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2.
Laryngoscope ; 133(2): 431-436, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36129159

RESUMEN

OBJECTIVE(S): Maneuvers during drug-induced sleep endoscopy (DISE), for patients with obstructive sleep apnea (OSA), have been used as predictors for success with oral appliances. Hypoglossal nerve stimulation (HGNS) promotes opening at the velum through palatoglossus coupling. In this study, we evaluate maneuvers during DISE as predictors for HGNS treatment efficacy. METHODS: We evaluated patients undergoing HGNS between November, 2014 and February, 2021. We assessed maneuvers including jaw thrust and chin lift during preoperative DISE. The impact of tongue base and palatal opening during these maneuvers were rated from 1 to 4 (1: no improvement, 2: mild improvement, 3: moderate improvement, 4: significant improvement). Patients were grouped by a score of 1-2 (weak response) or 3-4 (strong response). Apnea hypopnea index (AHI) change was calculated from the difference between preoperative and postoperative sleep study. RESULTS: One hundred and seventy one patients were included. With jaw thrust, there was no significant difference in AHI change between patients with weak or strong response at the palate (n = 68 vs. 94, 9.5 vs. 13.6, p = 0.21) or tongue base (n = 24 vs. 138, 16.6 vs. 11.3, p = 0.24). On chin lift, there was no significant difference at the palate (n = 82 vs. 18, 13.9 vs. 11.4, p = 0.63) or tongue base (n = 92 vs. 72, 10.8 vs. 14.6, p = 0.24). On multiple linear regression analysis, lower body mass index, higher preoperative AHI, and higher preoperative oxygen nadir were associated with a larger AHI change. CONCLUSION: Palatal coupling maneuvers during DISE are not predictive of AHI change with HGNS. Findings using these maneuvers should not preclude HGNS candidacy. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:431-436, 2023.


Asunto(s)
Nervio Hipogloso , Apnea Obstructiva del Sueño , Humanos , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/terapia , Polisomnografía , Resultado del Tratamiento , Endoscopía , Hueso Paladar/cirugía
3.
Ann Otol Rhinol Laryngol ; 132(6): 667-673, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35833578

RESUMEN

INTRODUCTION: To determine if there is a recovery time difference between patients with and without obstructive sleep apnea (OSA) when using total intravenous anesthesia (TIVA) compared to volatile gas inhalational anesthesia. PATIENTS AND METHODS: OSA and Non-OSA patients were identified at a tertiary institution between January 2019 and November 2020. Non-OSA patients were defined as those who have not been formerly diagnosed with OSA. A modified STOP-BANG score (MSBS) was performed to screen Non-OSA patients for OSA. Recovery was measured by Phase I recovery time, or time it took a patient to reach ≥9/10 on the Aldrete scoring system. RESULTS: A total of 334 patients were included with 142 in the OSA cohort (59 TIVA, 83 inhalational anesthesia) and 192 in the Non-OSA cohort (119 TIVA, 73 inhalational anesthesia). In OSA patients, there was a 41.29-minute recovery time reduction when using TIVA versus sevoflurane (P < .0001). Non-OSA patients recovered faster than OSA patients when undergoing inhalational anesthesia by 46.76 minutes and TIVA by 18.58 minutes (P < .0001 and P = .0907, respectively). Non-OSA patients with a MSBS < 3 and ≥3 had a shorter recovery time compared to OSA patients when both underwent sevoflurane anesthesia (57.27 minutes, P < .0001 and 56.23 minutes, P = .040, respectively). Non-OSA patients with a MSBS of <3 had a decrease in recovery time of 26.68 minutes when compared to OSA patients who underwent TIVA (P = .0004). CONCLUSIONS: When utilizing TIVA over inhalational anesthesia, patients with OSA have significantly increased benefit in terms of reduced Phase I recovery times as compared to Non-OSA patients.


