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1.
Carcinogenesis ; 39(4): 522-533, 2018 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-29462271

RESUMO

Cancer remains a leading cause of death in the USA and around the world. Although the current synthetic inhibitors used in targeted therapies have improved patient prognosis, toxicity and development of resistance to these agents remain a challenge. Plant-derived natural products and their derivatives have historically been used to treat various diseases, including cancer. Several leading chemotherapeutic agents are directly or indirectly based on botanical natural products. Beyond these important drugs, however, a number of crude herbal or botanical preparations have also shown promising utility for cancer and other disorders. One such natural resource is derived from certain plants of the family Annonaceae, which are widely distributed in tropical and subtropical regions. Among the best known of these is Annona muricata, also known as soursop, graviola or guanabana. Extracts from the fruit, bark, seeds, roots and leaves of graviola, along with several other Annonaceous species, have been extensively investigated for anticancer, anti-inflammatory and antioxidant properties. Phytochemical studies have identified the acetogenins, a class of bioactive polyketide-derived constituents, from the extracts of Annonaceous species, and dozens of these compounds are present in different parts of graviola. This review summarizes current literature on the therapeutic potential and molecular mechanism of these constituents from A.muricata against cancer and many non-malignant diseases. Based on available data, there is good evidence that these long-used plants could have both chemopreventive and therapeutic potential. Appropriate attention to safety studies will be important to assess their effectiveness on various diseases caused or promoted by inflammation.


Assuntos
Annona/química , Antineoplásicos Fitogênicos/farmacologia , Neoplasias/tratamento farmacológico , Fitoterapia/métodos , Extratos Vegetais/farmacologia , Acetogeninas/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Humanos , Extratos Vegetais/química
2.
N Engl J Med ; 368(25): 2366-76, 2013 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-23692173

RESUMO

BACKGROUND: Adenotonsillectomy is commonly performed in children with the obstructive sleep apnea syndrome, yet its usefulness in reducing symptoms and improving cognition, behavior, quality of life, and polysomnographic findings has not been rigorously evaluated. We hypothesized that, in children with the obstructive sleep apnea syndrome without prolonged oxyhemoglobin desaturation, early adenotonsillectomy, as compared with watchful waiting with supportive care, would result in improved outcomes. METHODS: We randomly assigned 464 children, 5 to 9 years of age, with the obstructive sleep apnea syndrome to early adenotonsillectomy or a strategy of watchful waiting. Polysomnographic, cognitive, behavioral, and health outcomes were assessed at baseline and at 7 months. RESULTS: The average baseline value for the primary outcome, the attention and executive-function score on the Developmental Neuropsychological Assessment (with scores ranging from 50 to 150 and higher scores indicating better functioning), was close to the population mean of 100, and the change from baseline to follow-up did not differ significantly according to study group (mean [±SD] improvement, 7.1±13.9 in the early-adenotonsillectomy group and 5.1±13.4 in the watchful-waiting group; P=0.16). In contrast, there were significantly greater improvements in behavioral, quality-of-life, and polysomnographic findings and significantly greater reduction in symptoms in the early-adenotonsillectomy group than in the watchful-waiting group. Normalization of polysomnographic findings was observed in a larger proportion of children in the early-adenotonsillectomy group than in the watchful-waiting group (79% vs. 46%). CONCLUSIONS: As compared with a strategy of watchful waiting, surgical treatment for the obstructive sleep apnea syndrome in school-age children did not significantly improve attention or executive function as measured by neuropsychological testing but did reduce symptoms and improve secondary outcomes of behavior, quality of life, and polysomnographic findings, thus providing evidence of beneficial effects of early adenotonsillectomy. (Funded by the National Institutes of Health; CHAT ClinicalTrials.gov number, NCT00560859.).


