considered in select adult patients with restrictive ankyloglossia affecting optimal direct laryngoscopy exposure., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: This study assesses the acute effects of combining a plyometric-based conditioning activity (CA) with different musical stimuli during warm-up on taekwondo (TKD) performance and related psychological aspects., Methods: In a randomized cross-over study design, 16 male TKD athletes (age: 19.94 ± 1.12 years) performed the TKD-specific agility test (TSAT), frequency speed of kick test (FSKT-10s) and its multiple version (FSKT-mult) under 7 experimental and one control condition. For the experimental conditions, participants experienced varying combinations of music selection process [self-selected (SSM) vs. pre-selected (PSM)], and music tempo [fast (F) vs. slow (S)], within preferred (PG) and non-preferred (NPG) music genre; all in the presence of a plyometric based-CA. Athletes were instructed to rate their perceived exertion (RPE) after each test and their felt arousal (FAS), feeling scale (FS), and motivation after testing completion., Results: Findings showed that combining a plyometric-based CA with SSMPG at both fast and slow tempo improved TSAT, FSK-10s, FSKT-mult, FAS, motivation, and RPE post-TSAT greater than the other conditions (all p < 0.05). Additionally, FSSMPG combined with CA improved FS, and RPE after both FSKT-10s and FSKT-mult better than the other conditions (all p < 0.05)., Conclusion: In conclusion, listening to fast self-selected music from a preferred genre in combination with a plyometric-based CA during warm-up setups an individualized warm-up strategy and serves to improve the subsequent specific performances and the related psychological aspects in TKD athletes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Messaoudi, Ouergui, Delleli, Ballmann, Ardigò and Chtourou.)

This systematic review summarized the studies that examined the pre-task music effects on performance aspects and quantitatively analyzed their outcomes. A systematic search for controlled studies investigating the acute effects of pre-task music on physical performance, cognitive aspects and associated psycho-physiological responses was performed through Scopus, PubMed, Web of Science and Cochrane Library databases up to 17 May 2023, with thirty studies fulfilled the inclusion criteria. Data was analyzed using the robust multilevel meta-analysis model of standardized mean difference "SMD" with 95% confidence intervals (95%CI) and prediction intervals (PI) were reported. Pre-task music induced improvements of completion time (SMD = -0.24; 95% CI = -0.46 to -0.01; PI = -0.82 to 0.35; p  = 0.04), relative mean power (RMP) (SMD = 0.38; 95% CI = 0.16 to 0.60; PI = -0.36 to 1.12; p  = 0.003) and fatigue (SMD = -0.20; 95% CI = -0.32 to -0.09; PI = -0.36 to -0.05; p  = 0.01), moderate effects on relative peak power (RPP) (SMD = 0.53; 95% CI = 0.21 to 0.85; PI = -0.42 to 1.48; p  = 0.005), and high effect on feeling scale (FS) (SMD = 2.42; 95% CI = 0.52 to 4.31; PI = -11.43 to 16.26; p  = 0.03). Greater benefits were recorded in jumping performance in males than females ( p  = 0.01), and for active than trained subjects for completion time ( p  = 0.02), RPP ( p  = 0.02) and RMP ( p  = 0.03). Larger benefits were obtained for FS post-warming up than after testing ( p  = 0.04). Self-selected music induced greater effects than pseudo- and pre-selected for performance decrement index ( p  = 0.05) and FS ( p  = 0.02). It could be concluded that pre-task music improved psychological responses and fatigue-related symptoms associated with exercise performance enhancement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Delleli, Ouergui, Ballmann, Messaoudi, Trabelsi, Ardigò and Chtourou.)

The effects of caffeine (CAF) and music have been well documented when used separately, but their combined effects are not yet studied. Thus, the present study assessed the acute effects of combining a low dose of CAF with listening to music during warm-up on taekwondo physical performance, perceived exertion (RPE), and psychological responses during taekwondo-specific tasks in male elite athletes. In a double-blinded, randomized, placebo-controlled crossover study design, male taekwondo athletes (n = 16; age: 18.25 ± 0.75 years) performed the taekwondo-specific agility test (TSAT), 10 s frequency speed of kick test (FSKT-10s) and the multiple version of FSKT (FSKT-mult) under the following conditions: 1) CAF without music (CAF+NoM), 2) placebo (PL) without music (PL+NoM), 3) CAF with music (CAF+M), 4) PL with music (PL+M), 5) no supplement with music (NoS+M) and no supplement without music (control). RPE, feeling scale (FS), felt arousal scale (FAS) and physical enjoyment (PACES) were determined after each test. Findings showed the CAF+M condition induced better performances than other conditions for TSAT, FSKT-10s, FSKT-mult, RPE, FAS and FS and PACES post FSKT-10s (all p<0.05). Moreover, CAF+M resulted in better responses than other conditions for PACES post TSAT (p<0.05) with the exception of CAF+NoM. Likewise, CAF+M condition induced better physical enjoyment than PL+NoM, NoS+M and PL+M conditions post FSKT-mult (p<0.05). Combining low dose of CAF with music during warm-up was an effective strategy that induced greater effects than their isolated use during taekwondo specific tasks., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Delleli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The purpose of this study was to assess the effects of acute caffeine supplementation on physical performance and perceived exertion during taekwondo-specific tasks in male and female athletes with varying expertise. In a double-blinded, randomized, placebo-controlled crossover study design, 52 young athletes from elite (n = 32; 16 males and 16 females) and sub-elite competitive level (n = 20; 10 males and 10 females) participated. Athletes performed taekwondo-specific tasks including the taekwondo-specific agility test (TSAT), 10 s frequency speed of kick test (FSKT-10 s) and multi-bout FSKT (FSKT-multi) under the following conditions: (1) Caffeine (CAF; 3 mg kg -1 ), placebo (PLA), and no supplement control (CON). Session rating of perceived exertion (s-RPE) was determined after the tests. Findings show that regardless of condition, males performed better than females (p < 0.05) and elite athletes had superior performance compared to their sub-elite counterparts (p < 0.05). For the TSAT (p < 0.001), FSKT-10s (p < 0.001), and FSKT-multi (p < 0.001), CAF enhanced performance in elite female athletes compared to sub-elite females. Likewise, CAF ingestion resulted in superior performance in elite males compared to sub-elite males for FSKT-10s (p = 0.003) and FSKT-multi (p < 0.01). The ergogenic potential of CAF during taekwondo-specific tasks appears to be related to a competitive level, with greater benefits in elite than sub-elite athletes., (© 2023. Springer Nature Limited.)

