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Dysphagia is a common gastrointestinal complaint in the pediatric population and should raise concern for oropharyngeal as well as esophageal disorders. We describe a 7-year old patient who was admitted to the hospital for sudden onset dysphagia, abdominal pain, and decreased oral intake. Extensive evaluations including endoscopy eventually revealed herpes simplex esophagitis as well as eosinophilic esophagitis. Herpes simplex esophagitis is a rare condition in the immunocompetent population and is typically self-resolving. Eosinophilic esophagitis is a chronic, inflammatory condition characterized by esophageal eosinophilia and signs of esophageal dysfunction. The concurrent presentation of both conditions in the pediatric population has rarely been described. [ABSTRACT FROM AUTHOR]

Pain and inflammation are the consequences of sore throat, dental and oral procedures, infections, ulcers and head and neck chemotherapy/radiotherapy, and their management is of fundamental importance to avoid distress in patients. Benzydamine hydrochloride (HCl) is a topical indolic nonsteroidal anti-inflammatory drug, endowed with analgesic and anesthetic activity, and with antimicrobial (including both gram-positive and gram-negative bacteria) and antifungal properties (targeting Candida albicans and non-albicans strains), used in odontostomatology, otorhinolaryngology, and gynecology for its properties. This molecule has a lipophilic nature, showing high affinity with cell membranes and exhibiting membrane stabilization properties, resulting in local anesthesia, an effect related also to the interaction of the drug with cationic channels. In addition, benzydamine HCl is able to inhibit the production of pro-inflammatory cytokines, with consequent analgesia. Moreover, benzydamine HCl is able to inhibit leukocyte-endothelial interactions and platelet aggregation. Unlike other non-steroidal anti-inflammatory drugs, benzydamine HCl does not inhibit cyclooxygenase or lipoxygenase. Here we review the most updated clinical data available on benzydamine HCl local application as spray, mouthwash or gargling and evidence of its effectiveness in inflammatory and/or septic conditions in the otorhinolaryngology and odontostomatology settings, with particular reference to sore throat, oral inflammation, dental plaque, tonsillitis/tonsillectomy and chemo- or radiotherapy-induced oral mucositis. Novel formulations for oral administration of benzydamine HCl are also reviewed, including in situ gelling formulations to be sprayed onto the damaged oral mucosa. Finally, novel data on the potential role of benzydamine HCl in nociceptor excitability are introduced.

Basaloid squamous cell carcinoma (BSCC) is a rare and aggressive variant of squamous cell carcinoma. It is commonly seen in the oropharynx and strongly associated with p16-expressivity and high-risk human papilloma virus (HPV). We report the first case of primary cutaneous p16-positive BSCC in an elderly woman, with a background of chronic inverse psoriasis of the natal cleft. P16-expressivity is a common surrogate marker for oncogenic HPV16, routinely tested for oropharyngeal/anogenital squamous cell carcinoma. This is not routinely done for primary cutaneous disease. Pilonidal disease is uncommon in the elderly population, and malignant transformation is rarer still. Surgical resection is considered the mainstay of treatment for primary cutaneous BSCC, however due to this patient's broad distribution of cutaneous field change and p16-expressivity, she was effectively treated with primary radiotherapy. This is a unique case of malignant transformation of pilonidal disease in an atypical demographic, with a rare/aggressive disease variant. [ABSTRACT FROM AUTHOR]

Background Poor oral health has been identified as a prognostic factor potentially affecting the survival of patients with head and neck squamous cell carcinoma. However, evidence to date supporting this association has emanated from studies based on single cohorts with small-to-modest sample sizes. Methods Pooled analysis of 2449 head and neck squamous cell carcinoma participants from 4 studies of the International Head and Neck Cancer Epidemiology Consortium included data on periodontal disease, tooth brushing frequency, mouthwash use, numbers of natural teeth, and dental visits over the 10 years prior to diagnosis. Multivariable generalized linear regression models were used and adjusted for age, sex, race, geographic region, tumor site, tumor-node-metastasis stage, treatment modality, education, and smoking to estimate risk ratios (RR) of associations between measures of oral health and overall survival. Results Remaining natural teeth (10-19 teeth: RR = 0.81, 95% confidence interval [CI] = 0.69 to 0.95; ≥20 teeth: RR = 0.88, 95% CI = 0.78 to 0.99) and frequent dental visits (>5 visits: RR = 0.77, 95% CI = 0.66 to 0.91) were associated with better overall survival. The inverse association with natural teeth was most pronounced among patients with hypopharyngeal and/or laryngeal, and not otherwise specified head and neck squamous cell carcinoma. The association with dental visits was most pronounced among patients with oropharyngeal head and neck squamous cell carcinoma. Patient-reported gingival bleeding, tooth brushing, and report of ever use of mouthwash were not associated with overall survival. Conclusions Good oral health as defined by maintenance of the natural dentition and frequent dental visits appears to be associated with improved overall survival among head and neck squamous cell carcinoma patients. [ABSTRACT FROM AUTHOR]

