Congenital Cytomegalovirus Testing Outcomes From the ValEAR Trial.

OBJECTIVE: 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. STUDY DESIGN: Prospective survey of birth hospitals performing early CMV testing. SETTING: Multiple institutions. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Long-term Outcomes of Vocal Fold Paralysis Following Patent Ductus Arteriosus Ligation in Neonates.

INTRODUCTION: In patients undergoing patent ductus arteriosus (PDA) ligation there is a significant risk of left vocal fold paralysis (LVFP) particularly in premature neonates who are small for gestational age. The objective of this study is to determine the incidence of LVFP in infants following PDA ligation and report on long-term outcomes in patients with LVFP. METHODS: We performed a prospective study of patients undergoing PDA ligation in the newborn intensive care unit (NICU) between April 2004 and May 2014. Following PDA ligation, flexible laryngoscopy was performed to assess vocal fold mobility. Patients were then followed longitudinally to determine long-term outcomes. RESULTS: A total of 163 infants underwent PDA ligation. Thirty-six patients (22%) developed LVFP following the procedure. Twenty-five percent of neonates <1500 g experienced LVFP versus 5% of patients >1500 g (p = 0.033). Patients with LVFP were more likely to require a feeding tube (64% vs. 19.6%; p < 0.05) and spent more time in the NICU (135 days vs. 106 days; p < 0.05). Twenty-four patients received long-term follow-up. Six (25%) had complete resolution of LVFP, 10 (42%) were compensated, and 8 (33%) demonstrated persistent LVFP with no improvement. CONCLUSIONS: The incidence of LVFP after PDA ligation is high especially in extremely low birth weight children. The majority of patients recovered well with time, but further surgical intervention was required in uncompensated cases. Long-term follow-up of these patients is needed to ensure improvement. Laryngoscope, 133:1257-1261, 2023.

Using anxiolytics in a pediatric otolaryngology clinic to avoid the operating room.

INTRODUCTION: There is increasing concern regarding the risks associated with the use of general anesthesia in pediatric patients. Many otolaryngologic procedures performed under general anesthesia can also be performed in clinic. We hypothesize that anxiolytics can aid in performing common procedures in clinic thus avoiding the need to undergo general anesthesia in the OR. METHODS: We performed a retrospective review of patients undergoing inoffice procedures with anxiolytics in our pediatric otolaryngology outpatient clinic between February 2013 and January 2017. Charts were reviewed for age, past medical history, procedure type/duration, and outcome. These results were then compared to a cohort undergoing similar procedures in the OR. RESULTS: A total of 34 patients underwent an in-office procedure with an anxiolytic. The success rate was 97% (33/34). The average age was 6.2 years. Six children (17%) had a known history of chromosomal abnormalities and 2 children (6%) had autism. The four most common procedures performed were cerumen impaction removal (8), flexible laryngoscopy (6), ear canal foreign body removal (5), and septal cautery (4). Performing similar procedures in the OR resulted in an average additional cost of $822. CONCLUSIONS: Performing procedures with anxiolytics in a pediatric otolaryngology clinic is safe, expeditious, and cost-effective. Anxiolytics can provide an effective alternative to general anesthesia.

Correlation between systemic inflammatory response and quality of life in patients with chronic rhinosinusitis.

BACKGROUND: Local sinonasal inflammation resulting from altered T-cell immune signaling is a contributor to the pathogenesis of chronic rhinosinusitis (CRS). CRS patients experience negative impacts on quality of life (QOL) and suffer from comorbidities linked to systemic inflammation. However, systemic inflammatory profiling to evaluate the association between systemic inflammation and QOL in CRS has not been performed. Our objectives were to compare local and systemic inflammatory gene expression in patients with CRS to determine if systemic markers of inflammation associate with disease severity and disease-specific QOL. METHODS: A prospective observational study was conducted comparing 16 patients with CRS to 10 controls. Inflammatory gene expression in the anterior ethmoid tissues and peripheral blood of patients was measured using multiplex gene expression analysis and correlated to disease severity (computed tomography and nasal endoscopy) and disease-specific QOL (22-item Sino-Nasal Outcome Test [SNOT-22] and Rhinosinusitis Disability Index) using linear regression analyses. RESULTS: Patients with CRS showed significant increases in the expression of ctla4 and jak1 in sinonasal tissue and blood (p < 0.05), whereas the gene expression of hla-dqa1, hla-dqb1, and dusp4 was significantly decreased in patients with CRS compared to controls (p < 0.05). Soluble and local ctla4 and jak1 showed a significant positive correlation with clinical markers of disease severity and disease-specific QOL (p < 0.05). CONCLUSION: Local and systemic gene expression involved in T-cell immune signaling was found to be significantly altered in the blood and sinonasal tissues of patients with CRS compared to controls and significantly correlated to disease severity and QOL in patients with CRS.