In this study, we aimed to investigate the effects of warm-up music preference and loudness on physical performance, perceived exertion (RPE), and enjoyment in young taekwondo athletes. In a crossover counterbalanced design, 20 taekwondo athletes (10 male, 10 female) performed a battery of physical tasks specific to taekwondo under the following five conditions: (a) No music (NM), (b) Preferred music-Soft (60 dB; PMS), (c) Preferred music-Loud (80 dB; PML), (d) Non-preferred music-Soft (60 dB; NPMS), and (e) Non-preferred music-Loud (80 dB; NPML). On each lab visit, participants completed a taekwondo-specific agility test (TSAT), a10-second kick test (KSKT-10s) and a multiple frequency speed of kick tests (FSKT) within each music condition. Pre-exercise enjoyment was assessed using the Physical Activity Enjoyment Scale (PACES) after the warm-up, while we obtained RPE scores after each test. The PML condition resulted in significantly better agility test times on the TSAT compared to PMS ( p < .001), and NPML ( p < .001). Furthermore, PML led to a greater number of total kicks during the FSKT-10s test compared to the PMS ( p < .001), and NPML ( p < .001) conditions. The decrement index on the FSKT was lower in PML than in PMS and NPML conditions ( p < .001). For RPE, values were significantly lower with preferred than non-preferred music ( p < .001). These findings lend support to ergogenic benefits of listening to PML prior to taekwondo physical tasks, with important implications for enhancing taekwondo training and performance.

BCRs (Abs) and TCRs (or adaptive immune receptors [AIRs]) are the means by which the adaptive immune system recognizes foreign and self-antigens, playing an integral part in host defense, as well as the emergence of autoimmunity. Importantly, the interaction between AIRs and their cognate Ags defies a simple key-in-lock paradigm and is instead a complex many-to-many mapping between an individual's massively diverse AIR repertoire, and a similarly diverse antigenic space. Understanding how adaptive immunity balances specificity with epitopic coverage is a key challenge for the field, and terms such as broad specificity, cross-reactivity, and polyreactivity remain ill-defined and are used inconsistently. In this Immunology Notes and Resources article, a group of experimental, structural, and computational immunologists define commonly used terms associated with AIR binding, describe methodologies to study these binding modes, as well as highlight the implications of these different binding modes for therapeutic design., (Copyright © 2023 by The American Association of Immunologists, Inc.)

Emerging rodent-borne hantaviruses cause severe diseases in humans with no approved vaccines or therapeutics. We recently isolated a monoclonal broadly neutralizing antibody (nAb) from a Puumala virus-experienced human donor. Here, we report its structure bound to its target, the Gn/Gc glycoprotein heterodimer comprising the viral fusion complex. The structure explains the broad activity of the nAb: It recognizes conserved Gc fusion loop sequences and the main chain of variable Gn sequences, thereby straddling the Gn/Gc heterodimer and locking it in its prefusion conformation. We show that the nAb's accelerated dissociation from the divergent Andes virus Gn/Gc at endosomal acidic pH limits its potency against this highly lethal virus and correct this liability by engineering an optimized variant that sets a benchmark as a candidate pan-hantavirus therapeutic.

The North American Airway Collaborative (NoAAC) previously published a 3-year multi-institutional prospective cohort study showing variation in treatment effectiveness between 3 primary surgical techniques for idiopathic subglottic stenosis (iSGS). In this report, we update these findings to include 5 years of data evaluating treatment effectiveness. Patients in the NoAAC cohort were re-enrolled for 2 additional years and followed using the prespecified published protocol. Consistent with prior data, prospective observation of 487 iSGS patients for 5 years showed treatment effectiveness differed by modality. Cricotracheal resection maintained the lowest rate of recurrent operation (5%), followed by endoscopic resection with adjuvant medical therapy (30%) and endoscopic dilation (50%). These data support the initial observations and continue to provide value to providers and patients navigating longitudinal decision-making. Level of evidence: 2-prospective cohort study., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Viruses infect millions of people each year. Both endemic viruses circulating throughout the population as well as novel epidemic and pandemic viruses pose ongoing threats to global public health. Developing more effective tools to address viruses requires not only in-depth knowledge of the virus itself but also of our immune system's response to infection. On June 29 to July 2, 2022, researchers met for the Keystone symposium "Viral Immunity: Basic Mechanisms and Therapeutic Applications." This report presents concise summaries from several of the symposium presenters., (© 2023 New York Academy of Sciences.)

