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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.
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Implantación Coclear , Implantes Cocleares , Dehiscencia del Canal Semicircular , Hueso Temporal , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Implantación Coclear/métodos , Adulto , Anciano , Dehiscencia del Canal Semicircular/cirugía , Resultado del Tratamiento , Hueso Temporal/diagnóstico por imagen , Hueso Temporal/cirugía , Canales Semicirculares/cirugía , Canales Semicirculares/diagnóstico por imagen , Sordera/cirugía , Sordera/diagnóstico por imagenRESUMEN
BACKGROUND: Accurate identification of the tumor bed after breast-conserving surgery (BCS) ensures appropriate radiation to the tumor bed while minimizing normal tissue exposure. The BioZorb® three-dimensional (3D) bioabsorbable tissue marker provides a reliable target for radiation therapy (RT) planning and follow-up evaluation while serving as a scaffold to maintain breast contour. METHODS: After informed consent, 818 patients (826 breasts) implanted with the BioZorb® at 14 U.S. sites were enrolled in a national registry. All the patients were prospectively followed with the BioZorb® implant after BCS. The data collected at 3, 6, 12, and 24 months included all demographics, treatment parameters, and provider/patient-assessed cosmesis. RESULTS: The median follow-up period was 18.2 months (range, 0.2-53.4 months). The 30-day breast infection rate was 0.5 % of the patients (n = 4), and re-excision was performed for 8.1 % of the patients (n = 66), whereas 2.6 % of the patients (n = 21) underwent mastectomy. Two patients (0.2 %) had local recurrence. The patient-reported cosmetic outcomes at 6, 12, and 24 months were rated as good-to-excellent by 92.4 %, 90.6 %, and 87.3 % of the patients, respectively and similarly by the surgeons. The radiation oncologists reported planning of target volume (PTV) reduction for 46.2 % of the patients receiving radiation boost, with PTV reduction most commonly estimated at 30 %. CONCLUSIONS: This report describes the first large multicenter study of 818 patients implanted with the BioZorb® tissue marker during BCS. Radiation oncologists found that the device yielded reduced PTVs and that both the patients and the surgeons reported good-to-excellent long-term cosmetic outcomes, with low adverse effects. The BioZorb® 3D tissue marker is a safe adjunct to BCS and may add benefits for both surgeons and radiation oncologists.
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Neoplasias de la Mama , Implantes Absorbibles , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Humanos , Mastectomía , Mastectomía Segmentaria , Recurrencia Local de Neoplasia/radioterapia , Medición de Resultados Informados por el PacienteRESUMEN
PURPOSE: There have been multiple proposed etiologies of reparative granuloma following stapes surgery. In this report, we present the first case of post-stapedectomy reparative granuloma following the use of Biodesign (Cook Medical, Bloomington, IN) otologic graft material, an acellular matrix derived from porcine small intestinal submucosa, and review the literature of post-stapes surgery reparative granuloma. PATIENT: 50-year-old woman who developed a reparative granuloma following stapedotomy with acellular porcine intestinal submucosa presenting with profound hearing loss and vertigo. INTERVENTION: Middle ear exploration with excision of granuloma and revision stapedotomy. MAIN OUTCOME MEASURES: Audiologic outcomes as measured by pure-tone air and bone conduction thresholds and word recognition scores. Improvement in vertigo. MAIN FINDINGS: Surgical excision of the reparative granuloma with revision stapedotomy resolved vertigo. Hearing has improved progressively postoperatively. CONCLUSIONS: We report the first case of post-stapedotomy reparative granuloma following the use of acellular porcine intestinal submucosa. Although exact etiology cannot be determined from a single case report, this illustrates the need for careful use of novel foreign graft material. This case additionally confirms that removal of granuloma and inciting materials can salvage serviceable hearing.
