Otologic Manifestations of Langerhans Cell Histiocytosis: A Systematic Review.

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.

Diagnosis and management of eosinophilic otitis media: a systematic review.

BACKGROUND: Eosinophilic Otitis Media (EOM) is a relatively newly defined entity of recurrent and resistant otitis media. OBJECTIVE: To perform a systematic review of otologic manifestations, diagnosis and management of eosinophilic otitis media (EOM). METHODS: 393 patients diagnosed with EOM of 26 studies met inclusion criteria and were assessed for demographics, otologic manifestations, diagnostic criteria fulfilled, and medical and surgical treatments. RESULTS: Most common otologic manifestations were hearing loss (65%), otitis media with effusion (16%), tympanic membrane perforation (13%), and otorrhea (13%). 93% had a predominantly eosinophilic middle ear effusion, 95% had asthma, 85% had a highly viscous middle ear effusion, 71% had nasal polyposis, and 58% had resistance to conventional treatment. For treatment, 39% received intratympanic steroid injections, 33% received systemic steroids, 17% received steroid ear drops and 13% received a biological agent. 39% of patients underwent a surgical intervention with 26% receiving functional endoscopic sinus surgery and 18% receiving myringotomy with tube insertion. Success rates were highest with use of intratympanic steroids (45%), systemic steroids (26%), and biological agents (58%). CONCLUSION: Intratympanic steroids show the most efficacy in treating EOM, and aggressive optimization of asthma may be beneficial in resolving otologic symptoms. Surgery should be reserved for refractory cases and complications.

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.

Otologic Manifestations of Eosinophilic Granulomatosis With Polyangiitis: A Systematic Review.

OBJECTIVE: To perform a systematic review of the diagnosis, treatment, and management of patients with otologic manifestations of eosinophilic granulomatosis with polyangiitis. DATABASES REVIEWED: PubMed, Embase, Cochrane. METHODS: A systematic search for relevant published literature in PubMed, Cochrane Library, and EMBASE databases was done. Data was collected on demographics, otologic manifestations, specific diagnostic criteria fulfilled, common clinical, and imaging findings as well as medical and surgical treatments received. RESULTS: Fifteen articles encompassing 219 patients met inclusion criteria including 8 case reports and 7 case series. The mean age was 52.8 (range of 24-70). The most common otologic presenting symptoms were hearing loss (76%), otitis media with effusion (44%), vertigo (22%), tinnitus (21%), and chronic otitis media (20%). The most common diagnostic criteria observed in these patients were paranasal sinus abnormalities (75%), asthma (66%), and eosinophilia >10% (44%). The most common treatment was systemic steroids (66%), followed by surgery (52%), with myringotomy with tube insertion (M&T) (32%) and endoscopic sinus surgery (21%) being the most prevalent. Thirty-four percent of patients received an immunosuppressive agent. Successful treatments included systemic steroids (23%), surgical modalities (13%) with M&T being the most common (7%), topical nasal steroids (12%), and cyclophosphamide (10%). CONCLUSION: Hearing loss and a middle ear effusion are the most common presenting otologic manifestations of eosinophilic granulomatosis with polyangiitis. Sinonasal disease was more prevalent in patients with otologic manifestations. Primary treatment consists of systemic steroids and immunomodulation. M&T, endoscopic sinus surgery, and local steroid administration can be adjunctive measures to alleviate local disease.Level of Evidence: Level 1.