Objective: The purpose of this study was to quantitatively compare the effectiveness of unilateral and bilateral botulinum toxin A (BTX-A) injections for mitigating undesirable weak/breathy voice quality and dysphagia for patients with adductor spasmodic dysphonia and/or essential tremor of voice (ETV)., Methods: Data were collected from the medical records of 319 patients, yielding three treatment cohorts: patients who received an equal dose bilateral injection regimen (BL=) throughout their course of treatment at VUMC, patients who switched to a unilateral injection regimen (UL), and patients who switched to an unequal dose bilateral injection regimen (BL≠). Changes in length of improvement, duration of weak/breathy voice, and dysphagia severity were compared., Results: The BL = treatment group reported the longest duration of improved voice. Shorter periods of improved voice were reported at baseline by patients who later switched to UL or BL ≠ injection regimens. Patients receiving UL injections reported significantly reduced weak/breathy voice and dysphagia. Patients receiving BL ≠ injections reported increased length of improved voice; however, dysphagia symptoms increased. Ninety-two percent of patients with ETV switched to a UL regimen, with 61% of patients transitioning within the first three injections., Conclusions: Patients with pronounced dysphagia and extended periods of weak/breathy voice may benefit from a UL injection approach to mitigate side effects from BTX-A without sacrificing improved voice outcomes. For patients seeking to extend their length of improved voice, a BL ≠ injection regimen may be effective provided the adverse side effects from BTX-A are minimal. Patients with ETV may benefit from a UL injection approach at the outset of their course of treatment with BTX-A., Level of Evidence: III., Competing Interests: The authors have no conflicts of interest to disclose., (© 2022 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Human metapneumovirus (hMPV) is a leading cause of acute lower respiratory tract infections in high-risk populations, yet there are no vaccines or anti-viral therapies approved for the prevention or treatment of hMPV-associated disease. Here, we used a high-throughput single-cell technology to interrogate memory B cell responses to the hMPV fusion (F) glycoprotein in young adult and elderly donors. Across all donors, the neutralizing antibody response was primarily directed to epitopes expressed on both pre- and post-fusion F conformations. However, we identified rare, highly potent broadly neutralizing antibodies that recognize pre-fusion-specific epitopes and structurally characterized an antibody that targets a site of vulnerability at the pre-fusion F trimer apex. Additionally, monotherapy with neutralizing antibodies targeting three distinct antigenic sites provided robust protection against lower respiratory tract infection in a small animal model. This study provides promising monoclonal antibody candidates for passive immunoprophylaxis and informs the rational design of hMPV vaccine immunogens., Competing Interests: Declaration of interests C.G.R., E.S.E., J.C.G., A.Z.W., M.S., and L.M.W. are current or former employees of Adimab, LLC and may hold shares in Adimab, LLC. L.M.W. is an employee of Adagio Therapeutics Inc. and holds shares in Adagio Therapeutics Inc., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

While immune checkpoint blockade results in durable responses for some patients, many others have not experienced such benefits. These treatments rely upon reinvigorating specific T cell-antigen interactions. However, it is often unknown what antigens are being recognized by T cells or how to potently induce antigen-specific responses in a broadly applicable manner. Here, we characterized the CD8 + T cell response to a murine model of melanoma following combination immunotherapy to determine the basis of tumor recognition. Sequencing of tumor-infiltrating T cells revealed a repertoire of highly homologous TCR sequences that were particularly expanded in treated mice and which recognized an antigen from an endogenous retrovirus. While vaccination against this peptide failed to raise a protective T cell response in vivo , engineered antigen mimotopes induced a significant expansion of CD8 + T cells cross-reactive to the original antigen. Vaccination with mimotopes resulted in killing of antigen-loaded cells in vivo yet showed modest survival benefit in a prophylactic vaccine paradigm. Together, this work demonstrates the identification of a dominant tumor-associated antigen and generation of mimotopes which can induce robust functional T cell responses that are cross-reactive to the endogenous antigen across multiple individuals., Competing Interests: BG is currently an employee of Repertoire Immune Medicines. MB is a co-founder, equity holder, and advisor of Kelonia Therapeutics and Abata Therapeutics, an equity holder in 3T Biosciences, and an inventor on patents related to yeast display approaches licensed to 3T Biosciences. DI is a co-founder, SAB member, and equity holder in Elicio Therapeutics, and is an inventor on patents licensed to Elicio Therapeutics related to the amphiphile-vaccine technology. JL has interests in Honeycomb Biotechnologies, and is an inventor on patents related to the SeqWell technology. MB, DI, and JL’s interests are reviewed and managed under MIT’s policies for potential conflicts of interest. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Grace, Backlund, Morgan, Kang, Singh, Huisman, Rappazzo, Moynihan, Maiorino, Dobson, Kyung, Gordon, Holec, Mbah, Garafola, Wu, Love, Wittrup, Irvine and Birnbaum.)

Objective: The objective of this study is to understand how patients at a large academic hospital perceive the training levels of residents and attendings and their perspectives on resident involvement in surgery., Design: This is a cross-sectional survey-based study., Setting: Patients who received care at Vanderbilt University Medical Center were asked to respond to our anonymous electronic survey via email., Participants: There were 3370 patients who underwent plastic surgery within the last 3 years at Vanderbilt University Medical Center were asked to participate. Eight hundred thirty-seven surveys were returned, representing a 24.8% response rate., Results: There were 58.7% of the patients that were confident that a resident has completed medical school. There were 58.4% that report that they usually know if a resident will be assisting their surgeon in the OR, but 86.3% agree that they would like to know if a resident will be involved in their surgery. There were 76.3% that are comfortable with a resident performing parts of their surgery as long as their surgeon is ready to take over if needed., Conclusions: Patient understanding of a resident physician's education and abilities remains low. There is a discrepancy between the number of patients who would like to know if a resident will be involved in their surgery versus the number who are actually told if a resident will be involved., Competing Interests: Conflicts of interest: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives/hypothesis: To identify the most influential publications in laryngology since 2000., Study Design: Modified Delphi process., Methods: Samples of laryngologists drawn from editors of leading journals, organization officers, and thought leaders were invited to participate in a modified Delphi identification of influential laryngology papers. Influential was defined as follows: yielding meaningful practice changes, catalyzing further work as a foundation for an important topic, altering traditional views, or demonstrating durability over time. Quality and validity were not among the selection criteria. Each participant nominated 5 to 10 papers in Round 1. These nominations, augmented with papers from bibliometric analysis, were narrowed further in Round 2 as participants identified their top 20. The 40 papers with the most Round 2 votes were discussed by video conference and then subjected to Round 3 voting, with each participant again selecting their top 20 most influential papers. Final results were collated by the number of Round 3 votes., Results: Sixteen of 18 invited laryngologists participated overall (all 16 in Rounds 1 and 3; 14 in Round 2). Twenty-one papers were identified as most influential. One paper appeared on all 16 Round 3 lists; three papers with eight (50%) votes each were lasted to make the list. Eleven of these 21 focused on voice; three each related to cancer, airway, and swallowing; and one encompassed all of these clinical areas., Conclusions: This list of 21 influential laryngology papers serves to focus further research, provides perspective on recent advances within the field, and is an educational resource for trainees and practicing physicians., Level of Evidence: NA Laryngoscope, 132:406-412, 2022., (© 2021 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Approximately 7 cases of spontaneous regression of adult laryngeal carcinoma have been published in the literature since 1900. This case presents a 62-year-old male with a 6-month history of hoarseness who was subsequently diagnosed with a T1aN0M0 left true vocal fold squamous cell carcinoma (SCC) after biopsy. One month following the initial biopsy, histopathological findings on repeat biopsy revealed absence of malignancy and regression of the tumor without radiation. There has been no evidence of tumor recurrence. This case exemplifies how innate immune modulation may play a role in the spontaneous regression of laryngeal SCC, although the mechanism remains unknown.

