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1.
Am J Otolaryngol ; 45(2): 104179, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38118384

RESUMEN

PURPOSE: Tracheostomy care is supply- and resource-intensive, and airway-related adverse events in community settings have high rates of readmission and mortality. Devices are often implicated in harm, but little is known about insurance coverage, gaps, and barriers to obtaining tracheostomy-related medically necessary durable medical equipment. We aimed to identify barriers patients may encounter in procuring tracheostomy-related durable medical equipment through insurance plan coverage. MATERIALS AND METHODS: Tracheostomy-related durable medical equipment provisions were evaluated across insurers, extracting data via structured telephone interviews and web-based searches. Each insurance company was contacted four times and queried iteratively regarding the range of coverage and co-pay policies. Outcome measures include call duration, consistency of explanation of benefits, and the number of transfers and disconnects. We also identified six qualitative themes from patient interviews. RESULTS: Tracheostomy-related durable medical equipment coverage was offered in some form by 98.1 % (53/54) of plans across 11 insurers studied. Co-pays or deductibles were required in 42.6 % (23/54). There was significant variability in out-of-pocket expenditures. Fixed co-pays ranged from $0-30, and floating co-pays ranged from 0 to 40 %. During phone interviews, mean call duration was 19 ± 10 min, with an average of 2 ± 1 transfers between agents. Repeated calls revealed high information variability (mean score 2.4 ± 1.5). Insurance sites proved challenging to navigate, scoring poorly on usability, literacy, and information quality. CONCLUSIONS: Several factors may limit access to potentially life-saving durable medical equipment for patients with tracheostomy. Barriers include out-of-pocket expenditures, lack of transparency on coverage, and low-quality information. Further research is necessary to evaluate patient outcomes.


Asunto(s)
Equipo Médico Durable , Traqueostomía , Humanos , Cobertura del Seguro
2.
Am J Otolaryngol ; 43(1): 103234, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34560598

RESUMEN

OBJECTIVES: Several studies have shown that HIV infected individuals are at higher risk compared to the general population of developing non-AIDS defining conditions such as some types of cancer, kidney disease, liver disease and others. In this case-control study, we compared the incidence of laryngeal disorders between a treatment-seeking HIV-positive population and uninfected controls. We aimed to investigate whether there are any laryngeal disorders that are overrepresented in HIV-positive individuals. METHODS: This was a case-control study based on retrospective chart review, comparing the incidence of laryngeal, airway, and swallowing disorders in sixty-nine HIV positive individuals and 4178 HIV negative controls treated between January 1, 2016 and December 31, 2017, at the Johns Hopkins Voice Center. RESULTS: A majority of HIV-infected patients (59.4%) had at least one diagnosis belonging to the Vocal cord pathology category compared to 48.2% of controls (OR 1.57, p = 0.065). Compared to the entire treatment-seeking population, HIV patients were more likely to present with laryngeal cancer (15.9% vs. 3.4% in controls, OR 5.43, p < 0.001) and chronic laryngitis (17.4% vs. 4.2%, OR 4.79, p < 0.001). Fungal and ulcerative laryngitis were also overrepresented in HIV-positive individuals (OR 9.45, p < 0.001 and 6.29, p < 0.001, respectively). None of the diagnoses categorized as functional voice disorders, swallowing, or airway problems showed a significant difference between groups. Laryngeal papillomatosis, which is an HPV-dependent disease, had similar prevalence in both groups. CONCLUSIONS: Treatment-seeking HIV-positive patients presenting to a laryngology clinic suffer significantly more often from laryngeal squamous cell carcinoma as well as chronic, fungal, and ulcerative laryngitis compared to HIV-negative individuals. LEVEL OF EVIDENCE: 4.


Asunto(s)
Trastornos de Deglución/epidemiología , Infecciones por VIH/complicaciones , VIH , Enfermedades de la Laringe/epidemiología , Fármacos Anti-VIH/uso terapéutico , Estudios de Casos y Controles , Trastornos de Deglución/virología , Femenino , Infecciones por VIH/virología , Humanos , Incidencia , Enfermedades de la Laringe/virología , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos
3.
J Virol ; 94(12)2020 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-32295905

RESUMEN

We demonstrate that female C57BL/6J mice are susceptible to a transient lower genital tract infection with MmuPV1 mouse papillomavirus and display focal histopathological abnormalities resembling those of human papillomavirus (HPV) infection. We took advantage of strains of genetically deficient mice to study in vivo the role of innate immune signaling in the control of papillomavirus. At 4 months, we sacrificed MmuPV1-infected mice and measured viral 757/3139 spliced transcripts by TaqMan reverse transcription-PCR (RT-PCR), localization of infection by RNAscope in situ hybridization, and histopathological abnormities by hematoxylin and eosin (H&E) staining. Among mice deficient in receptors for pathogen-associated molecular patterns, MyD88-/- and STING-/- mice had 1,350 and 80 copies of spliced transcripts/µg RNA, respectively, while no viral expression was detected in MAVS-/- and Ripk2-/- mice. Mice deficient in an adaptor molecule, STAT1-/-, for interferon signaling had 46,000 copies/µg RNA. Among mice with targeted deficiencies in the inflammatory response, interleukin-1 receptor knockout (IL-1R-/-) and caspase-1-/- mice had 350 and 30 copies/µg RNA, respectively. Among mice deficient in chemokine receptors, CCR6-/- mice had 120 copies/µg RNA, while CXCR2-/- and CXCR3-/- mice were negative. RNAscope confirmed focal infection in MyD88-/-, STAT1-/-, and CCR6-/- mice but was negative for other gene-deficient mice. Histological abnormalities were seen only in the latter mice. Our findings and the literature support a working model of innate immunity to papillomaviruses involving the activation of a MyD88-dependent pathway and IL-1 receptor signaling, control of viral replication by interferon-stimulated genes, and clearance of virus-transformed dysplastic cells by the action of the CCR6/CCL20 axis.IMPORTANCE Papillomaviruses infect stratified squamous epithelia, and the viral life cycle is linked to epithelial differentiation. Additionally, changes occur in viral and host gene expression, and immune cells are activated to modulate the infectious process. In vitro studies with keratinocytes cannot fully model the complex viral and host responses and do not reflect the contribution of local and migrating immune cells. We show that female C57BL/6J mice are susceptible to a transient papillomavirus cervicovaginal infection, and mice deficient in select genes involved in innate immune responses are susceptible to persistent infection with variable manifestations of histopathological abnormalities. The results of our studies support a working model of innate immunity to papillomaviruses, and the model provides a framework for more in-depth studies. A better understanding of mechanisms of early viral clearance and the development of approaches to induce clearance will be important for cancer prevention and the treatment of HPV-related diseases.


