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1.
J Neurosurg ; : 1-8, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38759236

RESUMO

OBJECTIVE: The goal of this study was to evaluate the feasibility of a minimally invasive approach to the middle cranial fossa using a novel endaural keyhole. METHODS: The charts of all patients who underwent this novel minimally invasive approach to the middle cranial fossa were retrospectively reviewed. In addition, cadaveric dissection was performed to demonstrate the feasibility of the endaural keyhole to the middle cranial fossa. RESULTS: Six patients (5 female and 1 male; age range 47-77 years) who underwent craniotomy for CSF leak (n = 3), intracerebral hematoma evacuation (n = 2), and tumor resection (n = 1) via the endaural subtemporal approach were identified. There were no approach-related complications noted. Representative imaging from cadaveric dissection is provided with a stepwise discussion of the procedure. CONCLUSIONS: The endaural subtemporal keyhole craniotomy provides a novel approach to middle fossa skull base pathology, as well as a minimally invasive approach to intra-axial pathology of the temporal lobe and basal ganglia. Further research is needed to establish the limitations and potential complications of this novel approach.

2.
Chin Med J (Engl) ; 137(6): 651-656, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-37407223

RESUMO

ABSTRACT: Cochlear spiral ganglion neurons (SGNs) are bipolar ganglion cells and are the first neurons in the auditory transduction pathway. They transmit complex acoustic information from hair cells to second-order sensory neurons in the cochlear nucleus for sound processing. Injury to SGNs causes largely irreversible hearing impairment because these neurons are highly differentiated cells and cannot regenerate, making treatment of sensorineural hearing loss (SNHL) arising from SGN injury difficult. When exposed to ototoxic drugs or damaging levels of noise or when there is loss of neurotrophic factors (NTFs), aging, and presence of other factors, SGNs can be irreversibly damaged, resulting in SNHL. It has been found that NTFs and stem cells can induce regeneration among dead spiral ganglion cells. In this paper, we summarized the present knowledge regarding injury, protection, and regeneration of SGNs.


Assuntos
Perda Auditiva Neurossensorial , Gânglio Espiral da Cóclea , Humanos , Gânglio Espiral da Cóclea/metabolismo , Neurônios , Cóclea , Células Ciliadas Auditivas/metabolismo
3.
Clin Imaging ; 105: 110026, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37992626

RESUMO

RATIONALE AND OBJECTIVES: The aim of this study was to examine the impact of an educational website on patient understanding of Interventional Radiology (IR). MATERIAL AND METHODS: An informational website with descriptions and images of 12 common IR procedures was developed with the aim of educating patients. One hundred patients referred to a large, academic institution were randomly selected to participate. Anonymous 11-question, 5-point Likert-scale assessments were administered before and after engaging with the educational website. The survey evaluated patients' understanding of IR procedures and satisfaction with the website as an educational tool. RESULTS: One hundred patients completed the pre-/post-implementation evaluations. Among matched questions, there was an increase in patient understanding of IR with mean score improvement from 2.10 to 4.57 (p < 0.001), their knowledge of common procedures from 1.74 to 4.66 (p < 0.001), and their consideration for their next procedure to be with IR from 2.24 to 4.62 (p < 0.001). Additionally, patients had an overall positive impression of the website (mean 4.80). Over 75% of patients found the descriptions and images "very helpful". CONCLUSION: This study demonstrated that website use for patient education has the potential to be effective in increasing overall patient understanding of IR and familiarity with common interventional procedures.