Most known SARS-CoV-2 neutralizing antibodies (nAbs), including those approved by the FDA for emergency use, inhibit viral infection by targeting the receptor-binding domain (RBD) of the spike (S) protein. Variants of concern (VOC) carrying mutations in the RBD or other regions of S reduce the effectiveness of many nAbs and vaccines by evading neutralization. Therefore, therapies that are less susceptible to resistance are urgently needed. Here, we characterized the memory B-cell repertoire of COVID-19 convalescent donors and analyzed their RBD and non-RBD nAbs. We found that many of the non-RBD-targeting nAbs were specific to the N-terminal domain (NTD). Using neutralization assays with authentic SARS-CoV-2 and a recombinant vesicular stomatitis virus carrying SARS-CoV-2 S protein (rVSV-SARS2), we defined a panel of potent RBD and NTD nAbs. Next, we used a combination of neutralization-escape rVSV-SARS2 mutants and a yeast display library of RBD mutants to map their epitopes. The most potent RBD nAb competed with hACE2 binding and targeted an epitope that includes residue F490. The most potent NTD nAb epitope included Y145, K150, and W152. As seen with some of the natural VOC, the neutralization potencies of COVID-19 convalescent-phase sera were reduced by 4- to 16-fold against rVSV-SARS2 bearing Y145D, K150E, or W152R spike mutations. Moreover, we found that combining RBD and NTD nAbs did not enhance their neutralization potential. Notably, the same combination of RBD and NTD nAbs limited the development of neutralization-escape mutants in vitro , suggesting such a strategy may have higher efficacy and utility for mitigating the emergence of VOC. IMPORTANCE The U.S. FDA has issued emergency use authorizations (EUAs) for multiple investigational monoclonal antibody (MAb) therapies for the treatment of mild to moderate COVID-19. These MAb therapeutics are solely targeting the receptor-binding domain of the SARS-CoV-2 spike protein. However, the N-terminal domain of the spike protein also carries crucial neutralizing epitopes. Here, we show that key mutations in the N-terminal domain can reduce the neutralizing capacity of convalescent-phase COVID-19 sera. We report that a combination of two neutralizing antibodies targeting the receptor-binding and N-terminal domains may be beneficial to combat the emergence of virus variants.

Objectives: To examine whether social determinants of health (SDH) factors are associated with time to diagnosis, treatment selection, and time to recurrent surgical intervention in idiopathic subglottic stenosis (iSGS) patients., Methods: Adult patients with diagnosed iSGS were recruited prospectively (2015-2017) via clinical providers as part of the North American Airway Collaborative (NoAAC) and via an online iSGS support community on Facebook. Patient-specific SDH factors included highest educational attainment (self-reported), median household income (matched from home zip code via U.S. Census data), and number of close friends (self-reported) as a measure of social support. Main outcomes of interest were time to disease diagnosis (years from symptom onset), treatment selection (endoscopic dilation [ED] vs cricotracheal resection [CTR] vs endoscopic resection with adjuvant medical therapy [ERMT]), and time to recurrent surgical intervention (number of days from initial surgical procedure) as a surrogate for disease recurrence., Results: The total 810 participants were 98.5% female, 97.2% Caucasian, and had a median age of 50 years (IQR, 43-58). The cohort had a median household income of $62 307 (IQR, $50 345-$79 773), a median of 7 close friends (IQR, 4-10), and 64.7% of patients completed college or graduate school. Education, income, and number of friends were not associated with time to diagnosis via multivariable linear regression modeling. Univariable multinominal logistic regression demonstrated an association between education and income for selecting ED versus ERMT, but no associations were noted for CTR. No associations were noted for time to recurrent surgical procedure via Kaplan Meier modeling and Cox proportional hazards regression., Conclusions: Patient education, income, and social support were not associated with time to diagnosis or time to disease recurrence. This suggests additional patient, procedure, or disease-specific factors contribute to the observed variations in iSGS surgical outcomes.

Objectives/hypothesis: To evaluate the safety and complications of endoscopic airway surgery using supraglottic jet ventilation with a team-based approach., Study Design: Retrospective cohort study., Methods: Subjects at two academic institutions diagnosed with laryngotracheal stenosis who underwent endoscopic airway surgery with jet ventilation between January 2008 and December 2018 were identified. Patient characteristics (age, gender, race, follow-up duration) and comorbidities were extracted from the electronic health record. Records were reviewed for treatment approach, intraoperative data, and complications (intraoperative, acute postoperative, and delayed postoperative)., Results: Eight hundred and ninety-four patient encounters from 371 patients were identified. Intraoperative complications (unplanned tracheotomy, profound or severe hypoxic events, barotrauma, laryngospasm) occurred in fewer than 1% of patient encounters. Acute postoperative complications (postoperative recovery unit [PACU] rapid response, PACU intubation, return to the emergency department [ED] within 24 hours of surgery) were rare, occurring in fewer than 3% of patient encounters. Delayed postoperative complications (return to the ED or admission for respiratory complaints within 30 days of surgery) occurred in fewer than 1% of patient encounters. Diabetes mellitus, active smoking, and history of previous tracheotomy were independently associated with intraoperative, acute, and delayed complications., Conclusions: Employing a team-based approach, jet ventilation during endoscopic airway surgery demonstrates a low rate of complications and provides for safe and successful surgery., Level of Evidence: 4 Laryngoscope, 131:2292-2297, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