Asunto(s)
Interacciones Huésped-Patógeno/inmunología , Factor 88 de Diferenciación Mieloide/inmunología , Papillomaviridae/inmunología , Infecciones por Papillomavirus/inmunología , ARN Mensajero/inmunología , ARN Viral/inmunología , Receptores Tipo I de Interleucina-1/inmunología , Proteínas Adaptadoras Transductoras de Señales/deficiencia , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/inmunología , Empalme Alternativo , Animales , Caspasa 1/deficiencia , Caspasa 1/genética , Caspasa 1/inmunología , Cuello del Útero/inmunología , Cuello del Útero/virología , Femenino , Regulación de la Expresión Génica , Interacciones Huésped-Patógeno/genética , Humanos , Inmunidad Innata , Proteínas de la Membrana/deficiencia , Proteínas de la Membrana/genética , Proteínas de la Membrana/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Factor 88 de Diferenciación Mieloide/deficiencia , Factor 88 de Diferenciación Mieloide/genética , Papillomaviridae/crecimiento & desarrollo , Papillomaviridae/metabolismo , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/virología , ARN Mensajero/genética , ARN Viral/genética , Proteína Serina-Treonina Quinasa 2 de Interacción con Receptor/deficiencia , Proteína Serina-Treonina Quinasa 2 de Interacción con Receptor/genética , Proteína Serina-Treonina Quinasa 2 de Interacción con Receptor/inmunología , Receptores CCR6/deficiencia , Receptores CCR6/genética , Receptores CCR6/inmunología , Receptores CXCR3/deficiencia , Receptores CXCR3/genética , Receptores CXCR3/inmunología , Receptores Tipo I de Interleucina-1/deficiencia , Receptores Tipo I de Interleucina-1/genética , Receptores de Interleucina-8B/deficiencia , Receptores de Interleucina-8B/genética , Receptores de Interleucina-8B/inmunología , Factor de Transcripción STAT1/deficiencia , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT1/inmunología , Transducción de Señal , Vagina/inmunología , Vagina/virología
4.
Anesth Analg ; 132(4): 1023-1032, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33196479

RESUMEN

Laryngeal injury from intubation can substantially impact airway, voice, and swallowing, thus necessitating multidisciplinary interventions. The goals of this systematic review were (1) to review the types of laryngeal injuries and their patient-reported symptoms and clinical signs resulting from endotracheal intubation in patients intubated for surgeries and (2) to better understand the overall the frequency at which these injuries occur. We conducted a search of 4 online bibliographic databases (ie, PubMed, Embase, Cumulative Index of Nursing and Allied Health Literature [CINAHL], and The Cochrane Library) and ProQuest and Open Access Thesis Dissertations (OPTD) from database inception to September 2019 without restrictions for language. Studies that completed postextubation laryngeal examinations with visualization in adult patients who were endotracheally intubated for surgeries were included. We excluded (1) retrospective studies, (2) case studies, (3) preexisting laryngeal injury/disease, (4) patients with histories of or surgical interventions that risk injury to the recurrent laryngeal nerve, (5) conference abstracts, and (6) patient populations with nonfocal, neurological impairments that may impact voice and swallowing function, thus making it difficult to identify isolated postextubation laryngeal injury. Independent, double-data extraction, and risk of bias assessment followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Cochrane Collaboration's criteria. Twenty-one articles (1 cross-sectional, 3 cohort, 5 case series, 12 randomized controlled trials) representing 21 surgical studies containing 6140 patients met eligibility criteria. The mean patient age across studies reporting age was 49 (95% confidence interval [CI], 45-53) years with a mean intubation duration of 132 (95% CI, 106-159) minutes. Studies reported no injuries in 80% (95% CI, 69-88) of patients. All 21 studies presented on type of injury. Edema was the most frequently reported mild injury, with a prevalence of 9%-84%. Vocal fold hematomas were the most frequently reported moderate injury, with a prevalence of 4% (95% CI, 2-10). Severe injuries that include subluxation of the arytenoids and vocal fold paralysis are rare (<1%) outcomes. The most prevalent patient complaints postextubation were dysphagia (43%), pain (38%), coughing (32%), a sore throat (27%), and hoarseness (27%). Overall, laryngeal injury from short-duration surgical intubation is common and is most often mild. No uniform guidelines for laryngeal assessment postextubation from surgery are available and hoarseness is neither a good indicator of laryngeal injury or dysphagia. Protocolized screening for dysphonia and dysphagia postextubation may lead to improved identification of injury and, therefore, improved patient outcomes and reduced health care utilization.