Assuntos
Educação de Pacientes como Assunto , Avaliação de Resultados da Assistência ao Paciente , Radiologia Intervencionista , Humanos , Radiologia Intervencionista/educação , Distribuição Aleatória , Inquéritos e Questionários , Internet , Educação de Pacientes como Assunto/métodos
4.
J Neurosurg Case Lessons ; 6(11)2023 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-37728168

RESUMO

BACKGROUND: Cranial and spinal cerebrospinal fluid (CSF) leaks are associated with opposite CSF fluid dynamics. The differing pathophysiology between spontaneous cranial and spinal CSF leaks are, therefore, mutually exclusive in theory. OBSERVATIONS: A 66-year-old female presented with tension pneumocephalus. The patient underwent computed tomography (CT) scanning, which demonstrated left-sided tension pneumocephalus, with an expanding volume of air directly above a bony defect of the tegmen tympani and mastoideum. The patient underwent a left middle fossa craniotomy for repair of the tegmen CSF leak. In the week after discharge, she developed a recurrence of positional headaches and underwent head CT. Further magnetic resonance imaging of the brain and thoracic spine showed bilateral subdural hematomas and multiple meningeal diverticula. LESSONS: Cranial CSF leaks are caused by intracranial hypertension and are not associated with subdural hematomas. Clinicians should maintain a high index of suspicion for intracranial hypotension due to spinal CSF leak whenever "otogenic" pneumocephalus is found. Close postoperative follow-up and clinical monitoring for symptoms of intracranial hypotension in any patients who undergo repair of a tegmen defect for otogenic pneumocephalus is recommended.

5.
Diagnostics (Basel) ; 13(16)2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37627929

RESUMO

There is an expanding body of literature that describes the application of deep learning and other machine learning and artificial intelligence methods with potential relevance to neuroradiology practice. In this article, we performed a literature review to identify recent developments on the topics of artificial intelligence in neuroradiology, with particular emphasis on large datasets and large-scale algorithm assessments, such as those used in imaging AI competition challenges. Numerous applications relevant to ischemic stroke, intracranial hemorrhage, brain tumors, demyelinating disease, and neurodegenerative/neurocognitive disorders were discussed. The potential applications of these methods to spinal fractures, scoliosis grading, head and neck oncology, and vascular imaging were also reviewed. The AI applications examined perform a variety of tasks, including localization, segmentation, longitudinal monitoring, diagnostic classification, and prognostication. While research on this topic is ongoing, several applications have been cleared for clinical use and have the potential to augment the accuracy or efficiency of neuroradiologists.

6.
Ear Nose Throat J ; 102(9_suppl): 31S-34S, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37515329

RESUMO

We present a case of a 58-year-old male with type II diabetes managed with metformin and insulin, who presented to the clinic with left chronic otitis media, persistent drainage, a stenotic meatus, and a prior history of 3 canal wall-down mastoidectomies and antibiotic therapy. A revision tympanoplasty with mastoidectomy was performed, and during the postoperative period, the patient had persistent pain and otorrhea, which were managed with opioids and several courses of antibiotic therapy. After symptoms persisted, imaging and culture ultimately led to the diagnosis of fungal skull base osteomyelitis, which was eventually treated successfully. While these complications are rare, their likelihood is increased with treatment delay and in the immunocompromised patient. Close management of immunocompromised patients, including diabetic patients, is vital in identifying complications early to aid in timely diagnosis and treatment to lead to the best possible outcome.


Assuntos
Diabetes Mellitus Tipo 2 , Osteomielite , Otite Média , Masculino , Humanos , Pessoa de Meia-Idade , Processo Mastoide/cirurgia , Diabetes Mellitus Tipo 2/complicações , Osteomielite/diagnóstico , Osteomielite/etiologia , Osteomielite/terapia , Otite Média/complicações , Otite Média/cirurgia , Antibacterianos/uso terapêutico , Base do Crânio
7.
ACS Biomater Sci Eng ; 9(6): 2838-2845, 2023 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-37303163

