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1.
Ann Neurol ; 96(1): 110-120, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38578115

RESUMO

OBJECTIVES: The adult-onset focal dystonias are characterized by over-active muscles leading to abnormal movements. For most cases, the etiology and pathogenesis remain unknown. In the current study, unbiased proteomics methods were used to identify potential changes in blood plasma proteins. METHODS: A large-scale unbiased proteomics screen was used to compare proteins (N = 6,345) in blood plasma of normal healthy controls (N = 49) with adult-onset focal dystonia (N = 143) consisting of specific subpopulations of cervical dystonia (N = 45), laryngeal dystonia (N = 49), and blepharospasm (N = 49). Pathway analyses were conducted to identify relevant biological pathways. Finally, protein changes were used to build a prediction model for dystonia. RESULTS: After correction for multiple comparisons, 15 proteins were associated with adult-onset focal dystonia. Subgroup analyses revealed some proteins were shared across the dystonia subgroups while others were unique to 1 subgroup. The top biological pathways involved changes in the immune system, metal ion transport, and reactive oxygen species. A 4-protein model showed high accuracy in discriminating control individuals from dystonia cases [average area under the curve (AUC) = 0.89]. INTERPRETATION: These studies provide novel insights into the etiopathogenesis of dystonia, as well as novel potential biomarkers. ANN NEUROL 2024;96:110-120.


Assuntos
Distúrbios Distônicos , Proteômica , Humanos , Proteômica/métodos , Feminino , Masculino , Distúrbios Distônicos/sangue , Distúrbios Distônicos/diagnóstico , Pessoa de Meia-Idade , Adulto , Idoso , Biomarcadores/sangue , Proteínas Sanguíneas/metabolismo
2.
Laryngoscope ; 134(2): 577-581, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37470254

RESUMO

OBJECTIVES: Pulmonary papillomatosis is a rare but severe manifestation of recurrent respiratory papillomatosis (RRP). Efficacy data of systemic bevacizumab for pulmonary RRP are limited. This study's objective was to characterize disease response of pulmonary RRP to systemic bevacizumab. METHODS: A retrospective review was performed to identify patients with pulmonary RRP seen at three medical institutions. Clinical symptoms, CT findings, and disease response were compared before and after initiation of systemic bevacizumab therapy. Disease response was categorized as complete response, partial response, stabilization, or progression for each subsite involved by papilloma. RESULTS: Of the 12 pulmonary RRP patients treated with systemic bevacizumab, 4 (33.3%) were male, and 11 (91.7%) were juvenile-onset RRP patients. All presented with laryngeal, tracheal, and pulmonary RRP. The median (range) age at first bevacizumab infusion was 48.1 (19.5-70.2) years. Progression to pulmonary malignancy was identified in 3 (25.0%) patients, 2 before initiation of and 1 after complete cessation of bevacizumab therapy. Clinical symptoms such as dyspnea (75.0% vs. 25.0%; p = 0.01) and dysphagia and/or odynophagia (33.3 vs. 0.0%; p = 0.03) were significantly decreased following bevacizumab therapy. Compared with pre-treatment baseline, 9 (75.0%) patients experienced a stable-to-partial response in the lungs to systemic bevacizumab, and 10 (83.3%) experienced partial-to-complete responses in the larynx and trachea. CONCLUSION: Systemic bevacizumab is effective in stabilizing progression in even the most severe cases of RRP, with both a dramatic reduction in laryngeal and tracheal disease as well as a stable-to-partial response of pulmonary involvement in a majority of patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:577-581, 2024.