Asunto(s)
Extubación Traqueal/efectos adversos , Anestesia , Intubación Intratraqueal/efectos adversos , Laringe/lesiones , Complicaciones Posoperatorias/etiología , Femenino , Humanos , Laringe/fisiopatología , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/fisiopatología , Medición de Riesgo , Factores de Riesgo , Resultado del Tratamiento
5.
Am J Otolaryngol ; 42(1): 102747, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33038783

RESUMEN

PURPOSE: While dysphagia is a recognized manifestation of autoimmune inflammatory myopathy, a relationship between myositis and dysphonia or laryngeal pathology is not well-documented. We therefore sought to describe the spectrum of laryngeal disorders present in myositis patients, evaluate whether any specific conditions are overrepresented among these patients compared to a large treatment-seeking population, and examine the clinical course and outcomes of these symptoms. MATERIALS AND METHODS: This was a retrospective chart review, including all patients seen at the Johns Hopkins Voice Center between January 2016 and December 2017. Demographic data, comorbidities, and laryngeal diagnoses were extracted from the electronic medical record. The charts of patients with myositis were reviewed further to ascertain details of their laryngeal symptoms and myositis disease course. Associations between myositis and dysphonia/dysphagia were evaluated using binary regression and multinomial logistic regression models to adjust for age, sex, race, and smoking status. RESULTS: Of 4252 patients, sixteen had myositis. Compared to 4236 controls, these patients had significantly higher odds of presenting with muscular voice disorders (adjusted odds ratio (OR*) = 4.503, p* = 0.005) and dysphagia (OR* = 6.823, p* < 0.001). A majority (64.3%, CI:35.6-93.0%) of myositis patients had laryngeal pathology among the presenting symptoms of their myositis. Across all diagnostic categories, there was a non-significant trend towards better outcomes in patients receiving specific interventions for their laryngeal symptoms. CONCLUSIONS: Muscular voice disorders and dysphagia are significantly overrepresented in myositis patients presenting to a laryngology clinic, and in these patients, both are frequently among the presenting symptoms of myositis.


Asunto(s)
Enfermedades Autoinmunes/complicaciones , Trastornos de Deglución/epidemiología , Trastornos de Deglución/etiología , Disfonía/epidemiología , Disfonía/etiología , Miositis/complicaciones , Factores de Edad , Enfermedades Autoinmunes/diagnóstico , Diagnóstico Precoz , Femenino , Humanos , Masculino , Persona de Mediana Edad , Miositis/diagnóstico , Calidad de Vida , Estudios Retrospectivos , Factores Sexuales , Fumar
6.
Radiographics ; 40(7): 2011-2028, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33035134

RESUMEN

Nonepithelial tumors of the larynx are rare and represent a minority of all laryngeal neoplasms. Imaging has an important role in the diagnosis, treatment planning, and surveillance of these entities. However, unfamiliarity with these neoplasms can cause diagnostic difficulties for radiologists, especially because many of the imaging findings are nonspecific. By using a systematic approach based on clinical history, patient age and gender, lesion location, endoscopic results, and specific imaging findings, the differential diagnosis can often be narrowed. These tumors typically affect the submucosal layer, so if a tumor has an intact mucosa at endoscopy, a nonepithelial neoplasm is the most likely diagnosis. Nonepithelial tumors of the larynx can arise from the laryngeal cartilage or muscle or from the surrounding lymphoid tissue or blood vessels. Consequently, imaging findings typically correspond to the specific cell type from which it originated. Recognizing specific features (eg, metaplastic bone formation, macroscopic fat, or enhancement pattern) can often help narrow the differential diagnosis. In addition, identification of noncircumscribed borders of the lesion and invasion of the adjacent structures is key to diagnosis of a malignant process rather than a benign neoplasm. Understanding the pathologic correlation is fundamental to understanding the radiologic manifestations and is ultimately crucial for differentiation of nonepithelial laryngeal neoplasms. Online supplemental material is available for this article. ©RSNA, 2020.


Asunto(s)
Neoplasias Laríngeas/diagnóstico por imagen , Neoplasias Laríngeas/patología , Condroma/diagnóstico por imagen , Condroma/patología , Diagnóstico Diferencial , Granuloma de Células Gigantes/diagnóstico por imagen , Granuloma de Células Gigantes/patología , Tumor de Células de la Granulosa/diagnóstico por imagen , Tumor de Células de la Granulosa/patología , Humanos , Neoplasias Laríngeas/epidemiología , Linfoma/diagnóstico por imagen , Linfoma/patología , Neurilemoma/diagnóstico por imagen , Neurilemoma/patología , Plasmacitoma/diagnóstico por imagen , Plasmacitoma/patología , Sarcoma/diagnóstico por imagen , Sarcoma/patología , Neoplasias Vasculares/diagnóstico por imagen , Neoplasias Vasculares/patología
7.
Am J Otolaryngol ; 40(4): 520-524, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31005338

