Effect of Rurality in Head and Neck Cancer: A Scoping Review.

OBJECTIVES: This scoping review sought to evaluate the current literature regarding the following outcomes in relation to rurality: stage at diagnosis, clinical characteristics, treatment characteristics, and survival outcomes of head and neck cancer (HNC). DATA SOURCES: A literature search was performed using PubMed (MEDLINE), Science Direct, EMBASE, SCOPUS, and Web of Science databases. REVIEW METHODS: A 20-year study cutoff from the initial search was used to increase the comparability of the studies regarding population and standards of clinical care. These searches were designed to capture all primary studies reporting HNC incidence, presenting characteristics, treatments, and treatment outcomes. Two reviewers independently screened abstracts, selected articles for exclusion, extracted data, and appraised studies. Critical appraisal was done according to the Joanna Briggs Institute Quality Assessment Tool for Cohort Studies. FINDINGS: Twenty eligible original articles were included. Stage at diagnosis, clinical characteristics, treatment characteristics, and survival outcomes were measured. Our review indicates that although this relationship is unclear, there may be variations in treatment choice for laryngeal cancer based on geographic location and rural residency status. The studies assessing HNC outcomes related to stage at diagnosis, clinical characteristics, treatment characteristics, and overall survival demonstrated conflicting findings, indicating a need for further research examining HNC outcomes with a focus on rurality as the main exposure. CONCLUSIONS: The relationship between HNC and rural-urban status remains unclear. More studies are needed, along with a consistent metric for measuring rurality and recruitment of comparable populations from both rural and urban areas. Laryngoscope, 2024.

Associations Between Social Vulnerability Indicators and Pediatric Tonsillectomy Outcomes.

OBJECTIVE: To investigate the impact of neighborhood-level social vulnerability on pediatric tonsillectomy outcomes. METHODS: This single-center retrospective cohort study included tonsillectomies performed on children aged 1 to 18 between August 2019 and August 2020. Geographic information systems were used to geocode addresses, and spatial overlays were used to assign census-tract level social vulnerability index (SVI) scores to each patient. For categorical variables, two-sided Pearson chi-square tests were used, whereas for continuous variables, paired t-tests, means, and standard deviations were calculated. SVI and its four subthemes were investigated using binomial logistic regressions to determine their impact on post-T&A complications and readmissions. RESULTS: The study included 397 patients, with 52 having complications (13.1%) and 33 (8.3%) requiring readmissions due to their complications. Controlling for age, gender, race, insurance status, surgical indication, comorbidities, obesity, and obstructive sleep apnea, postoperative complications were associated with high overall SVI (odds ratio [OR] 5.086, 95% confidence interval [CI] 1.128-22.938), high socioeconomic vulnerability (SVI theme 1, OR 6.003, 95% CI 1.270-28.385), and high house composition vulnerability (SVI theme 2, OR 6.340, 95% CI 1.275-31.525). Readmissions were also associated with high overall SVI (10.149, 95% CI 1.293-79.647) and high housing/transportation vulnerability (SVI theme 4, OR 5.657, 95% CI 1.089-29.396). CONCLUSION: Social vulnerability at the neighborhood level is linked to poorer surgical outcomes in otherwise healthy children, suggesting a target for community-based interventions. Because of the increased risk, it may have implications for preoperative decision-making, treatment plans, and clinic follow-ups. LEVEL OF EVIDENCE: 3: Laryngoscope, 134:954-962, 2024.

The Use and Utility of Food and Drug Administration Adverse Event Data from the Manufacturer and User Facility Device Experience Database in Otology: A Systematic Review.