Familial clustering of oropharyngeal squamous cell carcinoma in the Utah population.

BACKGROUND: The main purpose of the current study was to define the familial aggregation of oropharyngeal squamous cell carcinoma (SCC) and risk to relatives of patients with oropharyngeal SCC. METHODS: We conducted a retrospective study utilizing linked population-based genealogy and state cancer registry databases between 1966 and 2012. Relative risks for oropharyngeal SCC and other malignancies among patients with oropharyngeal SCC and their relatives were estimated. RESULTS: Significant excess pairwise relatedness was observed for oropharyngeal SCC diagnosed before age 65 years. Significant excess risk for oropharyngeal SCC was observed for first-degree relatives of patients. Relatives of oropharyngeal SCC patients also demonstrated elevated rates of multiple other malignancies, including both lung and cervical cancers. CONCLUSION: Relatives of patients with oropharyngeal SCC display elevated risks of oropharyngeal, lung, and cervical cancers among others, suggesting a possible shared genetic etiology involving tobacco-related and human papillomavirus (HPV)-related malignancies.

Sleep dysfunction and its association to chronic rhinosinusitis: Updated review.

BACKGROUND: Poor sleep has significant effects on health contributing to increased morbidity and mortality. The direct and indirect costs of sleep dysfunction total well in to the billions of dollars annually in the US. Chronic rhinosinusitis (CRS) affects up to 16% of the US population and has been linked to poor sleep quality with up to three quarters of patients with CRS reporting poor sleep quality. There is a growing body of literature evaluating the relationship between sleep and CRS. In this review, we organize and present the current knowledge on the associations between sleep and CRS as well as identify areas for further investigation. DATA SOURCES: A structured literature search from 1946 to 2016 was conducted in the English language using OVID MEDLINE database, PubMed and EMBASE. REVIEW METHODS: Abstracts were reviewed for relevance and appropriate studies were included in the narrative review. RESULTS: Studies were analyzed and discussed as they pertained to the following categories of CRS and sleep: (1) subjective measures of sleep dysfunction, (2) objective measures of sleep dysfunction, and (3) outcomes on sleep quality following treatment of CRS. Articles on the pathophysiology of sleep dysfunction in CRS were separately reviewed. CONCLUSIONS: An evolving body of research demonstrates that quality of sleep is compromised in the majority of patients with CRS. Following treatment of CRS, there is significant improvement in subjective sleep quality, but additional research investigating objective measures following treatment is still needed. Additionally, further investigation is required to better elucidate the underlying pathophysiology of the relationship between sleep dysfunction and CRS.

The role of sinus surgery in sleep outcomes.

PURPOSE OF REVIEW: Poor sleep is associated with reduced health, increased morbidity, and increased mortality. RECENT FINDINGS: Chronic rhinosinusitis (CRS) is one of the most prevalent chronic diseases in the United States, affecting up to 16% of the U.S. POPULATION: It has been linked to poor sleep with up to 75% of patients with CRS reporting reduced sleep. Yet there has been little examining the improvement in sleep following surgical treatment of patients with CRS. SUMMARY: In this review, we examine the current knowledge on the association between sleep and CRS as well as review the current data examining the role of sinus surgery. After a structured literature search, we conclude that an evolving body of research demonstrates that sleep is compromised in the majority of patients with CRS. Following surgical treatment of CRS, there is a significant improvement in reported sleep quality that is correlated with subsequent improvement in disease-specific quality of life. Furthermore, we acknowledge that additional research characterizing both objective and subjective measures of sleep following surgical treatment is still needed. Additional investigation is required to better elucidate the underlying pathophysiology of the relationship between sleep dysfunction and CRS.