RESUMEN

OBJECTIVES: After the publication of large clinical trials, in January 2014 The U.S. Preventive Services Task Force (USPSTF) recommended annual lung cancer screening with low-dose CT in a well-defined group of high-risk smokers. A significant proportion of patients with laryngeal cancer (LC) meet the introduced criteria, and we hypothesized that clinical practice would change as a result of these evidence-based guidelines. METHODS: Retrospective chart review of patients diagnosed with LC and treated at Johns Hopkins Hospital who met USPSTF criteria for annual chest screening and were followed for at least 3 consecutive years in the years surrounding the introduction of screening guidelines (January 2010 to December 2017) was performed to identify those who had recommended screening CT chest. RESULTS: A total of 151 patients met the inclusion criteria of the study and were followed for a total of 746 patient-years. 184/332 (55%) patient-years in the pre-guidelines period and 246/414 (59%) in the post-guidelines period included at least one recommended chest imaging (CT or PET-CT; p = 0.27). 248/332 (75%) patient-years in the pre-guidelines period and 314/414 (76%) in the post-guidelines period included any radiological chest imaging (X-ray, CT or PET-CT; p = 0.72). Screening scans were ordered by OHNS (45%), Medical Oncology (31%), Radiation Oncology (8%), and primary care (14%) with 70% of patients missing at least one year of indicated screening. CONCLUSIONS: The implementation of new lung cancer screening guidelines did not change clinical practice in the management of patients with LC and many patients do not receive recommended screening. Further study concerning potential barriers to effective evidence-based screening and coordination of care is warranted.


Asunto(s)
Neoplasias Laríngeas/diagnóstico por imagen , Neoplasias Laríngeas/prevención & control , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/prevención & control , Tamizaje Masivo , Pautas de la Práctica en Medicina , Anciano , Anciano de 80 o más Años , Práctica Clínica Basada en la Evidencia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Guías de Práctica Clínica como Asunto , Fumadores , Tomografía Computarizada por Rayos X
8.
Am J Otolaryngol ; 40(2): 213-217, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30553600

RESUMEN

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is strongly associated with tobacco use, but recent reports suggest an increasing incidence of LSCC in patients without traditional risk factors, suggesting an alternative etiology of tumorigenesis. The purpose of this study is to characterize this non-smoking population and to compare immunohistochemical markers in tumor specimens from non-smokers and smokers with LSCC. METHODS: A retrospective chart review of patients with LSCC at Johns Hopkins Hospital (JHH) was performed. A tissue microarray (TMA) was constructed with tumor specimen from non-smokers with stage and age-matched smokers and stained for a variety of immunologic and molecular targets. RESULTS: In the JHH cohort of 521 patients, 12% (n = 63) were non-smokers. Non-smokers were more likely to be <45 years old at time of diagnosis (OR 4.13, p = 0.001) and to have glottic tumors (OR 2.46, p = 0.003). The TMA was comprised of tumors from 34 patients (14 non-smokers, 20 smokers). Only 2 patients (6%) were human-papillomavirus (HPV) positive by high-risk RNA in situ hybridization (ISH). There was no correlation between smoking status and p16 (p = 0.36), HPV-ISH positivity (p = 0.79), phosphatase and tensin homolog (PTEN, p = 0.91), p53 (p = 0.14), or programmed death-ligand 1 (PD-L1, p = 0.27) expression. CONCLUSIONS: Non-smokers with LSCC are more likely to be younger at the time of diagnosis and have glottic tumors than smokers with LSCC. In TMA analysis of stage and age-matched specimens from smoker and non-smokers with LSCC, the pattern of expression for common molecular and immunologic markers is similar. Further, HPV does not appear to be a major causative etiology of LSCC in either smokers or non-smokers in our cohort of patients.


Asunto(s)
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/inmunología , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/inmunología , Fumadores , Fumar/efectos adversos , Factores de Edad , Anciano , Antígenos CD , Antígeno B7-H1 , Carcinoma de Células Escamosas/etiología , Carcinoma de Células Escamosas/patología , Estudios de Cohortes , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Femenino , Humanos , Neoplasias Laríngeas/etiología , Neoplasias Laríngeas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Fosfohidrolasa PTEN , Papillomaviridae/genética , Receptor de Muerte Celular Programada 1 , ARN Viral , Estudios Retrospectivos
9.
Crit Care Med ; 46(12): 2010-2017, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30096101

RESUMEN

OBJECTIVES: To systematically review the symptoms and types of laryngeal injuries resulting from endotracheal intubation in mechanically ventilated patients in the ICU. DATA SOURCES: PubMed, Embase, CINAHL, and Cochrane Library from database inception to September 2017. STUDY SELECTION: Studies of adult patients who were endotracheally intubated with mechanical ventilation in the ICU and completed postextubation laryngeal examinations with either direct or indirect visualization. DATA EXTRACTION: Independent, double-data extraction and risk of bias assessment followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias assessment followed the Cochrane Collaboration's criteria. DATA SYNTHESIS: Nine studies (seven cohorts, two cross-sectional) representing 775 patients met eligibility criteria. The mean (SD; 95% CI) duration of intubation was 8.2 days (6.0 d; 7.7-8.7 d). A high prevalence (83%) of laryngeal injury was found. Many of these were mild injuries, although moderate to severe injuries occurred in 13-31% of patients across studies. The most frequently occurring clinical symptoms reported post extubation were dysphonia (76%), pain (76%), hoarseness (63%), and dysphagia (49%) across studies. CONCLUSIONS: Laryngeal injury from intubation is common in the ICU setting. Guidelines for laryngeal assessment and postextubation surveillance do not exist. A systematic approach to more robust investigations could increase knowledge of the association between particular injuries and corresponding functional impairments, improving understanding of both time course and prognosis for resolution of injury. Our findings identify targets for future research and highlight the long-known, but understudied, clinical outcomes from endotracheal intubation with mechanical ventilation in ICU.