Background: Oropharyngeal squamous carcinoma (OPSC) continues to increase in incidence secondary to human papillomavirus (HPV) infection. Despite the good overall prognosis for these patients, treatment with chemoradiation is associated with morbidity and treatment failure. Better predictors for disease outcome are needed to guide de-intensification regimens. We hypothesized that estrogen receptor α (ERα), a prognostic biomarker in oncology with therapeutic implications, might have similar utility in OPSC.Methods: To investigate associations among ERα and demographics, HPV status, and survival, we analyzed ERα mRNA expression of head and neck squamous carcinomas (HNSC) from The Cancer Genome Atlas (TCGA) and immunohistochemistry (IHC) of pretreatment biopsy specimens from an independent group of 215 OPSC patients subsequently treated with primary chemoradiation (OPSC-CR). Associations among variables were evaluated with Fisher exact tests and logistic regression; associations with survival were evaluated with log-rank tests and Cox proportional hazards regression.Results: Among 515 patients in TCGA, ERα mRNA expression was highest in HPV-positive OPSC. High ERα mRNA expression was associated with improved survival among those receiving chemoradiation (hazard ratio adjusted for HPV status = 0.44, 95% confidence interval = 0.21 to 0.92). In OPSC-CR, ERα was positive by IHC in 51.6% of tumors and was associated with improved overall, disease-specific, progression-free, and relapse-free survival (log-rank tests: P < .001, P < .001, P = .002, P = .003, respectively); statistically significant associations of ERα positivity with improved survival were maintained after adjusting for clinical risk factors including HPV status.Conclusion: In two independent cohorts, ERα is a potential biomarker for improved survival that also may represent a therapeutic target in OPSC. [ABSTRACT FROM AUTHOR]

Objectives This was a parallel, assessor-blinded, randomized, non-controlled prospective trial with the objective to evaluate and compare the effects of maximum advancement (MA) and incremental advancement (IA) of mandible with cast-splint-type Herbst-rapid palatal expander (RPE) appliance on pharyngeal airway dimensions and hyoid bone position in skeletal Class II late adolescents and young adults. Materials and methods A total of 48 patients (19 male and 29 female, mean age: 15.45 ± 1.42 years) with skeletal Class II malocclusion were treated with cast-splint Herbst-RPE appliance. Inclusion criteria were skeletal Class II malocclusion, mandibular retrognathia, bilateral Class II molar and canine relationship, increased overjet, normal or decreased vertical dimensions, minimal crowding, and no missing teeth. Enrolled subjects were randomly allocated into two groups according to mandibular advancement type: IA and MA Herbst-RPE therapy. The outcome assessor was blinded. Advancement in MA group was adjusted until tête-à-tête incisor relationship or super Class I molar relationship was obtained. Initial forward movement in IA group was 4–5 mm and followed by bimonthly 2 mm of subsequent advancements. Skeletal, pharyngeal airway, and hyoid measurements were performed using lateral cephalometric films. Statistical significance was set at P value of less than 0.05. Results Hypopharyngeal airway dimensions (P < 0.000), oropharyngeal airway dimensions (P < 0.001, P < 0.007), and PASmin values (P < 0.010, P < 0.009) were increased and soft palate angle (P < 0.018, P < 0.007) was decreased in MA and IA groups significantly. Hyoid bone measurements revealed a significant difference in H-Cv2 distance (MA: P < 0.002– P < 0.002; IA: P < 0.001— P < 0.043) and H-Cv3 distance (P < 0.005, P < 0.001) for both groups. However, all these changes did not differ among the MA and IA activation groups. ANB°, Wits, overjet, and overbite measurements decreased and SNB°, Co-Gn, Na-Me, ANS-Me, and S-Go increased with the treatment significantly in both mandibular advancement groups (P < 0.000 –P < 0.040). Conclusions Herbst-RPE appliance provided a similar improvement in the oropharyngeal and hypopharyngeal airway dimensions and similar changes in sagittal and vertical hyoid position for both maximum and IA protocols in patients with skeletal Class II malocclusion. Trial registration ISRCTN69743543 [ABSTRACT FROM AUTHOR]