Implications of Transcranial Magnetic Stimulation as a Treatment Modality for Tinnitus.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive, neuromodulating technique for brain hyperexcitability disorders. The objective of this paper is to discuss the mechanism of action of rTMS as well as to investigate the literature involving the application of rTMS in the treatment of tinnitus. The reviewed aspects of the protocols included baseline evaluation, the total number of sessions, frequency and the total number of stimuli, the location of treatment, and the outcome measures. Even with heterogeneous protocols, most studies utilized validated tinnitus questionnaires as baseline and outcome measures. Low frequency (1 Hz) stimulation throughout 10 consecutive sessions was the most widely used frequency and treatment duration; however, there was no consensus on the total number of stimuli necessary to achieve significant results. The auditory cortex (AC) was the most targeted location, with most studies supporting changes in neural activity with multi-site stimulation to areas in the frontal cortex (FC), particularly the dorsolateral prefrontal cortex (DLPFC). The overall efficacy across most of the reviewed trials reveals positive statistically significant results. Though rTMS has proven to impact neuroplasticity at the microscopic and clinical level, further studies are warranted to demonstrate and support the clinical use of rTMS in tinnitus treatment with a standardized protocol.

Otoprotection to Implanted Cochlea Exposed to Noise Trauma With Dexamethasone Eluting Electrode.

Cochlear implantation (CI) is now widely used to provide auditory rehabilitation to individuals having severe to profound sensorineural hearing loss (SNHL). However, CI can lead to electrode insertion trauma (EIT) that can cause damage to sensory cells in the inner ear resulting in loss of residual hearing. Even with soft surgical techniques where there is minimal macroscopic damage, we can still observe the generation of molecular events that may initiate programmed cell death via various mechanisms such as oxidative stress, the release of pro-inflammatory cytokines, and activation of the caspase pathway. In addition, individuals with CI may be exposed to noise trauma (NT) due to occupation and leisure activities that may affect their hearing ability. Recently, there has been an increased interest in the auditory community to determine the efficacy of drug-eluting electrodes for the protection of residual hearing. The objective of this study is to determine the effect of NT on implanted cochlea as well as the otoprotective efficacy of dexamethasone eluting electrode to implanted cochlea exposed to NT in a guinea pig model of CI. Animals were divided into five groups: EIT with dexamethasone eluting electrode exposed to NT; EIT exposed to NT; NT only; EIT only and naïve animals (control group). The hearing thresholds were determined by auditory brainstem recordings (ABRs). The cochlea was harvested and analyzed for transcript levels of inflammation, apoptosis and fibrosis genes. We observed that threshold shifts were significantly higher in EIT, NT or EIT + NT groups compared to naive animals at all the tested frequencies. The dexamethasone eluting electrode led to a significant decrease in hearing threshold shifts in implanted animals exposed to NT. Proapoptotic tumor necrosis factor-α [TNF-α, TNF-α receptor 1a (TNFαR1a)] and pro-fibrotic transforming growth factor ß1 (TGFß) genes were more than two-fold up-regulated following EIT and EIT + NT compared to the control group. The use of dexamethasone releasing electrode significantly decreased the transcript levels of pro-apoptotic and pro-fibrotic genes. The dexamethasone releasing electrode has shown promising results for hearing protection in implanted animals exposed to NT. The results of this study suggest that dexamethasone releasing electrode holds great potential in developing effective treatment modalities for NT in the implanted cochlea.

Levels of polychlorinated biphenyls (PCB) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) in fillets of farmed Southern Bluefin Tuna (Thunnus maccoyii).

Southern Bluefin Tuna (SBT) (Thunnus maccoyii) is the only farmed tuna species in the southern hemisphere, with production centred offshore of Port Lincoln, South Australia. SBT farming is a quota-based fishery where farmers fatten wild-caught stock for subsequent sale as fresh-chilled or frozen product, mainly to Japanese markets. Fillets from wild-caught and farmed SBT were analysed and the concentration of polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) are reported for the first time. Time of farming was separated into two periods: a typical farming period of approximately five months and an experimental scenario that involved holding (farming) these fish for an additional 12 months. WHO-PCB and WHO-PCDD/F TEQ concentrations in fillets on a fresh weight basis at the same times and over the same periods were, 0.67-1.18pg-TEQg(-1) and 0.16-0.29pg-TEQg(-1), respectively. All WHO-PCB congeners, and only three WHO-PCDD/F congeners, were found to biomagnify during farming, after blank correction. Caution should be exercised when extrapolating these results to SBT farming as a whole because of the use of varying husbandry and feeding practices employed by different companies.