Asunto(s)
Cuidados Críticos/estadística & datos numéricos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Intubación Intratraqueal/efectos adversos , Laringe/lesiones , Respiración Artificial/efectos adversos , Humanos , Prevalencia , Índices de Gravedad del Trauma
10.
J Virol ; 91(15)2017 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-28515303

RESUMEN

Mus musculus papillomavirus 1 (MmuPV1/MusPV1) induces persistent papillomas in immunodeficient mice but not in common laboratory strains. To facilitate the study of immune control, we sought an outbred and immunocompetent laboratory mouse strain in which persistent papillomas could be established. We found that challenge of SKH1 mice (Crl:SKH1-Hrhr) with MmuPV1 by scarification on their tail resulted in three clinical outcomes: (i) persistent (>2-month) papillomas (∼20%); (ii) transient papillomas that spontaneously regress, typically within 2 months (∼15%); and (iii) no visible papillomas and viral clearance (∼65%). SKH1 mice with persistent papillomas were treated by using a candidate preventive/therapeutic naked-DNA vaccine that expresses human calreticulin (hCRT) fused in frame to MmuPV1 E6 (mE6) and mE7 early proteins and residues 11 to 200 of the late protein L2 (hCRTmE6/mE7/mL2). Three intramuscular DNA vaccinations were delivered biweekly via in vivo electroporation, and both humoral and CD8 T cell responses were mapped and measured. Previously persistent papillomas disappeared within 2 months after the final vaccination. Coincident virologic clearance was confirmed by in situ hybridization and a failure of disease to recur after CD3 T cell depletion. Vaccination induced strong mE6 and mE7 CD8+ T cell responses in all mice, although they were significantly weaker in mice that initially presented with persistent warts than in those that spontaneously cleared their infection. A human papillomavirus 16 (HPV16)-targeted version of the DNA vaccine also induced L2 antibodies and protected mice from vaginal challenge with an HPV16 pseudovirus. Thus, MmuPV1 challenge of SKH1 mice is a promising model of spontaneous and immunotherapy-directed clearances of HPV-related disease.IMPORTANCE High-risk-type human papillomaviruses (hrHPVs) cause 5% of all cancer cases worldwide, notably cervical, anogenital, and oropharyngeal cancers. Since preventative HPV vaccines have not been widely used in many countries and do not impact existing infections, there is considerable interest in the development of therapeutic vaccines to address existing disease and infections. The strict tropism of HPV requires the use of animal papillomavirus models for therapeutic vaccine development. However, MmuPV1 failed to grow in common laboratory strains of mice with an intact immune system. We show that MmuPV1 challenge of the outbred immunocompetent SKH1 strain produces both transient and persistent papillomas and that vaccination of the mice with a DNA expressing an MmuPV1 E6E7L2 fusion with calreticulin can rapidly clear persistent papillomas. Furthermore, an HPV16-targeted version of the DNA can protect against vaginal challenge with HPV16, suggesting the promise of this approach to both prevent and treat papillomavirus-related disease.


Asunto(s)
Modelos Animales de Enfermedad , Papillomaviridae/inmunología , Infecciones por Papillomavirus/inmunología , Infecciones por Papillomavirus/terapia , Vacunas contra Papillomavirus/administración & dosificación , Vacunas contra Papillomavirus/inmunología , Animales , Anticuerpos Antivirales/sangre , Linfocitos T CD8-positivos/inmunología , Inyecciones Intramusculares , Ratones , Resultado del Tratamiento , Vacunas de ADN/administración & dosificación , Vacunas de ADN/inmunología
11.
J Sport Exerc Psychol ; 40(6): 312-324, 2018 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-30514157

RESUMEN

Few studies have examined the association between sleep and burnout symptoms in elite athletes. We recruited 257 young elite athletes (Mage = 16.8 years) from Swiss Olympic partner schools. Of these, 197 were reassessed 6 months later. Based on the first assessment, 24 participants with clinically relevant burnout symptoms volunteered to participate in a polysomnographic examination and were compared with 26 (matched) healthy controls. Between 12% and 14% of young elite athletes reported burnout symptoms of potential clinical relevance, whereas 4-11% reported clinically relevant insomnia symptoms. Athletes with clinically relevant burnout symptoms reported significantly more insomnia symptoms, more dysfunctional sleep-related cognitions, and spent less time in bed during weeknights (p < .05). However, no significant differences were found for objective sleep parameters. A cross-lagged panel analysis showed that burnout positively predicted self-reported insomnia symptoms. Cognitive-behavioral interventions to treat dysfunctional sleep-related cognitions might be a promising measure to reduce subjective sleep complaints among young elite athletes.


Asunto(s)
Atletas/psicología , Agotamiento Psicológico , Trastornos del Inicio y del Mantenimiento del Sueño , Adolescente , Estudios de Casos y Controles , Cognición , Estudios Transversales , Femenino , Humanos , Estudios Longitudinales , Masculino , Polisomnografía , Autoinforme
12.
Cancer Immunol Immunother ; 65(3): 261-71, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26759151

RESUMEN

Recurrent respiratory papillomatosis is caused by human papillomavirus (HPV) infection, most commonly types 6 (HPV-6) and 11 (HPV-11). Due to failed host immune responses, HPV is unable to be cleared from the host, resulting in recurrent growth of HPV-related lesions that can obstruct the lumen of the airway within the upper aerodigestive tract. In our murine model, the HPV-6b and HPV-11 E7 antigens are not innately immunogenic. In order to enhance the host immune responses against the HPV E7 antigen, we linked calreticulin (CRT) to HPV-6b E7 and found that vaccinating C57BL/6 mice with the HPV-6b CRT/E7 DNA vaccine is able to induce a CD8+ T cell response that recognizes an H-2D(b)-restricted E7aa21-29 epitope. Additionally, vaccination of HLA-A*0201 transgenic mice with HPV-6b CRT/E7 DNA generated a CD8+ T cell response against the E7aa82-90 epitope that was not observed in the wild-type C57BL/6 mice, indicating this T cell response is restricted to HLA-A*0201. In vivo cytotoxic T cell killing assays demonstrated that the vaccine-induced CD8+ T cells are able to efficiently kill target cells. Interestingly, the H-2D(b)-restricted E7aa21-29 sequence and the HLA-A*0201-restricted E7aa82-90 sequence are conserved between HPV-6b and HPV-11 and may represent shared immunogenic epitopes. The identification of the HPV-6b/HPV-11 CD8+ T cell epitopes facilitates the evaluation of various immunomodulatory strategies in preclinical models. More importantly, the identified HLA-A*0201-restricted T cell epitope may serve as a peptide vaccination strategy, as well as facilitate the monitoring of vaccine-induced HPV-specific immunologic responses in future human clinical trials.