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Granuloma/etiología , Mucosa Intestinal/trasplante , Intestino Delgado/trasplante , Complicaciones Posoperatorias/etiología , Cirugía del Estribo/efectos adversos , Cirugía del Estribo/métodos , Trasplante Heterólogo/efectos adversos , Animales , Femenino , Granuloma/cirugía , Pérdida Auditiva/etiología , Pérdida Auditiva/cirugía , Humanos , Persona de Mediana Edad , Complicaciones Posoperatorias/cirugía , Reoperación , Estribo , Porcinos , Resultado del Tratamiento , Vértigo/etiología , Vértigo/cirugíaRESUMEN
PURPOSE: To determine the utility of medical clearance exams by otolaryngologists prior to the distribution of hearing aids to patients with hearing loss. MATERIAL AND METHODS: Medical records of 313 consecutive hearing-impaired individuals seeking financial assistance for hearing aids from the Lions Hearing Center of Michigan and who presented for medical clearance exams between January 2014 and May 2017 were retrospectively analyzed. Separate determinations were made for each patient about (1) benefit from the exam and (2) avoidance of significant harm. RESULTS: Majority (64.2%; n = 201) of patients benefited from medical clearance exams. Furthermore, 5.4% of patients (n = 17) were found to have avoided significant harm due to administration of the medical clearance exam. Finally, 14.4% (n = 45) were offered alternative interventions over conventional hearing aids. CONCLUSIONS: Medical clearance exams are beneficial to a majority of patients with hearing loss prior to receiving hearing aids. With the impending arrival of over-the-counter hearing aids in the United States, special consideration should be placed on educating the general public about the importance of the medical evaluation prior to purchasing any type of hearing aid.
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Audífonos , Pérdida Auditiva/diagnóstico , Pérdida Auditiva/rehabilitación , Seguridad del Paciente , Anciano , Femenino , Audífonos/economía , Pérdida Auditiva/economía , Humanos , Masculino , Educación del Paciente como Asunto , Estudios RetrospectivosRESUMEN
PURPOSE: In the largest reported United States (U.S.) cohort of benign paroxysmal positional vertigo (BPPV), does the presence or absence of migraine correlate with increased associations of other factors? MATERIALS & METHODS: A retrospective chart review from a single U.S. neurotology center. Adult patients with BPPV from 2003 to 2017 classified into two groups: 1) with migraine; 2) without migraine. RESULTS: The prevalence of self-reported migraine history in a BPPV-positive population (n = 1481) was 25.8% (n = 382). Among those with BPPV and migraine, 88.5% were female, 8.1% had diabetes, 22.5% had prior history of BPPV, 8.9% had Meniere's disease and recurrence rate was 38.3%. No statistically significant differences between recurrence or resolution rates between the two groups were demonstrated (p > 0.05). Adjusted logistic regression model found that women and those with a prior history of BPPV had significantly higher odds of having both BPPV and migraine conditions compared to their counterparts. In contrast, older age and diabetes were associated with significantly lower odds of concomitant BPPV and migraine. CONCLUSIONS: The prevalence of migraine among the study sample was 25.8%. Female gender, prior history of BPPV, younger age, and lack of diabetes were independently associated with the concurrent comorbidity of BPPV and migraine. These data further substantiate previously reported rates (from smaller studies); and, demonstrate that recurrence and resolution rates are not worse in those with BPPV and migraine compared to the general BPPV population. Findings support an association between migraine and BPPV and enhances one's ability to accurately counsel patients regarding these diseases.
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Vértigo Posicional Paroxístico Benigno/epidemiología , Trastornos Migrañosos/epidemiología , Factores de Edad , Estudios de Cohortes , Comorbilidad , Consejo , Diabetes Mellitus/epidemiología , Femenino , Humanos , Masculino , Enfermedad de Meniere/epidemiología , Prevalencia , Recurrencia , Estudios Retrospectivos , Factores Sexuales , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVES: To assess the accuracy of pre-operative diagnosis of masses of the cerebellopontine angle (CPA) when compared to surgical pathology. DESIGN: Retrospective chart review. PARTICIPANTS: Patients who underwent surgery for CPA masses at two tertiary care institutions from 2007 to 2017. MAIN OUTCOME MEASURES: Percent concordance between pre-operative and surgical pathologic diagnosis; sensitivity, specificity, positive predictive value, and negative predictive value for predicted diagnoses. RESULTS: Concordance between pre-operative diagnosis and surgical pathology was 93.2% in 411 sampled patients. Concordance was 57.9% for masses other than vestibular schwannoma. Prediction of vestibular schwannoma and meningioma had high positive (0.95 and 0.97, respectively) and negative (0.76 and 0.99, respectively) predictive values. Prediction of facial neuroma had sensitivity of 0.13 and positive predictive value of 0.25. Headache (pâ¯=â¯0.001) and facial weakness (pâ¯=â¯0.003) were significantly associated with different pathologic profiles. Hearing loss was associated with differences in diagnostic prediction (pâ¯=â¯0.02) but not with differences in surgical pathology (pâ¯>â¯0.05). CONCLUSIONS: Comparison between pre-operative predicted diagnosis and surgical pathology for cerebellopontine angle masses is presented. Vestibular schwannoma and meningioma were effectively identified while rarer CPA masses including facial neuroma were rarely identified correctly. Clinicians caring for patients with CPA masses should be mindful of diagnostic uncertainty which may lead to changes in treatment plan or prognosis.