Rates of bacterial sexually transmitted infections (STIs) continue to rise, demanding treatments to be highly effective. However, curing infections faces significant challenges due to antimicrobial resistance in Neisseria gonorrhoeae and Mycoplasma genitalium and especially treating STIs at extragenital sites, particularly rectal chlamydia and oropharyngeal gonorrhoea. As no new antimicrobials are entering the market, clinicians must optimize the currently available treatments, but robust data are lacking on how the properties or pharmacokinetics of antimicrobials can be used to inform STI treatment regimens to improve treatment outcomes. This paper provides a detailed overview of the published pharmacokinetics of antimicrobials used to treat STIs and how factors related to the drug (tissue distribution, protein binding and t½), human (pH, inflammation, site of infection, drug side effects and sexual practices) and organism (organism load and antimicrobial resistance) can affect treatment outcomes. As azithromycin is commonly used to treat chlamydia, gonorrhoea and M. genitalium infections, and its pharmacokinetics are well studied, it is the main focus of this review. Suggestions are also provided on possible dosing regimens when using extended and/or higher doses of azithromycin, which appropriately balance efficacy and side effects. The paper also emphasizes the limitations of currently published pharmacokinetic studies including oropharyngeal gonococcal infections, where very limited data exist around ceftriaxone pharmacokinetics and its use in combination with azithromycin. In future, the different anatomical sites of infections may require alternative therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background Upper airway analysis is an often-cited use of CBCT imaging by orthodontists; however, the reliability of airway measurements using this technology is not fully established. Objective To determine the intra-examiner and inter-examiner reliability of the complete process of volumetric and cross-sectional area assessments of the upper airway using CBCT imaging. Materials and Methods Six examiners of varying levels of education and clinical experience performed the steps necessary for airway analysis, including manual orientation, slice and threshold selection and measured nasopharyngeal, oropharyngeal, hypopharyngeal and total upper pharyngeal airway volumes in addition to minimum cross-sectional area on the CBCT images of 10 patients. All measurements were repeated after 4-weeks. Intra- and inter-examiner reliability was calculated using ICC and 95% CI. Results Threshold selection showed poor intra- and poor inter-examiner reliability, whereas minimum cross-sectional area showed moderate intra- and poor inter-examiner reliability. Intra-examiner reliability of volumetric measurements varied based on the region assessed with ICC ranging from 0.747 to 0.976, and was worst for hypopharynx and best for the oropharynx. Inter-examiner reliability of volume measurements was generally lower, with ICC ranging from 0.175 to 0.945, and was worst for nasopharynx and best for the oropharynx. Conclusions This study, for the first time, assessed the reliability of upper airway analysis with CBCT when all steps of image processing and measurement are performed by each examiner. Reliability improved with examiner experience, though was generally low for the hypopharynx and nasopharynx volumes and overall minimal cross-sectional area. The oropharyngeal volume was the only parameter to have excellent intra- and inter-examiner reliability. [ABSTRACT FROM AUTHOR]

Background: Previous studies have reported conflicting information regarding the prognostic role of p16 in nonoropharyngeal head and neck squamous cell carcinoma (HNSCC).Methods: Using the US Veterans Affairs database, we analyzed 1448 patients with locoregionally advanced HNSCC and known p16 status diagnosed between 2005 and 2015 and treated with surgery, radiotherapy, or chemoradiotherapy. Tumor p16 status was determined through manual review of pathology reports of primary tumor specimens. Oropharyngeal (n = 1061) or nonoropharyngeal (n = 387; hypopharyngeal, laryngeal, or oral cavity) tumor site was determined from tumor registry data and manually reviewed for accuracy. We used multivariable Cox regression to analyze the effect of p16 status on overall survival (OS), cancer-specific survival (CSS), and competing mortality (CM) for oropharyngeal or nonoropharyngeal tumor sites. All statistical tests were two-sided.Results: In multivariable models adjusting for treatment, stage, age, comorbidity, and body mass index, patients with p16-positive tumors had improved OS, CSS, and CM compared with patients with p16-negative tumors in both oropharyngeal (OS: hazard ratio [HR] = 0.53, 95% confidence interval [CI] = 0.40 to 0.71, P < .001; CSS: HR = 0.50, 95% CI = 0.35 to 0.73, P < .001; CM: HR = 0.59, 95% CI = 0.38 to 0.93, P = .02) and nonoropharyngeal primary sites (OS: HR = 0.41, 95% CI = 0.25 to 0.69, P < .001; CSS: HR = 0.37, 95% CI = 0.18 to 0.77, P = .008; CM: HR = 0.46, 95% CI = 0.23 to 0.95, P = .04). The prognostic impact of p16 status did not statistically significantly differ by primary tumor site for OS, CSS, or CM (Pinteraction > .05).Conclusions: Our findings support the hypothesis that p16 has a similar prognostic role in both nonoropharyngeal and oropharyngeal cancer. Consideration should be given to increased testing for p16 in laryngeal, hypopharyngeal, and oral cavity primaries. [ABSTRACT FROM AUTHOR]