RESUMO

Oral delivery of biologic drugs is a highly desired yet challenging goal because of the many barriers posed by the GI tract. Ionic liquids (ILs) and deep eutectic solvents (DESs) such as choline and geranate (CAGE) have demonstrated the potential to improve intestinal absorption of insulin and poorly soluble drugs. As with other delivery agents, localization of the ILs in the intestine can enhance the delivery potential by increasing local concentrations while maintaining low off-target concentrations, thus improving the therapeutic window of the ILs. Here, we describe a method of encapsulating CAGE into a gel using PVA, forming a mucoadhesive ionogel patch (CAGE-patch) designed to adhere to the intestine. CAGE-patches formed via repeated freeze-thaw cycles demonstrated mucoadhesive strength, swelling, and controlled release of both CAGE and insulin. In vitro transport studies revealed a more than 30% increase in insulin transport when compared to controls across Caco-2 and HT29-MTX-E12 coculture layers. This design provides a novel approach to localize ionic liquids and therapeutics in the GI tract for enhanced oral delivery.


Assuntos
Insulinas , Líquidos Iônicos , Humanos , Células CACO-2 , Colina
9.
Ear Nose Throat J ; : 1455613221135644, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36282680

RESUMO

MYH9 is a gene that encodes for a subunit of the myosin heavy chain IIA protein. Mutations in MYH9 are associated with hematologic abnormalities, renal dysfunction, and hearing loss. Bony cochlear nerve canal stenosis (CNCS), which is diagnosed on computed tomography (CT) imaging, has been associated with congenital deafness, cochlear nerve aplasia/hypoplasia, and inner ear malformations. We report two cases of CNCS presenting with profound congenital hearing loss whom we diagnosed with mutations in MYH9 and discuss the genotype-phenotype association and implications for management.

10.
Otol Neurotol ; 43(8): e841-e845, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35900912

RESUMO

OBJECTIVE: In the current era of modern neurosurgery, the treatment strategies have been shifted to "nerve-preservation approaches" for achieving a higher facial and hearing function preservation rate following facial nerve tumors. We have conducted this novel report on determining the outcome of patients with facial nerve schwannomas (FNS) treated with hypofractionated stereotactic radiosurgery (hfSRS). PATIENTS: Retrospective chart review of a prospectively maintained database search was conducted. INTERVENTION: Patients who underwent hfSRS CyberKnife (Accuray Inc, Sunnyvale, CA, U.S.A.) for FNS were included. MAIN OUTCOME MEASURES: Outcomes consisted of tumor control, facial and hearing nerve function as graded by House-Brackmann and American Academy of Otolaryngology-Head and Neck Surgery recommendations, and adverse radiation effects. RESULTS: With an institutional board review approval, we retrospectively identified five patients with FNS (four intracranial [80%] and one extracranial [20%]) treated with hfSRS (2011-2019). Patients received definitive SRS in three patients (60.0%), whereas adjuvant to surgical resection in two patients (40.0%). A median tumor volume of 7.5 cm 3 (range, 1.5-19.6 cm 3 ) received a median prescription dose of 23.2 Gy (range, 21-25 Gy) administered in median of three fractions (range, three to five sessions). With a median radiographic follow-up of 31.4 months (range, 13.0-71.0 mo) and clinical follow-up of 32.6 months (range, 15.1-72.0 mo), the local tumor control was 100.0%. At the last clinical follow-up, the facial nerve function improved or remained unchanged House-Brackmann I-II in 80.0% of the patients, whereas the hearing nerve function improved or remained stable in 100.0% of the patients. Temporary clinical toxicity was observed in three patients (60.0%), which resolved. None of the patients developed adverse radiation effect. CONCLUSION: From our case series, hfSRS in FNS seems to be safe and efficacious in terms of local tumor control, and improved facial and hearing nerve function.


