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2.
Sci Rep ; 14(1): 12870, 2024 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834632

RESUMO

One of the most recent advances in the genome editing field has been the addition of "TALE Base Editors", an innovative platform for cell therapy that relies on the deamination of cytidines within double strand DNA, leading to the formation of an uracil (U) intermediate. These molecular tools are fusions of transcription activator-like effector domains (TALE) for specific DNA sequence binding, split-DddA deaminase halves that will, upon catalytic domain reconstitution, initiate the conversion of a cytosine (C) to a thymine (T), and an uracil glycosylase inhibitor (UGI). We developed a high throughput screening strategy capable to probe key editing parameters in a precisely defined genomic context in cellulo, excluding or minimizing biases arising from different microenvironmental and/or epigenetic contexts. Here we aimed to further explore how target composition and TALEB architecture will impact the editing outcomes. We demonstrated how the nature of the linker between TALE array and split DddAtox head allows us to fine tune the editing window, also controlling possible bystander activity. Furthermore, we showed that both the TALEB architecture and spacer length separating the two TALE DNA binding regions impact the target TC editing dependence by the surrounding bases, leading to more restrictive or permissive editing profiles.


Assuntos
Citosina , Edição de Genes , Timina , Edição de Genes/métodos , Humanos , Citosina/metabolismo , Citosina/química , Timina/metabolismo , Timina/química , Efetores Semelhantes a Ativadores de Transcrição/metabolismo , Efetores Semelhantes a Ativadores de Transcrição/genética , DNA/metabolismo , DNA/genética , Células HEK293
3.
Nat Commun ; 15(1): 4965, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862518

RESUMO

Sickle cell disease is a devastating blood disorder that originates from a single point mutation in the HBB gene coding for hemoglobin. Here, we develop a GMP-compatible TALEN-mediated gene editing process enabling efficient HBB correction via a DNA repair template while minimizing risks associated with HBB inactivation. Comparing viral versus non-viral DNA repair template delivery in hematopoietic stem and progenitor cells in vitro, both strategies achieve comparable HBB correction and result in over 50% expression of normal adult hemoglobin in red blood cells without inducing ß-thalassemic phenotype. In an immunodeficient female mouse model, transplanted cells edited with the non-viral strategy exhibit higher engraftment and gene correction levels compared to those edited with the viral strategy. Transcriptomic analysis reveals that non-viral DNA repair template delivery mitigates P53-mediated toxicity and preserves high levels of long-term hematopoietic stem cells. This work paves the way for TALEN-based autologous gene therapy for sickle cell disease.


Assuntos
Anemia Falciforme , Edição de Genes , Terapia Genética , Células-Tronco Hematopoéticas , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição , Anemia Falciforme/terapia , Anemia Falciforme/genética , Edição de Genes/métodos , Animais , Células-Tronco Hematopoéticas/metabolismo , Humanos , Feminino , Camundongos , Terapia Genética/métodos , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição/metabolismo , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição/genética , Transplante de Células-Tronco Hematopoéticas , Globinas beta/genética , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Reparo do DNA , Mutação , Talassemia beta/terapia , Talassemia beta/genética , Modelos Animais de Doenças , Técnicas de Transferência de Genes
4.
Otol Neurotol ; 45(5): e363-e365, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38626773

RESUMO

OBJECTIVE: To analyze the effect of visual abstracts versus automated tweets on social media participation in Otology & Neurotology . PATIENTS: N/A. INTERVENTIONS: Introduction of visual abstracts developed by the social media editorial team to established automated tweets created by the dlvr.it computer program on the Otology & Neurotology Twitter account. MAIN OUTCOME MEASURES: Twitter analytics including the number of new followers per month, impressions per tweet, and engagements per tweet. The Kruskal-Wallis analysis of variance test was used to compare means. RESULTS: From October 2016 to October 2017 (average of 20 new followers per month), 101 automated tweets averaged 536 impressions and 16 engagements per tweet. The visual abstract was introduced in November 2017. From November 2017 to November 2020 (average of 39 new followers per month), 447 automated tweets averaged 747 impressions and 22 engagements per tweet, whereas 157 visual abstracts averaged 1977 impressions and 78 engagements per tweet. Automated tweets were discontinued in December 2020. From December 2020 to December 2022 (average of 44 new followers per month), 95 visual abstracts averaged 1893 impressions and 103 engagements per tweet. With the introduction of the visual abstract, the average number of followers, impressions per tweet, and engagements per tweet significantly increased (all p -values <0.01; all large effect sizes of 0.16, 0.47, and 0.47, respectively). CONCLUSIONS: Visual abstracts created by a social media editorial team have a positive impact on social media participation in the field of otology and neurotology. The impact is greater than that of social media content generated by Twitter automation tools.