Minimally Invasive Trigeminal Ablation: Novel Transoral Technique for Targeted Treatment of V3.

BACKGROUND: Trigeminal neuralgia (TN) is a chronic orofacial pain syndrome that presents with debilitating shooting pains in the V3 nerve distribution. The condition is traditionally responsive to anticonvulsant therapy; however, cases that become refractory to medications often require surgical intervention. CASE DESCRIPTION: We present a case of TN that was treated with minimally invasive trigeminal ablation. The patient presented with a 6-year history of TN that had been resistant to medical management. The patient opted for minimally invasive management, refused stereotactic radiosurgery, and was treated using the minimally invasive trigeminal ablation approach. At 16 weeks postoperatively, the patient reported complete alleviation of pain with minimal sensorineural numbness. CONCLUSIONS: The endoscopic approach allows for precise targeting through visual guidance, which is ideal in patients undergoing neuroablation for pain within specific nerve distributions. This is the first documented case of an endoscopic minimally invasive transoral approach toward ablative TN management.

Emission characteristics of a pyrolysis-combustion system for the co-production of biochar and bioenergy from agricultural wastes.

The co-production of biochar and bioenergy using pyrolysis-combustion processes can potentially minimize the emission problems associated with conventional methods of agricultural by-product disposal. This approach also provides significant added-value potential through biochar application to soil. Despite these advantages, variations in biomass composition, including sulfur, nitrogen, ash, and volatile matter (VM) content, may significantly influence both the biochar quality and the emissions of harmful particulate matter (PM) and gaseous pollutants (SO2, H2S, NO2, NO). Using a laboratory-scale continuous pyrolysis-combustion facility, the influence of biomass composition (rice husk and grape pruning) and volatile production (pyrolysis) temperature (400-800 °C) on the biochar properties and emissions during combustion of the raw pyrolysis volatiles were evaluated. Utilization of grape pruning resulted in higher energy-based yields of PM10 than the rice husk, the majority of which consisted of the PM1.1 fraction due to the elevated pyrogas content of the volatiles. The PM emissions were found to be independent of the feedstock ash content due to its retainment in the biochar. Greater volatilization of biomass sulfur and nitrogen during pyrolysis at higher temperatures resulted in higher yields of sulfurous and nitrogenous gaseous pollutants. The energy-based yields of NO and NO2 were found to increase by 16% and 50% for rice husk and 21% and 189% for grape pruning respectively between 400 and 800 °C. The same trend was also observed for the emissions of H2S and SO2 for both feedstocks.

Racial disparities in cancer-related survival in patients with squamous cell carcinoma of the esophagus in the US between 1973 and 2013.