Background Eastern equine encephalitis virus (EEEV) is an alphavirus with a high mortality rate and serious neurological sequelae in infected persons making this virus an important human pathogen. Methods Following written informed consent, eligible subjects received two priming doses of EEEV vaccine, inactivated, TSI-GSD 104, 0.5 mL subcutaneously on days 0 and 28 days followed by a mandatory booster, 0.1 mL intradermal, at 6 months. Serum samples were collected pre-vaccination, days 21–35 following dose 2, as well as before and 21–35 days after dose 3. Sera with a Plaque Reduction Neutralization Test80 titer (PRNT80) ≥ 1:40 were considered responders with adequate titers for the purpose of biocontainment suite entry. Results Sixty-seven (67) subjects were enrolled in this study to receive the primary vaccination series. All 67 subjects received at least 1 primary vaccination; 66 completed the 2 primary doses; 58 completed the 2 primary doses and the 6-month dose. Of these, 38 (56.7%) reported one or more adverse events. Fatigue was reported in 13 (19.4%), headache in 9 (13.4%), upper respiratory tract infection in 6 (9.0%), nausea in 5 (7.5%), pyrexia in 5 (7.5%), oropharyngeal pain in 4 (6.0%), myalgia in 4 (6.0%), injection site pain in 7 (10.4%), injection site hematoma in 4 (6.0%) and injection site erythema in 3 (4.5%) subjects. Adverse events were mostly mild or moderate and transient. PRNT80 titers ≥ 1:40 was observed in 39/65 (60%) subjects who received both primary doses of EEEV vaccine compared with 48/57 (84%) subjects who completed the 2-dose primary series and the 6-month dose and also had blood drawn for titer. Females had a higher response rate (61.5%) at the pre 6-month boost titer than did males (34.3%) (p = 0.0231). Similarly, the pre 6-month boost geometric mean titer (GMT) for females was 35.5 vs. 21.9 for males (p = 0.0231). The post 6-month boost GMT for females was 146.7 and 181.5 for males (P = 0.13). Conclusion Inactivated Eastern Equine Encephalitis Virus vaccine, TSI-GSD 104, Lot 2-1-89 appears to be safe and immunogenic. This Phase 2 vaccine study supports a priming dose schedule of Days 0 and 28 and 6-month. The 6 month dose is anamnestic improving the overall response rate and level of antibody for this primary dosing schedule. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Low rates of mother to child HIV transmission in Zambia, translates into a high number of children who are HIV exposed but uninfected (HEU) who have increased mortality and morbidity when compared with children HIV unexposed and uninfected (HUU). We performed a secondary analysis on The Pneumonia Etiology Research in Child Health (PERCH), a case–control study focused on identifying the etiologies of pediatric pneumonia including two pathogens, Streptococcus pneumoniae and Pneumocystis jirovecii in Zambian children to evaluate if HIV exposure status influences carriage rates and density for these pathogens. Methods Children ages 1–59 months were enrolled as cases if they met the World Health Organization (WHO) definition of severe or very severe pneumonia. Controls did not have a diagnosis of pneumonia and were matched by age and HIV status to cases. Each case and control had a nasopharyngeal (NP) swab and an oropharyngeal (OP) swab specimen. A multiplex real-time polymerase chain reaction (PCR) assay was used to test the NP/OP specimens for S. pneumoniae and P. jirovecii. A density of log10 copies/mL in microbiology confirmed cases compared with controls was used to define positive infection with S. pneumoniae and P. jirovecii. Results The highest S. pneumoniae carrier rates were seen in HIV unexposed controls and the lowest carrier rates seen in HIV-infected controls. HIV-infected children who were S. pneumoniae carriers and were classified as controls had the highest S. pneumoniae density of all groups. Overall, the HIV-infected group had the highest S. pneumoniae density rates. There was minimal variation in the S. pneumoniae density of those in the HIV exposed and HIV unexposed. P. jirovecii was present only in 31% of HIV-infected cases and 7% of the same group controls. HIV exposed cases had half the carrier rates of their counterparts in the HIV-infected group, but the P. jirovecii carriage rates were the same as the carriage rates in HIV-infected controls. The P. jirovecii carriage density in HIV-infected and HIV-exposed cases was similar. Conclusion HIV exposure status in children can be a predictor factor in S. pneumoniae and P. jirovecii carriage and density. The results of our analysis could potentially explain the high rates of pneumonia in children exposed to HIV but uninfected. Our findings open the door to more in-depth studies about the immunological status in children exposed to HIV but uninfected. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Data are limited about the burden of respiratory syncytial virus (RSV)-related hospitalizations in older adults and those with COPD or CHF. Methods We conducted prospective surveillance at two hospitals from October 2018 to March 2019 for adults ≥50 years of age admitted with acute respiratory infections (ARI) and adults of any age with COPD or CHF-related admissions. Adults were eligible if they were residents of an 8 county region in Atlanta, Georgia. Asymptomatic adults ≥50 years of age were enrolled as controls. Nasopharyngeal and oropharyngeal swabs were tested for RSV and influenza (Flu) using BioFire® FilmArray® Respiratory Viral Panel (RVP) and acute/convalescent serology was obtained for RSV antibodies detection by enzyme immunoassay against RSV lysate. Standard of care results were included for enrollees. We compare the number of RSV+, Flu+ and RSV−/Flu− cases along with demographic features and outcomes. Results We screened 12,453 patients to identify 1,515 eligible adults of which 617 (41%) were enrolled. The most common reasons for failing to enroll were refusal (676, 75%) and inability to obtain informed consent (221, 25%). Of the 617, 36 (6%) were RSV+ and 41 (7%) were Flu+. RSV was detected in 1/126 (0.8%) and Flu in 0/126 healthy controls. RSV+ occurred earlier in surveillance and peaked at a higher frequency (figure). Clinical characteristics and outcomes are in the table. In a convenience sample, a four-fold rise in RSV antibody titer was detected among 8/15 RSV+, 0/42 RSV−/Flu−, and 0/42 healthy controls. Conclusion The burden and outcomes for RSV are similar to Flu in adults admitted to the hospital with ARI, CHF, or COPD. A vaccine for RSV would be beneficial. Disclosures Nadine Rouphael, MD, Merck: I conduct as Emory PI the PNEUMO MERCK study at Emory, Research Grant; Pfizer: I conduct as co-PI the RSV PFIZER study at Emory, Research Grant; Sanofi-Pasteur: I conducted as Emory PI the CDIFFENSE trial at Emory, Research Grant. [ABSTRACT FROM AUTHOR]

Background Native Americans experience a high burden of community-acquired pneumonia (CAP). Thirteen-valent pneumococcal conjugate vaccine (PCV13) was introduced for adults ≥65yrs in 2014. Data on CAP etiology can guide prevention and treatment. Methods We enrolled adults hospitalized with CAP and age-group-matched non-hospitalized controls on Navajo and White Mountain Apache tribal lands. Nasopharyngeal/oropharyngeal (NP/OP) swabs from cases and controls were tested by multiplex PCR for respiratory pathogens. Urine from cases and controls was tested for pneumococcus (Sp) by conventional (BinaxNOW) and serotype-specific urine antigen detection (UAD) for 24 serotypes (PCV13 types plus 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20, 22F, 33F). Blood culture and chest radiographs (CXRs) were obtained from cases at the provider's discretion. Radiographic pneumonia was determined by clinical interpretation of CXRs. Results From March 2016 to March 2018, we enrolled 580 CAP cases with CXR confirmation and 411 controls. Positive blood culture was identified in 42/483 (9%), of which 29 (69%) were Sp. Sp was detected in 164/572 (29%) cases (table). Of 125 cases with serotype information available, serotypes 3 (n = 35; 28%) 8 (n = 19; 15%) and 20 (n = 15; 12%) were the most common. Among 53 Sp cases aged ≥65 years, 26 (49%) were PCV13-type. Compared with blood culture, UAD was 100% sensitive and 100% concordant (n = 24). Viruses were detected by NP/OP PCR in 43% of CAP cases and 18% of controls. Influenza A, parainfluenza type 3, rhinovirus, and RSV were statistically significantly associated with case status. Among 263 cases in whom all diagnostic tests were collected, 63% had a pathogen detected: bacteria alone in 19%, viruses alone in 23%, and both bacterial and viral infection in 22%. Bacterial causes outnumbered viral causes when adjusting for virus detection in the control population. Conclusion Pneumococci were the most common etiology identified among Native American adults with CAP. UAD improved detection of pneumococcal CAP. Respiratory viruses also contributed substantially to CAP burden. Broader prevention strategies, including new vaccines, are required to prevent viral pneumonia and pneumococcal pneumonia caused by serotypes not contained in currently-available vaccines. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background We evaluated the long-term impact of full PCV13 vaccination in a 3 + 1 schedule on pneumococcal colonization patterns of children in order to clarify PCV13 serotype persistence/enhancement and re-colonization. Methods From January 18 to August 29, 2017, consecutive children who had received the 4-dose course of PCV13, as per the National Immunization Program recommendations, were prospectively enrolled through 45 general pediatric practice facilities in 30 municipalities in Greece. A single oropharyngeal sample was obtained from each subject in a standardized manner (questionnaire, procedure). Based on the time interval since the fourth dose of PCV13, the children sampled were grouped for analysis in 6 groups: 26 days to 11 months; 12–23 months; 24–35 months; 36–47 months; 48–59 months, and 60–71 months. Carriage and distribution of Streptococcus pneumoniae serotypes was detected by RT–PCR. Results A total of 1212 children aged 14–83 months were investigated. S. pneumoniae was identified in the pharyngeal swab of 617 children (50.9%); 172/617 (27.9%) children carried > 1 pneumococcal serotypes. As a consequence of co-colonization, a total number of 718 S. pneumoniae (belonging to 28 serotypes) was identified. The carriage rate of non-PCV13 serotypes escalated within 3 years after the fourth dose and plateaued during the fourth and fifth year. The carriage rate of PCV13 serotypes escalated during the 4 years after the fourth dose and declined thereafter. 22/305 children (7.2%) carried one or more PCV13 serotypes in the first year after the fourth vaccine dose, 27/201 (13.4%) in the second year, 34/207 (16.4%) in the third year, 48/224 (21.4%) in the fourth year, 40/191 (20.9%) in the fifth year and 13/84 (15.5%) in the sixth year (P < 0.0001) (Figure 1). The colonization frequency of serotypes 3 and 19A increased with the rise of the vaccination time interval (Figure 2). Changes in the frequency of other PCV13 serotypes were not significant. Serotypes 7F, 14 and 23F were not recovered. Conclusion Our study suggests that S. pneumoniae is present in the pharynx of children 26 days to 71 months after the completion of PCV13 vaccination, and that non-PCV13 serotypes predominate throughout this period. The carriage rate of PCV13 serotypes 3 and 19A increases significantly as the time interval from the fourth dose of PCV13 increases. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Several enteroviruses (EVs), including EV-A71 and EV-D68, have been associated with acute flaccid myelitis (AFM). Clinical features distinguishing AFM presentations associated with specific EV types are not well described. Methods EV-associated AFM was defined as any child presenting to Children's Hospital Colorado in 2013–2018 who met the Council of State and Territorial Epidemiologists definition for confirmed AFM (flaccid limb weakness with longitudinal gray-matter-predominant spinal cord lesion on MRI) and had EV-A71 or EV-D68 identified in any biologic specimen (cerebrospinal fluid [CSF], nasopharyngeal [NP], oropharyngeal [OP], rectal) by VP1-specific RT-PCR and sequencing. Summative limb strength scores (SLSS) were calculated by adding Medical Research Council strength scores (1–5) for all limbs. Results Ten cases of EV-A71-associated AFM were identified, all from 2018; 8 cases of EV-D68-associated AFM were identified from 2013 (1), 2014 (4), 2016 (1), and 2018 (2) [Table 1]. Viral detection rates were higher in rectal and OP swabs in EV-A71 cases and NP specimens in EV-D68 cases. Virus was not detected in CSF of EV-D68 cases and in 1 EV-A71 case. EV-A71 cases were younger (median 19 vs. 100 months) and had neurologic onset earlier after prodromal symptom onset (median 1 vs. 5.5 days) than EV-D68 cases. Hand, foot, and/or mouth lesions distinguished EV-A71 cases, whereas respiratory symptoms were uniformly noted in EV-D68 cases. Associated neurologic findings more commonly associated with EV-A71 cases than EV-D68 cases included irritability, myoclonus, and ataxia. Weakness was more generalized with EV-A71 and more asymmetric with EV-D68, though patterns of brainstem and spinal cord involvement on MRI were similar. Compared with EV-D68, EV-A71 cases had milder weakness at onset and improved strength at 1- to 2-month follow-up (Figure 1), shorter length of stay (median 5.5 vs. 32 days) and a greater rate of full neurologic recovery (90% vs. 13%). Conclusion EV-D68 and EV-A71 are both associated with AFM with similar MRI findings, but cases can be distinguished by associated prodromal symptoms, neurologic findings, and outcomes. Timely collection and testing of nonsterile site specimens, particularly NP for EV-D68 and OP and rectal for EV-A71, are key to case identification. Disclosures All Authors: No reported Disclosures. [ABSTRACT FROM AUTHOR]

Background A favorable response to (chemo) radiotherapy (CCRT) is seen in human papillomavirus (HPV)-positive OPSCC patients. Apparent diffusion coefficient (ADC) derived from MRI has shown to predict treatment response. We evaluated the correlation between clinico-demographic profile of oropharyngeal squamous cell carcinomas patients (OPSCC patients) HPV status and ADC values, SUV uptake obtained from FDG- PET-CT. Methods The study population was obtained from a historical cohort diagnosed with HPV-related OPSCC. A total of 105 OPSCC patients who had undergone molecular testing for HPV status by p16 with Immuno-histochemistry (IHC) were identified. 