OBJECTIVE: To review otology-related studies using the US Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database to identify the opportunities and limitations of using MAUDE. DATABASES REVIEWED: PubMed, Science Direct, Web of Science, SCOPUS, and EMBASE. METHODS: All studies reporting otology-related adverse events extracted from MAUDE were included from June 20, 2002, to 2022. Two reviewers independently screened abstracts, selected articles for exclusion, extracted data, and appraised studies. Critical appraisal was done according to the National Institutes of Health quality assessment tool for case series. RESULTS: The search yielded 5,645 studies, of which 8 studies met the inclusion criteria. All eight studies were case series; three evaluated cochlear implants, two evaluated osseointegrated hearing implants, and one evaluated illuminated operating microscope use. Quality assessment revealed all studies to be of poor quality. The most common domains contributing to these ratings included unclear study population, lack of consecutive participants, comparability of participants, clear and consistent outcome measures, and appropriate statistical analysis. CONCLUSION: Otology studies using the MAUDE database are of poor quality. This was primarily due to MAUDE's structural limitations as a passive surveillance system using nonstandardized free-text reports. The quality of studies also suffered from inappropriate analysis of MAUDE data, given its design. The utility of MAUDE could be improved by implementing case report best practices and converting the free fields to allow controlled and adaptive responses wherever possible to help standardize adverse event reporting.

Quality of Life, Neurosensory Disorders and Co-Occurring Medical Conditions in Individuals on the Spectrum, with a Special Focus on Females Diagnosed with Autism: A Systematic Review.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that has a high prevalence and a significant economic impact. Our knowledge regarding neurosensory disorders and co-occurring medical conditions in the ASD population is limited, particularly for autistic women. Most of the studies include male participants or do not make comparisons with their female counterparts. The objective of this systematic review article is to explore the quality of life as well as the prevalence of neurosensory disorders and co-occurring medical conditions in individuals on the spectrum, with a special focus on autistic females. The literature search was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. A protocol of this systematic review was designed a priori and was registered in the PROSPERO database (registration number: CRD42022330368). We concluded that numerous medical areas were of concern. Autistic females are more likely than their male counterparts with ASD to suffer from psychiatric conditions such as post-traumatic stress syndrome, depression, and eating disorders. They are also more likely to report GI-related disturbances and chronic pain. Further investigations are warranted to determine quality of life, as well as the prevalence and severity of neurosensory disorders in individuals with ASD, specifically studies comparing autistic females with their male counterparts. The information derived from these studies will help develop better support systems for individuals with autism, particularly females on the spectrum, in pursuit of improving their quality of life.

Systematic review of cochlear implantation in patients with inner ear malformations.

OBJECTIVES: To evaluate the outcomes of cochlear implantation in patients with severe to profound sensorineural hearing loss due to inner ear malformations (IEMs) when compared to patients without IEMs. We discussed audiological outcomes such as open-set testing, closed-set testing, CAP score, and SIR score as well as postoperative outcomes such as cerebrospinal fluid gusher and incomplete insertion rate associated with cochlear implantation in individuals with IEMs. DATA SOURCES: PubMed, Science Direct, Web of Science, Scopus, and EMBASE databases. REVIEW METHODS: After screening a total of 222 studies, twelve eligible original articles were included in the review to analyze the speech and hearing outcomes of implanted patients with IEMs. Five reviewers independently screened, selected, and extracted data. The "Tool to Assess Risk of Bias in Cohort Studies" published by the CLARITY group was used to perform quality assessment on eligible studies. Systematic review registration number: CRD42021237489. RESULTS: IEMs are more likely to be associated with abnormal position of the facial nerve, raising the risk of intraoperative complications. These patients may benefit from cochlear implantation, but audiological outcomes may also be less favorable than in individuals without IEMs. Furthermore, due to the risk of cerebrospinal fluid gusher, incomplete insertion of electrodes, and postoperative facial nerve stimulation, surgeons can employ precautionary measures such as preoperative imaging and proper counseling. Postoperative imaging is suggested to be beneficial in ensuring proper electrode placement. CONCLUSIONS: Cochlear implants (CIs) have the potential to provide auditory rehabilitation to individuals with IEMs. Precise classification of the malformation, preoperative imaging and anatomical mapping, appropriate electrode selection, intra-operative techniques, and postoperative imaging are recommended in this population.