We examined how baseline CD4 + T cell repertoire and precursor states impact responses to pathogen infection in humans using primary immunization with yellow fever virus (YFV) vaccine. YFV-specific T cells in unexposed individuals were identified by peptide-MHC tetramer staining and tracked pre- and post-vaccination by tetramers and TCR sequencing. A substantial number of YFV-reactive T cells expressed memory phenotype markers and contained expanded clones in the absence of exposure to YFV. After vaccination, pre-existing YFV-specific T cell populations with low clonal diversity underwent limited expansion, but rare populations with a reservoir of unexpanded TCRs generated robust responses. These altered dynamics reorganized the immunodominance hierarchy and resulted in an overall increase in higher avidity T cells. Thus, instead of further increasing the representation of dominant clones, YFV vaccination recruits rare and more responsive T cells. Our findings illustrate the impact of vaccines in prioritizing T cell responses and reveal repertoire reorganization as a key component of effective vaccination., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: Current patient-reported outcome measures do not adequately capture the impact of spasmodic dysphonia (SD) on communication in daily life situations. The aim of this study was to validate the Communicative Participation Item Bank (CPIB), which specifically measures a disease's impact on daily conversational situations, as an outcome measure for SD., Study Design: Multi-institutional prospective cohort study., Methods: A prospective study was conducted with administration of the 46-question CPIB and the Voice Handicap Index-10 (VHI-10) to 190 participants with SD before (time 1) and 6 weeks after (time 2) botulinum toxin injection. Differential item function (DIF) analyses were performed to examine potential item bias. Paired t-tests were used to assess change in each of the CPIB and VHI-10 scores after treatment. Pearson correlations were calculated between the CPIB and VHI-10., Results: DIF analyses revealed no clinically meaningful difference between the item parameters generated for this SD sample and the original CPIB calibration sample. There were statistically significant changes between the pre-treatment and post-treatment time points for both the CPIB and VHI-10. Correlations between the CPIB and VHI were moderate-high., Conclusions: The CPIB item bank, General Short Form, and scoring parameters can be used with people with SD for valid and reliable measurement of the impact of communication disorders on communication in everyday life. The CPIB is sensitive to changes with intervention, proving useful for clinical and research purposes to assess the efficacy and effectiveness of interventions., Level of Evidence: Level 2, prospective observational research with an experimental design (ie, cohort study). Laryngoscope, 131:859-864, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

A comprehensive understanding of the kinetics and evolution of the human B cell response to SARS-CoV-2 infection will facilitate the development of next-generation vaccines and therapies. Here, we longitudinally profiled this response in mild and severe COVID-19 patients over a period of five months. Serum neutralizing antibody (nAb) responses waned rapidly but spike (S)-specific IgG + memory B cells (MBCs) remained stable or increased over time. Analysis of 1,213 monoclonal antibodies (mAbs) isolated from S-specific MBCs revealed a primarily de novo response that displayed increased somatic hypermutation, binding affinity, and neutralization potency over time, providing evidence for prolonged antibody affinity maturation. B cell immunodominance hierarchies were similar across donor repertoires and remained relatively stable as the immune response progressed. Cross-reactive B cell populations, likely re-called from prior endemic beta-coronavirus exposures, comprised a small but stable fraction of the repertoires and did not contribute to the neutralizing response. The neutralizing antibody response was dominated by public clonotypes that displayed significantly reduced activity against SARS-CoV-2 variants emerging in Brazil and South Africa that harbor mutations at positions 501, 484 and 417 in the S protein. Overall, the results provide insight into the dynamics, durability, and functional properties of the human B cell response to SARS-CoV-2 infection and have implications for the design of immunogens that preferentially stimulate protective B cell responses., (Copyright © 2021, American Association for the Advancement of Science.)

The recurrent zoonotic spillover of coronaviruses (CoVs) into the human population underscores the need for broadly active countermeasures. We employed a directed evolution approach to engineer three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies for enhanced neutralization breadth and potency. One of the affinity-matured variants, ADG-2, displays strong binding activity to a large panel of sarbecovirus receptor binding domains and neutralizes representative epidemic sarbecoviruses with high potency. Structural and biochemical studies demonstrate that ADG-2 employs a distinct angle of approach to recognize a highly conserved epitope that overlaps the receptor binding site. In immunocompetent mouse models of SARS and COVID-19, prophylactic administration of ADG-2 provided complete protection against respiratory burden, viral replication in the lungs, and lung pathology. Altogether, ADG-2 represents a promising broad-spectrum therapeutic candidate against clade 1 sarbecoviruses., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Purpose of Review: Present the state-of-the-art overview of laryngeal pacing for treatment of bilateral vocal fold paralysis. A minimally invasive unilateral pacing system and a fully implantable bilateral pacing system are currently in clinical trials. The relative advantages and disadvantages of each are discussed., Recent Findings: Research in functional electrical stimulation for the reanimation of the posterior cricoarytenoid muscle has successfully translated from animal models to human clinical trials for unilateral pacing and bilateral pacing. Current findings suggest unilateral pacing in humans significantly improves ventilation but only marginally better than cordotomy. Bilateral pacing in canines increases glottal opening greater than 2-fold over unilateral pacing and restores exercise tolerance to normal., Summary: Unilateral pacing can be considered a breathing assist device and may not be appropriate for active individuals. Bilateral pacing may be preferable for patients who wish to engage in strenuous exercise. Minimally invasive systems may be ideal for patients who prefer less invasive implantation and are not concerned with cosmesis. Fully implantable pacing systems offer greater electrode redundancy and stability, resulting in a system that is robust against electrode migration or damage., Competing Interests: Conflict of Interest David L. Zealear reports two patents issued (US patent 7,805,195 and US patent 8,050,766). The other authors declare that they have no conflict of interest.