96 patients had pretreatment imaging (either PET-CT or MRI) and post CCRT imaging was included. Imaging was evaluated by head and neck radiologists to calculate mean ADC and SUV max. Pearson Chi- Square and ANOVA analyses were performed to evaluate the correlation. Results 26 OPSCC were HPV-positive. HPV-positive HNSCC showed significantly association with smoking, grade & stage of the tumor, T status, Response to CCRT, lymph nodes, and ADC values on follow up imaging. Conclusions In OPSCC patient's positive HPV status correlates with follow up mean apparent diffusion coefficient. The complimentary prognostic value of post treatment apparent diffusion coefficient might be partially ascribed to patients with a positive HPV status. Further studies are reasonable to determine whether PET-CT is a useful imaging biomarker in comparison to ADC to risk-stratify patients with HPV-related OPSCC. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background We have applied CyberKnife(CK)-based Stereotactic irradiation (SBRT) to patients with primary advanced head and neck cancer(AHNC). The immune checkpoint inhibitor(ICI) was approved for head and neck cancer refractory to cDDP. Synergistic effect of SBRT with ICIs is theoretically expected. Case 60-year-old male patient complained right huge cervical swelling. Endoscopic finding revealed large ulcerative tumor centered in the right valecula and inferiorly extending into the upper aero-digestive tract. Diagnosis was T4aN3bM0 stage IVB oropharyngeal squamous cell cancer (p16 negative, PDL 1 <1%). None was noted in the past history including no smoking history but with a large amount of drinking. SBRT was applied to the primary neck lesion as a bulk source, and 1 month later followed by chemotherapy(TXT/CDGP), which Resulted in CR. Four months later, recurrence of both cervical lymph nodes and early esophageal cancer around the EGJ occurred. He underwent SBRT for the neck lesions, then TXT/ CDGP was administered. After 4 months PETCT proved suspicious residual lesions in the oropharynx and mediastinum, the latter was proved by GIF to be type II advanced esophageal cancer at 30 cm from incisors besides early esophageal cancer lesion in EGJ. Nivolumab was then started. Results At the time of 7th course of nivolumab, when GIF was performed, prominent shrinkage of advanced esophageal lesion was recognized. Laryopharyngeal lesions are not observed and CR has been maintained. The epiglottis extinguished but normal deglutition was spared without gastrostomy-dependence. Conclusion Induction SBRT followed by chemotherapy comprised taxoid and cDDP derivative and subsequent ICI based immunotherapy might be a most potent strategy for primary AHNC. The fact that advanced esophageal cancer detected just before nivolumab remarkably shrank, might suggest that it shares neoantigens with pharyngeal cancer, and SBRT might exert as in situ vaccination. [ABSTRACT FROM AUTHOR]

Background In the CheckMate 141 trial, nivolumab, a human IgG4 anti-PD-1 monoclonal antibody, provided a significant improvement in overall survival (OS) of patients with recurrent or metastatic squamous cell carcinoma (SCC) of the oral cavity, pharynx, or larynx. In Japan, nivolumab has been approved for platinum pretreated head and neck cancers regardless of histologic type and subsite. In other words, nivolumab is also available for non-SCC and subsites of head and neck cancer which were not included in the CheckMate 141 trial. However, the efficacy of nivolumab for cancers arising from these other subsites has not been clarified. Methods: We retrospectively reviewed data for 122 consecutive patients with head and neck cancers treated with nivolumab in our institution between March 2017 and December 2018. Patients with head and neck SCC of oral, oropharyngeal, hypopharyngeal, and laryngeal cancer were excluded. Final analysis of the study population was restricted to those 37 patients with non-SCC histological type or SCC arising from other subsites of the head and neck. Results: Median age was 57 years (range 30 to 77). Primary sites were nasopharynx/sinonasal/salivary/other regions of the head and neck (n = 8/10/8/11). Nineteen patients had SCC and 18 had non-SCC. In patients who could be evaluated by RECIST (n = 32), objective response rate was 18.8% in the total study population, 37.5% in NPC, 10.0% in sinonasal cancer and 25.0% in salivary cancer. Median OS and time to treatment failure (TTF) in the total study population was 12.1 months and 2.3 months, respectively. Median TTF in NPC patients was better than that in patients with other primary sites (7.6 vs. 2.5 months, p = 0.016). There was a trend toward improved TTF in SCC group compared to non-SCC group (4.2 vs. 2.4 months, p = 0.31). Conclusion: Nivolumab showed favorable efficacy in head and neck cancers arising from subsites which were not included in the CheckMate141 trial, especially NPC patients. [ABSTRACT FROM AUTHOR]

