Resident microbiota affect Bordetella pertussis infectious dose and host specificity.

Before contacting host tissues, invading pathogens directly or indirectly interact with host microbiota, but the effects of such interactions on the initial stages of infection are poorly understood. Bordetella pertussis is highly infectious among humans but requires large doses to colonize rodents, unlike a closely related zoonotic pathogen, Bordetella bronchiseptica, raising important questions about the contributions of bacterial competition to initial colonization and host selection. We observed that <100 colony-forming units (CFU) of B. bronchiseptica efficiently infected mice and displaced culturable host microbiota, whereas 10 000 CFU of B. pertussis were required to colonize murine nasal cavities and did not displace host microorganisms. Bacteria isolated from murine nasal cavities but not those from the human lower respiratory tract limited B. pertussis growth in vitro, indicating that interspecies competition may limit B. pertussis colonization of mice. Further, a broad-spectrum antibiotic treatment delivered before B. pertussis inoculation reduced the infectious dose to <100 CFU, and reintroduction of single Staphylococcus or Klebsiella species was sufficient to inhibit B. pertussis colonization of antibiotic-treated mice. Together, these results reveal that resident microorganisms can prevent B. pertussis colonization and influence host specificity, and they provide rationale for manipulating microbiomes to create more-accurate animal models of infectious diseases.

Enzymatic modification of lipid A by ArnT protects Bordetella bronchiseptica against cationic peptides and is required for transmission.

Pathogen transmission cycles require many steps: initial colonization, growth and persistence, shedding, and transmission to new hosts. Alterations in the membrane components of the bacteria, including lipid A, the membrane anchor of lipopolysaccharide, could affect any of these steps via its structural role protecting bacteria from host innate immune defenses, including antimicrobial peptides and signaling through Toll-like receptor 4 (TLR4). To date, lipid A has been shown to affect only the within-host dynamics of infection, not the between-host dynamics of transmission. Here, we investigate the effects of lipid A modification in a mouse infection and transmission model. Disruption of the Bordetella bronchiseptica locus (BB4268) revealed that ArnT is required for addition of glucosamine (GlcN) to B. bronchiseptica lipid A. ArnT modification of lipid A did not change its TLR4 agonist activity in J774 cells, but deleting arnT decreased resistance to killing by cationic antimicrobial peptides, such as polymyxin B and ß-defensins. In the standard infection model, mutation of arnT did not affect B. bronchiseptica colonization, growth, persistence throughout the respiratory tract, recruitment of neutrophils to the nasal cavity, or shedding of the pathogen. However, the number of bacteria necessary to colonize a host (50% infective dose [ID50]) was 5-fold higher for the arnT mutant. Furthermore, the arnT mutant was defective in transmission between hosts. These results reveal novel functions of the ArnT lipid A modification and highlight the sensitivity of low-dose infections and transmission experiments for illuminating aspects of infectious diseases between hosts. Factors such as ArnT can have important effects on the burden of disease and are potential targets for interventions that can interrupt transmission.

Exclusively endoscopic surgical resection of esthesioneuroblastoma: A systematic review.

Background: Historically sinonasal malignancies were always addressed via open craniofacial surgery for an oncologic resection. Increasingly esthesioneuroblastomas are excised using an exclusively endoscopic approach, however, the rarity of this disease limits the availability of long-term and large scale outcomes data. Objective: The primary objective is to evaluate the treatment modalities used and the overall survival of patients with esthesioneuroblastoma managed with exclusively endoscopic surgery. Methods: In accordance with PRISMA guidelines, PubMed was queried to identify studies describing outcomes associated with endoscopic management of esthesioneuroblastomas. Results: Forty-four out of 2462 articles met inclusion criteria, totaling 399 patients with esthesioneuroblastoma treated with an exclusively endoscopic approach. Seventy-two patients (18.0%) received adjuvant chemotherapy and 331 patients (83.0%) received postoperative radiation therapy. The average age was 50.6 years old (range 6-83). Of the 399 patients, 57 (16.6%) were Kadish stage A, 121 (35.2%) were Kadish stage B, 145 (42.2%) were Kadish stage C, and 21 (6.1%) were Kadish stage D. Pooled analysis demonstrated that 66.0% of patients had Hyams histologic Grade Ⅰ or Ⅱ, while 34.0% of patients had Grade Ⅲ or Ⅳ disease. Negative surgical margins were achieved in 86.9% of patients, and recurrence was identified in 10.3% of patients. Of those with 5-year follow-up, reported overall survival was 91.1%. Conclusion: Exclusively endoscopic surgery for esthesioneuroblastoma is performed for a wide range of disease stages and grades, and the majority of these patients are also treated with adjuvant chemotherapy or radiation therapy. Reported overall recurrence rate is 10.3% and 5-year survival is 91.1%.