Identification of Target Proteins Involved in Cochlear Hair Cell Progenitor Cytotoxicity following Gentamicin Exposure.

Given the non-labile, terminal differentiation of inner-ear sensory cells, preserving their function is critical since sensory cell damage results in irreversible hearing loss. Gentamicin-induced cytotoxicity is one of the major causes of sensory cell damage and consequent sensorineural hearing loss. However, the precise molecular mechanisms and target proteins involved in ototoxicity are still unknown. The objective of the present study was to identify target proteins involved in gentamicin-induced cytotoxicity to better characterize the molecular pathways involved in sensory cell damage following ototoxic drug administration using House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). We identified several unique proteins involved in gentamicin-induced cytotoxicity, expression of which were further confirmed using confocal microscopy. Further investigation of these pathways can inform the design and discovery of novel treatment modalities to prevent sensory cell damage and preserve their function.

Carbohydrate-to-Fiber Ratio, a Marker of Dietary Intake, as an Indicator of Depressive Symptoms.

OBJECTIVE: The aim of this study is to evaluate the association between a marker of dietary intake, the carbohydrate-to-fiber (CF) ratio, and moderate-to-severe depressive symptoms. DESIGN: Cross-sectional study. SETTING: National Health and Nutrition Examination Survey (NHANES) database from 2013-2016. PARTICIPANTS: Individuals 18 years and older were included. Participants with total energy intake outside of three standard deviations of the mean, pregnant or breastfeeding women, and those with missing data were excluded. MEASUREMENTS: The main independent variable, CF ratio, was generated using corresponding variables in NHANES and divided into quartiles. The main outcome was depressive symptoms using the Patient Health Questionnaire-9. Unadjusted and adjusted logistic regression analyses were used to calculate odds ratios and their corresponding 95% confidence interval (CI).  Results: Among all participants (n=9,728), 8.3% reported to have moderate-to-severe depressive symptoms (n=833). The highest proportion of depressive symptoms was reported in respondents in quartile 4 (Q4), with the highest CF ratio (13.0%; p<0.001). After adjustment, the odds of depressive symptoms significantly increased in Q4 of the CF ratio compared with Q1 (adjusted odds ratio 1.4, 95% CI 1.0-1.9). The prevalence of depressive symptoms significantly increased in females, lower federal poverty levels, non-married individuals, smokers, and hypertension patients.  Conclusion: This nationally representative sample suggests that a higher CF dietary intake ratio increases the risk of moderate-to-severe depressive symptoms. These results suggest that the CF ratio may help clinicians and patients evaluate their dietary risk for depressive symptoms. Further prospective studies are needed to validate this ratio as a dietary measurement.

Altering the gut microbiome to potentially modulate behavioral manifestations in autism spectrum disorders: A systematic review.

There is a potential association between gastrointestinal (GI) symptoms and the severity of autism spectrum disorder (ASD). Given this correlation, the possible impact of probiotics and prebiotics have been explored in research studies to modify the gut microbiome and ameliorate behavioral manifestations of ASD via modulating the gut-brain-microbiome axis. This systematic review focuses on the interplay between these factors in altering the behavioral manifestations of ASD. Probiotic supplementation tended to mitigate some of the behavioral manifestations of ASD, with less of a discernible trend on the microbiome level. Studies supplementing multiple probiotic species, such as microbiota transfer therapy, or including prebiotics performed better than single strain supplementation. Our analysis suggests that gut dysbiosis may increase intestinal permeability, leading to more severe GI symptoms and a systemic inflammatory response, which can alter permeability across the blood-brain barrier and synaptogenesis in the brain. Future studies are warranted to understand the precise contribution of altering gut microbiome on clinical manifestations of ASD that will open up avenues to develop preventive and treatment modalities.

