The SARS‐CoV‐2 virus, which causes coronavirus disease 2019 (COVID‐19), has rapidly swept across the world since its identification in December 2019. Otolaryngologists are at unique risk due to the ...close contact with mucus membranes of the upper respiratory tract and have been among the most affected healthcare workers in Wuhan, China. We present information on COVID‐19 management relevant to otolaryngologists on the frontlines of this pandemic and provide preliminary guidance based on practices implemented in China and other countries and practical strategies deployed at Stanford University. Laryngoscope, 130:2537–2543, 2020
The incidence of thyroid cancer is increasing by 3% annually. This increase is often thought to be attributable to overdiagnosis in adults. A previous study reported a 1.1% annual increase in the ...incidence of pediatric thyroid cancer. However, the analysis was limited to the period from 1973 to 2004 and was performed in a linear fashion, which does not account for changes in incidence trends over time.
To analyze trends in pediatric thyroid cancer incidence based on demographic and tumor characteristics at diagnosis.
This cross-sectional study included individuals younger than 20 years who had a diagnosis of thyroid cancer in the Surveillance, Epidemiology, and End Results (SEER) 9 database from 1973 to 2013. Cases of thyroid cancer were identified using the International Classification of Diseases for Oncology, Third Edition and were categorized by histologic type, stage, and tumor size.
Annual percent change (APC) in the incidence rates was calculated using joinpoint regression analysis.
Among 1806 patients included in the analysis, 1454 (80.5%) were female and 1503 (83.2%) were white; most patients were aged 15 to 19 years. The overall incidence rates of thyroid cancer increased annually from 0.48 per 100 000 person-years in 1973 to 1.14 per 100 000 person-years in 2013. Incidence rates gradually increased from 1973 to 2006 (APC, 1.11%; 95% CI, 0.56%-1.67%) and then markedly increased from 2006 to 2013 (APC, 9.56%; 95% CI, 5.09%-14.22%). The incidence rates of large tumors (>20 mm) gradually increased from 1983 to 2006 (APC, 2.23%; 95% CI, 0.93%-3.54%) and then markedly increased from 2006 to 2013 (APC, 8.84%; 95% CI, 3.20%-14.79%); these rates were not significantly different from incidence rates of small (1-20 mm) tumors. The incidence rates of regionally extended thyroid cancer gradually increased from 1973 to 2006 (APC, 1.44%; 95% CI, 0.68%-2.21%) and then markedly increased from 2006 to 2013 (APC, 11.16%; 95% CI, 5.26%-17.40%); these rates were not significantly different from the incidence rates of localized disease.
The incidence rates of pediatric thyroid cancer increased more rapidly from 2006 to 2013 than from 1973 to 2006. The findings suggest that there may be a co-occurring increase in thyroid cancer in the pediatric population in addition to enhanced detection.
Current clinical interest lies in the relationship between hearing loss and cognitive impairment. Previous work demonstrated that noise exposure, a common cause of sensorineural hearing loss (SNHL), ...leads to cognitive impairments in mice. However, in noise-induced models, it is difficult to distinguish the effects of noise trauma from subsequent SNHL on central processes. Here, we use cochlear hair cell ablation to isolate the effects of SNHL. Cochlear hair cells were conditionally and selectively ablated in mature, transgenic mice where the human diphtheria toxin (DT) receptor was expressed behind the hair-cell specific Pou4f3 promoter. Due to higher Pou4f3 expression in cochlear hair cells than vestibular hair cells, administration of a low dose of DT caused profound SNHL without vestibular dysfunction and had no effect on wild-type (WT) littermates. Spatial learning/memory was assayed using an automated radial 8-arm maze (RAM), where mice were trained to find food rewards over a 14-day period. The number of working memory errors (WME) and reference memory errors (RME) per training day were recorded. All animals were injected with DT during P30-60 and underwent the RAM assay during P90-120. SNHL animals committed more WME and RME than WT animals, demonstrating that isolated SNHL affected cognitive function. Duration of SNHL (60 versus 90 days post DT injection) had no effect on RAM performance. However, younger age of acquired SNHL (DT on P30 versus P60) was associated with fewer WME. This describes the previously undocumented effect of isolated SNHL on cognitive processes that do not directly rely on auditory sensory input.
There is a critical disparity in knowledge regarding the rate and nature of hearing loss in the older old (80 years and older).
To determine if the rate of age-related hearing loss is constant in the ...older old.
We performed a retrospective review that began on August 1, 2014, with audiometric evaluations at an academic medical center of 647 patients aged between 80 and 106 years, of whom 141 had multiple audiograms.