Assuntos
Neuro-Otologia , Otolaringologia , Mídias Sociais , Humanos , Indexação e Redação de Resumos
5.
Am J Otolaryngol ; 45(4): 104320, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38677151

RESUMO

PURPOSE: Determine whether adult cochlear implant users with radiographic superior semicircular canal dehiscence experience clinically significant differences in audiological outcomes when compared to cochlear implant users with normal temporal bone anatomy. MATERIALS AND METHODS: Retrospective, single institution review. Adult, post-lingual deaf patients implanted between 2010 and 2020. Inclusion criteria included age 18 years or older, available preoperative computed tomography imaging, and preoperative and postoperative AzBio audiological data for at least 6 months of cochlear implant use. Preoperative and postoperative AzBio Sentence Test scores were compared between patients with normal temporal bone anatomy and those with radiographic superior semicircular canal dehiscence or near dehiscence. RESULTS: 110 patients met inclusion criteria. Mean AzBio score for normal temporal bone anatomy group improved from 35.2 % (SD 28.2) preoperatively to 70.3 % (SD 25.7) postoperatively, an improvement of 35.1 % (SD 28.6). Mean AzBio score for near dehiscent temporal bone anatomy group improved from 26.6 % (SD 28.9) preoperatively to 64.5 % (SD 30.6) postoperatively, an improvement of 37.9 % (SD 27.9). Mean AzBio score for dehiscent temporal bone anatomy group improved from 26.3 % (SD 20.4) preoperatively to 65.1 % (SD 27.6) postoperatively, an improvement of 38.7 % (SD 26.9). Utilizing the one-way analysis of variance test, there was no significant difference in audiologic outcomes between the three groups. CONCLUSIONS: Patients with complete or near complete radiographic superior canal dehiscence at the time of cochlear implantation achieve similar improvements in speech perception scores compared to normal anatomy adult cochlear implant users.


Assuntos
Implante Coclear , Implantes Cocleares , Deiscência do Canal Semicircular , Osso Temporal , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Implante Coclear/métodos , Adulto , Idoso , Deiscência do Canal Semicircular/cirurgia , Resultado do Tratamento , Osso Temporal/diagnóstico por imagem , Osso Temporal/cirurgia , Canais Semicirculares/cirurgia , Canais Semicirculares/diagnóstico por imagem , Surdez/cirurgia , Surdez/diagnóstico por imagem
6.
OTO Open ; 8(1): e105, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38259521

RESUMO

Objective: To review new drugs and devices relevant to otolaryngology approved by the Food and Drug Administration (FDA) in 2022. Data Sources: Publicly available FDA data on drugs and devices approved in 2022. Review Methods: A preliminary screen was conducted to identify drugs and devices relevant to otolaryngology. A secondary screen by members of the American Academy of Otolaryngology-Head and Neck Surgery's (AAO-HNS) Medical Devices and Drugs Committee differentiated between minor updates and new approvals. The final list of drugs and devices was sent to members of each subspecialty for review and analysis. Conclusion: A total of 1251 devices and 37 drugs were identified on preliminary screening. Of these, 329 devices and 5 drugs were sent to subspecialists for further review, from which 37 devices and 2 novel drugs were selected for further analysis. The newly approved devices spanned all subspecialties within otolaryngology. Many of the newly approved devices aimed to enhance patient experience, including over-the-counter hearing aids, sleep monitoring devices, and refined CPAP devices. Other advances aimed to improve surgical access, convenience, or comfort in the operating room and clinic. Implications for Practice: Many new devices and drugs are approved each year to improve patient care and care delivery. By staying up to date with these advances, otolaryngologists can leverage new innovations to improve the safety and quality of care. Given the recent approval of these devices, further studies are needed to assess long-term impact within the field of otolaryngology.