Assuntos
Neoplasias Pulmonares , Infecções por Papillomavirus , Infecções Respiratórias , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Bevacizumab/uso terapêutico , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/tratamento farmacológico , Infecções por Papillomavirus/patologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Resposta Patológica Completa
3.
Laryngoscope ; 134(3): 1313-1315, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37462348

RESUMO

Intermittent left supraclavicular swelling is an uncommon and elusive condition that can lead to extensive diagnostic workups to determine the etiology and treatment. One potential cause is partial, intermittent, or complete thoracic duct occlusion (TDO). We report on a patient who presented with chronic, intermittent left supraclavicular swelling and abdominal pain that was relieved by thoracic duct angioplasty. Thoracic duct occlusion should be included in the differential diagnosis of left supraclavicular swelling. Lymphatic imaging can facilitate the diagnosis and allows for potential percutaneous treatment. Laryngoscope, 134:1313-1315, 2024.


Assuntos
Vasos Linfáticos , Cisto Mediastínico , Pancreatite , Humanos , Ducto Torácico/diagnóstico por imagem , Ducto Torácico/cirurgia , Cisto Mediastínico/diagnóstico , Cisto Mediastínico/cirurgia , Tomografia Computadorizada por Raios X , Edema/etiologia
4.
Laryngoscope ; 134(5): 2295-2299, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37909788

RESUMO

OBJECTIVES: Adult-onset idiopathic laryngeal dystonia (LD) can be associated with the risk of spread to muscles in the body. Subjects with extralaryngeal onset of dystonia have exhibited spread to the larynx. Previous studies analyze the spread of other dystonias but emphasis has not been placed on LD. The objective was to identify demographic and clinical factors contributing to the spread of dystonia to and from the larynx. METHODS: Data were obtained from the Dystonia Coalition (DC)-patients from 49 international clinical centers. Clinical and demographic data was taken from 143 out of 409 patients with diagnosed LD. Patient criteria included adult-onset LD diagnosed on exam with no co-morbid neurologic conditions and no dystonia in other locations. RESULTS: Among the 143 patients, 94 (65.7%) patients were diagnosed with focal laryngeal onset, with the remainder having extralaryngeal onset. Family history and age at study were statistically significant indicators of a patient developing laryngeal versus extralaryngeal onset of dystonia. Among the laryngeal onset group, 21 cases (22.3%) had an average time of 5.81 ± 5.79 years to spread from diagnosis, most commonly to neck (61.9%). Among extralaryngeal onset patients, mean time of larynx spread was 7.92 ± 7.737 years, most commonly to neck (22.7%). CONCLUSIONS: Our data indicates approximately a quarter of patients with laryngeal-onset dystonia will exhibit spread. There were no demographic or clinical factors that were statistically predictive of the likelihood of spread from larynx. Patients with dystonia elsewhere in the body should be counseled on the possibility of spread to larynx, and vice versa. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2295-2299, 2024.


Assuntos
Distonia , Distúrbios Distônicos , Adulto , Humanos , Distonia/epidemiologia , Distonia/diagnóstico , Idade de Início , Distúrbios Distônicos/epidemiologia , Pescoço , Demografia
5.
Laryngoscope ; 133(11): 3087-3093, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37204106

RESUMO

OBJECTIVE: To evaluate the safety, immunogenicity, and efficacy of INO-3107, a DNA immunotherapy designed to elicit targeted T-cell responses against human papillomavirus (HPV) types 6 and 11, in adult patients with recurrent respiratory papillomatosis (RRP; NCT04398433). METHODS: Eligible patients required ≥2 surgical interventions for RRP in the year preceding dosing. INO-3107 was administered by intramuscular (IM) injection followed by electroporation (EP) on weeks 0, 3, 6, and 9. Patients underwent surgical debulking within 14 days prior to first dose, with office laryngoscopy and staging at screening and weeks 6, 11, 26, and 52. Primary endpoint was safety and tolerability, as assessed by treatment-emergent adverse events (TEAEs). Secondary endpoints included frequency of surgical interventions post-INO-3107 and cellular immune responses. RESULTS: An initial cohort of 21 patients was enrolled between October 2020 and August 2021. Fifteen (71.4%) patients had ≥1 TEAE; 11 (52.4%) were Grade 1, and 3 (14.3%) were Grade 3 (none treatment related). The most frequently reported TEAE was injection site or procedural pain (n = 8; 38.1%). Sixteen (76.2%) patients had fewer surgical interventions in the year following INO-3107 administration, with a median decrease of 3 interventions versus the preceding year. The RRP severity score, modified by Pransky, showed improvement from baseline to week 52. INO-3107 induced durable cellular responses against HPV-6 and HPV-11, with an increase in activated CD4 and CD8 T cells and CD8 cells with lytic potential. CONCLUSION: The data suggest that INO-3107 administered by IM/EP is tolerable and immunogenic and provides clinical benefit to adults with RRP. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3087-3093, 2023.


