Impact of Systemic versus Intratympanic Dexamethasone Administration on the Perilymph Proteome.

Glucocorticoids are the first-line treatment for sensorineural hearing loss, but little is known about the mechanism of their protective effect or the impact of route of administration. The recent development of hollow microneedles enables safe and reliable sampling of perilymph for proteomic analysis. Using these microneedles, we investigate the effect of intratympanic (IT) versus intraperitoneal (IP) dexamethasone administration on guinea pig perilymph proteome. Guinea pigs were treated with IT dexamethasone (n = 6), IP dexamethasone (n = 8), or untreated for control (n = 8) 6 h prior to aspiration. The round window membrane (RWM) was accessed via a postauricular approach, and hollow microneedles were used to perforate the RWM and aspirate 1 µL of perilymph. Perilymph samples were analyzed by liquid chromatography-mass spectrometry-based label-free quantitative proteomics. Mass spectrometry raw data files have been deposited in an international public repository (MassIVE proteomics repository at https://massive.ucsd.edu/) under data set # MSV000086887. In the 22 samples of perilymph analyzed, 632 proteins were detected, including the inner ear protein cochlin, a perilymph marker. Of these, 14 proteins were modulated by IP, and three proteins were modulated by IT dexamethasone. In both IP and IT dexamethasone groups, VGF nerve growth factor inducible was significantly upregulated compared to control. The remaining adjusted proteins modulate neurons, inflammation, or protein synthesis. Proteome analysis facilitated by the use of hollow microneedles shows that route of dexamethasone administration impacts changes seen in perilymph proteome. Compared to IT administration, the IP route was associated with greater changes in protein expression, including proteins involved in neuroprotection, inflammatory pathway, and protein synthesis. Our findings show that microneedles can mediate safe and effective intracochlear sampling and hold promise for inner ear diagnostics.

Coronavirus disease 2019, vitamin D and kidney function.

PURPOSE OF REVIEW: The purpose of this review is to summarize the emerging studies analyzing the association between vitamin D and risk of COVID-19 infection and severity, as well as the early interventional studies investigating the protective effect of vitamin D supplementation against COVID-19. RECENT FINDINGS: Studies investigating the association between vitamin D levels and risk of COVID-19 infection and risk of severe disease and mortality among those infected have yielded mixed results. Thus far, the majority of studies investigating the association between vitamin D and COVID-19 have been observational and rely on vitamin D levels obtained at the time of admission, limiting causal inference. Currently, clinical trials assessing the effects of vitamin D supplementation in individuals with COVID-19 infection are extremely limited. Randomized, interventional trials may offer more clarity on the protective effects of vitamin D against COVID-19 infection and outcomes. SUMMARY: Decreased levels of vitamin D may amplify the inflammatory effects of COVID-19 infection, yet, data regarding the mortality benefits of vitamin D supplementation in COVID-19-infected individuals are still limited. Current observational data provides the impetus for future studies to including randomized controlled trials to determine whether vitamin D supplementation in COVID-19-infected individuals with kidney disease can improve mortality outcomes.

Vitamin D Status and COVID-19 Clinical Outcomes in Hospitalized Patients.

Context: Populations severely affected by COVID-19 are also at risk for vitamin D deficiency. Common risk factors include older age, chronic illness, obesity, and non-Caucasian race. Vitamin D deficiency has been associated with risk for respiratory infections and failure, susceptibility and response to therapy for enveloped virus infection, and immune-mediated inflammatory reaction.Objective: To test the hypothesis that 25-hydroxyvitamin D[25(OH)D] deficiency is a risk factor for severity of COVID-19 respiratory and inflammatory complications.Design: We examined the relationship between prehospitalization 25(OH)D levels (obtained 1-365 days prior to admission) and COVID-19 clinical outcomes in 700 COVID-19 positive hospitalized patients.Primary Outcomes: Discharge status, mortality, length of stay, intubation status, renal replacement.Secondary Outcomes: Inflammatory markers.Results: 25(OH)D levels were available in 93 patients [25(OH)D:25(IQR:17-33)ng/mL]. Compared to those without 25(OH)D levels, those with measurements did not differ in age, BMI or distribution of sex and race, but were more likely to have comorbidities. Those with 25(OH)D < 20 ng/mL (n = 35) did not differ from those with 25(OH)D ≥ 20 ng/mL in terms of age, sex, race, BMI, or comorbidities. Low 25(OH)D tended to be associated with younger age and lower frequency of preexisting pulmonary disease. There were no significant between-group differences in any outcome. Results were similar in those ≥50 years, in male/female-only cohorts, and when differing 25(OH)D thresholds were used (<15 ng/mL and <30 ng/mL). There was no relationship between 25(OH)D as a continuous variable and any outcome, even after controlling for age and pulmonary disease.Conclusions: These preliminary data do not support a relationship between prehospitalization vitamin D status and COVID-19 clinical outcomes.