From a population perspective, the degree of hearing loss was compared across the following age brackets: 80 to 84 years, 85 to 89 years, 90 to 94 years, and 95 years and older. From an individual perspective, the rate of hearing decrease between 2 audiograms was compared with age.
Changes in hearing among age brackets were higher during the 10th decade of life than the 9th decade at all frequencies (5.4-11.9 dB hearing level dB HL) for the 647 patients (mean SD age, 90 5.5 years). Correspondingly, the annual rate of low-frequency hearing loss was faster during the 10th decade by the 3.8 dB HL per year at 0.25 kHz, 3.8 dB HL per year at 0.5 kHz, and 3.2 dB HL per year at 1 kHz. Despite the universal presence of hearing loss in our sample, 382 patients (59%) used hearing aids.
There is a significant increase in the rate of hearing loss in patients during the 10th decade of life compared with the 9th decade that represents a fundamental change in the mechanistic process of presbycusis. Despite the potential benefit of hearing aids, they remain underused in the older old. Use may be improved by changing the method of hearing rehabilitation counseling from a patient-initiated model to a chronic disease example.
The activity of bacteriophages poses a major threat to bacterial survival. Upon infection, a temperate phage can either kill the host cell or be maintained as a prophage. In this state, the bacteria ...carrying the prophage is at risk of superinfection, where another phage injects its genetic material and competes for host cell resources. To avoid this, many phages have evolved mechanisms that alter the bacteria and make it resistant to phage superinfection. The mechanisms underlying these phentoypic conversions and the fitness consequences for the host are poorly understood, and systematic studies of superinfection exclusion mechanisms are lacking. In this study, we examined a wide range of Pseudomonas aeruginosa phages and found that they mediate superinfection exclusion through a variety of mechanisms, some of which affected the type IV pilus and O-antigen, and others that functioned inside the cell. The strongest resistance mechanism was a surface modification that we showed is cost-free for the bacterial host in a natural soil environment and in a Caenorhabditis. elegans infection model. This study represents the first systematic approach to address how a population of prophages influences phage resistance and bacterial behavior in P. aeruginosa.
In the United States, the population of individuals older than 80 years is expected to double in the next 40 years. Cardiovascular comorbidities are prevalent in this older old population, and their ...relationship with hearing loss has not been well characterized.
To investigate the association of cardiovascular disease (CVD)-related risk factors with auditory function among the older old (>80 years).
Audiological data and medical records from 2001 through 2014 of 433 patients aged 80 to 106 years at an academic medical center were analyzed in 2017.
The degree of low- and high-frequency hearing loss of participants with coronary artery disease, diabetes, hypertension, history of cerebrovascular accident, and smoking status was compared with that of disease-free individuals. Rate of hearing loss was also determined.
Among the 433 patients (67% female; mean SD age, 89 5.8 years), the presence of at least 1 cardiovascular morbidity was associated with elevated mean (SD) low-frequency pure-tone average (LFPTA) of 42.4 (1.6) vs 36.9 (3.5) decibels hearing loss (dB HL), a difference of 5.47 (95% CI, 4.15-9.49) dB HL. Among the 96 patients with 2 audiograms performed at age 80 years or older from which the rate of hearing loss could be calculated, 32 patients had CVD or related risk factors and 64 were healthy controls. Those with at least 1 disease had accelerated hearing loss. Patients with cardiovascular morbidity experienced a faster mean (SD) decline in LFPTA of 1.90 (0.27) vs 1.18 (0.42) dB HL/y, a difference of 0.72 (95% CI, 0.08-1.36) dB HL/y. Of the conditions studied, coronary artery disease had the highest association with audiometric thresholds and was associated with hearing loss at all frequencies tested and with poor word recognition score. Hearing loss was more strongly associated with CVD risk factors in men than in women.
In this study of the older old, cardiovascular risk factors and disease were associated with worse hearing and a greater rate of hearing deterioration. Hearing loss in women was less associated with the presence of CVD, possibly owing to the cardioprotective effects of estrogen. The association of hearing with CVD severity and management remains to be determined.
Rapid, inexpensive, robust diagnostics are essential to control the spread of infectious diseases. Current state of the art diagnostics are highly sensitive and specific, but slow, and require ...expensive equipment. Here we report the development of a molecular diagnostic test for SARS-CoV-2 based on an enhanced recombinase polymerase amplification (eRPA) reaction. eRPA has a detection limit on patient samples down to 5 viral copies, requires minimal instrumentation, and is highly scalable and inexpensive. eRPA does not cross-react with other common coronaviruses, does not require RNA purification, and takes ~45 min from sample collection to results. eRPA represents a first step toward at-home SARS-CoV-2 detection and can be adapted to future viruses within days of genomic sequence availability.
