Abstract Objectives In this study, we estimate an ex ante cost–benefit analysis of a Utah law directed at improving early cytomegalovirus (CMV) detection. Study design We use a differential cost of ...treatment analysis for publicly insured CMV-infected infants detected by a statewide hearing-directed CMV screening program. Methods Utah government administrative data and multi-hospital accounting data are used to estimate and compare costs and benefits for the Utah infant population. Results If antiviral treatment succeeds in mitigating hearing loss for one infant per year, the public savings will offset the public costs incurred by screening and treatment. If antiviral treatment is not successful, the program represents a net cost, but may still have non-monetary benefits such as accelerated achievement of diagnostic milestones. Conclusions The CMV education and treatment program costs are modest and show potential for significant cost savings.
Compare outcomes between a microscopic and endoscopic technique for anterior tympanic membrane (TM) perforation.
Results of microscopic overlay (MT) and endoscopic tympanoplasty (ET) for management ...of anterior TM perforations from a single surgeon.
There were 28 patients in the MT group and 35 in the ET group. The mean age was 7.1 years and 10.9 years (p < 0.001) MT and ET groups respectively. There was no statistical differences in perforation location (p = 0.1), etiology (p = 0.52) or size (p = 0.1) between both groups. Mean operating time was 119.0 min and 131.0 min in the MT and ET groups respectively (p = 0.23). Follow up was 30.9 months and 9.0 months (p = 0.001) MT and ET respectively. The perforation was successfully closed in 29 patients at 6 weeks in the ET (82.9%) and 25 in the MT (89.3%), p = 0.47. Adjusting for age revealed no significant difference between groups. Long term follow up, resulted in 10 failures (28.6%) and 7 patients (25.0%) in the ET and MT groups respectively, p = 0.75. Adjusting for the follow-up period or age, there was no significant difference between groups. The change in ABG and PTA measures were not statistically different between groups.
An anteriorly based ET is a novel technique for management of anterior TM perforations. Results from this pilot study indicate that this ET approach may be an appropriate alternative to MT for difficult to repair anterior perforations. A longer follow-up will be necessary to determine its role in these perforations.
Objectives
To determine whether common otolaryngology procedures generate viable aerosolized virus through a murine cytomegalovirus (mCMV) model for infection.
Study Design
mCMV model of infection.
...Setting
University of Utah laboratory.
Methods
Three-day-old BALB/c mice were inoculated with mCMV or saline. Five days later, each mouse underwent drilling, microdebrider, coblation, and electrocautery procedures. Particle size distribution and PM2.5 (particulate matter <2.5 µm) concentration were determined with a scanning mobility particle sizer and an aerosol particle sizer in the range of 15 nm to 32 µm. Aerosolized samples from these procedures were collected with an Aerosol Devices BioSpot sampler for viral titer based on polymerase chain reaction and for viable virus through viral culture.
Results
As compared with the background aerosol concentrations, coblation and electrocautery showed statistically significant increases in airborne aerosols (Tukey-adjusted P value <.040), while microdebrider and drilling at 30,000 rpm did not (.870 < Tukey-adjusted P value < .930). We identified viral DNA in samples from coblation and drilling procedures, although we did not identify viable viruses in aerosol samples from any of the 4 procedures.
Conclusion
Coblation and electrocautery procedures generate >100-fold increases in aerosol concentrations over background; only coblation and drilling produce aerosolized viral DNA. The high concentration of aerosols from coblation and electrocautery suggests the need for appropriate safeguards against particle exposure to health care workers. The presence of viral DNA from drilling and coblation procedures warrants the need for appropriate protection against droplet and aerosol exposure.
Objective
To determine whether ganciclovir (GCV) treatment reduces sensorineural hearing loss in cytomegalovirus (CMV)‐infected mice. The effects of GCV on viral load, absolute neutrophil count ...(ANC), and outer hair cell (OHC) integrity were also investigated.
Methods
Infected BALB/c mice were inoculated with murine CMV on postnatal day 3. Those treated with GCV received an intraperitoneal injection twice a day for 14 days. Auditory thresholds were assessed using distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) testing 4 weeks after inoculation. Temporal bones were used for determination of viral load by quantitative polymerase chain reaction and hair cell quantification by scanning electron microscopy. ANCs were completed by an automated hematology analyzer, with manual review for confirmation.