BACKGROUND: Esophageal cancer makes up approximately 1% of all diagnosed cancers in the US. There is a persistent disparity in incidence and cancer-related mortality rates among different races for esophageal squamous cell carcinoma (SCC). Most previous studies investigated racial disparities between black and white patients, occasionally examining disparities for Hispanic patients. Studies including Asians/Pacific Islanders (API) as a subgroup are rare. Our objective was to determine whether there is an association between race and cancer-related survival in patients with esophageal SCC. METHODS AND FINDINGS: This was a retrospective cohort study using the National Cancer Institute's Surveillance, Epidemiology, and End Result (SEER) database. The SEER registry is a national database that collects information on all incident cancer cases in 13 states of the United States and covers nearly 26% of the US population Patients aged 18 and over of White, Black, or Asian/Pacific Islander (API) race with diagnosed esophageal SCC from 1973 to 2013 were included (n = 13,857). To examine overall survival, Kaplan-Meier curves were estimated for each race and the log-rank test was used to compare survival distributions. Cox proportional hazards models were used to estimate unadjusted and adjusted hazard ratios with 95% confidence intervals. The final adjusted model controlled for sex, marital status, age at diagnosis, decade of diagnosis, ethnicity, stage at diagnosis, and form of treatment. Additional analyses stratified by decade of diagnosis were conducted to explore possible changes in survival disparities over time. After adjustment for potential confounders, black patients had a statistically significantly higher hazard ratio compared to white patients (HR 1.08; 95% confidence interval (CI) 1.03-1.13). However, API patients did not show a statistically significant difference in survival compared with white patients (HR 1.00; 95% CI 0.93-1.07). Patients diagnosed between 1973 and 1979 had twice the hazard of death compared to those diagnosed between 2000 and 2013 (HR 2.05, 95% CI 1.93-2.19). Patients diagnosed in 1980-1989 and 1990-1999 had had HRs of 1.59 (95% CI 1.51-1.68) and 1.33 (95% CI 1.26-1.41), respectively. After stratification according to decade of diagnosis, the HR for black patients compared with white patients was 1.14 (95% CI 1.02-1.29) in 1973-1979 and 1.12 (95% CI 1.03-1.23) in 1980-1989. These disparities were not observed after 1990; the HR for black patients compared with white patients was 1.03 (95% CI 0.93-1.13) in 1990-1999 and 1.05 (95% CI 0.96-1.15) in 2000-2013. CONCLUSIONS: Black patients with esophageal SCC were found to have a higher hazard of death compared to white and API patients. Survival disparities between races appear to have decreased over time. Future research that takes insurance status and other social determinants of health into account should be conducted to further explore possible disparities by race.

Polycyclic aromatic hydrocarbons on particulate matter emitted during the co-generation of bioenergy and biochar from rice husk.

The aim of this study was to evaluate the emissions of polycyclic aromatic hydrocarbons (PAHs) bound to the particulate matter (PM) during the combustion of raw pyrolysis volatiles (bio-oil and pyrogas mixture) generated from the pyrolysis of rice husk. Five different raw pyrolysis volatiles were produced at varying pyrolysis temperatures (400-800°C) and subsequently combusted in a laboratory-scale, continuous pyrolysis-combustion facility at 850°C. 15 priority pollutant PAH levels in the resulting biochar, bio-oil, and PM were evaluated. Results showed that combustion of the raw pyrolysis volatiles produced at elevated pyrolysis temperatures resulted in greater concentrations of PM-bound PAHs (119% increase between 400 and 800°C) due to the increased PAH and oxy-aromatic content of the bio-oil fraction. Significantly increased benzo(a)pyrene (BaP) - equivalent toxicity of the biochar and PM was observed at elevated pyrolysis temperatures.

Clinical, surgical, and electrical factors impacting residual hearing in cochlear implant surgery.

CONCLUSIONS: This study recommends using soft surgical principal and round window insertion to protect residual hearing with favorable anatomical exposure. Further studies are needed to evaluate the impact of the electrical stimulation on the organ of corti and hearing. OBJECTIVE: The objective of this study is to analyze various factors that impact on preservation of residual hearing post-implantation. METHODS: A retrospective study was performed to analyze loss of residual hearing in a cohort of 225 patients implanted in a large academic center. Sixty-four patients met the inclusion criteria. The impact of age at implantation, gender, etiology of hearing loss, cochleostomy vs round window insertion, partial vs full insertion, and effect of initial stimulation were analyzed using appropriate statistical analysis. RESULTS: The overall hearing preservation rate for all implanted patients was 64%. Loss of residual hearing was significantly more observed in cases of cochleostomy and/or non-soft surgical techniques. No correlation was observed with age at implantation, gender, side of implant, device manufacturer, and presence of pre-lingual deafness vs post-lingual, full or partial electrode insertion. In addition, there was a small but significant decrease in hearing between pre-stimulation and post-stimulation audiograms at 6000 Hz.

Improving adherence in mental health service users with severe mental illness in South Africa: a pilot randomized controlled trial of a treatment partner and text message intervention vs. treatment as usual.