Patients electing medical vs surgical treatment: emotional domain of the Rhinosinusitis Disability Index associates with treatment selection.

BACKGROUND: The Rhinosinusitis Disability Index (RSDI) consists of multiple subdomains shown to be useful in studying chronic rhinosinusitis (CRS). The objective of this study was to determine if RSDI subdomain scores are associated with selection of treatment modality (endoscopic sinus surgery [ESS] or continued medical management [CMM]) in subjects with CRS. METHODS: Patients with CRS were prospectively enrolled into a multi-institutional cohort study. Following an initial period of medical management, patients elected to undergo treatment with either ESS or CMM. Baseline RSDI total and subdomain scores were compared between patients electing different treatment modalities. RESULTS: A total of 684 subjects were enrolled with 122 (17.8%) electing CMM and 562 (82.2%) electing ESS. When compared to patients undergoing CMM, patients electing ESS exhibited significantly higher mean baseline RSDI total scores (mean ± standard deviation [SD]: 48.1 ± 24.9 vs 40.1 ± 24.1; p = 0.001) and subdomain scores (emotional: 13.2 ± 9.1 vs 10.4 ± 8.3; p = 0.001; functional: 15.3 ± 8.9 vs 12.6 ± 8.4; p = 0.002; and physical: 19.6 ± 9.3 vs 17.1 ± 9.6; p = 0.007). Emotional subdomain scores were found to be the most associated with choice of treatment modality. CONCLUSION: Patients with CRS electing ESS had worse baseline RSDI total and subdomain scores compared to those electing CMM. Although both rhinologic and nonrhinologic symptoms contributed to the selection of treatment modality, emotional symptoms appeared to exhibit the greatest influence on patient-centered treatment decisions.

Familial risk of pediatric chronic rhinosinusitis.

OBJECTIVES/HYPOTHESIS: To determine the risk of chronic rhinosinusitis (CRS) in relatives of children with a diagnosis of CRS. STUDY DESIGN: Retrospective observational cohort study with population-based matched controls. METHODS: A unique genealogical database linked to medical records was used to identify subjects ≤12 years old with a diagnosis of CRS from 1996 to 2011. The familial recurrence risks of CRS in first- through fifth-degree relatives of probands were calculated using Cox models and compared to controls randomly selected from the Utah population and matched 10:1 on sex and birth year. RESULTS: We identified 496 pediatric patients with CRS. Siblings of patients with CRS demonstrated a 57.5-fold increased risk (P < 10(-8) ) of also having pediatric CRS. First cousins had a 9.0-fold increased risk (P < 10(-3) ) and second cousins had a 2.9-fold increased risk (P = .002) of pediatric CRS. First-degree relatives, second-degree relatives, and first cousins of pediatric cases demonstrated a significant increased risk of having adult CRS. Parents of probands demonstrated a 5.6-fold increased risk (P < 10(-15) ). Fifty-five probands had one affected parent versus three probands with two affected parents. CONCLUSIONS: In the largest population study to date of children with CRS, a significant familial risk is confirmed. Parents of probands were also at increased risk, although it was much more likely for one parent to be affected than both, suggesting a genetic component of the disease. Further understanding of the genetic basis of CRS and its interplay with environmental factors could clarify the etiology and lead to more effective targeted treatments. LEVEL OF EVIDENCE: 3b Laryngoscope, 126:739-745, 2016.

Topical cathelicidin (LL-37) an innate immune peptide induces acute olfactory epithelium inflammation in a mouse model.