Assuntos
Adenoidectomia , Apneia Obstrutiva do Sono/cirurgia , Tonsilectomia , Conduta Expectante , Criança , Comportamento Infantil , Pré-Escolar , Feminino , Humanos , Masculino , Obesidade/complicações , Oxigênio/sangue , Polissonografia , Qualidade de Vida , Método Simples-Cego , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/psicologia , Resultado do Tratamento
3.
Laryngoscope ; 133(3): 457-466, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35561004

RESUMO

OBJECTIVES: Pediatric oropharyngeal trauma is common. Although most cases resolve uneventfully, there have been reports of internal carotid artery injury leading to devastating neurovascular sequelae. There is significant controversy regarding the utility of CT angiography (CTA) in children with seemingly minor oropharyngeal trauma. The goal of this study was to appraise changes in diagnosis and treatment based on CTA results. METHODS: A comprehensive search of PubMed, Embase, CINAHL, Scopus, the Cochrane Ear, Nose and Throat Disorders Group Trials Register, and the ClinicalTrials.gov database was performed following PRISMA guidelines. RESULTS: The search yielded 5,078 unique abstracts, of which 8 articles were included. A total of 662 patients were included, with 293 having any CT head/neck imaging, and 255 with CTA. Eleven injuries/abnormalities of the carotid were found on CTAs, comprising edema around the carotid (n = 8), potential intimal tear (n = 1), carotid spasm (n = 1), and carotid compression (n = 1). The pooled proportion of imaging findings on CTA that could lead to changes in clinical management was 0.00 (95% CI 0.00-0.43). Angiography was obtained in 10 patients, in 6 cases due to abnormal CTA. Angiography identified 1 patient with vessel spasm and two patients with carotid intima disruption without thrombus. No patient underwent vascular repair or suffered cerebrovascular injury. CONCLUSION: Imaging with CTA yielded radiological abnormalities in a few instances. These results do not support the routine use of CTA in screening pediatric oropharyngeal trauma when balanced against the risk of radiation, as it rarely resulted in management changes and was not shown to improve outcomes. LEVEL OF EVIDENCE: N/A Laryngoscope, 133:457-466, 2023.


Assuntos
Lesões das Artérias Carótidas , Angiografia por Tomografia Computadorizada , Criança , Humanos , Angiografia/métodos , Artérias Carótidas , Lesões das Artérias Carótidas/diagnóstico por imagem , Lesões das Artérias Carótidas/etiologia , Lesões das Artérias Carótidas/terapia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
4.
OTO Open ; 7(1): e45, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36998563

RESUMO

Selecting qualified candidates each year for residency positions has become more difficult in recent years, due to the sharp increase in Otolaryngology applicants. Although there are objective measures that can be used to directly compare medical students during the initial screening process, most information in the application is highly subjective and/or variable across institutions. Many programs count the total posters/presentations and publications to gauge scholarship. This measure of quantity may lead to negative bias toward those who have no home program, limited time outside of academics, and/or inadequate resources to engage in volunteer research. Evaluating the quality of research may be superior to quantity. A first-author publication is a viable proxy that demonstrates applicants have developed skills that set them apart from their peers. They likely possess non-clinical, translatable skills including internal motivation, self-regulation, curation of information, and task completion that map closely with qualities that make for excellent residents.

5.
Otolaryngol Head Neck Surg ; 164(5): 918-922, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32718239

RESUMO

OBJECTIVES: to Examine the practice characteristics of same-day clinic appointments and the use of same-day appointment scheduling to provide access to care in an otolaryngology-head and neck surgery clinic. METHODS: Retrospective chart review of same-day clinic appointments from January 1, 2016, to December 31, 2018, in patients aged >19 years at a single academic center. Demographic data, diagnoses, procedures completed, and operations completed were analyzed. RESULTS: There were 2696 visits by 2324 patients during the 3-year study period. More men than women (57% vs 43%) made same-day appointments. The mean age was 50.7 years (range, 19-99 years). Sinonasal and otologic diagnoses were the most frequently coded. A total of 1452 procedures were completed on the day of the visit, and 239 operations were completed as a result of the visit. Overall, a broad spectrum of otolaryngology care was delivered within the organizational new patient access goals. DISCUSSION: Access to otolaryngology-head and neck surgery care can be challenging. Many patients will seek care when they feel they need it, and patient conditions can change unexpectedly. Offering same-day scheduling can allow patients timely health care and appropriate care. IMPLICATIONS FOR PRACTICE: Same-day appointment scheduling can provide access to care and urgent care for patients. The department of otolaryngology-head and neck surgery has been able to maintain a high rate of providing new patient appointments within 10 days with this method. Further considerations for the impact of same-day scheduling on no-show rates and patient satisfaction can be evaluated.