Assuntos
Infecções por Papillomavirus , Infecções Respiratórias , Adulto , Humanos , Papillomavirus Humano 11 , Papillomavirus Humano 6
6.
Int Forum Allergy Rhinol ; 13(4): 293-859, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36878860

RESUMO

BACKGROUND: In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation from the full document. METHODS: ICAR-Allergic Rhinitis 2023 employed established evidence-based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work. RESULTS: ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. CONCLUSION: The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment.


Assuntos
Complexo Ferro-Dextran , Rinite Alérgica , Humanos , Rinite Alérgica/diagnóstico , Rinite Alérgica/terapia , Alérgenos
7.
Am J Speech Lang Pathol ; 32(3): 1154-1164, 2023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-36958015

RESUMO

PURPOSE: This study sought to investigate whether a significant difference exists in attendance, cancellations, and no-shows between in-person therapy and telepractice. The authors hypothesized that telepractice no-show and cancellation rates would be less than in-person no-show and cancellation rates. METHOD: This retrospective study manually reviewed and analyzed attendance, no-show, and cancellation data over a 3-month span of in-person-only visits (September 2019-November 2019) and a 3-month span of telepractice visits (September 2020-November 2020) conducted at the Emory Voice Center, a tertiary care practice in urban Atlanta, Georgia. Additionally, data were collected for each patient's full course of therapy outside of the 3-month windows and analyzed for attendance, no-show, and cancellation patterns. RESULTS: Data from 521 patients were available for review from the selected time frame. In 2019 (in-person), 157 patients met inclusion criteria, and in 2020 (telepractice), 176 patients were included. Therapy initiation, therapy attendance, and no-show rates had significant increases in the telepractice year, and cancellations made greater than 24 hr before the appointments had a significant decrease in the telepractice year. Furthermore, the overall course of therapy showed significantly fewer missed appointments and more attended appointments in the telepractice year. CONCLUSIONS: Patients participating in voice therapy via telepractice are more likely to initiate treatment and attend treatment and less likely to cancel sessions compared with patients receiving treatment in person. These data combined with extant data on telepractice treatment efficacy indicate that telepractice should be considered standard of care and offered to all patients seeking treatment, as it removes many reported barriers to treatment.


Assuntos
Voz , Humanos , Estudos Retrospectivos , Resultado do Tratamento
8.
Laryngoscope ; 133(10): 2725-2733, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36815602

RESUMO

OBJECTIVE: The clinical course of recurrent respiratory papillomatosis (RRP) varies from spontaneous remission to severe airway obstruction with wide variability in recurrence. Standard treatment involves debulking to improve voice and/or breathing. Non-surgical therapies are emerging in hopes of non-operative disease control. This retrospective review analyzes long-term safety, efficacy, and durability of clinical control in the largest reported series of parenteral bevacizumab in adults with RRP. METHODS: Twenty-three patients with known RRP who have been receiving off-label systemic bevacizumab were included. Dosage, infusion interval, number of cycles, debulking requirements, subjective outcomes, adverse events, and reasons for treatment termination were investigated. RESULTS: Patients have been followed for an average of 791.43 (21-1468) days. The most common starting dosing regimen was 15 mg/kg at 3 weeks in 11 followed by 10 mg/kg at 6 weeks intervals in 6 individuals. Long-term maintenance dosage varied with the least intensive regimen being 10 mg/kg at 14-week intervals. Subjective improvement of voice and/or breathing was reported in 18/23 subjects. The median time for patients that needed a procedure after treatment was 634 days. Procedures after infusions decreased from 3.08 ± 2.48 procedures in the year prior to 0.52 ± 1.12 during systemic Bevacizumab, and to 0.86 ± 2.05 after stopping bevacizumab. Therapy termination occurred in 8 subjects where only 3 were due to adverse events. CONCLUSION: Parenteral bevacizumab remains a well-tolerated treatment for patients with recalcitrant RRP. There appears to be a durable reduction in the frequency of debulking surgery requirements although on a maintenance regimen. Laryngoscope, 133:2725-2733, 2023.