Asunto(s)
Epítopos de Linfocito T/inmunología , Antígeno HLA-A2/inmunología , Antígeno de Histocompatibilidad H-2D/inmunología , Proteínas Oncogénicas Virales/inmunología , Linfocitos T Citotóxicos/inmunología , Animales , Calreticulina/farmacología , Línea Celular Tumoral , Femenino , Humanos , Ratones , Ratones Endogámicos C57BL , Vacunas contra Papillomavirus/inmunología , Vacunación , Vacunas de ADN/inmunología
13.
Ann Otol Rhinol Laryngol ; 125(3): 235-41, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26453486

RESUMEN

AIM: Recurrent respiratory papillomatosis (RRP) is classically described as a benign neoplasm of the larynx caused by the low-risk human papillomavirus (HPV) viral subtypes. Nevertheless, transformation to dysplasia and invasive carcinoma can occur. We aimed to assess the prevalence of dysplasia and carcinoma-ex-papilloma in both adult-onset and juvenile-onset RRP and identify patient risk factors for this dysplastic transformation. MATERIAL AND METHODS: Ten-year retrospective chart review of a tertiary otolaryngology referral center. Patients with papilloma were identified from a review of a pathology database and clinical records. Patient demographics, pathologic data, and treatment history, including use of cidofovir as an adjunctive therapy for papilloma, were extracted from electronic medical records. RESULTS: One hundred fifty-nine RRP patients were identified, 96 adult-onset (AORRP) and 63 juvenile-onset (JORRP) cases. Of this cohort, 139 (87%) had only benign papilloma as a pathologic diagnosis. In the AORRP cohort, 10 patients (10%) were diagnosed with dysplasia or carcinoma in situ in addition to papilloma, and 5 patients (5%) had malignant transformation to invasive carcinoma-ex-papilloma. There was a significantly higher age of disease onset for those with dysplasia or carcinoma versus those without dysplasia or carcinoma (56 vs 45 years old; P = .0005). Of the 63 JORRP patients, there were no cases of dysplasia but 3 (5%) cases of invasive carcinoma-ex-papilloma, all involving pulmonary disease. The JORRP patients with carcinoma-ex-papilloma had a younger average disease onset (2 vs 6 years old; P = .009) and a higher rate of tracheal involvement than those without carcinoma. Gender, smoking history, number of operations, or use of cidofovir showed no association with the development of dysplasia or carcinoma-ex-papillomatosis in either the AORRP or JORRP population. CONCLUSION: In a large series of RRP, age of disease onset is the strongest predictor of dysplastic transformation in the adult and pediatric population. Carcinoma-ex-papillomatosis was uniformly associated with pulmonary disease in the JORRP population in this series. No other demographic or behavioral factors, including adjunctive therapy with cidofovir, were statistically associated with dysplasia or carcinoma-ex-papilloma.


Asunto(s)
Carcinoma/patología , Transformación Celular Neoplásica , Infecciones por Papillomavirus/patología , Infecciones del Sistema Respiratorio/patología , Neoplasias del Sistema Respiratorio/patología , Adolescente , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Antivirales/uso terapéutico , Niño , Preescolar , Cidofovir , Citosina/análogos & derivados , Citosina/uso terapéutico , Humanos , Lactante , Persona de Mediana Edad , Organofosfonatos/uso terapéutico , Infecciones por Papillomavirus/tratamiento farmacológico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Fumar/efectos adversos , Adulto Joven
14.
Ann Otol Rhinol Laryngol ; 125(3): 257-63, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26466860

RESUMEN

OBJECTIVE: To assess intrinsic and extrinsic risk factors in the development of posterior glottic stenosis (PGS) in intubated patients. METHODS: Patients diagnosed with PGS between September 2012 and May 2014 at 3 tertiary care university hospitals were included. Patient demographics, comorbidities, duration of intubation, endotracheal tube (ETT) size, and indication for intubation were recorded. Patients with PGS were compared to control patients represented by patients intubated in intensive care units (ICU). RESULTS: Thirty-six PGS patients were identified. After exclusion, 28 PGS patients (14 male, 14 female) and 112 (65 male, 47 female) controls were studied. Multivariate analysis demonstrated ischemia (P < .05), diabetes (P < .01), and length of intubation (P < .01) were significant risk factors for the development of PGS. Fourteen of 14 (100%) males were intubated with a size 8 or larger ETT compared to 47 of 65 (72.3%) male controls (P < .05). Posterior glottic stenosis (P < .01), length of intubation (P < .001), and obstructive sleep apnea (P < .05) were significant risk factors for tracheostomy. CONCLUSION: Duration of intubation, ischemia, diabetes mellitus, and large ETT size (8 or greater) in males were significant risk factors for the development of PGS. Reducing the use of size 8 ETTs and earlier planned tracheostomy in high-risk patients may reduce the incidence of PGS and improve ICU safety.