Hearing Loss Is Associated with Increased Variability in Double Support Period in the Elderly.

Hearing loss is a disabling condition that increases with age and has been linked to difficulties in walking and increased risk of falls. The purpose of this study is to investigate changes in gait parameters associated with hearing loss in a group of older adults aged 60 or greater. Custom-engineered footwear was used to collect spatiotemporal gait data in an outpatient clinical setting. Multivariable linear regression was used to determine the relationship between spatiotemporal gait parameters and high and low frequency hearing thresholds of the poorer hearing ear, the left ear, and the right ear, respectively, adjusting for age, sex, race/ethnicity, and the Dizziness Handicap Inventory-Screening version score. Worsening high and low frequency hearing thresholds were associated with increased variability in double support period. Effects persisted after adjusting for the effects of age and perceived vestibular disability and were greater for increases in hearing thresholds for the right ear compared to the left ear. These findings illustrate the importance of auditory feedback for balance and coordination and may suggest a right ear advantage for the influence of auditory feedback on gait.

Outcomes and Safety Among Patients With Obstructive Sleep Apnea Undergoing Cancer Surgery Procedures in a Freestanding Ambulatory Surgical Facility.

BACKGROUND: Patients with obstructive sleep apnea (OSA) may be at increased risk for serious perioperative complications. The suitability of ambulatory surgery for patients with OSA remains controversial, and several national guidelines call for more evidence that assesses clinically significant outcomes. In this study, we investigate the association between OSA status (STOP-BANG risk, or previously diagnosed) and short-term outcomes and safety for patients undergoing cancer surgery at a freestanding ambulatory surgery facility. METHODS: We conducted a retrospective analysis of all patients having surgery at the Josie Robertson Surgery Center, a freestanding ambulatory surgery facility of the Memorial Sloan Kettering Cancer Center. Surgeries included more complex ambulatory extended recovery procedures for which patients typically stay overnight, such as mastectomy, thyroidectomy, and minimally invasive hysterectomy, prostatectomy, and nephrectomy, as well as typical outpatient surgeries. Both univariate and multivariable analyses were used to assess the association between OSA risk and transfer to the main hospital, urgent care center visit, and hospital readmission within 30 days postoperatively (primary outcomes) and length of stay and discharge time (secondary outcomes). Multivariable models were adjusted for age, American Society of Anesthesiologists score, robotic surgery, and type of anesthesia (general or monitored anesthesia care) and also adjusted for surgery start time for length of stay and discharge time outcomes. χ tests were used to assess the association between OSA risk and respiratory events and device use. RESULTS: Of the 5721 patients included in the analysis, 526 (9.2%) were diagnosed or at moderate or high risk for OSA. We found no evidence of a difference in length of stay when comparing high-risk or diagnosed patients with OSA to low- or moderate-risk patients whether they underwent outpatient (P = .2) or ambulatory extended recovery procedures (P = .3). Though a greater frequency of postoperative respiratory events were reported in high-risk or diagnosed patients with OSA compared to moderate risk (P = .004), the rate of hospital transfer was not significantly different between the groups (risk difference, 0.78%; 95% CI, -0.43% to 2%; P = .2). On multivariable analysis, there was no evidence of increased rate of urgent care center visits (adjusted risk difference, 1.4%; 95% CI, -0.68% to 3.4%; P = .15) or readmissions within 30 days (adjusted risk difference, 1.2%; 95% CI, -0.40% to 2.8%; P = .077) when comparing high-risk or diagnosed OSA to low- or moderate-risk patients. Based on the upper bounds of the CIs, a clinically relevant increase in transfers, readmissions, and urgent care center visits is unlikely. CONCLUSIONS: Our results contribute to the body of evidence supporting that patients with moderate-risk, high-risk, or diagnosed OSA can safely undergo outpatient and advanced ambulatory oncology surgery without increased health care burden of extended stay or hospital admission and avoiding adverse postoperative outcomes. Our results support the adoption of several national OSA guidelines focusing on preoperative identification of patients with OSA and clinical pathways for perioperative management and postoperative monitoring.

