Enhanced biofilm and extracellular matrix production by chronic carriage versus acute isolates of Salmonella Typhi.

Salmonella Typhi is the primary causative agent of typhoid fever; an acute systemic infection that leads to chronic carriage in 3-5% of individuals. Chronic carriers are asymptomatic, difficult to treat and serve as reservoirs for typhoid outbreaks. Understanding the factors that contribute to chronic carriage is key to development of novel therapies to effectively resolve typhoid fever. Herein, although we observed no distinct clustering of chronic carriage isolates via phylogenetic analysis, we demonstrated that chronic isolates were phenotypically distinct from acute infection isolates. Chronic carriage isolates formed significantly thicker biofilms with greater biomass that correlated with significantly higher relative levels of extracellular DNA (eDNA) and DNABII proteins than biofilms formed by acute infection isolates. Importantly, extracellular DNABII proteins include integration host factor (IHF) and histone-like protein (HU) that are critical to the structural integrity of bacterial biofilms. In this study, we demonstrated that the biofilm formed by a chronic carriage isolate in vitro, was susceptible to disruption by a specific antibody against DNABII proteins, a successful first step in the development of a therapeutic to resolve chronic carriage.

A dual-therapy approach for the treatment of biofilm-mediated Salmonella gallbladder carriage.

Asymptomatic carriage of Salmonella Typhi continues to facilitate the transmission of typhoid fever, resulting in 14 million new infections and 136,000 fatalities each year. Asymptomatic chronic carriage of S. Typhi is facilitated by the formation of biofilms on gallstones that protect the bacteria from environmental insults and immune system clearance. Here, we identified two unique small molecules capable of both inhibiting Salmonella biofilm growth and disrupting pre-formed biofilm structures without affecting bacterial viability. In a mouse model of chronic gallbladder Salmonella carriage, treatment with either compound reduced bacterial burden in the gallbladder by 1-2 logs resulting in bacterial dissemination to peripheral organs that was associated with increased mortality. Co-administration of either compound with ciprofloxacin not only enhanced compound efficacy in the gallbladder by a further 1-1.5 logs for a total of 3-4.5 log reduction, but also prevented bacterial dissemination to peripheral organs. These data suggest a dual-therapy approach targeting both biofilm and planktonic populations can be further developed as a safe and efficient treatment of biofilm-mediated chronic S. Typhi infections.

Cystic fibrosis mutation classes in pediatric otitis media - Fickle or faulty?

PURPOSE: Recent data have challenged the historical paradigm that cystic fibrosis (CF) protects against otitis media (OM). These findings raised questions about the pathogenesis of this ostensible change. In this study our aim is to characterize acute OM (AOM) risk based on CF genotype. METHODS: A retrospective chart review was completed at a tertiary care pediatric hospital. Charts of 159 CF patients seen at our facility from 2010 to 2019 were reviewed. Data collected included demographics, AOM infections, cystic fibrosis transmembrane conductance regulator (CFTR) allele mutations, pulmonary exacerbations (PE), and pancreatic insufficiency (PI) status. Mutation alleles were divided into five classes based on CF guidelines, which were further classified as severe (classes I-III) or mild (classes IV-V). RESULTS: 54% of patients had at least one episode of AOM with a mean of 1.5 episodes of AOM (standard deviation = 2.3). 86% of patients had severe/severe (S/S) alleles and 14% had severe/mild (S/M). S/S patients had significantly more PE (p = .004) and increased rates of PI (p < .001). Of the 131 patients with S/S mutations, 57% had an episode of AOM while only 46% the 22 S/M patients had an AOM episode (p = .357). CONCLUSIONS: To our knowledge this is the first report showing a clinical trend towards increased middle ear disease in patients with severe CFTR mutations. Future prospective studies will be powered to demonstrate whether this trend is statistically significant. Patients with S/S mutations not only have more severe clinical phenotypes but may have additional unexpected complications such as middle ear disease.

Moving Beyond the Temporal Bone Lab: Creating a Drilling Station in the Otolaryngology Clinic.