Assuntos
Neoplasias dos Nervos Cranianos , Neurilemoma , Neuroma Acústico , Radiocirurgia , Neoplasias dos Nervos Cranianos/radioterapia , Neoplasias dos Nervos Cranianos/cirurgia , Nervo Facial/cirurgia , Seguimentos , Humanos , Neurilemoma/radioterapia , Neurilemoma/cirurgia , Neuroma Acústico/patologia , Neuroma Acústico/radioterapia , Neuroma Acústico/cirurgia , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
11.
Ear Nose Throat J ; : 1455613221082625, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35649218

RESUMO

OBJECTIVE: To characterize the clinical features of patients with congenital hearing loss and unilateral cochlear nerve canal stenosis (CNCS). METHODS: A retrospective review of 12 patients with unilateral CNCS diagnosed between January 2018 and December 2019 at a tertiary referral hospital was performed. RESULTS: Of the 12 patients identified, there were 6 males and 6 females. All patients presented with hearing loss, with no other chief complaints. Two patients had accessory auricles. Eleven patients had a severe to profound sensorineural hearing loss on the affected side, while 1 patient had an isolated high-frequency hearing loss. Nine patients demonstrated atresia of the cochlear nerve canal (CNC), while three patients had a stenotic, but patent, CNC. CONCLUSION: Prompt radiologic diagnosis of patients with unilateral CNCS is important for patient counseling and appropriate rehabilitation.

12.
Laryngoscope Investig Otolaryngol ; 7(3): 847-853, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35734051

RESUMO

Objective: To examine device datalogging characteristics and postoperative performance in the very elderly CI users. Methods: Retrospective chart review of postoperative speech recognition outcomes and datalogging characteristics in patients older than 80 years old who underwent cochlear implantation and remain active users with longer than 6 months post-activation follow-up. Resultss: The mean age at implantation was 84.8 ± 3.8 years old. Pre- and post-operative AzBio sentences in quiet scores were 12.4 ± 16.4% and 53.0 ± 23.5%, respectively (p < .001). Pre- and post-operative consonant-nucleus-consonant (CNC) word scores were 9.4 ± 12.8% and 40.5 ± 20.7%, respectively (p < .001). A nonsignificant negative correlation was noted between the age of implantation and postoperative CNC words and AzBio sentence performance. Significantly decreased performance was noted in the subpopulation with a preoperative diagnosis of dementia. Mean daily use was 10.9 h per day. When available the mean daily usage distribution was 16% speech in noise, 19.1% speech, 51% quiet, 3.8% music, and 9.6% noise. A significant positive correlation was noted between daily use and AzBio sentence and CNC word performance. Conclusions: Very elderly patients have significant postoperative auditory performance benefits after CI. Mean daily use is comparable to previously published results in the younger population. Age of implantation does not play a significant role in overall performance. Elderly patients who are medically cleared for implantation receive significant postoperative benefits.

13.
Hum Gene Ther ; 33(13-14): 719-728, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35156857

RESUMO

Adeno-associated virus (AAV) are potent vectors to achieve treatment against hearing loss resulting from genetic defects. However, the effects of delivery routes and the corresponding transduction efficiencies for clinical applications remain elusive. In this study, we screened AAV vectors of three serotypes (AAV 8 and 9 and Anc80L65) into the inner ears of adult normal guinea pigs through trans-stapes (oval window) and trans-round window delivery routes in vivo. Trans-stapes route is akin to stape surgeries in humans. Then, auditory brainstem response (ABR) measurements were conducted to evaluate postoperative hearing, and inner ear tissues were harvested for transduction efficiency analysis. Results showed that AAV8 targeted partial inner hair cells (IHCs) in cochlear basal turn; AAV9 targeted IHCs in cochlear basal and second turn, also a part of vestibular hair cells (VHCs). In contrast, Anc80L65 contributed to green fluorescent proteins (GFP) signals of 80 - 95% IHCs and 67 - 91% outer hair cells (OHCs), as well as 69% VHCs through the trans-round window route, with 15-20 decibel (dB) ABR threshold shifts. And, through the trans-stapes (oval window) route, there were 71 - 90% IHCs and 42 - 81% OHCs, along with 64% VHCs demonstrating GFP positive, and the ABR threshold shifts were within 10 dB. This study revealed AAV could be efficiently delivered into mammalian inner ear cells in vivo through the trans-stapes (oval window) route with postoperative hearing preservation, and both delivery routes showed promise of virus-based clinical translation of hearing impairment treatment.