Return to illicit drug use post-incarceration among formerly incarcerated Black Americans.

AIMS: The number of drug dependent individuals incarcerated in the U.S. is exceptionally high, and reportedly 60 percent of incarcerated Black Americans have a substance abuse disorder. The purpose of this study was to identify factors associated with return to illicit drug use post-incarceration. METHODS: A cross-sectional study was conducted with 121 formerly incarcerated Black Americans in New York City to examine predictors of return to illicit drug use. Kaplan-Meier curves were generated on the outcome of time-to-drug use for various predictors and compared using the log-rank test. Cox proportional hazards models were used to identify significant predictors of return to illicit drug use post-incarceration. FINDINGS: Approximately 83 percent (n=100) of the participants reported a history of illicit drug use, not including participants who have only used marijuana. Out of 121 participants, 36 (29.8%) had used drugs within one day after release. By two weeks after release, half had used drugs. Gender and history of heroin use were significant predictors of time-to-drug use according to the log rank test. CONCLUSIONS: The potential for immediate return to drug use among our sample suggests that discharge support programs that focus specifically on healthy decision-making among women and heroin users are especially critical.

Examining factors associated with unprotected sexual behavior among Black Americans postrelease from incarceration in New York City.

Black Americans are overrepresented among incarcerated individuals and those infected with sexually transmitted infections. We assessed unprotected sexual behavior among 165 formerly incarcerated Black Americans in New York City, New York. Most participants (63%) reported engaging in unprotected sexual behavior post-incarceration. According to our regression results, less time spent in jail and reporting multiple sexual partnerships were associated with a greater likelihood of engaging in unprotected sexual behavior. High rates of unprotected sexual behavior may place formerly incarcerated Black Americans at risk for sexually transmitted infections. Discharge planning programs that include STI/HIV prevention information and education may be useful for this population.

Predictors of sexual behaviour among men and women in New York City area prisons.

The USA currently has the highest incarceration rate in the world. Individuals at greatest risk for HIV also tend to be among those at an elevated risk for incarceration. The HIV epidemic is driven by injection drug use and sexual behaviour, and estimates of prison-based sexual behaviour vary widely. This study examined sexual behaviour among 1369 incarcerated men and women in the New York City area. Approximately 13% of the sample (n = 176) reported being sexually active while incarcerated over the previous 6 months. Multiple logistic regression models were used to examine the predictors of prison sexual behaviour. The following variables were associated with increased odds of sexual activity in the previous six months: female gender (OR = 3.28; 95%CI = 1.95,5.51), Black race (OR = 2.26; 95%CI = 1.47,3.46), history of drug use (OR = 1.85; 95%CI = 1.04,3.30), bisexual (OR = 3.19; 95%CI = 1.90,5.38) or homosexual identity (OR = 8.50; 95%CI = 3.92,18.43) and conjugal visitation programme participation (OR = 66.26; 95%CI = 31.42,139.74). Educational programmes regarding sexually transmitted infections and appropriate harm reduction measures are warranted for this population. The expansion of conjugal visitation programmes may also be useful in helping prisoners sustain their relationships with partners from their community and reduce the risk of infectious disease transmission in this environment.

