Farrel J. Buchinsky

Do Adenoids Regrow After Excision

OBJECTIVE: The goal was to determine the incidence of symptomatic adenoidal regrowth after adenoidectomy. STUDY DESIGN: A cross-sectional follow-up study was done in a randomly selected group of 175 children who had undergone adenoidectomy 2 to 5 years earlier. Nasopharyngoscopy was performed in those children who still had symptoms of nasal obstruction. SETTING: All surgery was performed at an academic hospital-based practice in the northeastern United States by a single surgeon using a consistent operative technique. RESULTS: Forty-six (26%) patients had nasal airway obstruction symptoms at follow-up. Of the 35 who agreed to undergo nasopharyngoscopy, not a single one had adenoids occupying more than 40% of the nasopharynx, and most (71%) were found to have either no or only trace amounts of adenoidal tissue (usually in the pharyngeal recess). CONCLUSION: Adenoids rarely, if ever, regrow enough to cause symptoms of nasal obstruction after adenoidectomy that includes visualization and electrocautery of the adenoid bed.

Age of Child, More than HPV Type, Is Associated with Clinical Course in Recurrent Respiratory Papillomatosis

Background RRP is a devastating disease in which papillomas in the airway cause hoarseness and breathing difficulty. The disease is caused by human papillomavirus (HPV) 6 or 11 and is very variable. Patients undergo multiple surgeries to maintain a patent airway and in order to communicate vocally. Several small studies have been published in which most have noted that HPV 11 is associated with a more aggressive course. Methodology/Principal Findings Papilloma biopsies were taken from patients undergoing surgical treatment of RRP and were subjected to HPV typing. 118 patients with juvenile-onset RRP with at least 1 year of clinical data and infected with a single HPV type were analyzed. HPV 11 was encountered in 40% of the patients. By our definition, most of the patients in the sample (81%) had run an aggressive course. The odds of a patient with HPV 11 running an aggressive course were 3.9 times higher than that of patients with HPV 6 (Fishers exact p = 0.017). However, clinical course was more closely associated with age of the patient (at diagnosis and at the time of the current surgery) than with HPV type. Patients with HPV 11 were diagnosed at a younger age (2.4y) than were those with HPV 6 (3.4y) (p = 0.014). Both by multiple linear regression and by multiple logistic regression HPV type was only weakly associated with metrics of disease course when simultaneously accounting for age. Conclusions/Significance Abstract The course of RRP is variable and a quarter of the variability can be accounted for by the age of the patient. HPV 11 is more closely associated with a younger age at diagnosis than it is associated with an aggressive clinical course. These data suggest that there are factors other than HPV type and age of the patient that determine disease course.

Strain-specific virulence phenotypes of Streptococcus pneumoniae assessed using the Chinchilla laniger model of otitis media.

Background Streptococcus pneumoniae [Sp] infection is associated with local and systemic disease. Our current understanding of the differential contributions of genetic strain variation, serotype, and host response to disease phenotype is incomplete. Using the chinchilla model of otitis media [OM] we investigated the disease phenotype generated by the laboratory strain TIGR4 and each of thirteen clinical strains (BS68-75, BS290, BS291, BS293, BS436 and BS437); eleven of the thirteen strains have been genomically sequenced. Methodology/Principal Findings For each strain 100 colony forming units were injected bilaterally into the tympanic bullae of 6 young adult chinchillas under general anesthesia. All animals were examined daily for local and systemic disease by a blinded observer. Pneumatic otoscopy was used to evaluate local disease, and behavioral assessments served as the measure of systemic disease. Virulence scoring was performed using a 4-point scale to assess four clinical parameters [severity and rapidity of local disease onset; and severity and rapidity of systemic disease onset] during a 10-day evaluation period. Highly significant variation was observed among the strains in their ability to cause disease and moribundity. Conclusions/Significance As expected, there was a significant correlation between the rapidity of systemic disease onset and severity of systemic disease; however, there was little correlation between the severity of otoscopic changes and severity of systemic disease. Importantly, it was observed that different strains of the same serotype produced as broad an array of disease phenotypes as did strains of different serotypes. We attribute these phenotypic differences among the strains to the high degree of genomic plasticity that we have previously documented.