Assuntos
Infecções por Papillomavirus , Infecções Respiratórias , Adulto , Humanos , Bevacizumab/uso terapêutico , Inibidores da Angiogênese , Seguimentos , Infecções por Papillomavirus/cirurgia , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/cirurgia
9.
J Voice ; 36(4): 507-514, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32854999

RESUMO

OBJECTIVE: The objective of this study was to investigate the difference between vocal beauty and vocal attractiveness by determining whether perceptual ratings of vocal beauty and vocal attractiveness could be dissociated in a cohort of normal raters without a diagnosed sexual desire disorder. METHODS: Twenty five gay male participants were presented with randomly-chosen samples from the Geneva Voices and Faces Database, and were asked to rate each sample in terms of beauty, attractiveness for a relationship of short duration, and attractiveness for a relationship of long duration. Responses were recorded on a visual analog scale (0-100) using a touch-screen interface. The number of stimulus repetitions and the participant response times were also recorded. Statistical analyses were done using two-way Analysis of Variance tests and independent student's t tests. P values were considered statistically significant at the P < 0.05 level. RESULTS: Participants rated male voices significantly higher in terms of beauty, attractiveness for a relationship of long duration, and attractiveness for a relationship of short duration (P < 0.001). Participants rated female voices significantly higher for beauty than for attractiveness for relationship of long or short duration (P < 0.001). There was no significant difference in response time between male and female voices when rating vocal beauty (P = 0.5608). Response time was significantly longer for male voices than for female voices when assessing attractiveness for a relationship of short duration (P < 0.002) but not for long duration (P < 0.3496). Attractive voices (male and female) were repeated more often, and male voices were repeated more often than female voices for both long-term and short-term attractiveness. There was no difference in stimulus replay behavior as a function of the beauty ratings. CONCLUSION: In a cohort of gay male raters without a diagnosed sexual desire disorder, vocal beauty and vocal attractiveness ratings of male and female voices are two related but distinct perceptual constructs that can, under certain circumstances, be dissociated. In general, gay men rated male voices equivalently for beauty, short-term, and long-term attractiveness, while the same ratings for female voices showed a significant difference between ratings of beauty and ratings of short-term and long-term attractiveness.


Assuntos
Face , Voz , Bases de Dados Factuais , Feminino , Humanos , Masculino , Voz/fisiologia
11.
Laryngoscope ; 131(6): E1941-E1949, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33405268

RESUMO

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


Assuntos
Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Infecções por Papillomavirus/tratamento farmacológico , Infecções Respiratórias/tratamento farmacológico , Consenso , Técnica Delphi , Humanos , Internacionalidade
12.
J Voice ; 35(5): 789-792, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32156451