Assuntos
Orelha Interna , Perda Auditiva , Adulto , Animais , Cóclea , Dependovirus/genética , Proteínas de Fluorescência Verde/genética , Cobaias , Células Ciliadas Auditivas Internas , Perda Auditiva/genética , Perda Auditiva/terapia , Humanos , Mamíferos , Estribo , Suínos
14.
Otol Neurotol ; 43(2): e263-e267, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34855679

RESUMO

OBJECTIVE: To evaluate the safety of 3 Tesla (T) magnetic resonance imaging (MRI) in patients with auditory brainstem implants (ABI) with the magnet removed at implantation and report incidence of complications. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary neurotology ambulatory practice. PATIENTS: Patients with diagnosis of Neurofibromatosis, type 2 (NF2) with functional ABIs. INTERVENTIONS: Observational recordings. MAIN OUTCOME MEASURES: Of the 89 patients meeting inclusion criteria, 7 patients underwent 3T MRI, with a total of 39 scans done. Three patients had 1 scan each, one patient had 4 scans, one patient had 5 scans, one patient had 6 scans, and one patient had 21 scans. The mean time between ABI placement and first 3 T scan was 118 ±â€Š73 months. The most common indication for imaging was surveillance of NF2 lesions. The most frequent scans were MRI brain (25.6%), followed by MRI of cervical (15%), thoracic (15%) and lumbar (15%) spine, and MRI IAC (8%). There were no reported complications for any of the scans. No scans were interrupted due to patient discomfort. There were no device malfunctions. CONCLUSIONS: 3 T MRIs are safe in patients with ABIs as long as the magnet is removed. It is recommended that the magnet be removed at the time of implantation in all NF2 patients, who require frequent surveillance.


Assuntos
Implante Auditivo de Tronco Encefálico , Implantes Auditivos de Tronco Encefálico , Neurofibromatose 2 , Implante Auditivo de Tronco Encefálico/efeitos adversos , Implante Auditivo de Tronco Encefálico/métodos , Humanos , Imageamento por Ressonância Magnética/efeitos adversos , Imãs , Neurofibromatose 2/complicações , Neurofibromatose 2/diagnóstico por imagem , Neurofibromatose 2/patologia , Estudos Retrospectivos
15.
Eur Arch Otorhinolaryngol ; 279(1): 425-432, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34052864

RESUMO

OBJECTIVE: This study aims to evaluate the combination of myoelectric characteristics of tensor palatini muscle (TP) and collapsibility of upper airway in obstructive sleep apnea (OSA) patients with different external phenotypes of collapse pattern at velum level under drug-induced sleep endoscopy (DISE). STUDY DESIGN: Case series with planned data collection. SETTING: Operation room. SUBJECTS AND METHODS: 36 mainly collapse pattern at velum level OSA subjects underwent DISE with synchronous tensor palatini electromyograms (TP EMG), and polysomnography (ALICE 6). According to the phenotype of collapse pattern at velum level in DISE, the subjects were divided into group 1 (concentric collapse), group 2 (anteroposterior collapse), and group 3 (lateral collapse). Each group consisted of 13, 14, and 9 subjects, respectively, and was observed the electromyographic indexes at awake, sleep onset, during apnea and the third respiratory cycle after apnea. The active and passive upper airway critical closing pressure (Pcrit) of each group were measured at the same time, and the difference of neuromuscular response between different groups was evaluated. RESULTS: In tonic TPEMG, group 1 showed the highest value during awake and sleep onset, while group 2 was the highest during apnea and after apnea. In peak TPEMG, group 1 showed the highest value during awake. Group 2 showed the highest value during other states. In passive Pcrit and D value (difference between passive Pcrit and active Pcrit), group 2 was the highest, while group 1 was the highest in active Pcrit. Difference was statistically significant. CONCLUSIONS: Under different states of awake, sleep onset, apnea and after apnea, the response force of tensor palatini muscle of OSA subjects with different phenotypes under DISE was different. Group 1 showed the highest EMG values only when awake and sleep onset, and it was most prone to collapse. Group 2 had the highest anatomical load (passive Pcrit) and the highest neuromuscular compensatory effect (D value).