Asunto(s)
Anestésicos por Inhalación , Propofol , Apnea Obstructiva del Sueño , Humanos , Sevoflurano , Anestésicos Intravenosos , Anestesia Intravenosa , Anestesia General , Apnea Obstructiva del Sueño/diagnóstico
4.
Am J Cardiol ; 180: 155-162, 2022 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-35918232

RESUMEN

RespiCardia remede System (Minnetonka, MN 2017), a transvenous phrenic nerve stimulator, is indicated to treat central sleep apnea (CSA) by stimulating the phrenic nerve to cause diaphragmatic contraction to restore normal breathing during sleep. CSA is associated with decreased patient quality of life and worsens cardiovascular outcomes. Systematic review was conducted according to the Preferred Reporting of Systematic Reviews and Meta-Analysis guidelines. PubMed/MEDLINE, Cochrane, EBSCO CINAHL, and Ovid databases were queried by 2 independent reviewers for English-language studies published between 2000 and 2021. The initial search screened for all occurrences of "remede" then was further refined to include studies evaluating use of the RespiCardia remede System as a treatment for CSA in multiple patients. A total of 124 articles were identified from the initial search results. A total of 37 articles were identified through screening of title and abstracts from initial results. Full-text review of all the articles was then completed. Of the 13 articles included, a total of 232 patients underwent device implantation. We sought to summarize the available evidence regarding patient selection for implantation, immediate and delayed complications, adherence to therapy, and polysomnographic evidence of efficacy. All 13 articles detailed significant decreases in central apnea index and many patients reported significant mild to marked improvement in quality of life. In conclusion, the remede System has been demonstrated to improve sleep and respiratory parameters, with few complications. This device demonstrates safe and effective treatment of moderate to severe CSA in adult patients, including those with heart failure.


Asunto(s)
Terapia por Estimulación Eléctrica , Apnea Central del Sueño , Adulto , Terapia por Estimulación Eléctrica/métodos , Humanos , Nervio Frénico/fisiología , Calidad de Vida , Apnea Central del Sueño/diagnóstico , Revisiones Sistemáticas como Asunto
5.
Laryngoscope ; 132(7): 1487-1494, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35234282

RESUMEN

OBJECTIVES: To compare cost and time spent in surgical and postoperative courses in patients with obstructive sleep apnea (OSA) undergoing surgery with either total intravenous anesthesia (TIVA) or inhalational anesthesia. STUDY DESIGN: Retrospective chart review. METHODS: Retrospective review on patients undergoing surgery for OSA under general anesthesia from January 2019 to October 2020. Cost per service was acquired for the day of surgery. RESULTS: A total of 230 patients were included: 95 received TIVA; 135 received inhalation anesthesia. Total cost was significantly higher in the TIVA nasal surgery group by $286 (P = .035). TIVA produced significantly higher pharmacy and operating room costs across all surgeries and OSA severities. These increased costs were offset by significantly lower supply costs in upper airway stimulator (UAS, -$419.50; P = .007) and uvulopalatopharyngoplasty (UPPP, -$115.16; P = .015) patients receiving TIVA. In the TIVA cohort, there was a trend toward lower recovery room costs after UAS (-$111.09; P = .063) and nasal surgery (-$64.45; P = .096) and anesthesia costs after nasal surgery (-$36.67; P = .054). Total recovery time was reduced by 18 minutes (P = .004) for nasal surgery, 25 minutes (P = .043) for UAS, and 27 minutes (P = .147) for UPPP patients receiving TIVA. CONCLUSION: When used in an outpatient setting for patients with OSA, TIVA adds to pharmacy and operating room costs, but this is usually offset by lower supply, anesthesia, and recovery room costs. We found decreased recovery times in the TIVA cohort. TIVA has proven benefits in patient outcomes and can be cost-effective in OSA surgery. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:1487-1494, 2022.


Asunto(s)
Propofol , Apnea Obstructiva del Sueño , Anestesia General , Anestesia por Inhalación , Anestesia Intravenosa , Anestésicos Intravenosos , Humanos , Estudios Retrospectivos , Apnea Obstructiva del Sueño/cirugía
6.
Am J Otolaryngol ; 43(2): 103340, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34923278