BACKGROUND: Cathelicidin (LL-37) is an endogenous innate immune peptide that is elevated in patients with chronic rhinosinusitis (CRS). The role of LL-37 in olfactory epithelium (OE) inflammation remains unknown. We hypothesized that: (1) LL-37 topically delivered would elicit profound OE inflammation; and (2) LL-37 induced inflammation is associated with increased infiltration of neutrophils and mast cells. METHODS: To test our hypothesis we challenged C57BL/6 mice intranasally with increasing concentrations of LL-37. At 24 hours tissues were examined histologically and scored for inflammatory cell infiltrate, edema, and secretory hyperplasia. In separate experiments, fluorescently conjugated LL-37 was instilled and tissues were examined at 0.5 and 24 hours. To test our last hypothesis, we performed tissue myeloperoxidase (MPO) assays for neutrophil activity and immunohistochemistry for tryptase to determine the mean number of mast cells per mm(2) . RESULTS: LL-37 caused increased inflammatory cell infiltrate, edema, and secretory cell hyperplasia of the sinonasal mucosa, with higher LL-37 concentrations yielding significantly more inflammatory changes (p < 0.01). Fluorescent LL-37 demonstrated global sinonasal epithelial binding and tissue distribution. Further, higher concentrations of LL-37 led to significantly greater MPO levels with dose-dependent increases in mast cell infiltration (p < 0.01). CONCLUSION: LL-37 has dramatic inflammatory effects in the OE mucosa that is dose-dependent. The observed inflammatory changes in the olfactory mucosa were associated with the infiltration of both neutrophils and mast cells. Our biologic model represents a new model to further investigate the role of LL-37 in OE inflammation.

Familial risk of chronic rhinosinusitis with and without nasal polyposis: genetics or environment.

BACKGROUND: Chronic rhinosinusitis (CRS) is a highly prevalent inflammatory condition, with significant effects on morbidity and quality of life, yet little is known about its pathogenesis. Preliminary evidence suggests there is a heritable component to the multifactorial etiology of CRS; however, our understanding of this genetic susceptibility is limited. METHODS: Using an extensive genealogical database linked to medical records, the risk of CRS with nasal polyps (CRSwNP) and without polyps (CRSsNP) was calculated for relatives and spouses of adult probands (1638 CRSwNP and 24,200 CRSsNP patients diagnosed between 1996 and 2011) and were compared to random population controls matched 5:1 on sex and birth year from Cox regression models. RESULTS: First-degree relatives (1stDRs) of CRSwNP patients demonstrated a 4.1-fold increased risk (p < 10(-3) ) of carrying the same diagnosis, whereas second-degree relatives (2ndDRs) demonstrated a 3.3-fold increased risk (p < 0.004), compared to controls. In CRSsNP patients, 1stDRs were at 2.4-fold increased risk (p < 10(-15) ), whereas 2ndDRs were at 1.4-fold increased risk (p < 10(-15) ) of the same diagnosis. Third-degree relatives (3rdDRs) had a slight increased risk at 1.1-fold (p < 10(-7) ). Spouses of CRSsNP patients, who likely share environmental circumstances, exhibited a 2-fold increased risk (p < 10(-15) ). No increased risk was observed in spouses of CRSwNP patients. CONCLUSION: In the largest population study to date, a significant familial risk is confirmed in CRSwNP and CRSsNP, which may have a shared genetic and environmental component. Further understanding of the genetic basis of CRS and its interplay with environment factors could clarify disease etiology and lead to more effective targeted treatments.

Prevalence and interest in the practice of scratch testing for contact urticaria: a survey of the American contact dermatitis society members.

BACKGROUND: Contact urticaria (CU) is the development of a wheal and flare on the skin after topical exposure to a particular chemical or compound. It can be diagnosed through a variety of techniques. Many chemicals that cause a type IV allergy can also cause CU. The incidence of CU to these chemicals is unknown. OBJECTIVE: The aim of this study was to evaluate the opinions of the American Contact Dermatitis Society members regarding CU and scratch testing. METHODS: We distributed an electronic survey to the American Contact Dermatitis Society members regarding observed prevalence of CU, frequency of scratch testing in clinical practice, and interest in learning about scratch testing in diagnosing CU and other skin contact conditions. RESULTS: We distributed 508 surveys and received 133 responses. Seventeen percent reported that CU was extremely rare, 32% reported that CU was rare, and 38.9% reported that CU was infrequent. Alternatively, 10.7% believed that CU was common, and 1.5% believed that CU was extremely common. A minority, 19.1%, performed scratch testing on patients with suspected CU. Most respondents, 54.6%, were interested in learning about scratch testing. CONCLUSIONS: Additional education regarding scratch testing could increase comfort and use of scratch testing in clinical practice. Further studies are needed to evaluate the prevalence of CU in the general population and better guide the use of testing for dermatologic patients.