Assuntos
Instituições de Assistência Ambulatorial/estatística & dados numéricos , Agendamento de Consultas , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Otolaringologia , Centros Médicos Acadêmicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
6.
Ear Nose Throat J ; : 1455613211058101, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34851159

RESUMO

OBJECTIVES: This study aims to assess characteristics of same-day clinic appointments in a pediatric population at an academic otolaryngology practice. METHODS: Retrospective chart review of patients aged 18 or younger who had same-day clinic appointments between January 1, 2016, and December 31, 2018, at a single academic institution. Demographic data, diagnosis(es), procedures, and operations completed were included in the analysis. RESULTS: There were 363 same-day visits by 322 patients in the 3-year study period. Two hundred sixty-nine (269) of these visits were from new patients. Otitis media and rhinosinusitis were the most frequently coded diagnoses. One hundred forty-four (144) procedures were completed the day of the visit and 169 operations were performed as a result of the same-day visit. If the patient had a procedure or operation performed, they were more likely to have been referred by another provider. CONCLUSIONS: Providing same-day appointments can help provide timely and appropriate otolaryngology specialty care to pediatric patients. Further evaluation is needed to determine the effects on patient satisfaction as well as no-show rates.

7.
Cancer Lett ; 510: 79-92, 2021 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-33878394

RESUMO

Despite preclinical success, monotherapies targeting EGFR or cyclin D1-CDK4/6 in Head and Neck squamous cell carcinoma (HNSCC) have shown a limited clinical outcome. Here, we aimed to determine the combined effect of palbociclib (CDK4/6) and afatinib (panEGFR) inhibitors as an effective strategy to target HNSCC. Using TCGA-HNSCC co-expression analysis, we found that patients with high EGFR and cyclin D1 expression showed enrichment of gene clusters associated with cell-growth, glycolysis, and epithelial to mesenchymal transition processes. Phosphorylated S6 (p-S6), a downstream effector of EGFR and cyclin D1-CDK4/6 signalling, showed a progressive increase from normal oral tissues to leukoplakia and frank malignancy, and associated with poor outcome of the patients. This increased p-S6 expression was drastically reduced after combination treatment with afatinib and palbociclib in the cell lines and mouse models, suggesting its utiliy as a prognostic marker in HNSCC. Combination treatment also reduced the cell growth and induced cell senescence via increasing reactive oxygen species with concurrent ablation of glycolytic and tricarboxylic acid cycle intermediates. Finally, our findings in sub-cutaneous and genetically engineered mouse model (K14-CreERtam;LSL-KrasG12D/+;Trp53R172H/+) studies showed a significant reduction in the tumor growth and delayed tumor progression after combination treatment. This study collectively demonstrates that dual targeting may be a critical therapeutic strategy in blocking tumor progression via inducing metabolic alteration and warrants clinical evaluation.


Assuntos
Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Animais , Modelos Animais de Doenças , Progressão da Doença , Receptores ErbB/antagonistas & inibidores , Humanos , Camundongos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
8.
Cancer Lett ; 492: 44-53, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32738272

RESUMO

African Americans (AA) with Head and Neck Squamous Cell Carcinoma (HNSCC) have a worse disease prognosis than White patients despite adjusting for socio-economic factors, suggesting the potential biological contribution. Therefore, we investigated the genomic and immunological components that drive the differential tumor biology among race. We utilized the cancer genome atlas and cancer digital archive of HNSCC patients (1992-2013) for our study. We found that AA patients with HNSCC had a higher frequency of mutation compared to Whites in the key driver genes-P53, FAT1, CASP8 and HRAS. AA tumors also exhibited lower intratumoral infiltration of effector immune cells (CD8+, γδT, resting memory CD4+ and activated memory CD4+ T cells) with shorter survival than Whites. Unsupervised hierarchical clustering of differentially expressed genes demonstrated distinct gene clusters between AA and White patients with unique signaling pathway enrichments. Connectivity map analysis identified drugs (Neratinib and Selumetinib) that target aberrant PI3K/RAS/MEK signaling and may reduce racial disparity in therapy response.