RESUMEN

PURPOSE: To evaluate patient-reported quality of life pertaining to gastroesophageal reflux disease symptoms in patients undergoing upper airway surgery for comorbid obstructive sleep apnea. MATERIALS AND METHODS: A prospective survey-based study was conducted on patients with gastroesophageal reflux disease and comorbid obstructive sleep apnea receiving surgery from July 2020-December 2020. Patients completed the Gastroesophageal Reflux Disease-Health Related Quality of Life Questionnaire at two time-points: one week before surgery and at 6 months following surgery. Disease-related symptoms were rated from 0 (no symptoms) to 5 (incapacitating symptoms). Patient survey scores, demographics, medications, and sleep study parameters were collected for analysis. A p-value <0.05 indicated statistical significance. RESULTS: Twenty-two patients completed the baseline preoperative and 6-month postoperative questionnaires. Median baseline vs. 6-month survey scores significantly decreased for symptoms including heartburn in general (3.0 vs. 2.0, p = 0.006), when lying down (2.5 vs. 1.5, p = 0.046), when standing (2.0 vs 1.0, p = 0.003), following meals (2.0 vs. 2.0, p = 0.042), and cumulative survey score (15.5 vs. 11.0, p = 0.029). Heartburn altering diet or sleep, odynophagia, dysphagia, and medication burden did not change following surgery (p > 0.05). More patients were satisfied with their postoperative condition compared to baseline, however this did not reach statistical significance (40.9% vs. 18.2%, p = 0.18). CONCLUSIONS: Our results suggest that upper airway surgery to treat obstructive sleep apnea may have a positive impact on patient-reported symptoms of gastroesophageal reflux disease, and further investigation into the role of surgery in this setting for improvement of both quality of life and true clinical disease severity is merited.


Asunto(s)
Reflujo Gastroesofágico , Apnea Obstructiva del Sueño , Reflujo Gastroesofágico/epidemiología , Reflujo Gastroesofágico/etiología , Reflujo Gastroesofágico/cirugía , Humanos , Polisomnografía , Estudios Prospectivos , Calidad de Vida , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/cirugía
7.
J Clin Sleep Med ; 17(11): 2165-2169, 2021 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-34666883

RESUMEN

STUDY OBJECTIVES: The objective was to determine the prevalence and predictors of comorbid insomnia in patients presenting for sleep surgery evaluation. The insomnia severity index (ISI) was utilized to evaluate patients' insomnia severity. METHODS: A retrospective chart review was performed in patients presenting to an otolaryngology sleep surgery clinic; patients also completed a sleep history questionnaire. Patients were divided between those with and without clinically significant insomnia defined as ISI ≥ 15. RESULTS: A total of 119 patients were included in the study: 50 (42%) with an ISI ≥ 15 and 69 (58%) with an ISI < 15. Clinically significant insomnia was associated with respiratory disturbance index (P = .028) but not apnea-hypopnea index or SaO2 nadir (P > .05). Clinically significant insomnia was associated with frequency of wake ups (P = .008), time to fall back asleep (P = .049), history of continuous positive airway pressure device use (P = .012), Epworth Sleepiness Scale (P = .008), and Sino-nasal Outcome Test (SNOT-22) (P < .001). CONCLUSIONS: Patients reporting to a sleep surgery clinic are at an elevated risk for comorbid insomnia. The relationship between increased respiratory event-related arousals and nonsleep SNOT-22 scores to related sleep-maintenance insomnia supports the connection between insomnia, nasal obstruction, and continuous positive airway pressure intolerance. CITATION: Sagheer SH, Scott ER, Ananth A, Boon M, Huntley C. Incidence and predictors of comorbid insomnia in a sleep surgery clinic. J Clin Sleep Med. 2021;17(11):2165-2169.


Asunto(s)
Apnea Obstructiva del Sueño , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Incidencia , Estudios Retrospectivos , Sueño , Apnea Obstructiva del Sueño/epidemiología , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología
8.
Laryngoscope ; 131(6): 1235-1253, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33037835

RESUMEN

OBJECTIVE: To evaluate the effectiveness of neuromodulating agents for the management of atypical facial pain and primary facial neuralgias. METHODS: We searched MEDLINE, Embase, CINAHL, and ClinicalTrials.gov databases for original research articles that examine the effectiveness and adverse reactions of pharmacologic therapy for the treatment of trigeminal neuralgia and atypical facial pain. Studies that included surgical interventions for atypical facial pain or facial pain secondary to other causes were excluded. Meta-analysis was conducted for reductions in symptom scores and adverse effects. RESULTS: Of 3,409 articles screened, 73 full-text articles were included, consisting of 45 observational studies and 29 randomized controlled trials. Twenty-four different pharmacological agents were assessed; carbamazepine was the most frequently studied while botulinum toxin A demonstrated the highest consistency in reduction of symptom scores. Pooled estimate of three randomized controlled trials revealed that patients with trigeminal neuralgia who received botulinum toxin A had higher odds (odds ratio 7.46; 95% CI 3.53-15.78) of achieving a ≥50% reduction in visual analogue scale scores compared to controls. Pooled estimate of 15 observational studies showed that three-fourths of patients with trigeminal neuralgia who received carbamazepine experienced clinically significant pain reduction (prevalence proportion 0.75; 95% CI 0.66-0.83). CONCLUSIONS: Patients receiving botulinum toxin A for trigeminal neuralgia had higher odds of achieving ≥50% reduction in pain scores. A significant proportion of patients with trigeminal neuralgia experienced positive response to carbamazepine. There was moderate evidence for amitriptyline in patients with atypical facial pain. Standardization of outcome reporting would facilitate future quantitative comparisons of therapeutic effectiveness. Laryngoscope, 131:1235-1253, 2021.