RESUMO

OBJECTIVE: Office-based injection laryngoplasty (IL) has emerged as a useful procedure for otolaryngologists to correct glottic insufficiency while avoiding the costs and risks of general anesthesia. This is the first study focused on addressing the safety of bilateral IL for bilateral vocal fold (VF) atrophy. METHODS: Patient records were reviewed from Emory University Hospital Midtown during the period of 2005 to 2017. Patients who underwent awake, bilateral transthyrohyoid, transoral, transcricothyroid, or transthyroid cartilage IL for bilateral VF atrophy were analyzed. All procedures, including repeat injections, were bilateral. Complication rate was used to evaluate safety. Patients with vocal cord paralysis, paresis, scar, and sulcus were excluded from the study. RESULTS: Total 174 procedures met inclusion criteria. There were four complications, yielding a complication rate of 2.3%. Complications included aborted cases for difficult anatomy or poor patient tolerance, injection material not resorbing, and a VF hematoma. No patients had any airway emergencies or required admission to the hospital or evaluation in the emergency room. CONCLUSIONS: This study illustrates a low complication rate for awake, bilateral IL in treating bilateral VF atrophy. This supports other studies that promote the safety of this procedure in the awake setting. Complications were associated with patient tolerance, unique anatomy, and in one case, anticoagulant medication. The low complication rate supports the conclusion that bilateral medialization IL is safe to perform in the office-based, awake setting.


Assuntos
Doenças da Laringe , Laringoplastia , Atrofia , Humanos , Doenças da Laringe/diagnóstico , Doenças da Laringe/patologia , Doenças da Laringe/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Prega Vocal/patologia , Prega Vocal/cirurgia , Vigília
13.
Laryngoscope ; 131(4): 859-864, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32710809

RESUMO

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.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Comunicação , Disfonia/tratamento farmacológico , Disfonia/fisiopatologia , Fármacos Neuromusculares/administração & dosagem , Feminino , Humanos , Masculino , Estudos Prospectivos , Inquéritos e Questionários
14.
Laryngoscope ; 131(3): E921-E928, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33107615

RESUMO

OBJECTIVES/HYPOTHESIS: Recurrent respiratory papillomatosis (RRP) is a rare, potentially life-threatening, disease that impacts the voice, breathing, and quality of life of patients. Frequent surgical interventions may be needed to control symptoms. We examined the safety and efficacy of utilizing parenteral bevacizumab in the management of severe RRP in adults. STUDY DESIGN: This is a retrospective review of clinical management approaches in a group of patients with severe RRP defined as having a high disease burden, frequent need for debridement, and/or tracheobronchial disease. Patients were initially treated with 15 mg/kg of bevacizumab at 3-week intervals. Bevacizumab dosing and frequency was then individually titrated down. RESULTS: Fourteen adults received a median of 8.5 (range 2-17) bevacizumab infusions over approximately 24 months. All had a history of laryngeal RRP with 6/14 having additional tracheobronchial lesions. Patients required a median of 4 (range 2-11) procedures in the year prior to treatment. Only 3/10 (30%) patients who continued therapy required any additional procedures. Bevacizumab administration was generally well tolerated, with four patients discontinuing therapy. Medical reasons included severe epistaxis and hypertension and thrombocytopenia in an individual with systemic lupus erythematosus. Common side effects included hypertension (grade 2), headache (grades 1-2), elevated creatinine (grades 1-2), and epistaxis (grade 3). CONCLUSIONS: Intravenous bevacizumab for the primary treatment of severe RRP in adults appears clinically effective and safe. Expected and typically mild side effects related to bevacizumab were observed. Continued investigation of bevacizumab through a prospective clinical trial is warranted. LEVEL OF EVIDENCE: 4. Laryngoscope, 131:E921-E928, 2021.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Bevacizumab/administração & dosagem , Infecções por Papillomavirus/tratamento farmacológico , Infecções Respiratórias/tratamento farmacológico , Adulto , Idoso , Esquema de Medicação , Feminino , Humanos , Infusões Parenterais , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/patologia , Infecções Respiratórias/patologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
15.
Clin Cancer Res ; 26(22): 5860-5868, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-32943457

