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1.
Immunol Allergy Clin North Am ; 40(2): 303-315, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32278453

RESUMO

Antibiotic therapy has become an important adjunct in the management of recalcitrant chronic rhinosinusitis (CRS) because of some antibiotics' immunomodulatory properties even at subtherapeutic antimicrobial levels. Macrolide antibiotics, such as clarithromycin and azithromycin, decrease production of proinflammatory cytokines, impair neutrophil recruitment, inhibit bacterial biofilm formation, and improve mucus quality. Doxycycline, a tetracycline antibiotic, inhibits the activity of matrix metalloproteinases in CRS with nasal polyposis. This article reviews the clinical applications for macrolide and doxycycline use in CRS, considerations for dosing and duration of treatment, and important side effects and drug interactions associated with these medications.

2.
Otolaryngol Head Neck Surg ; 162(4): 530-537, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31986971

RESUMO

OBJECTIVE: To ascertain the relationship among vestibular schwannoma (VS) tumor volume, growth, and hearing loss. STUDY DESIGN: Retrospective cohort study. SETTING: Single tertiary center. SUBJECTS AND METHODS: Adults with observed VS and serviceable hearing at diagnosis were included. The primary outcome was the development of nonserviceable hearing as estimated using the Kaplan-Meier method. Associations of tumor volume with baseline hearing were assessed using Spearman rank correlation coefficients. Associations of volume and growth with the development of nonserviceable hearing over time were assessed using Cox proportional hazards models and summarized with hazard ratios (HRs). RESULTS: Of 230 patients with VS and serviceable hearing at diagnosis, 213 had serial volumetric tumor data for analysis. Larger tumor volume at diagnosis was associated with increased pure-tone average (PTA) (P < .001) and decreased word recognition score (WRS) (P = .014). Estimated rates of maintaining serviceable hearing at 6 and 10 years following diagnosis were 67% and 49%, respectively. Larger initial tumor volume was associated with development of nonserviceable hearing in a univariable setting (HR for 1-cm3 increase: 1.36, P = .040) but not after adjusting for PTA and WRS. Tumor growth was not significantly associated with time to nonserviceable hearing (HR, 1.57; P = .14), although estimated rates of maintaining serviceable hearing during observation were poorer in the group that experienced growth. CONCLUSION: Larger initial VS tumor volume was associated with poorer hearing at baseline. Larger initial tumor volume was also associated with the development of nonserviceable hearing during observation in a univariable setting; however, this association was not statistically significant after adjusting for baseline hearing status.


Assuntos
Perda Auditiva/etiologia , Neuroma Acústico/complicações , Neuroma Acústico/patologia , Carga Tumoral , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
3.
Otol Neurotol ; 40(9): 1224-1229, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31469794

RESUMO

OBJECTIVE: Previous research has shown that tumor growth during observation of small-to-medium sized sporadic vestibular schwannomas (VSs) occurs almost exclusively within 3 to 5 years following diagnosis. This has led some to consider ending surveillance after this interval. This study seeks to characterize a cohort of patients with tumors that exhibited late growth. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: Adults with sporadic VSs who initially elected observation with serial magnetic resonance imaging (MRI) surveillance. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Linear tumor growth was measured in accordance with AAO-HNS reporting guidelines. Delayed growth was defined as growth ≥2 mm in linear diameter that was first detected 5 years or more from the initial MRI. RESULTS: From a total of 361 patients, 172 experienced tumor growth during the interval of observation. Fourteen of these 172 patients (8.1%) experienced late growth occurring at 5 years or beyond. Among patients with delayed growth, the fastest growth rate after extended quiescence was 1.33 mm/yr, and the longest delay before tumor growth detection was 11.1 years. Additional treatment was recommended for six (42.9%) of the patients with delayed growth. Of 68 tumors that remained in the IAC, 11 (16.2%) demonstrated delayed growth. Of 66 tumors that presented in the CPA, 2 (3.0%) demonstrated delayed growth. Initial size was larger for tumors demonstrating early growth compared with those with delayed growth. For tumors within the IAC, those with early growth had a significantly higher median growth rate than those with delayed growth (1.40 vs. 0.45 mm/yr, p < 0.001). CONCLUSIONS: Delayed growth encompassed 8.1% of growing VSs and 3.9% of all observed tumors. Patients with delayed growth exhibited slower growth rates compared with those who were diagnosed with growth early in their observation course. These findings support the need for lifelong surveillance of untreated VSs given the possibility of clinically significant delayed growth. Increasing the time interval between MRI studies after 5 years is a reasonable concession to balance practicalities of cost and convenience with risk of delayed of tumor growth.