CD4 + helper T cells contribute important functions to the immune response during pathogen infection and tumor formation by recognizing antigenic peptides presented by class II major histocompatibility complexes (MHC-II). While many computational algorithms for predicting peptide binding to MHC-II proteins have been reported, their performance varies greatly. Here we present a yeast-display-based platform that allows the identification of over an order of magnitude more unique MHC-II binders than comparable approaches. These peptides contain previously identified motifs, but also reveal new motifs that are validated by in vitro binding assays. Training of prediction algorithms with yeast-display library data improves the prediction of peptide-binding affinity and the identification of pathogen-associated and tumor-associated peptides. In summary, our yeast-display-based platform yields high-quality MHC-II-binding peptide datasets that can be used to improve the accuracy of MHC-II binding prediction algorithms, and potentially enhance our understanding of CD4 + T cell recognition.

Many considerations affect the value that a new instrument or product may generate in a surgical practice. This review serves as a guide for surgeons considering new purchases and/or wishing to advocate for hospital acquisition of new items. A summary of data from academic and industry practices is presented, with pertinent examples using relevant surgical devices such as disposable devices, laparoscopic trocars, and otologic endoscopes. Surgeons considering incorporating a new instrument or technology within their practice should weigh the following factors before decision making: patient and clinical care factors, surgeon and care team factors, and hospital factors such as cost, revenue, and sourcing. A surgeon well-versed in stakeholder interests who is involved in the purchase of a new instrument may have significant influence in value-based decision making that not only affects his or her practice but ultimately maximizes value for the patient.

Importance: Surgical treatment comparisons in rare diseases are difficult secondary to the geographic distribution of patients. Fortunately, emerging technologies offer promise to reduce these barriers for research., Objective: To prospectively compare the outcomes of the 3 most common surgical approaches for idiopathic subglottic stenosis (iSGS), a rare airway disease., Design, Setting, and Participants: In this international, prospective, 3-year multicenter cohort study, 810 patients with untreated, newly diagnosed, or previously treated iSGS were enrolled after undergoing a surgical procedure (endoscopic dilation [ED], endoscopic resection with adjuvant medical therapy [ERMT], or cricotracheal resection [CTR]). Patients were recruited from clinician practices in the North American Airway Collaborative and an online iSGS community on Facebook., Main Outcomes and Measures: The primary end point was days from initial surgical procedure to recurrent surgical procedure. Secondary end points included quality of life using the Clinical COPD (chronic obstructive pulmonary disease) Questionnaire (CCQ), Voice Handicap Index-10 (VHI-10), Eating Assessment Test-10 (EAT-10), the 12-Item Short-Form Version 2 (SF-12v2), and postoperative complications., Results: Of 810 patients in this cohort, 798 (98.5%) were female and 787 (97.2%) were white, with a median age of 50 years (interquartile range, 43-58 years). Index surgical procedures were ED (n = 603; 74.4%), ERMT (n = 121; 14.9%), and CTR (n = 86; 10.6%). Overall, 185 patients (22.8%) had a recurrent surgical procedure during the 3-year study, but recurrence differed by modality (CTR, 1 patient [1.2%]; ERMT, 15 [12.4%]; and ED, 169 [28.0%]). Weighted, propensity score-matched, Cox proportional hazards regression models showed ED was inferior to ERMT (hazard ratio [HR], 3.16; 95% CI, 1.8-5.5). Among successfully treated patients without recurrence, those treated with CTR had the best CCQ (0.75 points) and SF-12v2 (54 points) scores and worst VHI-10 score (13 points) 360 days after enrollment as well as the greatest perioperative risk., Conclusions and Relevance: In this cohort study of 810 patients with iSGS, endoscopic dilation, the most popular surgical approach for iSGS, was associated with a higher recurrence rate compared with other procedures. Cricotracheal resection offered the most durable results but showed the greatest perioperative risk and the worst long-term voice outcomes. Endoscopic resection with medical therapy was associated with better disease control compared with ED and had minimal association with vocal function. These results may be used to inform individual patient treatment decision-making.

Regulatory T cells (T regs ) can impair anti-tumor immune responses and are associated with poor prognosis in multiple cancer types. T regs in human tumors span diverse transcriptional states distinct from those of peripheral T regs , but their contribution to tumor development remains unknown. Here, we use single-cell RNA sequencing (RNA-seq) to longitudinally profile dynamic shifts in the distribution of T regs in a genetically engineered mouse model of lung adenocarcinoma. In this model, interferon-responsive T regs are more prevalent early in tumor development, whereas a specialized effector phenotype characterized by enhanced expression of the interleukin-33 receptor ST2 is predominant in advanced disease. T reg -specific deletion of ST2 alters the evolution of effector T reg diversity, increases infiltration of CD8 + T cells into tumors, and decreases tumor burden. Our study shows that ST2 plays a critical role in T reg -mediated immunosuppression in cancer, highlighting potential paths for therapeutic intervention., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: Upper airway injury is a recognized complication of prolonged endotracheal intubation, yet little attention has been paid to the consequences of laryngeal injury and functional impact. The purpose of our study was to prospectively define the incidence of acute laryngeal injury and investigate the impact of injury on breathing and voice outcomes., Design: Prospective cohort study., Setting: Tertiary referral critical care center., Patients: Consecutive adult patients intubated greater than 12 hours in the medical ICU from August 2017 to May 2018 who underwent laryngoscopy within 36 hours of extubation., Interventions: Laryngoscopy following endotracheal intubation., Measurements and Main Results: One hundred consecutive patients (62% male; median age, 58.5 yr) underwent endoscopic examination after extubation. Acute laryngeal injury (i.e., mucosal ulceration or granulation tissue in the larynx) was present in 57 patients (57%). Patients with laryngeal injury had significantly worse patient-reported breathing (Clinical Chronic Obstructive Pulmonary Disease Questionnaire: median, 1.05; interquartile range, 0.48-2.10) and vocal symptoms (Voice Handicap Index-10: median, 2; interquartile range, 0-6) compared with patients without injury (Clinical Chronic Obstructive Pulmonary Disease Questionnaire: median, 0.20; interquartile range, 0-0.80; p < 0.001; and Voice Handicap Index-10: median, 0; interquartile range, 0-1; p = 0.005). Multivariable logistic regression independently associated diabetes, body habitus, and endotracheal tube size greater than 7.0 with the development of laryngeal injury., Conclusions: Acute laryngeal injury occurs in more than half of patients who receive mechanical ventilation and is associated with significantly worse breathing and voicing 10 weeks after extubation. An endotracheal tube greater than size 7.0, diabetes, and larger body habitus may predispose to injury. Our results suggest that acute laryngeal injury impacts functional recovery from critical illness.