Association of Quality of Life Measures and Otolaryngologic Care in Cystic Fibrosis Patients.

OBJECTIVES: Appropriate management of chronic rhinosinusitis (CRS) among patients with cystic fibrosis (CF) is important in improving quality of life. Otolaryngologists play a critical role in reducing CRS symptom burden. This study seeks to evaluate the role of patient-reported quality-of-life measures in guiding interventions for CF-related sinus disease. METHODS: We performed a prospective, cross-sectional study of 105 patients presenting to a CF-accredited clinic between July and September 2018. Demographic data and sinus surgery history were collected, in addition to Sino-Nasal Outcome Test (SNOT-22) and Questionnaire of Olfactory Disorders (QOD-NS) scores. Statistical analysis was conducted using correlation and non-parametric Mann-Whitney U tests. RESULTS: Baseline well-care visits accounted for 71.4% of all clinical evaluations. Prior otolaryngology intervention was noted in 69 (66%) patients, where the majority of these patients (63/69; 91%) underwent endoscopic sinus surgery (ESS). Patients with a history of otolaryngology intervention had an average SNOT-22 score of 33.2 (SD = 20.6) compared to 24.9 (SD = 18.5) for patients without prior intervention (P = .048). The average QOD-NS score was 5.5 (SD = 6.4) among patients referred to otolaryngologists and 3.1 (SD = 5.7) for non-referred patients (P = .012). SNOT-22 and QOD-NS scores were modestly correlated (R of .43). CONCLUSION: CF patients with symptoms resulting in worse quality-of-life assessments were more likely to have established coordinated care with an otolaryngologist. Further validation of the utility of SNOT-22 and QOD-NS questionnaires as care coordination metrics is necessary in the CF population.

Race in Rhinology Clinical Trials: A Decade of Disparity.

OBJECTIVE/HYPOTHESIS: The aim of this study is to assess the ethnic and racial demographics of patients enrolled in prospective chronic rhinosinusitis (CRS) studies relative to the corresponding geographic demographics of the United States (U.S.) census data. STUDY DESIGN: Systematic Review and Population analysis. METHODS: A systematic review was performed to identify CRS clinical trials, conducted in the U.S. and published between 2010 and 2020 in which patients were prospectively enrolled. Pooled racial and ethnicity data were compared to national and corresponding regional census data. RESULTS: Eighty-three studies were included, comprising 12,027 patients. 50.4% were male and the average age was 49.2 years. 8,810 patients underwent a surgical procedure. Of the 12,027 patients, 81.67% were identified as White, 5.35% as Black, 1.27% as Asian, 0.02% as Pacific Islander, 0.12% as American Indian, and 11.57% were classified as Other. The racial and ethnic composition of the pooled study population differs significantly from the national U.S. census data with the underrepresentation of each minority population (P ≤ .0002). Regional sub-analyses yield variable results. In the Northeast and West, there was an underrepresentation of all minority populations. In the South and Midwest, Black enrollment was similar to the U.S. census data, while all other minorities were underrepresented. CONCLUSIONS: The racial and ethnic composition of patients enrolled in prospective CRS clinical trials differs significantly from the demographics of the U.S. POPULATION: The generalizability and external validity of findings derived from studies comprised of demographically mismatched populations has not been established. Future efforts to enroll more representative populations should be emphasized by the research community, funding bodies, and editorial boards. LEVEL OF EVIDENCE: NA Laryngoscope, 131:1722-1728, 2021.