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Neoplasias Cerebelosas/diagnóstico , Neoplasias Cerebelosas/patología , Ángulo Pontocerebeloso , Neuroma Acústico/diagnóstico , Neuroma Acústico/patología , Adulto , Anciano , Neoplasias Cerebelosas/cirugía , Ángulo Pontocerebeloso/patología , Diagnóstico Diferencial , Neoplasias Faciales , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Neoplasias Meníngeas , Meningioma , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Neuroma , Neuroma Acústico/cirugía , Valor Predictivo de las Pruebas , Periodo Preoperatorio , Estudios Retrospectivos , Sensibilidad y Especificidad , Centros de Atención TerciariaRESUMEN
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.
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Otoneurología , Otolaringología , Medios de Comunicación Sociales , Humanos , Indización y Redacción de ResúmenesRESUMEN
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.
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Otosclerosis , Cirugía del Estribo , Humanos , Hombro , Otosclerosis/cirugía , Audición , Pruebas Auditivas , Estudios Retrospectivos , Resultado del Tratamiento , EstriboRESUMEN
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.
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Citosina , Edición Génica , Timina , Edición Génica/métodos , Humanos , Citosina/metabolismo , Citosina/química , Timina/metabolismo , Timina/química , Efectores Tipo Activadores de la Transcripción/metabolismo , Efectores Tipo Activadores de la Transcripción/genética , ADN/metabolismo , ADN/genética , Células HEK293RESUMEN
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.
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Anemia de Células Falciformes , Edición Génica , Terapia Genética , Células Madre Hematopoyéticas , Nucleasas de los Efectores Tipo Activadores de la Transcripción , Anemia de Células Falciformes/terapia , Anemia de Células Falciformes/genética , Edición Génica/métodos , Animales , Células Madre Hematopoyéticas/metabolismo , Humanos , Femenino , Ratones , Terapia Genética/métodos , Nucleasas de los Efectores Tipo Activadores de la Transcripción/metabolismo , Nucleasas de los Efectores Tipo Activadores de la Transcripción/genética , Trasplante de Células Madre Hematopoyéticas , Globinas beta/genética , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Reparación del ADN , Mutación , Talasemia beta/terapia , Talasemia beta/genética , Modelos Animales de Enfermedad , Técnicas de Transferencia de GenRESUMEN
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.
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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.
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Sordera , Oído Interno , Pérdida Auditiva , Enfermedad de Meniere , Humanos , Enfermedad de Meniere/diagnóstico , Enfermedad de Meniere/cirugía , Enfermedad de Meniere/complicaciones , Vértigo/tratamiento farmacológico , Vértigo/etiología , Gentamicinas/uso terapéutico , Pérdida Auditiva/complicacionesRESUMEN
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.
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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.
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Implantación Coclear , Implantes Cocleares , Percepción del Habla , Adulto , Humanos , Estados Unidos , Implantación Coclear/métodos , Cuidados Posteriores , Estudios Prospectivos , Audición , Percepción del Habla/fisiología , Resultado del TratamientoRESUMEN
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.
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Implantación Coclear , Implantes Cocleares , Pérdida Auditiva Unilateral , Neuroma Acústico , Percepción del Habla , Acúfeno , Adulto , Humanos , Acúfeno/etiología , Acúfeno/cirugía , Estudios Prospectivos , Audición , Pérdida Auditiva Unilateral/cirugía , Neuroma Acústico/complicaciones , Neuroma Acústico/cirugía , Percepción del Habla/fisiología , Resultado del TratamientoRESUMEN
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.