Results
GCV‐treated CMV‐infected mice had lower ABR (P < 0.0001, Kruskal‐Wallis test) and DPOAE (P < 0.0001) thresholds compared to CMV‐infected untreated mice, indicating that GCV protected mice from CMV‐induced hearing loss. Viral load in infected populations undergoing GCV treatment was significantly decreased (P = 0.03) relative to untreated mice. GCV treatment alone had no effect on ABR and DPOAE compared to untreated, uninfected controls (P = 0.1, P = 0.24, respectively). GCV‐treated mice received increased protection from OHC loss when compared to untreated groups, with total OHC losses of approximately 7% and 14%, respectively (P < 0.05). Neutropenia was absent after 7 days of GCV treatment.
Conclusion
Ganciclovir effectively ameliorated SNHL and partially protected from OHC loss in a preclinical model of congenital CMV infection, seemingly by reducing viral load.
Level of Evidence
NA Laryngoscope, 130:1064–1069, 2020
Some forms of sensorineural hearing loss involve damage or degenerative changes to the stria vascularis and/or other vascular structures in the cochlea. In animal models, many methods for anatomical ...assessment of cochlear vasculature exist, each with advantages and limitations. One methodology, corrosion casting, has proved useful in some species, however in the mouse model this technique is difficult to achieve because digestion of non vascular tissue results in collapse of the delicate cast specimen. We have developed a partial corrosion cast method that allows visualization of vasculature along much of the cochlear length but maintains some structural integrity of the specimen. We provide a detailed step-by-step description of this novel technique. We give some illustrative examples of the use of the method in mouse models of presbycusis and cytomegalovirus (CMV) infection.
•We describe a reliable protocol for corrosion casting of vasculature in the mouse cochlea.•A complete cast of capillary beds is achieved by pressure and temperature controlled perfusion of polymer.•A partial, timed corrosion method is essential to maintain the structural integrity of the cochlear cast.•This protocol consistently provides full perfusion of capillary beds in stria vascularis, spiral ligament and spiral limbus.•This novel method is described in detail; examples of its utility in models of presbyacusis and CMV infection are provided.
Congenital cytomegalovirus (cCMV) continues to be a major public health care issue due to its high prevalence throughout the world. However, there is a paucity of studies evaluating how providers ...manage this infection. This study surveyed North American Pediatric Infectious Disease (PID) physicians to elicit their approach towards the evaluation and treatment of this condition. Thirty-two PID physicians responded to this survey. Institutional testing and screening for cCMV were infrequently reported. The respondents in general agreed upon most laboratory and diagnostic testing except for neuroimaging. For those tests, there was a disparity in indications for head ultrasound versus brain MRI imaging. Most (68.8%) agreed with the clinical practice of starting valganciclovir in an infant less than 1 month of age with one sign or symptom of disease, and 62.5% would do so for an infant with isolated sensorineural hearing loss. However, only 28.1% would treat cCMV-infected infants older than 1 month of age. In conclusion, few healthcare institutions represented by PID physicians in this cohort had a cCMV screening or testing initiative, yet most respondents would test at a much higher level based on their clinical practice. While there is general consensus in evaluation and treatment of these children, there are disparities in practices regarding neuroimaging and indications for antiviral treatment with respect to age and severity of disease. There is a great need for an evidence based policy statement to standardize cCMV workup and treatment.
Usher syndrome (USH) is the leading cause of inherited deaf-blindness, with type 2 (USH2) being the most common clinical form. Studies suggest that proteins encoded by USH2 causative genes assemble ...into the ankle link complex (ALC) at the hair cell stereociliary bundle; however, little is known about the in vivo assembly and function of this complex. Using various USH2 mutant mice, we showed by immunofluorescence that USH2 proteins play different roles in cochlear ALC assembly, with G protein-coupled receptor 98 being the most important protein. Complex assembly likely occurs at the stereociliary bundle but not along the protein transport route in the cell body. Stereociliary morphological defects in USH2 mutant mice suggest roles for the ALC in regulating inner hair cell stereociliary growth and differentiation as well as outer hair cell stereociliary rigidity and organization during development. These roles are unique from the bundle cohesion role of Usher syndrome type 1 protein complexes. Loss of individual USH2 gene expressions leads to variable morphological and functional consequences, correlating with the severity of ALC disruption. This finding suggests a potential genotype-phenotype correlation in USH2 patients. In summary, this study provides novel insights into the molecular mechanism underlying cochlear stereociliary bundle development and hearing loss pathogenesis of various USH2 subtypes. Our thorough phenotypical characterization of USH2 mouse models is essential for future use of these animal models in therapeutic development.
Purpose
Glioblastoma (GBM) is the most common and aggressive malignant glioma, with an overall median survival of less than two years. The ability to predict survival before treatment in GBM patients ...would lead to improved disease management, clinical trial enrollment, and patient care.