Sinonasal quality-of-life declines in cystic fibrosis patients with pulmonary exacerbations.

BACKGROUND: In cystic fibrosis (CF), the relationship between chronic rhinosinusitis (CRS) and pulmonary disease is poorly understood. The purpose of this study was to evaluate the relationship between scores on the 22-item Sino-Nasal Outcome Test (SNOT-22) and CF Questionnaire-revised for adolescents and adults over 14 (CFQ-R 14+), and pulmonary function tests in 2 cohorts of CF patients: those at their baseline health and those with a pulmonary exacerbation. METHODS: Patients >18 years old seen in a Cystic Fibrosis Foundation-accredited clinic completed the SNOT-22 and CFQ-R 14+ instruments. Patients presenting for routine care represented the baseline cohort. Patients diagnosed with a pulmonary exacerbation represented the exacerbation cohort. Average SNOT-22 and CFQ-R 14+ scores for both groups were compared using a 2-sample t test, and correlation coefficient was calculated. RESULTS: One hundred three patients were enrolled over 3 months (30 exacerbations and 73 baseline). Patients' mean age was 32 years (56% female and 44% male). Average SNOT-22 and CFQ-R 14+ scores were significantly worse for exacerbation patients (p = 0.001 and p = 0.0003, respectively). Percent predicted forced expiratory volume in 1 second and forced vital capacity were both higher for baseline patients (p = 0.002 and p = 0.001, respectively). Average SNOT-22 score for all patients was worse than the average score for non-CF, non-CRS patients. CONCLUSION: CF patients with pulmonary exacerbations have worse SNOT-22 and CFQ-R 14+ scores than CF patients at their baseline health. This finding suggests a temporal relationship between sinonasal and pulmonary quality of life, and that worsening of both is associated with reduced pulmonary function.

Treatment Strategies and Outcomes of Pediatric Esthesioneuroblastoma: A Systematic Review.

Introduction: Esthesioneuroblastoma, also known as olfactory neuroblastoma, is a small round blue cell tumor of nasal neuroepithelium first described in 1924. Though this tumor is especially rare in the pediatric population with an incidence of <0.1 per 100,000, it is the most common pediatric nasal cavity neoplasm. The purpose of this systematic review is to examine the treatment modalities utilized for pediatric esthesioneuroblastoma and overall survival. Methods: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Pubmed, EMBASE, and Ovid MEDLINE databases were queried for studies pertinent to treatment modalities for pediatric esthesioneuroblatoma and survival outcomes. Results: Two hundred and seventy-sixth articles were identified, with seven meeting inclusion criteria. Ninety-four patients with an age range of 0.9-21 years old with esthesioneuroblastoma were included. Nearly 90% of patients were of stage Kadish B or C at time of presentation, while 20% presented with cervical lymphadenopathy. Only about 10% of patients underwent single modality therapy. Overall, 5-year survival ranged from 44 to 91% with a median follow-up of 3-13 years. Conclusion: Children with esthesioneuroblastoma usually present at an advanced stage and undergo multi-modality therapy at a higher rate than adult patients. There is a wide range of documented overall survival though this lack of precision could be due to a paucity of patients.

Gross Total Versus Subtotal Surgical Resection in the Management of Craniopharyngiomas.