7.
J Laryngol Otol ; 138(3): 258-264, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37203445

RESUMO

OBJECTIVE: To investigate the effect of body mass index on hearing outcomes, operative time and complication rates following stapes surgery. METHOD: This is a five-year retrospective review of 402 charts from a single tertiary otology referral centre from 2015 to 2020. RESULTS: When the patient's shoulder was adjacent to the surgeon's dominant hand, the average operative time of 40 minutes increased to 70 minutes because of a significant positive association between higher body mass index and longer operative times (normal body mass index group (<25 kg/m2) r = 0.273, p = 0.032; overweight body mass index group (25-30 kg/m2) r = 0.265, p = 0.019). Operative times were not significantly longer upon comparison of low and high body mass index groups without stratification by laterality (54.9 ± 19.6 minutes vs 57.8 ± 19.2 minutes, p = 0.127). CONCLUSION: There is a clinically significant relationship between body mass index and operating times. This may be due to access limitations imposed by shoulder size.


Assuntos
Otosclerose , Cirurgia do Estribo , Humanos , Ombro , Otosclerose/cirurgia , Audição , Testes Auditivos , Estudos Retrospectivos , Resultado do Tratamento , Estribo
8.
J Otol ; 18(4): 230-234, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37877067

RESUMO

Purpose: To construct a symptoms-based prediction tool to assess the likelihood of superior canal dehiscence (SSCD) on high-resolution CT. Materials and methods: Mathematical modeling was employed to predict radiologic evidence of SSCD at a tertiary neurotology referral center. Results: A total of 168 patients were included, of which 118 had imaging-confirmed SSCD. On univariate analysis significant predictors of SSCD presence were: sound/pressure-induced vertigo (p = 0.006), disequilibrium (p = 0.008), hyperacusis (p = 0.008), and autophony (p = 0.034). Multivariate analysis enabled a 14-point symptom-weighted tool to be developed, wherein a score of ≥6 raised the suspicion of SSCD (≥70% likelihood of being present), R2 = 0.853. Conclusions: The likelihood of SSCD on CT scan can be determined with a high degree of certainty based on symptoms recorded at presentation. Using the evidenced-based diagnostic tool validated herein, a score ≥6 with any symptom combination justifies ordering a CT scan.

9.
Curr Opin Otolaryngol Head Neck Surg ; 31(5): 325-331, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37266594

RESUMO

PURPOSE OF REVIEW: Meniere's disease is caused by hydropic changes in the endolymphatic system, and manifests as a collection of vertigo, hearing loss, tinnitus, and aural fullness. Although high-quality clinical practice guidelines exist for the diagnosis and initial management of Meniere's disease, there is no strong consensus for treatment of medically refractory Meniere's disease. This review summarizes treatment options and highlights controversies surrounding surgical treatment of Meniere's disease. RECENT FINDINGS: Intratympanic steroid and intratympanic gentamicin injections continue to be widely used as in-office therapies in medically refractory Meniere's disease. Despite historical controversy surrounding the use of endolymphatic sac (ELS) surgery, the use of ELS decompression has been widely adopted by the international neurotologic community due to high vertigo control rate, coupled with low risk of audiovestibular loss. Wider decompression of the sac and surgical manipulation of the endolymphatic duct may impact outcome and are the subject of discussion. An emerging surgical technique called Triple Semicircular Canal Occlusion (TSCO) holds promise as a partially ablative procedure with high vertigo control rate in Meniere's disease. Cochlear implants may be placed in active Meniere's disease patients, or during an ablative surgery such as labyrinthectomy. SUMMARY: For the medically refractory Meniere's disease patient, treatment options include intratympanic steroid injection, endolymphatic sac decompression, medical or surgical labyrinthectomy, and vestibular nerve section. TSCO holds promise as an emerging partially ablative procedure. Cochlear implants maintain an important role in the rehabilitation of hearing loss associated with Meniere's disease.


Assuntos
Surdez , Orelha Interna , Perda Auditiva , Doença de Meniere , Humanos , Doença de Meniere/diagnóstico , Doença de Meniere/cirurgia , Doença de Meniere/complicações , Vertigem/tratamento farmacológico , Vertigem/etiologia , Gentamicinas/uso terapêutico , Perda Auditiva/complicações
10.
World Neurosurg ; 178: e24-e33, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37268187