Objectives/Hypothesis
To determine the effect of povidone‐iodine (PVP‐I) nasal sprays on nasopharyngeal (NP) viral load as assessed by cycle threshold (Ct) on quantitative polymerase chain reaction ...(qPCR) of SARS‐CoV‐2 in outpatients.
Study Design
Three arm, triple blinded, randomized, placebo‐controlled clinical trial.
Methods
Participants were randomized within 5 days of testing positive for COVID‐19 to receive nasal sprays containing placebo (0.9% saline), 0.5% PVP‐I, or 2.0% PVP‐I. NP swabs for qPCR analysis were taken at baseline, 1‐hour post‐PVP‐I spray (two sprays/nostril), and 3 days post‐PVP‐I spray (20 sprays/nostril). Symptom and adverse event questionnaires were completed at baseline, day 3, and day 5. University of Pennsylvania Smell Identification Tests (UPSIT) were completed at baseline and day 30.
Results
Mean Ct values increased over time in all groups, indicating declining viral loads, with no statistically significant difference noted in the rate of change between placebo and PVP‐I groups. The 2.0% PVP‐I group showed statistically significant improvement in all symptom categories; however, it also reported a high rate of nasal burning. Olfaction via UPSIT showed improvement by at least one category in all groups. There were no hospitalizations or mortalities within 30 days of study enrollment.
Conclusions
Saline and low concentration PVP‐I nasal sprays are well tolerated. Similar reductions in SARS‐CoV‐2 NP viral load were seen over time in all groups. All treatment groups showed improvement in olfaction over 30 days. These data suggest that dilute versions of PVP‐I nasal spray are safe for topical use in the nasal cavity, but that PVP‐I does not demonstrate virucidal activity in COVID‐19 positive outpatients.
Level of Evidence
2 Laryngoscope, 132:2089–2095, 2022
Retroperitoneal lymph node dissection (RPLND) is the standard of care for testicular cancer in various disease settings. Deep vein thrombosis (DVT) complications have been reported to occur in <1% of ...primary RPLND cases and up to 3% of postchemotherapy (PC-RPLND) cases. While prophylactic anticoagulation (AC) has been well-documented to reduce DVT rates in patients undergoing surgery in general, the benefit of prophylactic AC in RPLND has not been assessed. In this retrospective cohort study, we seek to address this unmet need by evaluating the rates and associated risk factors of DVT and pulmonary embolism (PE) with a national and institutional database, assess the changing patterns in DVT prophylaxis with postoperative AC following RPLND, and quantify the potential benefit of prophylactic AC in patients who have undergone RPLND using a risk-stratified approach.
The National Surgical Quality Improvement Program (NSQIP) database was queried for patients who underwent RPLND during the 10-year period from 2011 to 2021. An institutional database was queried for all patients undergoing RPLND from 2013 to 2022. Patient characteristics and operative outcomes were compared between the NSQIP and the institutional database. The institutional database was stratified by prior oncologic treatment (i.e., primary RPLND vs. PC-RPLND) and outcomes were compared. Postoperative AC rate was determined and trended by year. The use of postoperative AC and PE events were stratified by clinical stage. The absolute risk reduction (ARR) of AC prophylaxis on PE events and the number needed to treat (NNT) with AC prophylaxis to prevent a single PE event was determined.
In total, the NSQIP database query resulted in 779 patients and our institutional database query resulted in 188 patients. The rate of DVT and PE was 1.2% and 0.5% vs. 2.1% and 1.6% in the NSQIP and institutional cohort, respectively. The rate of postoperative AC following RPLND in patients from the institutional database increased from 5% in 2013 to 43% in 2022 (P = 0.01). There were no statistically significant differences in complication rates, including bleeding events, chyle leaks, or hospital readmissions amongst patients who were prescribed AC at discharge and those who were not. No stage I patients developed PEs and no stage I patients were prescribed AC. The ARR for AC prophylaxis for development of PE was found to be 0.023 for the clinical stage II and stage III cohorts. The NNT to prevent a single PE with AC was 44 and 43 for the stage II and stage III cohorts, respectively.
AC appears beneficial with minimal risk of harm after RPLND, especially in patients with higher risk of developing DVT/PE, highlighting the safety and efficacy of this regimen. There was a significant increase in the rate of AC prophylaxis at discharge amongst patients undergoing RPLND in the institutional database from 2013 to 2022. A risk-stratified protocol of postoperative AC following RPLND appears reasonable, and further prospective trials are warranted to formally confirm this recommendation.