The Outcomes of Cochlear Implantation in Usher Syndrome: A Systematic Review.

OBJECTIVE: To systematically appraise the implementation of cochlear implantation (CI) in Usher Syndrome (USH) Types 1, 2, and 3 patients, and analyze who would benefit from CI. DATA SOURCES: A comprehensive search of PubMed, Embase, CINAHL, and Cochrane Library electronic databases from inception through June 2020 was performed. There were no language restrictions. STUDY SELECTION: The PRISMA strategy was followed. Included studies discuss USH patients who underwent CI regardless of age, nationality, or clinical subtype. All included studies report post-implantation functional, cognitive, or quality of life outcomes. Only reviews were excluded. RESULTS: Fifteen studies met the inclusion criteria. USH patients experienced improvements in PTA and speech perception and expression outcomes after CI, as well as improvements in phonological memory and quality of life measures. Overall, patients implanted at younger ages outperformed older patients in audiological testing. Similarly, patients with prolonged auditory deprivation had relatively poor performance outcomes in sentence recognition and speech detection following CI. CONCLUSIONS: Most USH patients benefit from CI. USH patients who undergo CI at younger ages generally achieve better hearing, speech, and cognitive outcomes. CI at older ages can still prove beneficial if appropriate auditory amplification is started at the right time. Further research is warranted to fill the gap in understanding regarding the gene mutations underlying the pathophysiology of USH that have favorable CI outcomes as well as the optimal time to perform CI.

Advancements in Stem Cell Technology and Organoids for the Restoration of Sensorineural Hearing Loss.

BACKGROUND: Sensorineural hearing loss (SNHL) is a significant cause of morbidity worldwide and currently has no curative treatment. Technological advancements in stem cell therapy have led to numerous studies that examine the generation of otic sensory cells from progenitors to restore inner ear function. Recently, organoids have emerged as a promising technique to further advance the process of creating functional replacement cells after irreversible hearing loss. Organoids are the three-dimensional generation of stem cells in culture to model the tissue organization and cellular components of the inner ear. Organoids have emerged as a promising technique to create functioning cochlear structures in vitro and may provide crucial information for the utilization of stem cells to restore SNHL. PURPOSE: The purpose of this review is to discuss the recent advancements in stem cell-based regenerative therapy for SNHL. RESULTS: Recent studies have improved our understanding about the developmental pathways involved in the generation of hair cells and spiral ganglion neurons. However, significant challenges remain in elucidating the molecular interactions and interplay required for stem cells to differentiate and function as otic sensory cells. A few of the challenges encountered with traditional stem cell therapy may be addressed with organoids. CONCLUSION: Stem cell-based regenerative therapy holds a great potential for developing novel treatment modalities for SNHL. Further advancements are needed in addressing the challenges associated with stem cell-based regenerative therapy and promote their translation from bench to bedside.

Gut-Induced Inflammation during Development May Compromise the Blood-Brain Barrier and Predispose to Autism Spectrum Disorder.

Recently, the gut microbiome has gained considerable interest as one of the major contributors to the pathogenesis of multi-system inflammatory disorders. Several studies have suggested that the gut microbiota plays a role in modulating complex signaling pathways, predominantly via the bidirectional gut-brain-axis (GBA). Subsequent in vivo studies have demonstrated the direct role of altered gut microbes and metabolites in the progression of neurodevelopmental diseases. This review will discuss the most recent advancements in our understanding of the gut microbiome's clinical significance in regulating blood-brain barrier (BBB) integrity, immunological function, and neurobiological development. In particular, we address the potentially causal role of GBA dysregulation in the pathophysiology of autism spectrum disorder (ASD) through compromising the BBB and immunological abnormalities. A thorough understanding of the complex signaling interactions between gut microbes, metabolites, neural development, immune mediators, and neurobiological functionality will facilitate the development of targeted therapeutic modalities to better understand, prevent, and treat ASD.