RESUMO

OBJECTIVE: Stereotactic radiosurgery (SRS) is a well-established treatment for vestibular schwannomas (VS). Hearing loss remains a main morbidity of VS and its treatments, including SRS. The effects of radiation parameters of SRS on hearing remain unknown. The goal of this study is to determine the effect of tumor volume, patient demographics, pretreatment hearing status, cochlear radiation dose, total tumor radiation dose, fractionation, and other radiotherapy parameters on hearing deterioration. METHODS: Multicenter retrospective analysis of 611 patients who underwent SRS for VS from 1990-2020 and had pre- and post-treatment audiograms. RESULTS: Pure tone averages (PTAs) increased and word recognition scores (WRSs) decreased in treated ears at 12-60 months while remaining stable in untreated ears. Higher baseline PTA, higher tumor radiation dose, higher maximum cochlear dose, and usage of single fraction resulted in higher post radiation PTA; WRS was only predicted by baseline WRS and age. Higher baseline PTA, single fraction treatment, higher tumor radiation dose, and higher maximum cochlear dose resulted in a faster deterioration in PTA. Below a maximum cochlear dose of 3 Gy, there were no statistically significant changes in PTA or WRS. CONCLUSIONS: Decline of hearing at one year in VS patients after SRS is directly related to maximum cochlear dose, single versus 3-fraction treatment, total tumor radiation dose, and baseline hearing level. The maximum safe cochlear dose for hearingtbrowd preservation at one year is 3 Gy, and the use of 3 fractions instead of one fraction was better at preserving hearing.


Assuntos
Neuroma Acústico , Radiocirurgia , Humanos , Neuroma Acústico/radioterapia , Neuroma Acústico/cirurgia , Estudos Retrospectivos , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Seguimentos , Audição , Resultado do Tratamento
11.
Otolaryngol Head Neck Surg ; 169(2): 358-366, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36939583

RESUMO

OBJECTIVE: Audiometric outcomes at 12 months following simultaneous translabyrinthine (TL) resection of vestibular schwannoma (VS) and cochlear implantation (CI). STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center. METHODS: Adult patients undergoing TL resection of sporadic, unilateral VS ≤ 2 cm were prospectively enrolled. Preoperative testing included binaural AZBio in noise and quiet and unilateral Consonant-Nucleus-Consonant (CNC). Tinnitus Handicap Index (THI) and Speech, Spatial, and Qualities of Hearing (SSQ) questionnaires were also completed. Patients underwent TL resection with simultaneous CI. The preoperative test battery was repeated at 1, 3, 6, and 12 months after activation. Statistical analysis was performed to characterize short-term outcomes (preoperative to 3 months), longer-term outcomes (3-12 months), and overall changes during the preoperative to 12-month period. RESULTS: AZBio, CNC, and THI improved at 3 months with no significant changes thereafter and showed durable improvement at 12 months compared to preoperative testing. While SSQ did not improve at 12 months, a subset of patients showed either recovery or improvement of SSQ-spatial subscores. Patients with cerebellopontine angle tumors had poorer performance, although the impact of tumor size and location could not be deduced based on the small sample size. CONCLUSION: Patients undergoing simultaneous CI and TL resection of VS had durable improvements in speech perception and tinnitus severity 12 months following surgery. Subjective improvements in localization were not observed. Additional studies are needed to determine which VS patients are optimal candidates for CI.


Assuntos
Implante Coclear , Implantes Cocleares , Perda Auditiva Unilateral , Neuroma Acústico , Percepção da Fala , Zumbido , Adulto , Humanos , Zumbido/etiologia , Zumbido/cirurgia , Estudos Prospectivos , Audição , Perda Auditiva Unilateral/cirurgia , Neuroma Acústico/complicações , Neuroma Acústico/cirurgia , Percepção da Fala/fisiologia , Resultado do Tratamento
12.
Cochlear Implants Int ; 24(6): 325-334, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-36927486

RESUMO

OBJECTIVES: To assess an evidence-based model (EBM) approach to cochlear implant (CI) aftercare that includes a modified, reduced treatment schedule for newly-implanted adult CI recipients consisting of four appointments (initial activation, 1-, 3- and 6- months postactivation) in the first year post-surgery. METHOD: This prospective multicenter proof-of-concept study was conducted across three clinics in the United States by five experienced CI clinicians. Seventeen newly-implanted adult patients with postlingual hearing loss enrolled in the study. Hearing outcomes were measured using objective speech testing and subjective self-report measures. RESULTS: Most recipients (14/17; 82%) were able to follow the four-appointment EBM schedule. The reduced number of visits translated into an average time savings of 3 hours per patient. Significant improvements in speech perception were observed at both 3- and 6-months postactivation, as measured by CNC words in quiet and AzBio sentences at +10 dB SNR, consistent with published results achieved by traditional practices. Recipients were significantly satisfied with telephone, music, small group conversation, and television listening at 6 months postactivation. Recipient satisfaction with overall service was rated as "excellent" by 14/14 (100%) respondents. CONCLUSION: The four-appointment EBM approach delivered efficient and effective audiological aftercare to CI recipients in the first year following CI implantation.