Assuntos
Negro ou Afro-Americano/genética , Neoplasias de Cabeça e Pescoço/etnologia , Disparidades nos Níveis de Saúde , Mutação , Carcinoma de Células Escamosas de Cabeça e Pescoço/etnologia , População Branca/genética , Adulto , Idoso , Benzimidazóis/uso terapêutico , Metilação de DNA , Feminino , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade
9.
Otolaryngol Head Neck Surg ; 141(1): 86-90, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19559964

RESUMO

OBJECTIVE: To determine the prevalence of sensorineural hearing loss (SNHL) in cystic fibrosis (CF) patients and its relationship to antibiotic use. STUDY DESIGN: Case series with chart review. SETTING: Tertiary care pediatric hospital. SUBJECTS AND METHODS: We reviewed the medical records of CF patients seen in our children's hospital between March 1994 and December 2007. Data collected included patient demographics, audiograms, tympanograms, genotype, and use of potentially ototoxic antibiotics. RESULTS: Seven of 50 (14%) patients had SNHL. Three percent of patients who received 10 courses (P<0.01). No patients who received five or fewer courses of nasal irrigation with aminoglycosides had SNHL versus 23 percent of those who received more than five courses (P<0.05). Nine percent of patients who received five or fewer courses of macrolides had SNHL versus 60 percent of those who received more than five courses (P=0.079). CONCLUSION: CF patients receiving aminoglycosides are at high risk for developing SNHL.


Assuntos
Aminoglicosídeos/efeitos adversos , Fibrose Cística/complicações , Perda Auditiva Neurossensorial/induzido quimicamente , Adolescente , Adulto , Aminoglicosídeos/administração & dosagem , Audiometria , Criança , Pré-Escolar , Feminino , Perda Auditiva Neurossensorial/epidemiologia , Humanos , Incidência , Lactente , Funções Verossimilhança , Modelos Logísticos , Masculino
10.
Case Rep Otolaryngol ; 2019: 2076798, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31019827

RESUMO

Lymphatic malformations are abnormalities that arise in the developing lymphatic system, most frequently presenting in the head and neck. They are typically treated with sclerotherapy, laser therapy, or surgery for localized lesions. Sirolimus, an inhibitor of the mammalian target of rapamycin, is a relatively new medical therapy for the treatment of vascular malformations. This case report presents the improvements and complications seen in a female infant who was diagnosed with a large lymphatic malformation on prenatal ultrasound and has been treated with sirolimus during the first 9 months of life.

11.
J Natl Cancer Inst ; 111(3): 233-244, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30615137

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer, with high morbidity and mortality. Racial disparity in HNSCC is observed between African Americans (AAs) and whites, effecting both overall and 5-year survival, with worse prognosis for AAs. In addition to socio-economic status and demographic factors, many epidemiological studies have also identified factors including coexisting human papillomavirus (HPV) infection, primary tumor location, and a variety of somatic mutations that contribute to the prognostic incongruities in HNSCC patients among AAs and whites. Recent research also suggests HPV-induced dysregulation of tumor metabolism and immune microenvironment as the major regulators of HNSCC patient prognosis. Outcomes of several preclinical and clinical studies on targeted therapeutics warrant the need to elucidate the inherent mechanistic and population-based disparities underlying patient responses. This review systematically reports the underlying reasons for inconsistency in disease prognosis and therapy responses among HNSCC patients from different racial populations. The focus of this review is twofold: aside from discussing the causes of racial disparity, we also seek to identify the consequences of such disparity in terms of HPV infection and its associated mutational, metabolic, and immune landscapes. Considering the clinical impact of differential patient outcomes among AA and white populations, understanding the underlying cause of this disparity may pave the way for novel precision therapy for HNSCC.


Assuntos
Neoplasias de Cabeça e Pescoço/etiologia , Disparidades nos Níveis de Saúde , Papillomaviridae/imunologia , Infecções por Papillomavirus/complicações , Carcinoma de Células Escamosas de Cabeça e Pescoço/etiologia , Microambiente Tumoral/imunologia , Negro ou Afro-Americano/estatística & dados numéricos , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Infecções por Papillomavirus/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , População Branca/estatística & dados numéricos
12.
Arch Otolaryngol Head Neck Surg ; 134(2): 136-40, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18283154