With the advent of operable 3-dimensional (3D)-printed models, case preparation could occur outside of the cadaveric laboratory. The objective of this study was to design a mobile drilling station that can be used for surgical practice in a variety of clean workplaces. Using materials obtained from hardware stores and online retailers, a wheelable drilling station was constructed to mimic laboratory conditions while also being easily maneuverable into clinic rooms. The station houses the otologic drill, suction, and irrigation mechanisms, is height adjustable, and has a shielded workspace. The mobile drilling station was moved into a microscope-containing otolaryngology clinic room where faculty and trainees were asked to drill a pediatric 3D-printed temporal bone followed by completing an evaluation survey. This is the first mobile drilling station described in the literature and can be easily constructed, mobilized, and used in an otolaryngology clinic for dedicated surgical practice using 3D-printed models.

Effect of Speaking Valves on Tracheostomy Decannulation.

Introduction Despite several pediatric tracheostomy decannulation protocols there remains tremendous variability in practice. The effect of tracheostomy capping on decannulation has been studied but the role of speaking valves (SVs) is unknown. Objective Given the positive benefits SVs have on rehabilitation, we hypothesized that SVs would decrease time to tracheostomy decannulation. The purpose of the present study was to evaluate this in a subset of patients with chronic lung disease of prematurity (CLD). Methods A retrospective chart review was performed at a tertiary care children's hospital. A total of 105 patients with tracheostomies and CLD were identified. Data collected included demographics, gestational age, congenital cardiac disease, airway surgeries, granulation tissue excisions, SV and capping trials, tracheitis episodes, and clinic visits. Statistics were performed with logistic and linear regression. Results A total of 75 patients were included. The mean gestational age was 27 weeks (standard deviation [SD] = 3.6) and the average birthweight was 1.1 kg (SD = 0.6). The average age at tracheostomy was 122 days (SD = 63). A total of 70.7% of the patients underwent decannulation and the mean time to decannulation (TTD) was 37 months (SD = 19). A total of 77.3% of the patients had SVs. Those with an SV had a longer TTD compared to those without (52 versus 35 months; p = 0.008). Decannulation was increased by 2 months for every increase in the number of hospital presentations for tracheitis ( p = 0.011). Conclusion The present study is the first, to our knowledge, to assess the effect of SVs on tracheostomy decannulation in patients with CLD showing a longer TTD when SVs are used.

Utility of Esophagrams to Detect Prevertebral Invasion in Hypopharyngeal Squamous Cell Carcinoma.

OBJECTIVES/HYPOTHESIS: Prevertebral fascia invasion is a feature of advanced hypopharyngeal squamous cell carcinoma (HPSCC) that predicts surgical futility. Magnetic resonance and computed topography imaging are used to identify prevertebral involvement, but reliable prediction remains a challenge. Our aims were to describe a new indication for esophagrams and assess its ability to detect prevertebral invasion preoperatively. STUDY DESIGN: Retrospective Review. METHODS: A retrospective review of advanced HPSCC patients from 2001 to 2019. Thirty-one patients underwent curative treatment (21 surgically, 10 with chemoradiation) with a preoperative esophagram. Operative and pathology reports, and fluoroscopic images were collected from the medical record. Esophagrams were read independently by two blinded radiologists. Excursion of the laryngeal complex was quantified relative to the height of vertebral bodies; <0.5 bodies was considered positive for fixation. Surgery or comparative imaging modalities were the gold-standard comparisons. RESULTS: Mean age at diagnosis was 63 years. Twenty-one patients underwent surgical treatment with laryngopharyngectomies. One patient had prevertebral invasion during surgical exploration. Ten patients underwent chemoradiation therapy, and three of these had prevertebral invasion. The average hyolaryngeal elevation was 1.05 vertebral bodies (standard deviation = 0.5). There was a strong correlation between radiologists (R = 0.80, P < .0001). Compared to the gold standard, esophagrams had sensitivity of 75%, specificity of 93%, positive predictive value of 60%, and a negative predictive value (NPV) of 96%. CONCLUSIONS: This study highlights the utility of a common radiologic modality in assessing prevertebral fascia invasion in an advanced-stage HPSCC cohort undergoing surgical treatment. With a high NPV and specificity, the esophagram's potential to rule out prevertebral fascia invasion is a useful predictor of resectability. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:800-805, 2021.

Should the Presence of Spondylodiscitis Alter the Surgical Treatment of Patients with Symptomatic Ventral Cervical Epidural Abscesses? An Institutional Analysiss.