Assuntos
Implante Coclear , Implantes Cocleares , Percepção da Fala , Adulto , Humanos , Estados Unidos , Implante Coclear/métodos , Assistência ao Convalescente , Estudos Prospectivos , Audição , Percepção da Fala/fisiologia , Resultado do Tratamento
13.
Front Bioeng Biotechnol ; 10: 1033669, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36440442

RESUMO

TALE base editors are a recent addition to the genome editing toolbox. These molecular tools are fusions of a transcription activator-like effector domain (TALE), split-DddA deaminase halves, and an uracil glycosylase inhibitor (UGI) that have the distinct ability to directly edit double strand DNA, converting a cytosine (C) to a thymine (T). To dissect the editing rules of TALE-BE, we combined the screening of dozens of TALE-BE targeting nuclear genomic loci with a medium/high throughput strategy based on precise knock-in of TALE-BE target site collections into the cell genome. This latter approach allowed us to gain in depth insight of the editing rules in cellulo, while excluding confounding factors such as epigenetic and microenvironmental differences among different genomic loci. Using the knowledge gained, we designed TALE-BE targeting CD52 and achieved very high frequency of gene knock-out (up to 80% of phenotypic CD52 knock out). We further demonstrated that TALE-BE generate only insignificant levels of Indels and byproducts. Finally, we combined two molecular tools, a TALE-BE and a TALEN, for multiplex genome engineering, generating high levels of double gene knock-out (∼75%) without creation of translocations between the two targeted sites.

14.
OTO Open ; 6(3): 2473974X221126495, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36171808

RESUMO

Objective: To evaluate new medical devices and drugs pertinent to otolaryngology-head and neck surgery that were approved by the Food and Drug Administration (FDA) in 2021. Data Sources: Publicly available FDA device and drug approvals from ENT (ear, nose, and throat), anesthesia, neurosurgery, plastic surgery, and general surgery FDA committees. Review Methods: FDA device and therapeutic approvals were identified and reviewed by members of the American Academy of Otolaryngology-Head and Neck Surgery's Medical Devices and Drugs Committee. Two independent reviewers assessed the relevance of devices and drugs to otolaryngologists. Medical devices and drugs were then allocated to their respective subspecialty fields for critical review based on available scientific literature. Conclusions: The Medical Devices and Drugs Committee reviewed 1153 devices and 52 novel drugs that received FDA approval in 2021 (67 ENT, 106 anesthesia, 618 general surgery and plastic surgery, 362 neurosurgery). Twenty-three devices and 1 therapeutic agent relevant to otolaryngology were included in the state of the art review. Advances spanned all subspecialties, including over-the-counter hearing aid options in otology, expanding treatment options for rhinitis in rhinology, innovative laser-safe endotracheal tubes in laryngology, novel facial rejuvenation and implant technology in facial plastic surgery, and advances in noninvasive and surgical treatment options for obstructive sleep apnea. Implications for Practice: FDA approvals for new technology and pharmaceuticals present new opportunities across subspecialties in otolaryngology. Clinicians' nuanced understanding of the safety, advantages, and limitations of these innovations ensures ongoing progress in patient care.

15.
16.
Otol Neurotol ; 43(4): e399-e407, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35213474