Assuntos
Apneia Obstrutiva do Sono , Endoscopia , Humanos , Fenótipo , Polissonografia , Sono , Apneia Obstrutiva do Sono/diagnóstico , Vigília
16.
Otol Neurotol ; 43(2): e259-e262, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34753875

RESUMO

OBJECTIVE: To investigate the utility of the so-called "second window" of indocyanine green (ICG) as a near-infrared fluorescent dye for intraoperative visualization. PATIENTS: Three patients who underwent surgical resection of vestibular schwannoma (two retrosigmoid and one middle fossa approach). INTERVENTIONS: Patients underwent intravenous infusion of ICG at a mean dose of 4.8 mg/kg at a mean of 15.3 hours before surgical incision. Once tumor dissection began, near-infrared fluorescence was used alongside conventional operative microscopy to visualize tumor tissue. MAIN OUTCOME MEASURES: Ability to distinguish tumor tissue from adjacent nerves. RESULTS: Intraoperative fluorescence allowed for enhanced visualization of the tumor-nerve plane in all patients. However, the effect varied among patients, and the effect faded with increasing surgical time. CONCLUSIONS: ICG, a well-tolerated cyanine dye, demonstrates late fluorescence hours after administration secondary to diffusion into tumor as well as normal tissues (the so-called "second window" of fluorescence). Its fluorescence in the near-infrared spectrum is a promising adjunct for enhancing visualization of tumor planes during vestibular schwannoma surgery.


Assuntos
Verde de Indocianina , Neuroma Acústico , Corantes Fluorescentes , Humanos , Neuroma Acústico/diagnóstico por imagem , Neuroma Acústico/cirurgia , Imagem Óptica
17.
Ear Nose Throat J ; : 1455613211045563, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34590888

RESUMO

To explore the correlation between the width of the bony cochlear nerve canal (CNC) and long-term auditory rehabilitation after unilateral cochlear implantation (CI) in pediatric patients with congenital deafness and bilateral cochlear nerve canal stenosis (CNCS). A retrospective review was performed on 10 patients with bilateral CNCS and bilateral congenital profound hearing loss who each underwent unilateral cochlear implantation. The width of the CNC was determined on computed tomography (CT) imaging and following CI, auditory and speech performance following CI were graded using categories of auditory performance (CAP), speech intelligibility rating (SIR), and the meaningful auditory integration scale (MAIS) at 24 months following implantation. No correlation was noted between CAP score and CNCS at 24 months post CI (P > .05). A positive correlation was noted between SIR score and CNC width (ρ = .81, P < .05). Similarly, a positive correlation was noted between MAIS and CNC width (ρ = .71, P < .05). The width of the CNC in patients with CNCS is positively correlated with some long-term auditory and speech outcomes after CI.