OBJECTIVES: Medication non-adherence is a significant problem in treatment of severe mental disorders and is associated with poor clinical outcomes and increased demand on services. Task-shifting interventions incorporating mobile health may improve adherence in mental health service users in low- and middle-income countries. Seventy-seven participants were recruited from a psychiatric hospital in Cape Town, with 42 randomized to receive the intervention and 35 to treatment as usual. Intervention pairs underwent treatment-partner contracting and psychoeducation, and received monthly text message reminders of clinic appointments. Primary outcomes were intervention acceptability and feasibility. Secondary outcome for efficacy were adherence to clinic visit; relapse; quality of life; symptomatic relief and medication adherence. RESULTS: Treatment partner and psychoeducation components were acceptable and feasible. The text message component was acceptable but not feasible in its current form. Efficacy outcomes favoured the intervention but did not reach statistical significance. A treatment-partner intervention is acceptable and feasible in a low- and middle-income setting. Work is needed to ensure that additional components of such interventions are tailored to the local context. Appropriately powered efficacy studies are needed. Trial Registration PACTR PACTR201610001830190, Registered 21 October 2016 (Retrospectively registered).

Technical issues in the large-scale hydrothermal liquefaction of microalgal biomass to biocrude.

Much of the current knowledge on the hydrothermic liquefaction of biomass to biocrude is on the basis of laboratory benchtop findings, and the step up to industrial scale reactors will require a range of information that is currently either unavailable or insufficient. This work highlights a number of these issues such as the heat of reaction, process heat recovery, optimal reaction time and waste product treatment. Effects of these knowledge gaps on the reactor design, process economics, and impacts on the environment are discussed. Although technologies do exist to deal with some of these issues, their applications are often limited by economic considerations and further studies are required.

Hydrothermal liquefaction of microalgae for biocrude production: Improving the biocrude properties with vacuum distillation.

This paper proposes a two-part process for producing biocrude with reduced impurities. The biocrude was produced from hydrothermal liquefaction (HTL) of Spirulina sp. and Tetraselmis sp. in a batch reactor at both 300 and 350°C, 5min, and 16%w/w solid feed composition. The resultant biocrudes were vacuum distilled at a maximum temperature of 360°C. It was shown that biocrude quality could be enhanced without using catalyst by vacuum distillation (VD). The biocrude yield for Spirulina sp. was 36wt% at 300°C, 42wt% at 350°C, and for Tetraselmis sp. was 34wt% at 300°C, and 58wt% at 350°C. VD of Spirulina sp. biocrude obtained at 300 and 350°C led to 62 and 67wt% distilled biocrudes yield, respectively. VD of Tetraselmis sp. biocrude obtained at 300°C was 70wt%, and 73wt% at 350°C. The higher heating values (HHV) increased from 32MJ/kg to 40MJ/kg. There were substantial reductions in oxygen, metallic content, and boiling point ranges in distilled biocrudes.

Force and energy requirement for microalgal cell disruption: an atomic force microscope evaluation.

Cell disruption is an essential step in the release of cellular contents but mechanical cell disruption processes are highly energy intensive. This energy requirement may become a critical issue for the sustainability of low valued commodities such as microalgal biofuels derived from extracted lipids. By the use of an atomic force microscope (AFM), this study evaluated the force and energy required to indent and disrupt individual cells of the marine microalga, Tetraselmis suecica. It was found that the force and energy required for the indentation and disruption varies according to the location of the cell with the average being 17.43 pJ. This amount is the equivalent of 673 J kg(-1) of the dry microalgal biomass. In comparison, the most energy efficient mechanical cell disruption process, hydrodynamic cavitation, has specific energy requirement that is approx. 5 orders of magnitude greater than that measured by AFM. The result clearly shows that existing mechanical cell disruption processes are highly energy inefficient and further research and innovation is required for sustainable microalgal biofuels production.