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Neuroma Acústico , Radiocirugia , Humanos , Neuroma Acústico/radioterapia , Neuroma Acústico/cirugía , Estudios Retrospectivos , Radiocirugia/efectos adversos , Radiocirugia/métodos , Estudios de Seguimiento , Audición , Resultado del TratamientoRESUMEN
Copper alloy surfaces are passive antimicrobial sanitizing agents that kill bacteria, fungi, and some viruses. Studies of the mechanism of contact killing in Escherichia coli implicate the membrane as the target, yet the specific component and underlying biochemistry remain unknown. This study explores the hypothesis that nonenzymatic peroxidation of membrane phospholipids is responsible for copper alloy-mediated surface killing. Lipid peroxidation was monitored with the thiobarbituric acid-reactive substances (TBARS) assay. Survival, TBARS levels, and DNA degradation were followed in cells exposed to copper alloy surfaces containing 60 to 99.90% copper or in medium containing CuSO(4). In all cases, TBARS levels increased with copper exposure levels. Cells exposed to the highest copper content alloys, C11000 and C24000, exhibited novel characteristics. TBARS increased immediately at a very rapid rate but peaked at about 30 min. This peak was associated with the period of most rapid killing, loss in membrane integrity, and DNA degradation. DNA degradation is not the primary cause of copper-mediated surface killing. Cells exposed to the 60% copper alloy for 60 min had fully intact genomic DNA but no viable cells. In a fabR mutant strain with increased levels of unsaturated fatty acids, sensitivity to copper alloy surface-mediated killing increased, TBARS levels peaked earlier, and genomic DNA degradation occurred sooner than in the isogenic parental strain. Taken together, these results suggest that copper alloy surface-mediated killing of E. coli is triggered by nonenzymatic oxidative damage of membrane phospholipids that ultimately results in the loss of membrane integrity and cell death.
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Aleaciones/toxicidad , Antibacterianos/toxicidad , Membrana Celular/metabolismo , Cobre/toxicidad , Escherichia coli/efectos de los fármacos , Peroxidación de Lípido , Fosfolípidos/metabolismo , Sulfato de Cobre/toxicidad , Medios de Cultivo/química , ADN Bacteriano/metabolismo , Escherichia coli/metabolismo , Viabilidad Microbiana/efectos de los fármacos , Factores de TiempoRESUMEN
High levels of translational errors, both truncation and misincorporation in an Fc-fusion protein were observed. Here, we demonstrate the impact of several commercially available codon optimization services, and compare to a targeted strategy. Using the targeted strategy, only codons known to have translational errors are modified. For an Fc-fusion protein expressed in Escherichia coli, the targeted strategy, in combination with appropriate fermentation conditions, virtually eliminated misincorporation (proteins produced with a wrong amino acid sequence), and reduced the level of truncation. The use of full optimization using commercially available strategies reduced the initial errors, but introduced different misincorporations. However, truncation was higher using the targeted strategy than for most of the full optimization strategies. This targeted approach, along with monitoring of translation fidelity and careful attention to fermentation conditions is key to minimizing translational error and ensuring high-quality expression. These findings should be useful for other biopharmaceutical products, as well as any other transgenic constructs where protein quality is important.
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Codón , Escherichia coli/genética , Escherichia coli/metabolismo , Fragmentos Fc de Inmunoglobulinas/genética , Fragmentos Fc de Inmunoglobulinas/metabolismo , Ingeniería Metabólica/métodos , Biosíntesis de Proteínas , Biotecnología/métodos , Fermentación , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismoRESUMEN
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited condition associated with ventricular tachycardia (VT) triggered by exercise or sympathetic stress. Incessant VT may develop due to defibrillator-induced storming-a condition where implantable cardioverter-defibrillator discharges result in a hyperadrenergic state, provoking further VT and defibrillator discharge. We describe the case of a 14-year-old boy with CPVT caused by a calsequestrin-2 mutation, who presented with defibrillator-induced storming refractory to ß-blockers, calcium-channel blockers, amiodarone, and dronedarone. Flecainide and ß-blocker use suppressed incessant VT and defibrillator-induced storming.
Asunto(s)
Desfibriladores Implantables/efectos adversos , Flecainida/uso terapéutico , Taquicardia Ventricular/etiología , Taquicardia Ventricular/prevención & control , Adolescente , Antiarrítmicos/uso terapéutico , Humanos , Masculino , Resultado del TratamientoRESUMEN
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.