Daytime Somnolence and Sleep Apnea Are Associated With Dizziness in the Elderly.

OBJECTIVE: Dizziness is a debilitating multifactorial disorder commonly affecting the elderly. Daytime somnolence and sleep apnea have been linked to dizziness, but previous studies were limited by small sample sizes. The purpose of this study was to examine the relationship between dizziness and daytime somnolence and sleep-disordered breathing, in a nationally representative sample of elderly adults, while adjusting for possible confounders and mediators. STUDY DESIGN: Data from the National Health and Nutrition Examination Study (NHANES; 2017-2020 prepandemic data) were analyzed in a cross-sectional manner using survey methods. SETTING: Community-based setting in the United States. PARTICIPANTS: A total of 1,490 nationally representative participants aged ≥70 years. MAIN OUTCOMES: Multivariable logistic regression was used to examine the relationship between dizziness and daytime somnolence, snoring, and apnea, while adjusting for covariates (gender, age, body mass index, and various medical conditions that may confound this relationship). RESULTS: Frequent daytime somnolence five or more times monthly (odds ratio, 2.13; 95% confidence interval, 1.49-3.06) and presence of apnea (odds ratio, 1.65; 95% confidence interval, 1.20-2.27) were found to be associated with greater odds of dizziness when adjusting for medical comorbidities. A significant association was not found between snoring and dizziness. CONCLUSIONS AND RELEVANCE: In the elderly, daytime somnolence and apnea were independently associated with increased odds of dizziness, even after adjusting for medical comorbidities. Daytime somnolence and sleep apnea should be added to the differential diagnosis in this patient population. Optimizing sleep may help reduce symptoms of dizziness in this population, but prospective studies would be required to confirm these findings.Level of evidence: 4.

Nuances in Forehead Flap Reconstruction for Large Nasal Defects.

The forehead flap is a time-tested and robust resurfacing flap used for nasal reconstruction. Owing to its excellent color and texture match, acceptable donor site morbidity, and robust and independent blood supply that can support both structural and internal lining grafts, this flap remains the workhorse flap for resurfacing large nasal defects. Various nuances of this technique relating to defect and template preparation, flap design, flap elevation, flap inset, donor site closure, and pedicle division are discussed in this article. These nuances are the guiding principles for improved outcomes using a forehead flap for the reconstruction of large nasal defects.

Anatomic, physiologic, and proteomic consequences of repeated microneedle-mediated perforations of the round window membrane.

BACKGROUND: We have developed 3D-printed microneedle technology for diagnostic aspiration of perilymph and intracochlear delivery of therapeutic agents. Single microneedle-mediated round window membrane (RWM) perforation does not cause hearing loss, heals within 48-72 h, and yields sufficient perilymph for proteomic analysis. In this study, we investigate the anatomic, physiologic, and proteomic consequences of repeated microneedle-mediated perforations of the same RWM at different timepoints. METHODS: 100-µm-diameter hollow microneedles were fabricated using two-photon polymerization (2PP) lithography. The tympanic bullae of Hartley guinea pigs (n = 8) were opened with adequate exposure of the RWM. Distortion product otoacoustic emissions (DPOAE) and compound action potential (CAP) were recorded to assess hearing. The hollow microneedle was introduced into the bulla and the RWM was perforated; 1 µL of perilymph was aspirated from the cochlea over the course of 45 s. 72 h later, the above procedure was repeated with aspiration of an additional 1 µL of perilymph. 72 h after the second perforation, RWMs were harvested for confocal imaging. Perilymph proteomic analysis was completed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Two perforations and aspirations were performed in 8 guinea pigs. In six, CAP, DPOAE, and proteomic analysis were obtained; in one, only CAP and DPOAE results were obtained; and in one, only proteomics results were obtained. Hearing tests demonstrated mild hearing loss at 1-4 kHz and 28 kHz, most consistent with conductive hearing loss. Confocal microscopy demonstrated complete healing of all perforations with full reconstitution of the RWM. Perilymph proteomic analysis identified 1855 proteins across 14 samples. The inner ear protein cochlin was observed in all samples, indicating successful aspiration of perilymph. Non-adjusted paired t-tests with p < 0.01 revealed significant changes in 13 of 1855 identified proteins (0.7%) between the first and second aspirations. CONCLUSIONS: We demonstrate that repeated microneedle perforation of the RWM is feasible, allows for complete healing of the RWM, and minimally changes the proteomic expression profile. Thus, microneedle-mediated repeated aspirations in a single animal can be used to monitor the response to inner ear treatments over time.