RESUMO

OBJECTIVE: To assess the benefits of adenotonsillectomy in the treatment of pediatric patients with PFAPA (periodic fever, aphthous ulcers, pharyngitis, and adenitis) syndrome. DESIGN: Prospective case series. SETTING: Tertiary care pediatric hospital. PATIENTS: Pediatric patients meeting criteria for PFAPA syndrome. INTERVENTION: Tonsillectomy with or without adenoidectomy. MAIN OUTCOME MEASURE: Resolution of PFAPA symptoms. RESULTS: Twenty-seven (14 female, 13 male) children with PFAPA syndrome underwent tonsillectomy with or without adenoidectomy from 2004 through 2006. The length of follow-up for all patients ranged from 8 to 41 months. A total of 26 patients experienced a complete resolution of their symptoms. The 1 child who continued to have febrile episodes had fever cycles that were not regular in duration or interval and in hindsight was not likely a patient with PFAPA syndrome. CONCLUSIONS: Our findings showed complete resolution of symptoms in 26 of 27 patients with PFAPA syndrome treated surgically. Patients who meet clinical criteria for PFAPA syndrome should be considered for tonsillectomy and adenoidectomy if they do not respond to medical management.


Assuntos
Tonsila Faríngea/cirurgia , Linfadenite/cirurgia , Faringite/cirurgia , Estomatite Aftosa/cirurgia , Tonsilectomia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Periodicidade , Síndrome
13.
Otolaryngol Head Neck Surg ; 139(4): 546-550, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18922342

RESUMO

OBJECTIVE: To determine the efficacy of a preoperative bleeding questionnaire (POBQ) and coagulation screening in predicting hemorrhage associated with adenotonsillectomy. STUDY DESIGN: Retrospective study. SUBJECTS AND METHODS: Between January 1998 and December 2003, 7730 tonsillectomy and adenotonsillectomy patients were administered the POBQ preoperatively. Further coagulation screening was based on POBQ responses. RESULTS: A total of 232 (3.0%) of 7730 had postoperative bleeding; 184 (3.2%) of 5782 patients who had negative questionnaires bled postoperatively compared with 48 (2.5%) of 1948 patients with positive questionnaires (P = 0.126). Of 1948 patients with positive questionnaires, 141 (7.2%) had abnormal preoperative coagulation screens and 9 (6.4%) of 141 bled; of the 1807 (92.8%) with negative coagulation screens, 39 (2.2%) bled (P = 0.005). CONCLUSION: The POBQ is an effective tool for identifying patients who are at potential risk for post-tonsillectomy bleeding. Patients with both a positive POBQ and coagulation screen had a statistically higher likelihood of postoperative bleeding than other patients. The POBQ allowed the identification of individuals with bleeding disorders to be treated before surgery, likely decreasing the risk of bleeding in these patients.


Assuntos
Adenoidectomia/efeitos adversos , Hemorragia Pós-Operatória/epidemiologia , Medição de Risco/métodos , Inquéritos e Questionários , Tonsilectomia/efeitos adversos , Testes de Coagulação Sanguínea , Criança , Eletrocoagulação , Humanos , Cuidados Pré-Operatórios , Prognóstico , Estudos Retrospectivos
14.
Laryngoscope ; 117(2): 323-7, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17277628

RESUMO

OBJECTIVE: The objectives of this study are to report outcomes of pediatric patients with nasolacrimal duct obstruction (NLDO) who underwent primary endoscopic dacryocystorhinostomy (DCR) and discuss causes of failure. STUDY DESIGN: The authors conducted a retrospective case series. METHODS: Charts of all patients less than 16 years of age who underwent primary endoscopic DCR from 1997 to 2004 were reviewed. Patients were grouped based on the presence or absence of facial anomalies or syndromes and whether the NLDO was congenital or acquired. Success was defined as complete resolution of symptoms, improvement included anatomic patency or partial symptoms, and failure as no improvement or demonstration of patency. RESULTS: Thirty-four patients (43 ducts) aged 11 months to 14 years were identified. There were 17 males and 17 females. Follow up ranged from 2 to 54 months (average, 21 months). Twenty-four patients (29 ducts) had congenital NLDO, seven patients (11 ducts) had congenital syndromes associated with craniofacial abnormalities, and three patients (three ducts) had acquired NLDO. In patients with congenital NLDO without craniofacial abnormalities or syndromes, 22 of 29 eyes (76%) were cured with another three (10%) showing improvement. Only one of 11 (9%) eyes of patients with congenital craniofacial abnormality or syndrome experienced complete resolution and only four of 11 (36%) eyes showed improvement. Of the patients with acquired NLDO, two of three (67%) of the eyes were cured and one (33%) improved. CONCLUSIONS: Endoscopic DCR is safe and effective for most children, although patients with craniofacial abnormalities or syndromes are extremely difficult to cure.