4.
Otolaryngol Head Neck Surg ; 160(6): 1081-1086, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30717626

RESUMO

OBJECTIVES: Conflicting research exists surrounding the utility of aspirin to prevent tumor growth in the medical management of vestibular schwannoma (VS). Recent studies demonstrated no association between aspirin and VS growth using linear tumor measurements. Given the heightened sensitivity of volumetric analyses to monitor tumor growth, the current study was conceived with the chief objective of assessing the association between aspirin or other nonsteroidal anti-inflammatory drug (NSAID) use and VS growth using volumetric analyses. STUDY DESIGN: Retrospective review. SETTING: Tertiary referral center. SUBJECTS AND METHODS: A total of 361 patients totaling 1601 volumetrically analyzed magnetic resonance imaging studies who underwent initial observation since January 1, 2003. RESULTS: In total, 123 (35%) patients took 81 mg aspirin daily, 23 (7%) took 325 mg aspirin daily, and 41 (11%) reported other NSAID use. Among those taking aspirin, 112 (72%) exhibited volumetric tumor growth during observation compared to 33 (80%) among other NSAID users and 137 (67%) among nonaspirin users. Patients taking aspirin or other NSAIDs were significantly older at time of diagnosis (median, 66 vs 56 years; P < .001). Neither aspirin use (hazard ratio [HR], 0.96; P = .73) nor other NSAID use (HR, 1.39; P = .081) was significantly associated with a reduced risk of volumetric tumor growth. These results were similar following age adjustment ( P = .81 and .087, respectively). When separating aspirin users by 81-mg or 325-mg dosing, neither group exhibited a reduced risk of growth ( P = .95 and .73, respectively). CONCLUSION: Despite promising initial results, the preponderance of existing literature suggests that aspirin and other NSAID use does not prevent tumor growth in VS.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Neuroma Acústico/patologia , Carga Tumoral , Idoso , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroma Acústico/diagnóstico por imagem , Neuroma Acústico/tratamento farmacológico , Estudos Retrospectivos
5.
Otol Neurotol ; 39(8): e704-e711, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30036205

RESUMO

OBJECTIVE: To characterize the risk of progression to nonserviceable hearing in patients with sporadic vestibular schwannomas (VS) who elect initial observation. STUDY DESIGN: Retrospective case series. SETTING: Two tertiary care centers. PATIENTS: VS patients with serviceable hearing who underwent at least two audiograms and two MRI studies before intervention or loss to follow-up. MAIN OUTCOME MEASURE(S): Serviceable hearing, defined as the pure tone average ≤ 50 dB HL and word recognition score ≥ 50%. RESULTS: Four-hundred sixty-six patients (median age of 57 yr and median tumor diameter of 7.3 mm) had serviceable hearing at presentation and were followed for a median of 2.3 years (IQR 1.0 - 4.0). Kaplan-Meier estimated rates of maintaining serviceable hearing (95% CI; number still at risk) at 1, 3, 5, 7, and 10 years following diagnosis were 94% (91-96; 357), 77% (73-82; 172), 66% (60-73; 81), 56% (49-65; 31), and 44% (33-59; 10), respectively. Each 10-dB increase in pure-tone averages at diagnosis was associated with a 2-fold increased likelihood of developing nonserviceable hearing (hazard ratio 2.07; p < 0.001). Each 10% decrease in word recognition score was associated with a 1.5-fold increased likelihood of developing nonserviceable hearing (hazard ratio 1.48; p < 0.001). CONCLUSIONS: Among patients with sporadic VS, good baseline word recognition score and low pure-tone average are jointly associated with maintenance of serviceable hearing. These data may be used to guide patient counseling and optimize management.