BACKGROUND: Spinal epidural abscess is a rare pathology with an incidence that has tripled in the past 2 decades. Ventral cervical epidural abscesses (vCEA) of the cervical spine pose particular treatment challenges because of the anatomical location. The aim of this report is to identify trends in the surgical management of these patients and to determine whether concomitant spondylodiscitis warrants fusion at the index surgery. METHODS: Patients presenting to a quaternary care institution from January 2009 to December 2018 with isolated vCEA were identified. Patients were excluded if they had dorsal or circumferential epidural abscesses. Clinical and radiographic data were collected. Patients with vCEA were stratified by the presence or absence of spondylodiscitis upon presentation. Clinical outcomes analyzed included neurological sequelae and the need for revision surgery. RESULTS: During the 10-year study period, 36 patients presented with symptomatic isolated vCEA and constituted the study cohort; 16 (44%) had concurrent spondylodiscitis. All 36 patients underwent surgical decompression; the initial surgical approach was anterior-only for 7 patients (19%), posterior-only for 27 patients (75%), and and a combined approach for 2 patients (6%). Four patients from the total cohort (11%) ultimately required a revision operation; all 4 were from the subset with concurrent spondylodiscitis (25% vs. 0%, P = 0.03). CONCLUSIONS: vCEA can be evacuated safely and effectively by a variety of strategies in patients with neurologic deficits. Concomitant spondylodiscitis with cervical epidural abscess may warrant instrumented fusion as part of the initial surgical strategy.

Pediatric ossiculoplasty: optimizing outcomes.

PURPOSE OF REVIEW: Despite years of research, pediatric ossiculoplasty remains a challenging surgery with numerous variables factoring into successful outcomes. The aim of this review is to summarize recent publications on surgical technique, timing, and reconstruction materials. RECENT FINDINGS: The cause behind ossicular discontinuity does not seem to play a role in hearing results after ossiculoplasty; however, revision surgery is associated with worsening outcomes. The status of the ossicles remains an active area of interest, but the data remain mixed in terms of them playing a role in predicting outcomes in adults and pediatric patients. There remains debate regarding the utility of staging the reconstruction and is often undertaken on a case-by-case basis. Other recent publications highlight positive outcomes associated with canal wall-up procedures, titanium prostheses, and partial ossicular reconstruction prostheses. Endoscopic middle ear surgery in ossiculoplasty has been shown to be successful in monitoring and removal of disease and helpful in reconstruction. SUMMARY: Pediatric ossiculoplasty remains a challenging yet rewarding procedure. The bulk of publications are retrospective making much of the literature difficult to interpret. There remains a need for prospective and well controlled studies in both adult and pediatric populations.

Effect of Speaking Valves on Tracheostomy Decannulation

Abstract Introduction Despite several pediatric tracheostomy decannulation protocols there remains tremendous variability in practice. The effect of tracheostomy capping on decannulation has been studied but the role of speaking valves (SVs) is unknown. Objective Given the positive benefits SVs have on rehabilitation, we hypothesized that SVs would decrease time to tracheostomy decannulation. The purpose of the present study was to evaluate this in a subset of patients with chronic lung disease of prematurity (CLD). Methods A retrospective chart review was performed at a tertiary care children's hospital. A total of 105 patients with tracheostomies and CLD were identified. Data collected included demographics, gestational age, congenital cardiac disease, airway surgeries, granulation tissue excisions, SV and capping trials, tracheitis episodes, and clinic visits. Statistics were performed with logistic and linear regression. Results A total of 75 patients were included. The mean gestational age was 27 weeks (standard deviation [SD] =3.6) and the average birthweight was 1.1 kg (SD = 0.6). The average age at tracheostomy was 122 days (SD = 63). A total of 70.7% of the patients underwent decannulation and the mean time to decannulation (TTD) was 37 months (SD = 19). A total of 77.3% of the patients had SVs. Those with an SV had a longer TTD compared to those without (52 versus 35 months; p = 0.008). Decannulation was increased by 2 months for every increase in the number of hospital presentations for tracheitis (p =0.011). Conclusion The present study is the first, to our knowledge, to assess the effect of SVs on tracheostomy decannulation in patients with CLD showing a longer TTD when SVs are used.