Pyrolyzed Ultrasharp Glassy Carbon Microneedles.

Polymeric microneedles fabricated via two-photon polymerization (2PP) lithography enable safe medical access to the inner ear. Herein, the material class for 2PP-lithography-based microneedles is expanded by pyrolyzing 2PP-fabricated polymeric microneedles, resulting in glassy carbon microneedles. During pyrolysis the microneedles shrink up to 81% while maintaining their complex shape when the exposed surface-area-to-volume ratio (SVR) is 0.025 < SVR < 0.04, for the temperature history protocol used herein. The derived glassy carbon is confirmed with energy-dispersive X-ray spectroscopy and Raman spectroscopy. The pyrolyzed glassy carbon has Young's modulus 9.0 GPa. As a brittle material, the strength is stochastic. Using the two-parameter Weibull distribution, the glassy carbon has Weibull modulus of 3.1 and characteristic strength of 710 MPa. The viscoelastic response has characteristic time scale of about 10000 s. In vitro experiments demonstrate that the glassy carbon microneedles introduce controlled perforations across the guinea pig round window membrane (RWM) from the middle ear space into the inner ear, without damaging the microneedle. The resultant controlled perforation of RWM is known to enhance diffusion of therapeutics across the RWM in a predictable fashion. Hence, the glassy carbon microneedles can be deployed for mediating inner ear delivery.

Antibiotic adverse effects in pediatric acute rhinosinusitis: Systematic review and meta-analysis.

BACKGROUND: Pediatric acute bacterial rhinosinusitis (ABRS) is often treated with oral antibiotics, with limited insight into adverse effects (AEs) across drug classes. In this systematic review and meta-analysis, we characterize AE incidence associated with oral antibiotics in these patients. METHODOLOGY/PRINCIPAL: We searched PubMed and Embase for English-language articles published from 1985 to September 2020 reporting AEs of oral antibiotic therapy for ABRS patients aged 0-18 years. Six-hundred and sixty-six articles underwent title and abstract screening, identifying 154 articles for full-length review. RESULTS: Eleven articles were included, most of which reported individual and aggregate AE incidences. Amoxicillin/clavulanate, amoxicillin, cephalosporin/carbacephem, and placebo groups were identified. Random-effects meta-analysis of prospective groups identified appreciable incidences of diarrhea and abdominal pain, and low incidence of rash, for amoxicillin-clavulanate and amoxicillin. All antibiotics as well as placebo were associated with non-zero overall AE incidence. Children receiving antibiotics were about twice as likely to incur any AE during treatment in placebo-controlled studies, though this association was not significant. High heterogeneity limited most point estimates, with risk of bias, typically in outcomes measurement, detected in most studies. CONCLUSIONS: Reporting of AEs associated with oral antibiotic use in pediatric ABRS is limited in current literature. Adverse effects are non-negligible, but may not significantly exceed placebo.

Low vitamin D status is associated with hearing loss in the elderly: a cross-sectional study.