RESUMO

PURPOSE: On the basis of synergistic effects between green tea polyphenon E (PPE) and EGFR-tyrosine kinase inhibitor in preclinical studies, we conducted a phase Ib study of the PPE and erlotinib combination in patients with advanced premalignant lesions (APL) of the oral cavity and larynx. PATIENTS AND METHODS: Patients were treated with a fixed dose of PPE (200 mg three times a day) and dose escalation of erlotinib (50, 75, 100 mg daily) for 6 months with tissue biopsy at baseline and 6 months. Primary endpoints were safety and toxicity; secondary endpoints were evaluation of pathologic response, cancer-free survival (CFS), overall survival (OS), and biomarker modulation. RESULTS: Among 21 enrolled patients, 19 began treatment and 17 completed 6 months of treatment with PPE and erlotinib. Main characteristics of treated patients: 15 severe dysplasia or carcinoma in situ and 17 oral cavity. Only skin rash was associated with dose-limiting toxicity and MTD. Recommended doses for phase II studies are PPE 600 mg daily plus erlotinib 100 mg daily for 6 months. Pathologic responses in 17 evaluable patients: pathologic complete response (47%) and pathologic partial response (18%). The 5-year CFS and OS were 66.3% and 93%, respectively. Among tested biomarkers, only phosphorylated ERK was correlated with response to treatment. CONCLUSIONS: Treatment with PPE and erlotinib combination was well tolerated in patients with APLs of the head and neck, and showed a high rate of pathologic response with excellent CFS. This combination deserves further investigation for the chemoprevention and/or prevention of second primary tumors in early-stage head and neck cancer.


Assuntos
Catequina/análogos & derivados , Cloridrato de Erlotinib/administração & dosagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Lesões Pré-Cancerosas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Catequina/administração & dosagem , Catequina/química , Cloridrato de Erlotinib/química , Feminino , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Chá/química
16.
IEEE J Transl Eng Health Med ; 8: 1600103, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32518738

RESUMO

OBJECTIVES: Worldwide efforts to protect front line providers performing endotracheal intubation during the COVID-19 pandemic have led to innovative devices. Authors evaluated the aerosol containment effectiveness of a novel intubation aerosol containment system (IACS) compared with a recently promoted intubation box and no protective barrier. METHODS: In a simulation center at the authors' university, the IACS was compared to no protective barrier and an intubation box. Aerosolization was simulated using a commercial fog machine and leakage of aerosolize mist was visually assessed. RESULTS: The IACS appeared to contain the aerosolized mist, while the intubation box allowed for mist to contact the laryngoscopist and contaminate the clinical space through arm port holes and the open caudal end. Both devices protected the laryngoscopist better than no protective barrier. DISCUSSION: The IACS with integrated sleeves and plastic drape appears to offer superior protection for the laryngoscopist and assistant providers from aerosolized particles.

17.
Laryngoscope ; 129(9): 2118-2120, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30593686

RESUMO

An anterior glottic web is an abnormal fusion of the anterior aspect of the membranous vocal folds. Noncongenital glottic webs are usually iatrogenic from intubation or laryngeal surgery. We present six adult patients whose initial in-office diagnoses were consistent with "idiopathic" benign anterior glottic webs as determined by three laryngologists (a.m.k., j.m.b., m.j.p.). Further evaluation revealed the diagnoses of laryngeal squamous cell carcinoma in all cases. The high risk of malignancy in cases of idiopathic anterior glottic web necessitates biopsy for tissue diagnosis of all such lesions. Laryngoscope, 129:2118-2120, 2019.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Glote/patologia , Neoplasias Laríngeas/diagnóstico , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Laríngeas/patologia , Laringoscopia , Masculino , Pessoa de Meia-Idade
18.
Otolaryngol Clin North Am ; 50(5): 903-922, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28669461

RESUMO

There is growing support from the Accreditation Council for Graduate Medical Education and the Joint Commission of Accreditation of Health Care Organizations for a competency-based evaluation of medical and surgical performance. This is part of the quality movement in health care whereby the Centers for Medicare and Medicaid Services and third-party insurance companies have begun to link reimbursement incentives to positive surgical outcomes. Laryngeal and airway surgery require precise technique and significant mastered skill that can be difficult to obtain during otolaryngology residency training. Simulators are useful for developing laryngeal and airway surgery skills ultimately evaluated in a competency-based manner.