Asunto(s)
Nervio Facial , Dolor Facial/tratamiento farmacológico , Neuralgia/tratamiento farmacológico , Neurotransmisores/uso terapéutico , Manejo del Dolor/métodos , Adulto , Amitriptilina/uso terapéutico , Toxinas Botulínicas Tipo A/uso terapéutico , Carbamazepina/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Observacionales como Asunto , Oportunidad Relativa , Dimensión del Dolor , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Neuralgia del Trigémino/tratamiento farmacológico
9.
Otolaryngol Head Neck Surg ; 158(2): 232-239, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29112487

RESUMEN

Objective Angioedema is a potentially life-threatening complication of angiotensin-converting enzyme inhibitor (ACEI) use, occurring in up to 0.5% of users. Although the pathophysiology of ACEI-induced angioedema is attributable to elevated serum bradykinin, standard management typically includes corticosteroids and antihistamines. We sought to summarize the evidence supporting pharmacotherapy for ACEI-induced angioedema. Data Sources PubMed, MEDLINE, and Embase portals. Methods A systematic literature review was conducted according to the PRISMA guidelines. Databases were queried by 3 independent reviewers for English-language studies published between 1980 and 2017. The initial search screened for all occurrences of "angioedema" and then was further refined to include studies of ACEI-related cases and exclude hereditary angioedema. Results Five articles representing 218 cases were identified, including 3 randomized controlled trials and 2 prospective case series with historical controls. One of 2 studies of icatibant (bradykinin B2 receptor antagonist) found more rapid symptom improvement than that with a control group of corticosteroids and antihistamines. Two studies of ecallantide (plasma kallikrein inhibitor) and 1 study of C1 inhibitor replacement found no significant benefit over control. No studies were identified that compared the efficacy of corticosteroids with antihistamines, of one dose with another, of fresh frozen plasma, or of combination therapy. Conclusion The efficacy of treatment of ACEI-induced angioedema with bradykinin antagonists, kallikrein inhibitor, and C1 inhibitor warrants further study. Although consistent benefit of these medications has not been demonstrated, their use has not caused harm. One study examining off-label use of icatibant has demonstrated efficacy over control. In addition, further study is needed to establish the efficacy and mechanism of action of standard pharmacotherapy such as corticosteroids and antihistamines in treatment of this condition.


Asunto(s)
Angioedema/inducido químicamente , Angioedema/tratamiento farmacológico , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Corticoesteroides/uso terapéutico , Antagonistas del Receptor de Bradiquinina B2/uso terapéutico , Antagonistas de los Receptores Histamínicos/uso terapéutico , Humanos
10.
Ear Nose Throat J ; 96(8): E20-E23, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28846795

RESUMEN

Neonatal nasal septal deviations can occur as a result of trauma in utero or during birth. They are associated with significant clinical implications, including respiratory distress and failure to thrive. The incidence and classification of these deformities are varied in the otolaryngology literature. Some authors advocate conservative observation, but no consensus on management has been reached. We present 2 cases of neonatal septal deviation that occurred during difficult deliveries. We repaired the defects with closed reduction in the operating room within the first 2 weeks of life to good effect.