RESUMO

OBJECTIVE: Assess opinions that influence treatment choice for single sided deafness (SSD). STUDY DESIGN: Retrospective chart review. SETTING: Tertiary neurotology referral center. PATIENTS: Patients with SSD were recruited between December 2020 and February 2021. Included patients were self-selected by voluntary completion of the study questionnaire. MAIN OUTCOME MEASURES: Tinnitus Handicap Inventory (THI), Hearing Handicap Inventory for Adults (HHIA), and a questionnaire containing 25 areas of inquiry relevant to management strategy decision making. RESULTS: In comparison to the surgical management group, patients opting for nonsurgical amplification were significantly more concerned about device visibility (p = 0.005, 1.32 ±â€Š0.22 versus 2.67 ±â€Š0.37), undergoing surgery (p = 0.017, 1.64 ±â€Š0.23 versus 2.89 ±â€Š0.51), and the thought of harboring an implanted device (p = 0.003, 1.46 ±â€Š0.22 versus 2.82 ±â€Š0.35). Patients with a major hearing handicap (grade 2-4) placed significantly less emphasis on out-of-pocket costs (p = 0.049, 2.38 ±â€Š0.17 versus 2.94 ±â€Š0.21) and were less concerned about experiencing discomfort from the device (p = 0.033, 3.13 ±â€Š0.11 versus 3.56 ±â€Š0.16) or ease of device use (p = 0.040, 3.20 ±â€Š0.13 versus 3.63 ±â€Š0.13) when compared with the minor handicap group. CONCLUSIONS: Lingering concerns about device visibility, undergoing surgery, and harboring an implanted device underscore the need for thorough patient counseling during SSD device selection consultations. These efforts should aim to address esthetic and surgical risk concerns while emphasizing the potential for improvements in quality of life.


Assuntos
Surdez , Perda Auditiva Unilateral , Adulto , Atitude , Surdez/cirurgia , Perda Auditiva Unilateral/cirurgia , Humanos , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
17.
Otolaryngol Head Neck Surg ; 166(1): 48-59, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33945752

RESUMO

OBJECTIVE: To perform a systematic review to investigate common otologic manifestations of Langerhans cell histiocytosis, the incidence of these findings, methods for diagnosis, as well as medical and surgical management. DATA SOURCES: PubMed/MEDLINE, Embase, and Cochrane Library. REVIEW METHODS: A search of PubMed/MEDLINE, Embase, and Cochrane Library for all articles published between 1963 to 2020 was performed with variations and combinations of the following search terms: Langerhans cell histiocytosis, eosinophilic granuloma, Letterer-Siwe, Hand-Schüller-Christian, otitis, otologic, ear. A review of the references of all included articles was also conducted. RESULTS: Sixty-two articles encompassing 631 patients met inclusion criteria. Otologic symptoms at presentation were found in 246 (39%) patients in the reported studies with 48% reporting bilaterality. The mean age was 14.8 years with a male predominance (64%). The most common otologic presenting symptom was otorrhea (46%). A majority had the multisystem variant (52%). The most common treatment modalities were chemotherapy (52%), followed by surgery (50%), systemic steroids (45%), and radiotherapy (31%). Surgery was performed in 75.8% with unisystem involvement and in 50.6% with multisystem involvement. The most effective treatments included radiotherapy (56% success rate, 17% of treated patients), systemic steroids (44% success, 20% treated), chemotherapy (41% success, 21% treated), and surgical modalities (36% success, 19% treated). CONCLUSIONS: Otologic manifestations that occur with the multisystem variant or are at high risk for central nervous system involvement necessitate systemic treatment. For unifocal lesions, surgery is recommended. Lastly, radiotherapy should be reserved for extensive lesions involving vital structures or presenting in older patients.


Assuntos
Otopatias/diagnóstico , Otopatias/epidemiologia , Histiocitose de Células de Langerhans/complicações , Otopatias/terapia , Feminino , Histiocitose de Células de Langerhans/diagnóstico , Histiocitose de Células de Langerhans/terapia , Humanos , Incidência , Masculino , Prognóstico
18.
Laryngoscope ; 132(3): 662-667, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34633085

RESUMO

OBJECTIVES: Venous thromboembolism (VTE) is a major cause of morbidity and mortality for surgical patients. This article aims to determine factors that may have contributed to the development of VTE in patients undergoing lateral skull base surgery, to assess the validity of the Caprini Risk Assessment Model (RAM) score in this subset of patients, and to determine the efficacy of mechanical DVT prophylaxis alone in preventing VTE. STUDY DESIGN: Retrospective chart review. METHODS: A retrospective chart review was conducted of patients who underwent skull base surgery for vestibular schwannoma, and the rate of VTE was assessed. Patient demographics, comorbidities, and treatment factors were examined to determine risk factors associated with the development of a postoperative thrombotic event. Caprini RAM scores were compared for patients who developed a VTE. RESULTS: Among 197 patients, the rate of VTE formation was 3.5%. No individual risk factor independently contributed to the development of a thrombotic event. The mean Caprini RAM score was 4.06 in patients who did not develop a VTE and 5.14 in the patients that did develop a VTE (P = .005). The Caprini score was significant for the risk of VTE formation, with an odds ratio of 2.8 (P = .009, 95% CI = 1.3-6.2). CONCLUSION: Venous thromboembolism rates are relatively low following lateral skull base surgery. While there is no individual risk factor associated with increased VTE risk, the Caprini RAM score appears to be a useful predictor of risk. The Caprini score may be useful in identifying high-risk patients who may benefit from chemoprophylaxis for VTE prevention. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:662-667, 2022.