18.
J Neurol Surg B Skull Base ; 82(Suppl 3): e184-e189, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34306935

RESUMO

Objective Data regarding the surgical advantages and anatomic constraints of a hearing-preserving endoscopic-assisted retrolabyrinthine approach to the IAC are scarce. This study aimed to define the minimum amount of retrosigmoid dural exposure necessary for endoscopic exposure of the IAC and the surgical freedom of motion afforded by this approach. Methods Presigmoid retrolabyrinthine approaches were performed on fresh cadaveric heads. The IAC was exposed under endoscopic guidance. The retrosigmoid posterior fossa dura was decompressed until the fundus of the IAC was exposed. Surgical freedom of motion at the fundus was calculated after both retrolabyrinthine and translabyrinthine approaches. Results The IAC was entirely exposed in nine specimens with a median length of 12 mm (range: 10-13 mm). Complete IAC exposure could be achieved with 1 cm of retrosigmoid dural exposure in eight of nine mastoids. For the retrolabyrinthine approach, the median anterior-posterior surgical freedom was 13 degrees (range: 6-23 degrees) compared with 46 degrees (range: 36-53 degrees) for the translabyrinthine approach ( p = 0.014). For the retrolabyrinthine approach, the median superior-inferior surgical freedom was 40 degrees (range 33-46 degrees) compared with 47 degrees (range: 42-51 degrees) for the translabyrinthine approach ( p = 0.022). Conclusion Using endoscopic assistance, the retrolabyrinthine approach can expose the entire IAC. We recommend at least 1.5 cm of retrosigmoid posterior fossa dura exposure for this approach. Although this strategy provides significantly less instrument freedom of motion in both the horizontal and vertical axes than the translabyrinthine approach, it may be appropriate for carefully selected patients with intact hearing and small-to-medium sized tumors involving the IAC.

19.
Sci Adv ; 7(24)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34117055

RESUMO

Skin cancer is one of the most common types of cancer in the United States and worldwide. Topical products are effective for treating cancerous skin lesions when surgery is not feasible. However, current topical products induce severe irritation, light-sensitivity, burning, scaling, and inflammation. Using hyaluronic acid (HA), we engineered clinically translatable polymer-drug conjugates of doxorubicin and camptothecin termed, DOxorubicin and Camptothecin Tailored at Optimal Ratios (DOCTOR) for topical treatment of skin cancers. When compared to the clinical standard, Efudex, DOCTOR exhibited high cancer-cell killing specificity with superior safety to healthy skin cells. In vivo studies confirmed its efficacy in treating cancerous lesions without irritation or systemic absorption. When tested on patient-derived primary cells and live-skin explants, DOCTOR killed the cancer with a selectivity as high as 21-fold over healthy skin tissue from the same donor. Collectively, DOCTOR provides a safe and potent option for treating skin cancer in the clinic.


Assuntos
Dermatopatias , Neoplasias Cutâneas , Administração Tópica , Camptotecina/farmacologia , Doxorrubicina/farmacologia , Humanos , Ácido Hialurônico , Neoplasias Cutâneas/tratamento farmacológico
20.
Adv Healthc Mater ; 10(13): e2002192, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34050617

RESUMO

The mucus barrier lining the gastrointestinal tract poses a significant barrier to the oral delivery of macromolecular drugs. Successful approaches to overcoming this barrier have primarily focused on reducing drug and carrier interactions with mucus or disrupting the mucus layer directly. Choline-based ionic liquids (ILs) such as choline geranate and choline glycolate (CGLY) have recently been shown to be effective in enhancing the intestinal absorption of macromolecules such as insulin and immunoglobulin (IgG), respectively. Herein, the use of choline-based ILs as mucus-modulating agents for safely improving drug penetration through mucus is described. Choline-based ILs significantly increase the diffusion rates of cationic dextrans through mucin solution. Choline-maleic acid (CMLC 2:1) enhances the diffusion of 4 kDa cationic dextran in mucin solution by more than fourfold when compared to phosphate-buffered saline control. Choline-based ILs also reduce mucus viscosity without significantly impacting the native mucus gel structure. In vitro studies in a mucus-secreting coculture model with Caco-2 and HT29MTX-E12 cells further demonstrate the effectiveness of ILs in improving transport of cationic molecules in the presence of secreted mucus. This work demonstrates the potential for choline-based ionic liquids to be used as nondestructive mucus-modulating agents for enabling enhanced oral delivery of macromolecular drugs.


Assuntos
Líquidos Iônicos , Preparações Farmacêuticas , Células CACO-2 , Sistemas de Liberação de Medicamentos , Humanos , Muco
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