BACKGROUND: The elderly are at increased risk of both hearing loss (HL) and osteoporosis. Bone mineral density (BMD) has been putatively linked to HL. However, the roles of serum calcium concentrations and vitamin D status have yet to be elucidated. OBJECTIVES: The purpose of this study was to examine the relation between vitamin D status, parathyroid hormone (PTH), total calcium, BMD, and HL in a nationally representative sample of elderly adults. METHODS: Using the NHANES (2005-2010), audiometry and BMD data of 1123 participants aged ≥70 y were analyzed in a cross-sectional manner. HL was defined as pure tone averages >25 dB HL at 500, 1000, and 2000 Hz (low frequency); 500, 1000, 2000, and 4000 Hz (speech frequency); and 3000, 4000, 6000, and 8000 Hz (high frequency) in either ear. Multivariable logistic regression was used to examine the relation between HL and total 25-hydroxyvitamin D [25(OH)D], PTH, total calcium, and BMD, adjusting for covariates. RESULTS: In multivariable analyses, total 25(OH)D < 20 ng/mL was found to be associated with greater odds of low-frequency HL (OR: 2.02; 95% CI: 1.28, 3.19) and speech-frequency HL (OR: 1.96; 95% CI: 1.12, 3.44). A 1-unit decrease in femoral neck BMD (OR: 4.55; 95% CI: 1.28, 16.67) and a 1-unit decrease in total spine BMD (OR: 6.25; 95% CI: 1.33, 33.33) were found to be associated with greater odds of low-frequency HL. Serum PTH and total calcium were not found to be associated with HL. CONCLUSIONS: In the elderly, low vitamin D status was associated with low-frequency and speech-frequency HL. Low vitamin D status may be a potential risk factor for age-related HL.

Radiologic Assessment of the Sinonasal Tract, Nasopharynx and Mastoid Cavity in Patients with SARS-Cov-2 Infection Presenting with Acute Neurological Symptoms.

BACKGROUND: Acute neurological sequela in patients with COVID-19 infection include acute thromboembolic infarcts related to cytokine storm and post infectious immune activation resulting in a prothrombotic state. Radiologic imaging studies of the sinonasal tract and mastoid cavity in patients with COVID-19 infection are sparse and limited to case series. In this report, we investigate the radiologic involvement of nasal cavity, nasopharynx, paranasal sinuses, and mastoid cavity in patients with SARS-CoV-2 infection who presented with acute neurological symptoms. METHODS: Retrospective review of medical records and neuroradiologic imaging in patients diagnosed with acute COVID-19 infection who presented with acute neurological symptoms to assess radiologic prevalence of sinus and mastoid disease and its correlation to upper respiratory tract symptoms. RESULTS: Of the 55 patients, 23 (42%) had partial sinus opacification, with no evidence for complete sinus opacification. The ethmoid sinus was the most commonly affected (16/55 or 29%). An air fluid level was noted in 6/55 (11%) patients, most commonly in the maxillary sinus. Olfactory recess and mastoid opacification were uncommon. There was no evidence of bony destruction in any of the studies, Cough, nasal congestion, rhinorrhea, and sore throat were not significantly associated with any radiological findings. CONCLUSION: In patients who present with acute neurological symptoms, COVID-19 infection is characterized by limited and mild mucosal disease within the sinuses, nasopharynx and mastoid cavity. LEVEL OF EVIDENCE: 4.

A Novel 3D-Printed Head Holder for Guinea Pig Ear Surgery.

BACKGROUND: Otologic surgery in guinea pig requires head immobilization for microscopic manipulation. Existing commercially available stereotaxic frames are expensive and impede access to the ear as they rely on ear bars or mouthpieces to secure the head. METHOD: Prototype head holders were designed using the Solidworks 2019 software and 3D-printed using Formlabs Form 2 Printers with photopolymer resin. The head holder consists of a C-shaped brace with adjustable radial inserts of 1/4-20 UNC standard screws with cone point tips providing head fixation for animals of various sizes. The C-shaped brace is attached to a rod that can be secured to a commercially available micromanipulator. The head holder design was tested during in vivo guinea pig experiments where their head motion with (n = 22) and without the head holder (n = 2) was evaluated visually through a stereotaxic microscope at 24× magnification during surgery. RESULTS: The head holder design was easy to use and allowed for both nose cone administration of anesthesia and access to the ear for intraoperative auditory testing and manipulation. Functionally, the head holder successfully minimized head movement. Furthermore, harvested round window membranes evaluated at 72 hours following surgery showed precise perforations with the use of head holder. CONCLUSION: The novel 3D-printed head holder enables simultaneous access for nose cone administration of anesthesia and surgical manipulation of the ear and brain. Moreover, it provides a modular, intuitive, and economical alternative to commercial stereotaxic devices for minimizing head motion during small animal surgery.