Assuntos
Dacriocistorinostomia/métodos , Endoscopia/métodos , Adolescente , Criança , Pré-Escolar , Anormalidades Craniofaciais/complicações , Feminino , Seguimentos , Humanos , Lactente , Obstrução dos Ductos Lacrimais/congênito , Masculino , Estudos Retrospectivos , Síndrome , Falha de Tratamento , Resultado do Tratamento
15.
Arch Otolaryngol Head Neck Surg ; 133(11): 1091-5, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18025311

RESUMO

OBJECTIVE: To evaluate the effectiveness of follow-up telephone interviews and questionnaires after tonsillectomy and adenoidectomy. DESIGN: Cohort study and retrospective review of the outcomes of patients whose follow-ups were conducted by telephone interview. Patients were contacted 2 to 4 weeks after surgery; responses were recorded on a standardized postoperative questionnaire. SETTING: Tertiary pediatric hospital. PATIENTS: A total of 2554 consecutive patients who had undergone tonsillectomy, adenoidectomy, or both procedures and completed a follow-up telephone interview during the period of January 8, 2000, to September 23, 2004. MAIN OUTCOME MEASURES: Time to return to normal diet and activities, postoperative complications, pain management, postoperative visits, and caregiver's evaluation of the follow-up telephone survey. RESULTS: A total of 2554 patient outcomes were reviewed. The mean patient age was 5.9 years. Follow-up contact occurred a mean of 24.1 days after surgery. Of the surgical procedures performed, there were 1957 adenotonsillectomies, 235 adenoidectomies, and 362 tonsillectomies. At the time of follow-up, 2.7% of the patients had undergone an additional surgical procedure to treat postoperative bleeding, 96.9% had resumed eating a normal diet, and 96.2% had resumed normal activities. Bleeding from the nose or mouth was reported to have occurred at some point during the recovery period in 12.8%. On a pain scale of 1 to 10, a mean pain peak of 6.7 was reported. For most patients, pain was highest on the second day after surgery. The percentage of patients who had temporary voice change was 62.7%, and 15.4% had a follow-up clinic visit. Regarding caregivers, 99.5% reported being given instructions for postoperative care, and 98.8% reported that they felt well prepared to care for their child at home. There were no adverse events reported from surgical intervention. CONCLUSIONS: Compared with our previous experience with scheduled postsurgical clinic follow-ups, telephone interviews and standardized postoperative questionnaires pose no additional risk to patients. Considerable cost reduction and patient convenience were realized with a reduction of patient visits.


Assuntos
Adenoidectomia , Inquéritos Epidemiológicos , Cuidados Pós-Operatórios , Telefone , Tonsilectomia , Adenoidectomia/efeitos adversos , Tonsila Faríngea/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Hipertrofia/cirurgia , Lactente , Masculino , Estudos Retrospectivos , Apneia Obstrutiva do Sono/cirurgia , Tonsilectomia/efeitos adversos , Tonsilite/cirurgia , Resultado do Tratamento
16.
Oncotarget ; 8(13): 20961-20973, 2017 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-28423495