Eradicating Chronic Ear, Nose, and Throat Infections: A Systematically Conducted Literature Review of Advances in Biofilm Treatment

Objective. Bacteria can grow as individual, planktonic organisms or as complex biofilm communities that are more resistant to treatment. This review was designed to systematically search to identify recent laboratory studies on eradication of biofilms in otolaryngologic infections to highlight promising advances in biofilm treatment. Data Sources. A systematic electronic literature search of Medline/PubMed, CINHAL, and Web of Science was conducted for articles describing the treatment of biofilm infections in ear, nose, and throat (ENT) diseases through March 2010. English-language articles and articles with an English abstract that focused on biofilm treatment were considered for review. Review Methods. Each included article was reviewed by one of the authors for study design, treatment intervention, and outcome. Data from in vitro and animal studies were considered separately from human studies. Results. A total of 30 articles were identified for this review, including 5 studies that included a human treatment component. In general, antibiotics were relatively ineffective for eradicating biofilm infections. Markedly higher antibiotic dosages were required to reduce biofilm presence compared with doses that were effective in eradicating planktonic bacteria. Mupirocin irrigation, gentian violet, and thiamphenicol glycinate acetylcysteine effectively eradicated biofilms. Physical disruption, surfactants, and probiotics were also shown to be beneficial in both nonhuman and human studies. Conclusion. Eradicating ENT biofilms is difficult when treating single-organism or mixed flora biofilms. Antibiotic therapy is often ineffective against biofilms, and clinical treatment may need to focus on nonantibiotic therapies that reduce, disrupt, or eradicate ENT biofilms.

Virulence phenotypes of low-passage clinical isolates of Nontypeable Haemophilus influenzae assessed using the chinchilla laniger model of otitis media

BackgroundThe nontypeable Haemophilus influenzae (NTHi) are associated with a spectrum of respiratory mucosal infections including: acute otitis media (AOM); chronic otitis media with effusion (COME); otorrhea; locally invasive diseases such as mastoiditis; as well as a range of systemic disease states, suggesting a wide range of virulence phenotypes. Genomic studies have demonstrated that each clinical strain contains a unique genic distribution from a population-based supragenome, the distributed genome hypothesis. These diverse clinical and genotypic findings suggest that each NTHi strain possesses a unique set of virulence factors that contributes to the course of the disease.ResultsThe local and systemic virulence patterns of ten genomically characterized low-passage clinical NTHi strains (PittAA – PittJJ) obtained from children with COME or otorrhea were stratified using the chinchilla model of otitis media (OM). Each isolate was used to bilaterally inoculate six animals and thereafter clinical assessments were carried out daily for 8 days by blinded observers. There was no statistical difference in the time it took for any of the 10 NTHi strains to induce otologic (local) disease with respect to any or all of the other strains, however the differences in time to maximal local disease and the severity of local disease were both significant between the strains. Parameters of systemic disease indicated that the strains were not all equivalent: time to development of the systemic disease, maximal systemic scores and mortality were all statistically different among the strains. PittGG induced 100% mortality while PittBB, PittCC, and PittEE produced no mortality. Overall Pitt GG, PittII, and Pitt FF produced the most rapid and most severe local and systemic disease. A post hoc determination of the clinical origins of the 10 NTHi strains revealed that these three strains were of otorrheic origin, whereas the other 7 were from patients with COME.ConclusionCollectively these data suggest that the chinchilla OM model is useful for discriminating between otorrheic and COME NTHi strains as to their disease-producing potential in humans, and combined with whole genome analyses, point the way towards identifying classes of virulence genes.

Unique challenges of obtaining regulatory approval for a multicenter protocol to study the genetics of RRP and suggested remedies

Objective Investigations that seek to generalize findings or to understand uncommon diseases must be conducted at multiple centers. This study describes the process of obtaining regulatory approval for a minimal risk genetic study in a multi-center setting as undertaken by the Recurrent Respiratory Papillomatosis (RRP) Task Force. Study Design and Setting Sequential cohort of American childrens hospitals. A single protocol was submitted to each Institutional Review Board (IRB). Results Documentation was prepared for 14 IRBs over 2.5 years. The median time between enlistment and approval at the first 8 sites was 15 months. Institutions varied considerably in their requirements and in the issues that were raised. Protocols were submitted sequentially and accumulated experience was used in the preparation of applications to subsequent IRBs. Nevertheless, there was no correlation between the accumulated experience and the number of issues that were raised. Conclusion Despite uniform federal standards, all local IRBs required unique and individualized submissions. For multicenter studies, investigators should seriously consider the establishment of cooperative authorization agreements. On a simpler level, a standardized format for applications needs to be adopted nationwide. EBM rating: B-3b

Multicenter Initiative Seeking Critical Genes in Respiratory Papillomatosis

Objectives: To determine the host genes that govern susceptibility to recurrent respiratory papillomatosis (RRP). RRP is caused by human papillomavirus (HPV) 6 and 11. Millions of babies are exposed during the birthing process, but relatively few develop the disease and the aggressiveness of the course is highly variable. Genetically encoded host susceptibility is postulated. Determining the host genes that govern susceptibility will enhance our understanding not only of RRP but also of host‐viral interaction in general.