Novel 3D-printed hollow microneedles facilitate safe, reliable, and informative sampling of perilymph from guinea pigs.

BACKGROUND: Inner ear diagnostics is limited by the inability to atraumatically obtain samples of inner ear fluid. The round window membrane (RWM) is an attractive portal for accessing perilymph samples as it has been shown to heal within one week after the introduction of microperforations. A 1 µL volume of perilymph is adequate for proteome analysis, yet the total volume of perilymph within the scala tympani of the guinea pig is limited to less than 5 µL. This study investigates the safety and reliability of a novel hollow microneedle device to aspirate perilymph samples adequate for proteomic analysis. METHODS: The guinea pig RWM was accessed via a postauricular surgical approach. 3D-printed hollow microneedles with an outer diameter of 100 µm and an inner diameter of 35 µm were used to perforate the RWM and aspirate 1 µL of perilymph. Two perilymph samples were analyzed by liquid chromatography-mass spectrometry-based quantitative proteomics as part of a preliminary study. Hearing was assessed before and after aspiration using compound action potential (CAP) and distortion product otoacoustic emissions (DPOAE). RWMs were harvested 72 h after aspiration and evaluated for healing using confocal microscopy. RESULTS: There was no permanent damage to hearing at 72 h after perforation as assessed by CAP (n = 7) and DPOAE (n = 8), and all perforations healed completely within 72 h (n = 8). In the two samples of perilymph analyzed, 620 proteins were detected, including the inner ear protein cochlin, widely recognized as a perilymph marker. CONCLUSION: Hollow microneedles can facilitate aspiration of perilymph across the RWM at a quality and volume adequate for proteomic analysis without causing permanent anatomic or physiologic dysfunction. Microneedles can mediate safe and effective intracochlear sampling and show great promise for inner ear diagnostics.

Inner Ear Gene Delivery: Vectors and Routes.

OBJECTIVES: Current treatments for hearing loss offer some functional improvements in hearing, but do not restore normal hearing. The aim of this review is to highlight recent advances in viral and non-viral vectors for gene therapy and to discuss approaches for overcoming barriers inherent to inner ear delivery of gene products. DATA SOURCES: The databases used were Medline, EMBASE, Web of Science, and Google Scholar. Search terms were [("cochlea*" or "inner ear" or "transtympanic" or "intratympanic" or "intracochlear" or "hair cells" or "spiral ganglia" or "Organ of Corti") and ("gene therapy" or "gene delivery")]. The references section of resulting articles was also used to identify relevant studies. RESULTS: Both viral and non-viral vectors play important roles in advancing gene delivery to the inner ear. The round window membrane is one significant barrier to gene delivery that intratympanic delivery methods attempt to overcome through diffusion and intracochlear delivery methods bypass completely. CONCLUSIONS: Gene therapy for hearing loss is a promising treatment for restoring hearing function by addressing innate defects. Recent technological advances in inner ear drug delivery techniques pose exciting opportunities for progress in gene therapy.

Inner ear delivery: Challenges and opportunities.

OBJECTIVES: The treatment of inner ear disorders remains challenging due to anatomic barriers intrinsic to the bony labyrinth. The purpose of this review is to highlight recent advances and strategies for overcoming these barriers and to discuss promising future avenues for investigation. DATA SOURCES: The databases used were PubMed, EMBASE, and Web of Science. RESULTS: Although some studies aimed to improve systemic delivery using nanoparticle systems, the majority enhanced local delivery using hydrogels, nanoparticles, and microneedles. Developments in direct intracochlear delivery include intracochlear injection and intracochlear implants. CONCLUSIONS: In the absence of a systemic drug that targets only the inner ear, the best alternative is local delivery that harnesses a combination of new strategies to overcome anatomic barriers. The combination of microneedle technology with hydrogel and nanoparticle delivery is a promising area for future investigation. LEVEL OF EVIDENCE: NA.