Asunto(s)
Intubación Intratraqueal/efectos adversos , Laringoestenosis/etiología , Adulto , Anciano , Estudios de Casos y Controles , Complicaciones de la Diabetes , Femenino , Humanos , Hipertensión/complicaciones , Intubación Intratraqueal/instrumentación , Isquemia/complicaciones , Laringoestenosis/patología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Apnea Obstructiva del Sueño/complicaciones , Factores de Tiempo , Traqueostomía , Resultado del Tratamiento
16.
ORL Head Neck Nurs ; 34(1): 17-8, 20-7, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27164767

RESUMEN

AIM: The aim of this review was to assess and synthesize current literature evaluating caregiver education and coping after children were discharged with a tracheostomy. BACKGROUND: Tracheostomy tube placement is a transformative event for the child who receives it and the family members who care for the child. As a result, it is imperative to provide caregivers a comprehensive and effective education on how to care for the tracheostomy and how to cope with a tracheostomy. DESIGN: A systematic review of literature was conducted to explore practices associated with tracheostomy education among caregivers of pediatric patients with a tracheostomy. METHODS: A search of PubMed, CINAHL, and Web of Science revealed potential 501 articles using keywords, tracheostomy, tracheotomy, education, discharge, caregiver, and family coping. After reviewing them in a systematic fashion, 12 articles were identified that were pertinent to tracheostomy education. FINDINGS: This review of literature showed that discrepancies existed in how discharge education was provided and the lack of knowledge regarding tracheostomy care among caregivers despite formal education. Moreover, the caregivers reported variations in their coping capabilities and quality of life while caring for their children with a tracheostomy tube. CONCLUSION: Literature on discharge education regarding tracheostomy management among caregivers of children with a tracheostomy tube is limited. Studies report poor coping strategies and quality of life among caregivers of children with a tracheostomy tube. Studies have significant limitations. Further research is warranted to understand the current practices with discharge education and follow-up of these patients at home settings.


Asunto(s)
Adaptación Psicológica , Cuidadores/educación , Cuidadores/psicología , Educación del Paciente como Asunto , Pacientes/psicología , Traqueostomía/educación , Traqueostomía/enfermería , Adolescente , Niño , Preescolar , Femenino , Educación en Salud , Humanos , Lactante , Masculino , Calidad de Vida , Estrés Psicológico
17.
Ann Otol Rhinol Laryngol ; 124(2): 110-5, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25124839

RESUMEN

OBJECTIVE: Identifying effective treatment for papillomatosis is limited by a lack of animal models, and there is currently no preclinical model for testing potential therapeutic agents. We hypothesized that xenografting of papilloma may facilitate in vivo drug testing to identify novel treatment options. METHODS: A biopsy of fresh tracheal papilloma was xenografted into a NOD-scid-IL2Rgamma(null) (NSG) mouse. RESULTS: The xenograft began growing after 5 weeks and was serially passaged over multiple generations. Each generation showed a consistent log-growth pattern, and in all xenografts, the presence of the human papillomavirus (HPV) genome was confirmed by polymerase chain reaction (PCR). Histopathologic analysis demonstrated that the squamous architecture of the original papilloma was maintained in each generation. In vivo drug testing with bevacizumab (5 mg/kg i.p. twice weekly for 3 weeks) showed a dramatic therapeutic response compared to saline control. CONCLUSION: We report here the first successful case of serial xenografting of a tracheal papilloma in vivo with a therapeutic response observed with drug testing. In severely immunocompromised mice, the HPV genome and squamous differentiation of the papilloma can be maintained for multiple generations. This is a feasible approach to identify therapeutic agents in the treatment of recurrent respiratory papillomatosis.


Asunto(s)
Anticuerpos Monoclonales Humanizados/farmacología , Papillomavirus Humano 11 , Papiloma/patología , Infecciones por Papillomavirus/tratamiento farmacológico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Neoplasias de la Tráquea/patología , Trasplante Heterólogo/métodos , Inhibidores de la Angiogénesis/farmacología , Animales , Bevacizumab , Evaluación Preclínica de Medicamentos/métodos , Papillomavirus Humano 11/efectos de los fármacos , Papillomavirus Humano 11/genética , Humanos , Ratones , Ratones Endogámicos NOD , Modelos Animales , Papiloma/virología , Neoplasias de la Tráquea/virología , Resultado del Tratamiento
18.
Ann Otol Rhinol Laryngol ; 124(5): 413-8, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25519815

RESUMEN

OBJECTIVE: To assess the impact of suspension microlaryngoscopy with balloon dilation on voice-related quality of life (V-RQOL) in laryngotracheal stenosis (LTS). METHODS: Retrospective chart review of LTS patients dilated at a tertiary-care academic hospital from 2010 to 2013. Data were obtained and then analyzed. LTS was stratified by (1) subglottic or tracheal stenosis and (2) multilevel stenosis (MLS; glottic and subglottic/tracheal). Pre- and postoperative V-RQOL and grade, roughness, breathiness, asthenia, strain (GRBAS) scores were compared. The number and frequency of balloon dilation procedures over the lifetime were secondary outcome variables. RESULTS: Thirty-eight patients were identified: 26 subglottic/tracheal and 12 multilevel. Of these, 71.4% required multiple dilations, with greatest dilations/patient for multilevel stenosis (4.8). V-RQOL improved in the 27 patients with completed pre- and postoperative scores from a mean of 70.4 to 80 (P=.025). Pre/postoperative V-RQOLs for tracheal/subglottic (mean, 82.8/93.8) were significantly higher (P=.0001/.0001) than multilevel stenosis (48/55.3). Voice quality-of-life improvement was significant for the subglottic/tracheal cohort (P=.036) but not for the MLS group. GRBAS was performed pre- and postoperatively in 10 patients with improvement in all domains except breathiness. CONCLUSION: Laryngotracheal stenosis is associated with dysphonia. Patients with glottic involvement have significantly worse voice quality of life than those with tracheal/subglottic stenosis. Endoscopic balloon dilation improves V-RQOL in patients with subglottic/tracheal stenosis.