Predicting outcome in pediatric coin ingestion.

OBJECTIVE To determine the relationship between coin size, coin location, patient age, and patient weight and likelihood of coin passage through the esophagus following pediatric coin ingestion. A secondary objective is to test the hypothesis that coin denomination can be determined based on radiographic appearance. METHODS A retrospective review was performed of all children seen and evaluated for coin ingestion at a single institution over a 25-month period. Outcome measures included the number of coins that were retained in the esophagus, and the number that passed. Various factors were assessed for their predictive value in judging outcome in coin ingestion cases. RESULTS Nineteen percent of patients (15/79) in the study passed their ingested coins. Coin denomination could be accurately determined on every patient that had a standard AP or lateral X-ray film. These findings were marked when compared with the lack of reliability of history in determining coin denomination. Patients who passed coins were as a group older (4.6 vs. 3.2 year, P=0.04), but did not differ significantly by weight (19.5 vs. 15.4 kg, P=0.07) from those that retained the coins. Coins located at the gastroesophageal junction had a significantly higher passage rate than coins located elsewhere in the esophagus (89 vs. 8.2%, P<0.01). Coin size was not predictive of coin passage (P=0.7 by chi(2)). CONCLUSIONS Radiographic assessment of coin denomination is reliable, but in this study could not be used to predict coin passage. Patient age and coin location at the gastroesophageal junction, however, do correlate with this event.

Biofilm formation by ica-positive and ica-negative strains of Staphylococcus epidermidis in vitro

Staphylococcus epidermidis is a clinically important opportunistic pathogen that forms biofilm infections on nearly all types of indwelling medical devices. The biofilm forming capability of S. epidermidis has been linked to the presence of the ica operon in the genome, and the amount of biofilm formation measured by the crystal violet (CV) adherence assay. Six S. epidermidis strains were characterized for their ica status using PCR, and their biofilm forming ability over 6 days, using the CV assay and a flow cell system. Ica-negative strains characterized as ‘negative for biofilm formation’ based on the CV assay were demonstrated to form strongly attached biofilms after 6 days. However, the biofilms were not as extensive as the ica-positive strains. It was concluded that ica is not required for biofilm formation, nor is the 24-h CV assay generalizable for predicting the 6-day biofilm-forming ability for all S. epidermidis strains.

In Vivo Capsular Switch in Streptococcus pneumoniae – Analysis by Whole Genome Sequencing

Two multidrug resistant strains of Streptococcus pneumoniae – SV35-T23 (capsular type 23F) and SV36-T3 (capsular type 3) were recovered from the nasopharynx of two adult patients during an outbreak of pneumococcal disease in a New York hospital in 1996. Both strains belonged to the pandemic lineage PMEN1 but they differed strikingly in virulence when tested in the mouse model of IP infection: as few as 1000 CFU of SV36 killed all mice within 24 hours after inoculation while SV35-T23 was avirulent. Whole genome sequencing (WGS) of the two isolates was performed (i) to test if these two isolates belonging to the same clonal type and recovered from an identical epidemiological scenario only differed in their capsular genes? and (ii) to test if the vast difference in virulence between the strains was mostly – or exclusively – due to the type III capsule. WGS demonstrated extensive differences between the two isolates including over 2500 single nucleotide polymorphisms in core genes and also differences in 36 genetic determinants: 25 of which were unique to SV35-T23 and 11 unique to strain SV36-T3. Nineteen of these differences were capsular genes and 9 bacteriocin genes. Using genetic transformation in the laboratory, the capsular region of SV35-T23 was replaced by the type 3 capsular genes from SV36-T3 to generate the recombinant SV35-T3* which was as virulent as the parental strain SV36-T3* in the murine model and the type 3 capsule was the major virulence factor in the chinchilla model as well. On the other hand, a careful comparison of strains SV36-T3 and the laboratory constructed SV35-T3* in the chinchilla model suggested that some additional determinants present in SV36 but not in the laboratory recombinant may also contribute to the progression of middle ear disease. The nature of this determinants remains to be identified.