Assuntos
Internato e Residência , Laringoscopia/educação , Procedimentos Cirúrgicos Otorrinolaringológicos/educação , Treinamento por Simulação , Animais , Competência Clínica , Desenho de Equipamento , Humanos , Capacitação em Serviço , Manequins , Modelos Animais
19.
Laryngoscope ; 127(4): 888-893, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27620827

RESUMO

OBJECTIVES: To validate the use of a high-fidelity phonomicrosurgical trainer. STUDY DESIGN: A high-fidelity phonomicrosurgical trainer, based on a previously validated model by Contag et al.,1 was designed with multilayered vocal folds that more closely mimic the consistency of true vocal folds, containing intracordal lesions to practice phonomicrosurgical removal. A training module was developed to simulate the true phonomicrosurgical experience. A validation study with novice and expert surgeons was conducted. METHODS: Novices and experts were instructed to remove the lesion from the synthetic vocal folds, and novices were given four training trials. Performances were measured by the amount of time spent and tissue injury (microflap, superficial, deep) to the vocal fold. An independent Student t test and Fisher exact tests were used to compare subjects. A matched-paired t test and Wilcoxon signed rank tests were used to compare novice performance on the first and fourth trials and assess for improvement. RESULTS: Experts completed the excision with less total errors than novices (P = .004) and made less injury to the microflap (P = .05) and superficial tissue (P = .003). Novices improved their performance with training, making less total errors (P = .002) and superficial tissue injuries (P = .02) and spending less time for removal (P = .002) after several practice trials. CONCLUSION: This high-fidelity phonomicrosurgical trainer has been validated for novice surgeons. It can distinguish between experts and novices; and after training, it helped to improve novice performance. LEVEL OF EVIDENCE: N/A. Laryngoscope, 127:888-893, 2017.


Assuntos
Competência Clínica , Simulação por Computador , Treinamento com Simulação de Alta Fidelidade/métodos , Microcirurgia/educação , Prega Vocal/cirurgia , Adulto , Educação Médica Continuada/métodos , Educação de Pós-Graduação em Medicina , Educação de Graduação em Medicina/métodos , Feminino , Humanos , Internato e Residência/estatística & dados numéricos , Masculino , Estatísticas não Paramétricas , Estudantes de Medicina/estatística & dados numéricos
20.
J Voice ; 31(3): 363-365, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27839987

RESUMO

OBJECTIVES: This study aimed to identify the changes in dosing of botulinum toxin-A for adductor spasmodic dysphonia (ADSD) over a prolonged period. STUDY DESIGN: This is a retrospective chart review. METHODS: One hundred thirteen subjects treated for ADSD from 2003 to 2013 were identified from a clinical database. Subject age, gender, and total injection dose amount were all recorded for all subjects who had at least 10 injections. RESULTS: Fifty-four subjects met criteria for inclusion. There were no age or gender differences in the starting dose for subjects. Dosing decreased significantly compared with the second dose (5.05 ± 1.623 Units), by the sixth dose (4.26 ± 1.698 Units), and continued through the 10th dose (4.08 ± 2.019 Units) (P < 0.005 for all). CONCLUSIONS: Botulinum toxin-A dosing for ADSD decreases consistently over subsequent injections after the initial two dose titrations.


Assuntos
Inibidores da Liberação da Acetilcolina/administração & dosagem , Toxinas Botulínicas Tipo A/administração & dosagem , Disfonia/tratamento farmacológico , Músculos Laríngeos/efeitos dos fármacos , Inibidores da Liberação da Acetilcolina/efeitos adversos , Toxinas Botulínicas Tipo A/efeitos adversos , Disfonia/diagnóstico por imagem , Disfonia/fisiopatologia , Feminino , Georgia , Humanos , Injeções Intramusculares , Músculos Laríngeos/diagnóstico por imagem , Músculos Laríngeos/fisiopatologia , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Estudos Retrospectivos , Estroboscopia , Fatores de Tempo , Resultado do Tratamento , Gravação em Vídeo
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