Asunto(s)
Traumatismos del Nacimiento/cirugía , Obstrucción Nasal/cirugía , Tabique Nasal/cirugía , Deformidades Adquiridas Nasales/cirugía , Traumatismos del Nacimiento/etiología , Parto Obstétrico/efectos adversos , Femenino , Humanos , Recién Nacido , Obstrucción Nasal/etiología , Deformidades Adquiridas Nasales/etiología , Fotograbar
11.
JAMA Otolaryngol Head Neck Surg ; 142(6): 590-5, 2016 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-27101229

RESUMEN

IMPORTANCE: Human papillomavirus (HPV) is a preventable disease that plays a causative role in a significant proportion of malignant neoplasms of the head and neck. Inner-city populations are at risk for HPV-related oropharyngeal cancer, are least likely to receive HPV vaccination, and report a lack of information regarding HPV. OBJECTIVE: To determine whether an educational platform affects knowledge, attitudes, and practices regarding HPV vaccination in an inner-city community. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study, conducted from March 1 to December 31, 2014, surveyed 128 participants at multiple inner-city community centers regarding their knowledge of, attitudes toward, and practices regarding HPV vaccination before and after a brief educational presentation. No eligible individuals refused to participate in the educational session. Surveys were excluded from analysis if they were incomplete. INTERVENTIONS: Participants completed two 20-question surveys separated by a 15-minute educational session on HPV-related disease, including a short PowerPoint presentation. MAIN OUTCOMES AND MEASURES: Presence of statistically significant differences in survey scores before and after the educational session. RESULTS: Eighty-six participants met eligibility criteria (61 male [70.9%]; 68 with a high school education [79.1%]). Baseline knowledge of HPV, its causal association with cancer, and the existence of a vaccine against HPV were poor: of a total composite score of 20, the mean knowledge score before the educational session was 9.69. Participants' self-rated knowledge regarding HPV disease and vaccination improved significantly as a result of the educational session; the absolute increase in mean knowledge composite score from before the educational session to after the session was 3.52 (17.6%) (95% CI, -2.87 to 9.92; P < .01). Attitudes regarding government involvement in vaccination did not change as a result of the educational session (composite attitudes score before the educational session, 16.57 of 28; score after the session, 15.22; P = .98). Participants' intent to vaccinate their children increased significantly following the educational presentation: before the presentation, 34 respondents (40%) intended to have their children vaccinated; after the presentation, 60 (70%) intended to do so (P = .002). CONCLUSIONS AND RELEVANCE: Lack of knowledge regarding HPV vaccination and unwillingness to undergo vaccination contribute to low rates of HPV vaccination within urban populations. Community-based educational sessions successfully teach the link between HPV and various cancers, provide information regarding the risks and benefits of vaccination, and increase participants' willingness to vaccinate their children against HPV. Attitudes regarding government involvement in health programs are resistant to change.


Asunto(s)
Educación en Salud , Conocimientos, Actitudes y Práctica en Salud , Vacunas contra Papillomavirus , Población Urbana , Estudios de Cohortes , Centros Comunitarios de Salud , Femenino , Humanos , Louisiana , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/virología , Encuestas y Cuestionarios
12.
Laryngoscope ; 126(2): 469-71, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26308370

RESUMEN

Objectives/Hypothesis: The human cochlea is most commonly considered to have two and a half turns. Although the causes of cochlear hypoplasia are well described, cochlear hyperplasia is a rarer entity that is poorly understood. We describe rare anatomic cochlear malformations identified in a 4-month-old male originally referred for evaluation after a failed newborn hearing screening. The full diagnostic evaluation, imaging findings, treatment, and follow-up are described in detail. Cochleae with three turns are an uncommon malformation that is not included in current classifications schemes and may represent a distinct type of anomaly not caused by developmental arrest.


Asunto(s)
Cóclea/anomalías , Pérdida Auditiva Sensorineural/congénito , Ventilación del Oído Medio/métodos , Audiometría , Cóclea/cirugía , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/cirugía , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Tomografía Computarizada por Rayos X
13.
Int J Pediatr Otorhinolaryngol ; 78(12): 2229-33, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25458165