Genotype-Phenotype Correlation for Predicting Cochlear Implant Outcome: Current Challenges and Opportunities.

The use and utility of cochlear implantation has rapidly increased in recent years as technological advances in the field have expanded both the efficacy and eligible patient population for implantation. This review aims to serve as a general overview of the most common hearing disorders that have favorable auditory outcomes with cochlear implants (CI). Hearing loss in children caused by congenital cytomegalovirus infection, syndromic conditions including Pendred Syndrome, and non-syndromic genetic conditions such as hearing impairment associated with GJB2 mutations have shown to be successfully managed by CI. Furthermore, cochlear implantation provides the auditory rehabilitation for the most common etiology of hearing loss in adults and age-related hearing loss (ARHL) or presbycusis. However, in some cases, cochlear implantation have been associated with some challenges. Regarding implantation in children, studies have shown that sometimes parents seem to have unrealistic expectations regarding the ability of CI to provide auditory rehabilitation and speech improvement. Given the evidence revealing the beneficial effects of early intervention via CI in individuals with hearing disorders especially hearing loss due to genetic etiology, early auditory and genetic screening efforts may yield better clinical outcomes. There is a need to better understand genotype-phenotype correlations and CI outcome, so that effective genetic counseling and successful treatment strategies can be developed at the appropriate time for hearing impaired individuals.

Biocompatibility of Bone Marrow-Derived Mesenchymal Stem Cells in the Rat Inner Ear following Trans-Tympanic Administration.

Recent advancements in stem cell therapy have led to an increased interest within the auditory community in exploring the potential of mesenchymal stem cells (MSCs) in the treatment of inner ear disorders. However, the biocompatibility of MSCs with the inner ear, especially when delivered non-surgically and in the immunocompetent cochlea, is not completely understood. In this study, we determined the effect of intratympanic administration of rodent bone marrow MSCs (BM-MSCs) on the inner ear in an immunocompetent rat model. The administration of MSCs did not lead to the generation of any oxidative stress in the rat inner ear. There was no significant production of proinflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and IL-12, due to BM-MSCs administration into the rat cochlea. BM-MSCs do not activate caspase 3 pathway, which plays a central role in sensory cell damage. Additionally, transferase dUTP nick end labeling (TUNEL) staining determined that there was no significant cell death associated with the administration of BM-MSCs. The results of the present study suggest that trans-tympanic administration of BM-MSCs does not result in oxidative stress or inflammatory response in the immunocompetent rat cochlea.

Evaluating the Efficacy of L-N-acetylcysteine and Dexamethasone in Combination to Provide Otoprotection for Electrode Insertion Trauma.

BACKGROUND: Electrode insertion trauma (EIT) during cochlear implantation (CI) can cause loss of residual hearing. L-N-acetylcysteine (L-NAC) and dexamethasone (Dex) have been individually shown to provide otoprotection albeit at higher concentrations that may be associated with adverse effects. Objective/Aims: The aim of this study is to determine whether L-NAC and Dex could be combined to decrease their effective dosage. MATERIALS AND METHODS: The organ of Corti (OC) explants were divided into various groups: 1) control; 2) EIT; 3) EIT treated with different concentrations of Dex; 4) EIT treated with different concentrations of L-NAC; 5) EIT treated with L-NAC and Dex in combination. Hair cell (HC) density, levels of oxidative stress, proinflammatory cytokines and nitric oxide (NO) was determined. RESULTS: There was a significant loss of HCs in explants subjected to EIT compared to the control group. L-NAC and Dex in combination was able to provide significant otoprotection at lower concentrations compared to individual drugs. CONCLUSIONS AND SIGNIFICANCE: A combination containing L-NAC and Dex is effective in protecting sensory cells at lower protective doses than each compound separately. These compounds can be combined allowing a decrease of potential side effects of each compound and providing significant otoprotection for EIT.