Asunto(s)
Dilatación/métodos , Laringoestenosis/fisiopatología , Estenosis Traqueal/fisiopatología , Calidad de la Voz , Adulto , Femenino , Estudios de Seguimiento , Humanos , Laringoestenosis/diagnóstico , Laringoestenosis/terapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Estenosis Traqueal/diagnóstico , Estenosis Traqueal/terapia , Resultado del Tratamiento
19.
Ann Otol Rhinol Laryngol ; 123(3): 188-94, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24633945

RESUMEN

OBJECTIVES: Mandibular tori have been identified as a contributing factor in difficult exposure during intubation. However, no investigation has measured the effect of mandibular tori on glottic exposure during suspension microlaryngoscopy (SML). The objective of this study was to measure how the size and location of mandibular tori affect glottic exposure during simulated SML at different thyromental distances. METHODS: Suspension microlaryngoscopy was modeled on an anatomically accurate skull and larynx with thyromental distances between 6 and 12 cm. Mandibular tori were simulated by protruding screws 5 to 15 mm from the lingual aspect of the mandible. The tori were positioned either 15 mm (anterior) or 25 mm (posterior) from the midline of the symphysis. The glottic exposure for the various-size tori in each location was measured by recording the displacement of the glottiscope tip relative to the most anterior exposure achievable without tori. The glottiscope angle relative to the horizontal plane was measured for each condition. RESULTS: Mandibular tori of more than 10 mm had a significant impact on glottic exposure. Displacement of the glottiscope tip ranged from 2 to 9 mm for anteriorly placed tori and from 7 to 29 mm for posteriorly placed tori, with larger tori causing greater displacement. Increasing the thyromental distance increased the posterior glottiscope tip displacement regardless of torus size or location. The glottiscope angle increased with larger tori (12º to 28º), but this angle did not change with increasing thyromental distance. CONCLUSIONS: Larger size and more-posterior location of mandibular tori more significantly reduce glottic exposure during SML. The inner table of the mandible is the most relevant anatomic constraint on glottic exposure, which varies with the presence or absence of mandibular tori independent of thyromental distance.


Asunto(s)
Exostosis/complicaciones , Glotis/cirugía , Laringoscopía/métodos , Enfermedades Mandibulares/complicaciones , Microcirugia/métodos , Glotis/patología , Humanos , Modelos Anatómicos
20.
Dysphagia ; 29(1): 68-77, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23943072

RESUMEN

Dysphonia and dysphagia are common complications of anterior cervical discectomy (ACD). We sought to determine the relationship between dysphagia and in-hospital mortality, complications, speech therapy/dysphagia training, length of hospitalization, and costs associated with ACD. Discharge data from the Nationwide Inpatient Sample for 1,649,871 patients who underwent ACD of fewer than four vertebrae for benign acquired disease between 2001 and 2010 were analyzed using cross-tabulations and multivariate regression modeling. Dysphagia was reported in 32,922 cases (2.0 %). Speech therapy/dysphagia training was reported in less than 0.1 % of all cases and in only 0.2 % of patients with dysphagia. Dysphagia was significantly associated with age ≥65 years (OR = 1.5 [95 % CI 1.4-1.7], P < 0.001), advanced comorbidity (OR = 2.3 [2.0-2.6], P < 0.001), revision surgery (OR = 2.7 [2.3-3.1], P < 0.001), disc prosthesis placement (OR = 1.5 [1.0-2.0], P = 0.029), and vocal cord paralysis (OR = 11.6 [8.3-16.1], P < 0.001). Dysphagia was a significant predictor of aspiration pneumonia (OR = 8.6 [6.7-10.9], P < 0.001), tracheostomy (OR = 2.3 [1.6-3.3], P < 0.001), gastrostomy (OR = 30.9 [25.3-37.8], P < 0.001), and speech therapy/dysphagia training (OR = 32.0 [15.4-66.4], P < 0.001). Aspiration pneumonia was significantly associated with in-hospital mortality (OR = 15.9 [11.0-23.1], P < 0.001). Dysphagia, vocal cord paralysis, and aspiration pneumonia were significant predictors of increased length of hospitalization and hospital-related costs, with aspiration pneumonia having the single largest impact on length of hospitalization and costs. Dysphagia is significantly associated with increased morbidity, length of hospitalization, and hospital-related costs in ACD patients. Despite the known risk of dysphagia in ACD patients and an established role for the speech-language pathologist in dysphagia management, speech-language pathology intervention appears underutilized in this population.


Asunto(s)
Vértebras Cervicales/cirugía , Trastornos de Deglución/etiología , Discectomía/efectos adversos , Costos de la Atención en Salud/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Enfermedades de la Columna Vertebral/cirugía , Parálisis de los Pliegues Vocales/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Trastornos de Deglución/economía , Trastornos de Deglución/terapia , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria/tendencias , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/economía , Complicaciones Posoperatorias/terapia , Estudios Retrospectivos , Factores de Tiempo , Estados Unidos/epidemiología , Parálisis de los Pliegues Vocales/economía , Parálisis de los Pliegues Vocales/terapia , Adulto Joven
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