We use scatter-limited phototherapy techniques to calculate the time-dependent temperature profiles of incisions made with a commercial carbon dioxide laser being used to make a 1-mm incision under computer control using the Digital Acublade™ and with incisions made with the same laser under manual control. The goal is to understand the differences in the amount of lateral thermal damage that is likely from the computer-controlled incisions versus the manually controlled incisions. The temperature profiles are calculated from the absorption and scatter of light in a homogeneous material. The resulting temperature profiles are presented as videos showing how the tissue heats up and cools down with the incident laser pulses. The time-dependent thermal distributions indicate that the computer-controlled laser incision could show as little as 210 μm of lateral thermal damage, whereas the manually controlled laser incisions could show as much as 375 μm of lateral thermal damage. The computer-controlled laser incision is able to control laser pulses fast enough that subsequent pulses can ablate away tissue with a significant amount of residual heat from the previous laser pulse. Using the scatter-limited phototherapy techniques, we can see how a computer-controlled laser can make incisions with less thermal damage by ablating away tissue holding a significant amount of heat from the previous pulse before it has time to diffuse through the tissue. This method of heat removal from laser incisions has not been previously described or demonstrated.

Objective: Acoustic analysis of voice has the potential to expedite detection and diagnosis of voice disorders. Applying an image-based, neural-network approach to analyzing the acoustic signal may be an effective means for detecting and differentially diagnosing voice disorders. The purpose of this study is to provide a proof-of-concept that embedded data within human phonation can be accurately and efficiently decoded with deep learning neural network analysis to differentiate between normal and disordered voices., Methods: Acoustic recordings from 10 vocally-healthy speakers, as well as 70 patients with one of seven voice disorders (n = 10 per diagnosis), were acquired from a clinical database. Acoustic signals were converted into spectrograms and used to train a convolutional neural network developed with the Keras library. The network architecture was trained separately for each of the seven diagnostic categories. Binary classification tasks (ie, to classify normal vs. disordered) were performed for each of the seven diagnostic categories. All models were validated using the 10-fold cross-validation technique., Results: Binary classification averaged accuracies ranged from 58% to 90%. Models were most accurate in their classification of adductor spasmodic dysphonia, unilateral vocal fold paralysis, vocal fold polyp, polypoid corditis, and recurrent respiratory papillomatosis. Despite a small sample size, these findings are consistent with previously published data utilizing deep neural networks for classification of voice disorders., Conclusion: Promising preliminary results support further study of deep neural networks for clinical detection and diagnosis of human voice disorders. Current models should be optimized with a larger sample size., Levels of Evidence: Level III.

Importance: Airway reconstruction for adults with laryngotracheal stenosis (LTS) is directed toward improving airway caliber to mitigate the patient's dyspnea and achieve prosthesis-free breathing (ie, without tracheostomy, intraluminal stent, or T-tube). Despite the importance of preoperative risk stratification to minimize postoperative complications, consensus on an objective predictive algorithm for open airway reconstruction is lacking., Objective: To determine whether the ability to achieve a prosthesis-free airway in adults after open airway reconstruction is associated with red blood cell distribution width (RDW) at the time of surgery., Design, Setting, and Participants: Case series study investigating 92 consecutive patients 18 years and older with laryngotracheal stenosis who underwent open airway reconstruction at a US tertiary care hospital from January 1, 2006, to January 1, 2017., Main Outcomes and Measures: The main outcome was a prosthesis-free airway (absence of tracheostomy, intraluminal stent, or T-tubes) at last follow-up. Multivariate logistic regression modeling was used to identify independent factors associated with this outcome., Results: Of the 92 patients who met inclusion criteria, the median (interquartile range) age was 44 (33.0-60.3) years; 50 (53%) were female, and 82 (89%) were white. In all, 74 patients (80%) were prosthesis free at the last follow-up (mean, 833 days; 95% CI, 10-4229 days). In multivariate analyses, airway decannulation was significantly correlated with reduced RDW (odds ratio [OR], 0.40; 95% CI, 0.19-0.84) and the absence of posterior glottic stenosis (OR, 0.12; 95% CI, 0.04-0.37)., Conclusions and Relevance: These data suggest that surgical success in open airway reconstruction is significantly associated with RDW and whether the patient had posterior glottic stenosis. The RDW is a routine laboratory parameter that may provide some insight to the preoperative probability of prosthesis removal, facilitate risk stratification, promote informed patient decision making, and optimize health care resource management.

Background: Recent studies using batch-fermentation suggest that the red macroalgae Asparagopsis taxiformis has the potential to reduce methane (CH 4 ) production from beef cattle by up to ~ 99% when added to Rhodes grass hay; a common feed in the Australian beef industry. These experiments have shown significant reductions in CH 4 without compromising other fermentation parameters (i.e. volatile fatty acid production) with A. taxiformis organic matter (OM) inclusion rates of up to 5%. In the study presented here, A. taxiformis was evaluated for its ability to reduce methane production from dairy cattle fed a mixed ration widely utilized in California, the largest milk producing state in the US., Results: Fermentation in a semi-continuous in-vitro rumen system suggests that A. taxiformis can reduce methane production from enteric fermentation in dairy cattle by 95% when added at a 5% OM inclusion rate without any obvious negative impacts on volatile fatty acid production. High-throughput 16S ribosomal RNA (rRNA) gene amplicon sequencing showed that seaweed amendment effects rumen microbiome consistent with the Anna Karenina hypothesis, with increased β-diversity, over time scales of approximately 3 days. The relative abundance of methanogens in the fermentation vessels amended with A. taxiformis decreased significantly compared to control vessels, but this reduction in methanogen abundance was only significant when averaged over the course of the experiment. Alternatively, significant reductions of CH 4 in the A. taxiformis amended vessels was measured in the early stages of the experiment. This suggests that A. taxiformis has an immediate effect on the metabolic functionality of rumen methanogens whereas its impact on microbiome assemblage, specifically methanogen abundance, is delayed., Conclusions: The methane reducing effect of A. taxiformis during rumen fermentation makes this macroalgae a promising candidate as a biotic methane mitigation strategy for dairy cattle. But its effect in-vivo (i.e. in dairy cattle) remains to be investigated in animal trials. Furthermore, to obtain a holistic understanding of the biochemistry responsible for the significant reduction of methane, gene expression profiles of the rumen microbiome and the host animal are warranted.