Craniopharyngiomas (CP) are suprasellar tumors that can grow into vital nearby structures and thus cause significant visual, endocrine, and hypothalamic dysfunction. Debate persists as to the optimal treatment strategy for these benign lesions, particularly with regards to the extent of surgical resection. The goals of tumor resection are to eliminate the compressive effect of the tumor on surrounding structures and minimize recurrence. It remains unclear whether a gross total resection (GTR) or subtotal resection (STR) with adjuvant therapy confers a better prognosis. Chemotherapy and radiation therapy (RT) have been explored as both neoadjuvant and adjuvant treatments to decrease tumor burden and prevent recurrence. The objective of this paper is to review the risks and benefits of GTR versus STR, specifically with regard to risk of recurrence and postoperative morbidity. Aggregated data suggest that STR monotherapy is associated with higher rates of recurrence relative to GTR (50.6% ± 22.1% vs 20.2% ± 13.5%), while STR combined with RT leads to recurrence rates similar to GTR. However, both GTR and RT are independently associated with higher rates of comorbidities including panhypopituitarism, diabetes insipidus, and visual deficits. The treatment strategy for CPs should ultimately be tailored to each patient's individual tumor characteristics, risk, symptoms, and therapeutic goals.

Surgical Management of Chronic Rhinosinusitis in Cystic Fibrosis.

Cystic fibrosis patients frequently develop chronic rhinosinusitis as a result of their propensity to form inspissated mucus and impairment of mucociliary clearance. They exhibit variable symptom burden even in the setting of positive radiographic and endoscopic findings. Current evidence suggests a positive effect of managing sinonasal disease on pulmonary health. Topical antimicrobial and mucolytic therapies are frequently required to manage the disease with surgery reserved for refractory cases. Endoscopic sinus surgery has been demonstrated to be safe and efficacious in controlling symptoms of chronic rhinosinusitis in patients with comorbid cystic fibrosis. However, the impact of surgery on pulmonary health remains an active area of investigation. In addition, a growing body of research has suggested a more extended surgical approach creating large sinonasal cavities with gravity-dependent drainage pathways, followed by adjuvant medical therapies, as an ideal strategy to optimally control disease and prevent pulmonary exacerbations. In this manuscript, we provide an up-to-date review of current evidence in the surgical management of chronic rhinosinusitis in cystic fibrosis patients.

Chronic Rhinosinusitis in Cystic Fibrosis: Diagnosis and Medical Management.

Chronic rhinosinusitis (CRS) is nearly ubiquitous in patients with cystic fibrosis (CF). CF CRS is a challenging entity to define, diagnose, and treat, as patients often have severe refractory sinus disease in addition to complex medical comorbidities. The purpose of this article is to review the literature on the medical management of CF CRS and determine how to best identify, diagnose, and manage CF CRS. Ultimately, the treatment of these patients requires a multi-disciplinary approach involving the pulmonologist and otolaryngologist.

Outcomes and imaging findings of respiratory epithelial adenomatoid hamartoma: a systematic review.

BACKGROUND: Respiratory epithelial adenomatoid hamartoma (REAH) is a recently classified histopathologic diagnosis often identified incidentally following endoscopic sinus surgery (ESS) for presumed chronic rhinosinusitis. Limited data exist defining preoperative imaging features and surgical outcomes. The purpose of this study is to examine characteristic imaging findings of REAH and postoperative olfactory and recurrence outcomes. METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines on articles published from 1995 to present. PubMed, EMBASE, and Ovid MEDLINE databases were queried for studies pertinent to imaging findings of REAH and surgical outcomes. Quality of articles was assessed using the Methodological Index for Non-Randomized Studies (MINORS). RESULTS: A total of 294 articles were identified, with 15 meeting inclusion criteria. Seven articles assessed both imaging findings and surgical outcomes. Three articles focused exclusively on imaging, whereas 5 examined surgical outcomes. Olfactory cleft (OC) widening greater than 10 mm on computed tomography (CT) was characteristic of REAH. A total of 441 patients with REAH were included; 221 patients (50.1%) had concurrent nasal polyposis, whereas 154 patients (34.9%) had isolated REAH. Surgical intervention ranged from simple excision to complete ESS. Sixty-five percent (65%) of patients reported improved olfaction; 4.1% of patients recurred with follow-up ranging from 4 months to 5 years. CONCLUSION: A widened OC may suggest the presence of REAH. This disease process has been identified in patients with nasal polyposis or encountered as an isolated lesion. Targeted surgery may result in improved olfaction and a low likelihood of recurrence, though long-term prospective studies are necessary.