RESUMO

The dismal prognosis of locally advanced and metastatic squamous cell carcinoma of the head and neck (HNSCC) is primarily due to the development of resistance to chemoradiation therapy (CRT). Deregulation of Epidermal Growth Factor Receptor (EGFR) signaling is involved in HNSCC pathogenesis by regulating cell survival, cancer stem cells (CSCs), and resistance to CRT. Here we investigated the radiosensitizing activity of the pan-EGFR inhibitor afatinib in HNSCC in vitro and in vivo. Our results showed strong antiproliferative effects of afatinib in HNSCC SCC1 and SCC10B cells, compared to immortalized normal oral epithelial cells MOE1a and MOE1b. Comparative analysis revealed stronger antitumor effects with afatinib than observed with erlotinib. Furthermore, afatinib enhanced in vitro radiosensitivity of SCC1 and SCC10B cells by inducing mesenchymal to epithelial transition, G1 cell cycle arrest, and the attenuating ionizing radiation (IR)-induced activation of DNA double strand break repair (DSB) ATM/ATR/CHK2/BRCA1 pathway. Our studies also revealed the effect of afatinib on tumor sphere- and colony-forming capabilities of cancer stem cells (CSCs), and decreased IR-induced CSC population in SCC1 and SCC10B cells. Furthermore, we observed that a combination of afatinib with IR significantly reduced SCC1 xenograft tumors (median weight of 168.25 ± 20.85 mg; p = 0.05) compared to afatinib (280.07 ± 20.54 mg) or IR alone (324.91 ± 28.08 mg). Immunohistochemical analysis of SCC1 tumor xenografts demonstrated downregulation of the expression of IR-induced pEGFR1, ALDH1 and upregulation of phosphorylated γH2AX by afatinib. Overall, afatinib reduces tumorigenicity and radiosensitizes HNSCC cells. It holds promise for future clinical development as a novel radiosensitizer by improving CSC eradication.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Quinazolinas/farmacologia , Tolerância a Radiação/efeitos dos fármacos , Radiossensibilizantes/farmacologia , Afatinib , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Receptores ErbB/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Camundongos , Camundongos Nus , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/efeitos da radiação , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Otolaryngol Head Neck Surg ; 135(1): 12-6, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16815175

RESUMO

OBJECTIVE: Determine if passive smoke exposure (PSE) increases airway complications during outpatient mask anesthesia procedures in children. METHODS: A prospective cohort of children who underwent surgical procedures under mask anesthesia was studied with the American Thoracic Society children's questionnaire on environmental and respiratory factors. Double-blinded outcomes with respect to adverse airway events were recorded both intraoperatively and in the recovery room for patients with and without passive smoke exposure. Multivariate comparisons assessing the likelihood of these airway complications were conducted between the PSE and nonexposed groups. RESULTS: Of 405 children, 168 (41.5%) had PSE. The incidence of airway complications during anesthesia or postanesthetic recovery was higher for all outcome measures for PSE children (all P

Assuntos
Procedimentos Cirúrgicos Ambulatórios , Espasmo Brônquico/etiologia , Complicações Intraoperatórias , Laringismo/etiologia , Poluição por Fumaça de Tabaco/efeitos adversos , Adolescente , Criança , Pré-Escolar , Método Duplo-Cego , Seguimentos , Humanos , Incidência , Lactente , Estudos Prospectivos , Fatores de Risco
18.
Laryngoscope ; 115(11): 1923-9, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16319600

RESUMO

OBJECTIVE: To identify the most common otolaryngologic causes of mortality in the 0 to 19 age group in the state of Massachusetts and to estimate the pediatric otolaryngologic mortality rate based on population data. STUDY DESIGN: Population-based retrospective cohort study. METHODS: The Massachusetts State Registry of Vital Records and Statistics electronic database was searched for all otolaryngology related causes of death from 1990 to 2002 for children aged 0 to 19. The individual death certificates were then reviewed, and a database of otolaryngology related pediatric deaths was created. RESULTS: A total of 59 otolaryngology related deaths were identified in the pediatric population from 1990 to 2002. Eighty-one percent of deaths occurred because of airway compromise caused by infection, anatomic obstruction, or congenital anomaly. The remaining 19% of deaths occurred because of aspiration, nonairway infections, and malignant neoplasms. Ninety-five percent of deaths in the children under age 10 were caused by airway compromise. Six of seven deaths (86%) in the age 15 to 19 group occurred because of malignant neoplasms. The overall mortality rate caused by otolaryngologic causes was estimated to be 0.28 per 100,000 population. CONCLUSIONS: The overall mortality rate for otolaryngology related deaths is low in the pediatric population. The vast majority of deaths are caused by airway compromise, primarily because of laryngotracheobronchitis or other upper airway obstruction. In older children (ages 15-19), malignant head and neck neoplasms are the leading cause of otolaryngology related deaths.