Assuntos
Audição/fisiologia , Neuroma Acústico/fisiopatologia , Idoso , Tratamento Conservador , Progressão da Doença , Feminino , Testes Auditivos , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroma Acústico/diagnóstico por imagem , Neuroma Acústico/terapia , Estudos Retrospectivos , Resultado do Tratamento
6.
Otolaryngol Head Neck Surg ; 159(3): 535-542, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29685084

RESUMO

Objective (1) Assess 3-dimensional volumetric growth of untreated sporadic vestibular schwannomas (VSs) in a large cohort of patients treated with conservative observation. (2) Compare volumetric and conventional linear diameter measurements for detecting tumor growth. Study Design Case series with chart review. Setting Tertiary skull base referral center. Subjects and Methods Patients with sporadic VS who elected initial conservative treatment with at least 2 serial magnetic resonance imaging (MRI) scans were included. Tumor volume was determined with 3-dimensional segmentation of MRI sequences. The volumetric threshold for tumor growth was an increase ≥20% from baseline tumor volume. Tumor size based on linear diameter was assessed with the 1995 American Academy of Otolaryngology-Head and Neck Surgery Foundation guidelines for VS outcome reporting, with growth defined as an increase ≥2 mm. Results A total of 361 patients were included with a median radiologic follow-up of 4.1 years (interquartile range [IQR], 2.5-6.8). At diagnosis, 232 VSs (64%) were purely intracanalicular, and 129 (36%) extended into the cerebellopontine angle. The median baseline tumor volume was 0.161 cm3 (IQR, 0.054-0.418). Overall, 69% of tumors demonstrated volumetric growth at a median of 1.1 years (IQR, 0.6-2.1) after initial MRI. In contrast, based on linear measurement assessment, 48% of tumors demonstrated growth at a median of 1.8 years (IQR, 0.8-3.1) from first MRI scan. Disequilibrium, facial hypoesthesia, aural fullness, initial tumor size, and nonincidental diagnosis were associated with tumor growth. Conclusion Three-dimensional volumetric assessment of VS provides a more sensitive measure of tumor growth when compared with linear diameter assessment. Through volumetric analysis, the current study revealed that a significant proportion of VSs demonstrate growth during observation.


Assuntos
Imageamento Tridimensional , Imagem por Ressonância Magnética/métodos , Neuroma Acústico/diagnóstico por imagem , Neuroma Acústico/fisiopatologia , Carga Tumoral/fisiologia , Conduta Expectante/métodos , Centros Médicos Acadêmicos , Adulto , Idoso , Estudos de Coortes , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neuroma Acústico/mortalidade , Neuroma Acústico/terapia , Prognóstico , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
7.
Laryngoscope ; 128(4): 864-870, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28833165

RESUMO

OBJECTIVE: To determine if the laterality of primary tumors in patients with olfactory neuroblastoma (ONB) influenced the pattern and development of neck disease. METHODS: Using a retrospective cohort study design from 1994 to 2015, the primary tumors of patients who either presented with or developed neck disease were volumetrically analyzed using iPlan software (version 3.0.0, BrainLAB, Feldkirchen, Germany) by two independent observers. Agreement of volume-derived sidedness was assessed with a kappa statistic, whereas agreement in volume-derived degree of tumor laterality was evaluated with an intraclass correlation coefficient. A one-sample t test was used to assess the difference in dominant percentage between the two observers. RESULTS: Sixty-one patients with histological diagnosis and treatment of ONB at our institution were identified. Twenty-four patients exhibited neck involvement, 13 of whom could be volumetrically analyzed. Tumors that were greater than 75% eccentric to one side all exhibited contralateral disease, whereas the majority of unilateral neck disease was associated with relatively midline masses. Within the entire cohort, ipsilateral level 2 lymph nodes displayed the highest involvement (83%, 20 of 24), followed by ipsilateral level 1 (54%, 13 of 24), contralateral level 2 (46%, 11 of 24), contralateral level 1 (21%, 5 of 24), and ipsilateral level 3 (21%, 5 of 24). CONCLUSION: Ipsilateral neck involvement frequently was observed; however, the degree of ONB primary site laterality did not appear to have implications on the development of contralateral neck disease. Therefore, when considering elective therapy to the neck, ONB laterality should not be used to justify unilateral neck treatment. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:864-870, 2018.