Methods
GBM patients (N = 133, mean age 60.8 years, median survival 14.1 months, 57.9% male) were retrospectively recruited from the neurosurgery brain tumor service at Washington University Medical Center. All patients completed structural neuroimaging and resting state functional MRI (RS-fMRI) before surgery. Demographics, measures of cortical thickness (CT), and resting state functional network connectivity (FC) were used to train a deep neural network to classify patients based on survival (< 1y, 1-2y, >2y). Permutation feature importance identified the strongest predictors of survival based on the trained models.
Results
The models achieved a combined cross-validation and hold out accuracy of 90.6% in classifying survival (< 1y, 1-2y, >2y). The strongest demographic predictors were age at diagnosis and sex. The strongest CT predictors of survival included the superior temporal sulcus, parahippocampal gyrus, pericalcarine, pars triangularis, and middle temporal regions. The strongest FC features primarily involved dorsal and inferior somatomotor, visual, and cingulo-opercular networks.
Conclusion
We demonstrate that machine learning can accurately classify survival in GBM patients based on multimodal neuroimaging before any surgical or medical intervention. These results were achieved without information regarding presentation symptoms, treatments, postsurgical outcomes, or tumor genomic information. Our results suggest GBMs have a global effect on the brain’s structural and functional organization, which is predictive of survival.
Abstract
Background
Intraoperative auditory brainstem response (ioABR) testing under general anesthesia is commonly performed on children when sleep-deprived ABR and behavioral testing are not ...reliable or feasible. Several studies have reported potential confounding results when tube insertion is combined with ABR testing.
Purpose
This article evaluates whether a temporary threshold shift (TTS) occurs following placement of tympanostomy tubes (TTs) in children who undergo ioABR testing.
Research Design
A case–control prospective study. Patients scheduled for combined TT and ioABR procedures were enrolled into this study.
Study Sample
Twenty children (38 ears), ranging in age from 6 months to 10.5 years, were enrolled.
Data Collection and Analysis
ABR thresholds for tone bursts with center frequencies of 2 and 4 kHz were compared before and after tube insertion. The indication for surgery, comorbidities, and status of the middle ear were also recorded. A paired
t
-test was used to determine statistical significance.
Results
Data collection did not necessarily indicate suctioning and tube placement were causing a TTS; however, fluid present in the middle ear space prior to TT placement appeared to influence results. Although a paired
t
-test did not show statistically significant differences in ABR thresholds between groups of individuals with and without fluid and before and after tube placement, 50% of patients with mucoid fluid (two out of four patients) were noted to have 10 dB or greater worsening in ABR thresholds in two out of six ears. Twenty-nine percent of patients with serous fluid (two out of seven patients) were noted to have at least a 10 dB worsening in ABR threshold in 2 out of 10 ears. Further testing is needed to confirm these trends.
Conclusion
This pilot study indicates that children with mucoid or serous fluid may experience worse ABR thresholds following TT insertion. ioABR testing immediately after TT tube placement and in the presence of middle ear fluid should be interpreted with caution. Additional studies with a larger sample size are needed to confirm these results.
To determine the positivity rate of congenital cytomegalovirus (cCMV) testing among universal, hearing-targeted CMV testing (HT-cCMV) and delayed targeted dried blood spot (DBS) testing newborn ...screening programs, and to examine the characteristics of successful HT-cCMV testing programs.
Prospective survey of birth hospitals performing early CMV testing.
Multiple institutions.
Birth hospitals participating in the National Institutes of Health ValEAR clinical trial were surveyed to determine the rates of cCMV positivity associated with 3 different testing approaches: universal testing, HT-cCMV, and DBS testing. A mixed methods model was created to determine associations between successful HT-cCMV screening and specific screening protocols.
Eighty-two birth hospitals were surveyed from February 2019 to December 2021. Seven thousand six hundred seventy infants underwent universal screening, 9017 infants HT-cCMV and 535 infants delayed DBS testing. The rates of cCMV positivity were 0.5%, 1.5%, and 7.3%, respectively. The positivity rate for universal CMV screening was less during the COVID-19 pandemic than that reported prior to the pandemic. There were no statistically significant drops in positivity for any approach during the pandemic. For HT-cCMV testing, unique order sets and rigorous posttesting protocols were associated with successful screening programs.
Rates of cCMV positivity differed among the 3 approaches. The rates are comparable to cohort studies reported in the literature. Universal CMV prevalence decreased during the pandemic but not significantly. Institutions with specific order set for CMV testing where the primary care physician orders the test and the nurse facilitates the testing process exhibited higher rates of HT-cCMV testing.
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