Assuntos
Otorrinolaringopatias/mortalidade , Vigilância da População , Adolescente , Distribuição por Idade , Causas de Morte/tendências , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Massachusetts/epidemiologia , Estudos Retrospectivos , Distribuição por Sexo , Taxa de Sobrevida/tendências
19.
Int J Pediatr Otorhinolaryngol ; 69(5): 669-79, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15850688

RESUMO

OBJECTIVES/HYPOTHESIS: Pediatric oropharyngeal trauma (OPT) is a common injury in children with rare, but at times severe complications including carotid injury and dissection of air/micro-organisms into the deep tissues of the neck or chest. Cervical CT scan with contrast (CT angiography (CTA)) is nearly universally available and may enhance the evaluation of OPT patients by screening for these potentially devastating complications. STUDY DESIGN: Retrospective record review, systematic review of the literature. METHODS: Twenty-three patients diagnosed with OPT from 1997 to 2003 at Boston Children's Hospital were identified by database review. Records were reviewed for site and mechanism of injury, use of diagnostic studies, management, and outcomes. Results were compared to previously published reports. The current literature was reviewed to assess the level of evidence pertaining to the evaluation of OPT patients with CT scan. An extrapolation was made to the general trauma literature to further evaluate the ability of CT angiography to detect carotid injury. RESULTS: Demographics and mechanism of injury in the current series were unchanged from previous reports. CT demonstrated superior detection and localization of free air. Systematic review of OPT literature revealed data on the use of CT scan as evaluation tool were lacking. Extrapolations to the trauma literature strongly indicate helical CTA has high sensitivity and specificity in detecting carotid injury. CONCLUSIONS: Pediatric oropharyngeal trauma is a common injury with rare, but severe complications. The routine use of CT scan with contrast may assist in the evaluation of these patients to detect injuries that could lead to severe complications. Collection of prospective data on the ability of CT scan to detect carotid injuries is needed but may not be feasible.


Assuntos
Orofaringe/diagnóstico por imagem , Orofaringe/lesões , Tomografia Computadorizada por Raios X , Adolescente , Lesões das Artérias Carótidas/diagnóstico por imagem , Lesões das Artérias Carótidas/cirurgia , Criança , Pré-Escolar , Meios de Contraste , Feminino , Corpos Estranhos/diagnóstico por imagem , Corpos Estranhos/cirurgia , Humanos , Lactente , Masculino , Orofaringe/cirurgia , Estudos Retrospectivos
20.
Chest ; 148(5): 1204-1213, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25811889

RESUMO

BACKGROUND: Adenotonsillectomy (AT) is commonly performed for childhood OSA syndrome (OSAS), but little is known about prognosis without treatment. METHODS: The Childhood Adenotonsillectomy Trial (CHAT) randomized 50% of eligible children with OSAS to a control arm (watchful waiting), with 7-month follow-up symptom inventories, physical examinations, and polysomnography. Polysomnographic and symptomatic resolution were defined respectively by an apnea/hypopnea index (AHI) <2 and obstructive apnea index (OAI) <1 and by an OSAS symptom score (Pediatric Sleep Questionnaire [PSQ]) < 0.33 with ≥ 25% improvement from baseline. RESULTS: After 194 children aged 5 to 9 years underwent 7 months of watchful waiting, 82 (42%) no longer met polysomnographic criteria for OSAS. Baseline predictors of resolution included lower AHI, better oxygen saturation, smaller waist circumference or percentile, higher-positioned soft palate, smaller neck circumference, and non-black race (each P < .05). Among these, the independent predictors were lower AHI and waist circumference percentile < 90%. Among 167 children with baseline PSQ scores ≥ 0.33, only 25 (15%) experienced symptomatic resolution. Baseline predictors were low PSQ and PSQ snoring subscale scores; absence of habitual snoring, loud snoring, observed apneas, or a household smoker; higher quality of life; fewer attention-deficit/hyperactivity disorder symptoms; and female sex. Only lower PSQ and snoring scores were independent predictors. CONCLUSIONS: Many candidates for AT no longer have OSAS on polysomnography after 7 months of watchful waiting, whereas meaningful improvement in symptoms is not common. In practice, a baseline low AHI and normal waist circumference, or low PSQ and snoring score, may help identify an opportunity to avoid AT. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00560859; URL: www.clinicaltrials.gov.


Assuntos
Apneia Obstrutiva do Sono/fisiopatologia , Sono/fisiologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Polissonografia , Prognóstico , Qualidade de Vida , Remissão Espontânea , Apneia Obstrutiva do Sono/cirurgia , Inquéritos e Questionários , Tonsilectomia
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