RESUMEN

OBJECTIVES: To identify factors associated with efficient operating room work flow on high volume pediatric otolaryngology days and the effects on provider and perceived parent satisfaction. METHODS: Retrospective review was performed of a sample of 20 days with greater than 10 cases per day performed by a pediatric otolaryngologist operating in 2 rooms. Turnover time and complications were the main outcome measures. Providers from otolaryngology and anesthesia that participated in these days were surveyed regarding efficiency, safety, and satisfaction. RESULTS: 223 cases were performed over 20 operative days. The average turnover time was significantly longer in "major" surgeries (p=0.03), cases with multispecialty involvement (p=0.01), cases requiring intubation (p<0.001), and in cases where a fellowship trained pediatric anesthesiologist (p=0.01) or CRNA was present (p<0.001). When comparing "fast" (<25min average turnover) operative days vs. "slow" (>25min average turnover) days, presence of a non-fellowship trained anesthesiologist (p<0.001), and the presence of an anesthesiology resident (p=0.03) were significantly associated with "fast" days, while the presence of a CRNA was associated with "slow" days (p<0.001). A significantly greater proportion of patients required intubation on "slow" turnover days vs. "fast" days (p=0.13). Only one complication was observed (0.4%). 48 providers were surveyed with a 63% response rate. Reported satisfaction amongst providers was significantly greater on days with at least 10 cases (p=0.047) and on days with turnover times of 25min or less (p<0.001). Pre-operative nursing evaluation/preparation of the patient, inter-provider communication and delays in room cleaning/setup were identified most often as causative factors responsible for delays in turnover. CONCLUSIONS: High-operative volume operating days are common in pediatric otolaryngology and can be safely performed in an efficient manner. Appropriate scheduling and high-level communication between providers is needed to ensure success on these days. Identified areas of potential inefficiency can be a starting point for work flow optimization practices.


Asunto(s)
Eficiencia Organizacional , Quirófanos/organización & administración , Tempo Operativo , Procedimientos Quirúrgicos Otorrinolaringológicos , Pediatría , Anestesiología , Niño , Preescolar , Femenino , Humanos , Masculino , Seguridad del Paciente , Satisfacción del Paciente , Admisión y Programación de Personal , Garantía de la Calidad de Atención de Salud , Estudios Retrospectivos , Estados Unidos , Carga de Trabajo
14.
Proc Natl Acad Sci U S A ; 106(3): 685-90, 2009 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-19129498

RESUMEN

A biodegradable positron-emitting dendritic nanoprobe targeted at alpha(v)beta(3) integrin, a biological marker known to modulate angiogenesis, was developed for the noninvasive imaging of angiogenesis. The nanoprobe has a modular multivalent core-shell architecture consisting of a biodegradable heterobifunctional dendritic core chemoselectively functionalized with heterobifunctional polyethylene oxide (PEO) chains that form a protective shell, which imparts biological stealth and dictates the pharmacokinetics. Each of the 8 branches of the dendritic core was functionalized for labeling with radiohalogens. Placement of radioactive moieties at the core was designed to prevent in vivo dehalogenation, a potential problem for radiohalogens in imaging and therapy. Targeting peptides of cyclic arginine-glycine-aspartic acid (RGD) motifs were installed at the terminal ends of the PEO chains to enhance their accessibility to alpha(v)beta(3) integrin receptors. This nanoscale design enabled a 50-fold enhancement of the binding affinity to alpha(v)beta(3) integrin receptors with respect to the monovalent RGD peptide alone, from 10.40 nM to 0.18 nM IC(50). Cell-based assays of the (125)I-labeled dendritic nanoprobes using alpha(v)beta(3)-positive cells showed a 6-fold increase in alpha(v)beta(3) receptor-mediated endocytosis of the targeted nanoprobe compared with the nontargeted nanoprobe, whereas alpha(v)beta(3)-negative cells showed no enhancement of cell uptake over time. In vivo biodistribution studies of (76)Br-labeled dendritic nanoprobes showed excellent bioavailability for the targeted and nontargeted nanoprobes. In vivo studies in a murine hindlimb ischemia model for angiogenesis revealed high specific accumulation of (76)Br-labeled dendritic nanoprobes targeted at alpha(v)beta(3) integrins in angiogenic muscles, allowing highly selective imaging of this critically important process.


Asunto(s)
Dendrímeros , Integrina alfaVbeta3/metabolismo , Nanotecnología , Neovascularización Fisiológica , Tomografía de Emisión de Positrones/métodos , Animales , Miembro Posterior/irrigación sanguínea , Isquemia/diagnóstico por imagen , Isquemia/fisiopatología , Masculino , Ratones , Ratones Endogámicos C57BL , Oligopéptidos/metabolismo , Polietilenglicoles/química , Distribución Tisular
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