Objective: To characterize the phenotype and function of fibroblasts derived from airway scar in idiopathic subglottic stenosis (iSGS) and to explore scar fibroblast response to interleukin 17A (IL-17A)., Study Design: Basic science., Setting: Laboratory., Subjects and Methods: Primary fibroblast cell lines from iSGS subjects, idiopathic pulmonary fibrosis subjects, and normal control airways were utilized for analysis. Protein, molecular, and flow cytometric techniques were applied in vitro to assess the phenotype and functional response of disease fibroblasts to IL-17A., Results: Mechanistically, IL-17A drives iSGS scar fibroblast proliferation ( P < .01), synergizes with transforming growth factor ß1 to promote extracellular matrix production (collagen and fibronectin; P = .04), and directly stimulates scar fibroblasts to produce chemokines (chemokine ligand 2) and cytokines (IL-6 and granulocyte-macrophage colony-stimulating factor) critical to the recruitment and differentiation of myeloid cells ( P < .01). Glucocorticoids abrogated IL-17A-dependent iSGS scar fibroblast production of granulocyte-macrophage colony-stimulating factor ( P = .02)., Conclusion: IL-17A directly drives iSGS scar fibroblast proliferation, synergizes with transforming growth factor ß1 to promote extracellular matrix production, and amplifies local inflammatory signaling. Glucocorticoids appear to partially abrogate fibroblast-dependent inflammatory signaling. These results offer mechanistic support for future translational study of clinical reagents for manipulation of the IL-17A pathway in iSGS patients.

Objective: To compare presenting characteristics of patients with adductor spasmodic dysphonia (ADSD), ADSD with laryngeal tremor (ADSD + LT), and laryngeal tremor without ADSD (LT)., Design: Cross-sectional analysis., Methods: Patients treated for laryngeal movement disorders (1990-2016) were included. Analysis of variance and chi square tests measured differences in patient characteristics across the three disease groups. Using ADSD as the referent, multivariable logistic regression models were used to determine whether potential risk factors including patient demographics, family history, presence of potential inciting events prior to disease onset, and coprevalent movement disorders were associated with ADSD + LT or LT., Results: In all, 652 patients with ADSD (n = 377), ADSD + LT (n = 98), and LT (n = 177) were included. ADSD patients were significantly younger than those with ADSD + LT and LT (52.5 ± 13.4, 63.9 ± 11.3, and 69.3 ± 10.5 years, respectively; P < 0.001). Coprevalent movement disorders were more common in ADSD + LT (38.7%) and LT (57.1%) groups than in the ADSD group (11.5%; P < 0.001). Compared to ADSD, patients with ADSD + LT and LT were more likely to develop an additional movement disorder during follow-up. In multivariable analyses, increasing age, female gender, and having a movement disorder at presentation were associated with significantly greater odds of having ADSD + LT or LT when compared to ADSD., Conclusion: ADSD + LT patients demonstrate intermediate gender composition and age distributions between those with ADSD and LT. These findings suggest that ADSD + LT may be a distinct phenotype in the spectrum of laryngeal movement disorders., Level of Evidence: 4 Laryngoscope, 129:170-176, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Background & Aims: It is not clear whether we should test for reflux in patients with refractory heartburn or extraesophageal reflux (EER) symptoms, such as cough, hoarseness, or asthma. Guidelines recommend testing patients by pH monitoring when they are on or off acid-suppressive therapies based on pretest probability of reflux, determined by expert consensus. However, it is not clear what constitutes a low or high pretest probability of reflux in these patients. We aimed to develop a model that clinicians can use at bedside to estimate pretest probability of abnormal reflux., Methods: We performed a prospective study of 471 adult patients with refractory heartburn (n = 214) or suspected EER symptoms (n = 257) who underwent endoscopy with wireless pH monitoring while they were off acid-suppressive treatment and assigned them to groups based on symptoms at presentation (discovery cohort). Using data from the discovery cohort, we performed proportional odds ordinal logistic regression to select factors (easy to obtain demographic criteria and clinical symptoms such as heartburn, regurgitation, asthma, cough, and hoarseness) associated with esophageal exposure to acid. We validated our findings in a cohort of 118 patients with the same features from 2 separate tertiary care centers (62% women; median age 59 years; 62% with cough as presenting symptom)., Results: Abnormal pH (>5.5% of time spent at pH <4) was found in 56% of patients with heartburn and 63% of patients with EER (P = .15). Within EER groups, abnormal pH was detected in a significantly larger proportion (80%) of patients with asthma compared with patients with cough (60%) or hoarseness (51%; P < .01). Factors significantly associated with abnormal pH in patients with heartburn were presence of hiatal hernia and body mass index >25 kg/m 2 . In patients with EER, the risk of reflux was independently associated with the presence of concomitant heartburn (odds ratio [OR] 2.0; 95% confidence interval [CI] 1.3-3.1), body mass index >25 kg/m 2 (OR 2.1; 95% CI 1.5-3.1), asthma (OR 2.0; 95% CI 1.2-3.5), and presence of hiatal hernia (OR 1.9; 95% CI 1.2-3.1). When we used these factors to create a scoring system, we found that a score of ≤2 excluded patients with moderate to severe reflux, with a negative predictive value of 80% in the discovery cohort and a negative predictive value of 85% in the validation cohort., Conclusion: We developed a clinical model to estimate pretest probability of abnormal pH in patients who were failed by proton pump inhibitor therapy. This system can help guide clinicians at bedside in determining the most appropriate diagnostic test in this challenging group of patients., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)