Assuntos
Base do Crânio/cirurgia , Tromboembolia Venosa/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Craniotomia/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuroma Acústico/cirurgia , Estudos Retrospectivos , Fatores de Risco , Tromboembolia Venosa/epidemiologia , Adulto Jovem
19.
OTO Open ; 5(4): 2473974X211057035, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790883

RESUMO

OBJECTIVES: To evaluate new drugs and devices relevant to otolaryngology-head and neck surgery that were approved by the US Food and Drug Administration (FDA) in 2020. DATA SOURCES: Publicly available device and therapeutic approvals from ENT (ear, nose, and throat), anesthesia, neurology (neurosurgery), and plastic and general surgery FDA committees. REVIEW METHODS: Members of the American Academy of Otolaryngology-Head and Neck Surgery's Medical Devices and Drugs Committee reviewed new therapeutics and medical devices from a query of the FDA's device and therapeutic approvals. Two independent reviewers assessed the drug's or device's relevance to otolaryngology, classified to subspecialty field, with a critical review of available scientific literature. CONCLUSIONS: The Medical Devices and Drugs Committee reviewed 53 new therapeutics and 1094 devices (89 ENT, 140 anesthesia, 511 plastic and general surgery, and 354 neurology) approved in 2020. Ten drugs and 17 devices were considered relevant to the otolaryngology community. Rhinology saw significant improvements around image guidance systems; indications for cochlear implantation expanded; several new monoclonal therapeutics were added to head and neck oncology's armamentarium; and several new approvals appeared for facial plastics surgery, pediatric otolaryngology, and comprehensive otolaryngology. IMPLICATIONS FOR PRACTICE: New technologies and pharmaceuticals offer the promise of improving how we care for otolaryngology patients. However, judicious introduction of innovations into practice requires a nuanced understanding of safety, advantages, and limitations. Working knowledge of new drugs and medical devices approved for the market helps clinicians tailor patient care accordingly.

20.
Adv Radiat Oncol ; 6(6): 100759, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34585025

RESUMO

PURPOSE: To evaluate the safety of stereotactic body radiation therapy (SBRT) for prostate cancer in men with inflammatory bowel disease (IBD). METHODS AND MATERIALS: We queried a consortium database for patients with IBD receiving SBRT for prostate cancer between 2006 and 2012. Identified patients were matched with patients without a history of IBD in a 3:1 fashion based on dose, fractionation, use of androgen deprivation therapy, and age distribution. Logistic regression was used to evaluate the association between having IBD and experiencing acute and late gastrointestinal (GI) and genitourinary (GU) toxicities as scored on the Common Terminology Criteria for Adverse Events scale. Time to late toxicity was evaluated using proportional hazard Cox models. Our study was limited by absence of data on prostate size, baseline International Prostate Symptom Score, and rectal dose-volume histogram parameters. RESULTS: Thirty-nine patients with flare-free IBD at time of treatment (median follow-up 83.9 months) and 117 matched controls (median follow-up 88.7 months) were identified. A diagnosis of IBD was associated with increased odds of developing any late grade GI toxicity (odds ratio [OR] 6.11, P <.001) and GU toxicity (odds ratio 6.14, P < .001), but not odds of developing late grade ≥2 GI (P = .08) or GU toxicity (P = .069). Acute GI and GU toxicity, both overall and for grade ≥2 toxicities, were more frequent in men with IBD (P < .05). Time to late GI and GU toxicity of any grade was significantly shorter in patients with IBD (P < .001). Time to late grade ≥2 GU, but not grade ≥2 GI toxicity, was also shorter in patients with IBD (P = .044 for GU and P = .144 for GI). CONCLUSIONS: Patients with IBD who received SBRT for PCa had a higher likelihood of developing acute GI and GU toxicity, in addition to experiencing lower grade late toxicities that occurred earlier. However, patients with IBD did not have a higher likelihood for late grade ≥2 GI or GU toxicity after SBRT compared with the control cohort. Interpretation of this data are limited by the small sample size. Thus, men with IBD in remission should be properly counseled about these risks when considering SBRT.

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