Assuntos
Estesioneuroblastoma Olfatório/diagnóstico , Linfonodos/patologia , Estadiamento de Neoplasias , Neoplasias Nasais/diagnóstico , Base do Crânio/diagnóstico por imagem , Carga Tumoral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Terapia Combinada , Estesioneuroblastoma Olfatório/secundário , Estesioneuroblastoma Olfatório/terapia , Feminino , Seguimentos , Humanos , Metástase Linfática , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Cavidade Nasal , Pescoço , Neoplasias Nasais/terapia , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
8.
Otolaryngol Head Neck Surg ; 156(4): 616-621, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28116973

RESUMO

Objective Human adipose-derived mesenchymal stem cells (ADSCs) were used to rehabilitate bone damaged by osteoradionecrosis (ORN) in an established animal model. Study Design Prospective animal study. Setting Academic department laboratory. Subjects and Methods After institutional review board and Institutional Animal Care and Use Committee approval, 24 athymic nude rats were divided into 5 groups: 4 groups irradiated (20 Gy) by brachytherapy catheter placed at the left hemimandible and 1 mock irradiation control (n = 4). For all groups, ORN was initiated by extraction of the central molar 1 week later. After 28 days, animals (n = 5/group) received injection at the extraction site with saline (SAL), ADSCs, platelet-rich plasma and collagen (PRP/COL), or ADSCs + PRP/COL. Rats were sacrificed 28 days later and their mandibles harvested for histopathology analysis (osteoblasts, osteoclasts, and fibrosis) and bone volume measurement using 3-dimensional micro-computed tomography. Results All but 1 rat survived the experiment period (23/24). Radiographic and histological analysis revealed 60% bone loss in the SAL group compared with the nonirradiated control. Injection of ADSCs increased jaw region bone volume by up to 36% ( P < .01). All experimental groups (ADSC, PRP/COL, and ADSC + PRP/COL) showed dramatically decreased osteoclast counts ( P < .001) while injection of PRP/COL with or without ADSCs increased osteoblasts. Increased fibrosis was observed after ADSC injection ( P < .05). Conclusion The application of human ADSCs to an induced mandibular osteoradionecrosis model in athymic rats results in increased deposition or preservation of bone, demonstrated both histologically and radiographically. This offers an encouraging possible treatment option for translational research in this difficult disease.


Assuntos
Doenças Mandibulares/terapia , Transplante de Células-Tronco Mesenquimais , Osteorradionecrose/terapia , Animais , Braquiterapia , Contagem de Células , Colágeno , Terapia Combinada , Modelos Animais de Doenças , Humanos , Mandíbula/patologia , Mandíbula/efeitos da radiação , Doenças Mandibulares/patologia , Osteoblastos , Osteoclastos , Osteorradionecrose/patologia , Plasma Rico em Plaquetas , Estudos Prospectivos , Lesões Experimentais por Radiação , Ratos Nus
9.
Otol Neurotol ; 37(9): 1435-41, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27576094

RESUMO

BACKGROUND: The clinical behavior of asymptomatic incidentally diagnosed vestibular schwannoma (VS) remains undefined. Specifically, it is unknown whether these tumors represent a more indolent biological variant. Such information would be beneficial toward patient counseling regarding treatment strategy and surveillance intervals during observation. STUDY DESIGN: Case series with matched cohort. SETTING: Single tertiary academic referral center. PATIENTS: All patients with asymptomatic incidentally diagnosed VS who were evaluated between January 2000 and December 2015 were analyzed. Only cases where imaging was obtained for unrelated indications in patients with symmetrical or normal hearing and lack of any attributable symptoms were included. A separate VS reference cohort composed of patients with typical symptomatology, matched according to tumor size, age and sex, was used for comparison. MAIN OUTCOME MEASURES: Growth, symptom progression, treatment. RESULTS: A total of 38 incidental VS were evaluated, representing approximately 1.6% of all VS evaluated during this time. There was a statistically significant increase in the rate of incidental tumor diagnosis over time. Estimated survival free of tumor growth or treatment (95% CI; number still at risk) at 1, 3, and 5 years after diagnosis was 89% (77-100; 22), 74% (57-95; 13), and 54% (35-84; 4), respectively. The median growth rate for the 11 patients with tumor growth was 1.3 mm/year. Time to growth or treatment (p = 0.18), growth rate (p = 0.60), and rate of audiometric decline was not statistically significantly different between incidentally discovered and symptomatic reference groups. CONCLUSION: The frequency of asymptomatic, incidentally diagnosed VS is rising. These data demonstrate that the clinical behavior of asymptomatic incidental VS is not different than that of age-, sex-, and size-matched symptomatic VS. Thus, if initial observation is undertaken, patients with asymptomatic incidental tumors still require long-term magnetic resonance imaging surveillance performed at regular time intervals.


Assuntos
Achados Incidentais , Neuroma Acústico/patologia , Adulto , Idoso , Audiometria , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
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