Background Between May and July 2018, four invasive cases of Haemophilus influenzae type a (Hia) occurred in a remote Alaska community. A public health response was performed to prevent further illness and to understand local Hia transmission. Methods The team identified close contacts of the Hia patients, collected oropharyngeal (OP) swabs and provided prophylactic rifampin. Close contacts were persons who spent ≥4 hours with a Hia patient for ≥ 5 of the 7 days preceding hospitalization. Five days later, OP swabs were collected community-wide and prophylactic rifampin was offered to community members aged <10 years. Eight weeks later, OP swabs were collected from all willing community members. Samples were tested using PCR and culture to identify Hi carriage. Results No Hia cases occurred in this community after the response. The pretreatment carriage prevalence is shown in Figure 1. There was a significant difference in prevalence of Hia carriage between contacts (4/27, 14.8%) and non-contacts (7/364, 1.9%) (P = 0.0043). Contacts aged <10 years were significantly more likely to carry Hia compared with contacts aged ≥10 years (11/18 [61.1%] vs. 3/34 [8.8%], P = 0.0001). The case households had the highest proportion of individuals who carried Hia at any time, with 54%–60% of individuals in three case households carrying Hia at least once. Hia carriage was eliminated in two carriers who completed treatment and were tested immediately after rifampin prophylaxis. Testing 8 weeks later found that the prevalence of carriage did not significantly change in the contacts (5/42 [11.9%] to 6/25 [24%], P = 0.18) or the non-contacts (7/368 [1.9%] to 2/114 [1.8%], P = 0.47). Conclusion Children aged <10 years who had close contact with the Hia patients were the most likely to carry Hia. These findings suggest that people who do not have close contact do not benefit from prophylaxis as they have very low Hia carriage. While rifampin prophylaxis eliminated carriage of Hia in the short term, carriage prevalence did not change in the long term. Further research is needed to understand why contacts have such a high prevalence of carriage even after receiving appropriate prophylactic medication. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Methicillin-resistant Staphylococcus aureus (MRSA) skin and soft-tissue infections (SSTIs) are common among military recruits. Identifying which strains are responsible for SSTI and understanding the underlying transmission dynamics is critical to developing appropriate interventions for this high-risk population. Methods A cohort study of US Army Infantry trainees at Fort Benning, GA (June and September 2015). Participants from two training Companies were screened for colonization on multiple anatomic sites throughout the 14-week cycle as well as the time of clinical infection. MRSA+ samples were sequenced with Illumina HiSeq. Multi-locus sequence type (MLST) and virulence genes were identified in silico. Single nucleotide polymorphism (SNP) distances between soldiers' bacteria were compared with assessing for potential transmission. Results Of 383 soldiers enrolled, 84 (22%) were colonized with MRSA during the study. Forty-two of 84 had a single positive colonization sample, of which 76% were from anatomical sites other than the nares (36% oropharyngeal, 26% perianal, 14% inguinal). Twelve trainees had MRSA SSTI during training (50% had colonization detected prior to or at infection). All were PFGE-type US300 (ST8) and were lukS/lukF-positive. SNP-based phylogenetic analyses and epidemiologic data indicate that most MRSA positives at baseline were due to unique importations from various community origins, suggesting that the ongoing MRSA epidemic is not due to a single endemic strain circulating on base. Following importation, extensive transmission then occurred, with multiple STs implicated. Transmission appeared restricted to within Companies, and predominantly within platoons. Conclusion Frequent colonization at baseline suggests a need for extensive MRSA screening and decolonization upon arrival to base, followed by ongoing infection control measures throughout training to prevent recolonization/infection. As multiple anatomical sites appear to play a role in transmission of MRSA, this may have important implications for screening protocols and control both in community and hospital-based settings. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Neisseria meningitidis (Nm) can cause invasive disease, but it also asymptomatically colonizes the pharynx in approximately 10% of the general population. Older studies have reported higher carriage rates (>30%) among individuals attending sexually transmitted disease (STD) clinics. This study examined the prevalence of oropharyngeal Nm carriage in STD clinic attendees in Columbus, Ohio. Methods Per normal procedures, all patients presenting for care in the STD clinic who report oral sex in the last year are screened for oropharyngeal Neisseria gonorrhoeae (Ng) using nucleic acid amplification testing (NAAT). For the same patients, we also initiate cultures using media selective for Neisseria spp. Analytical Profile Index Neisseria-Haemophilus (API NH) and Nm-specific PCR screening is performed on colonies with oxidase-positive Gram-negative diplococci to distinguish between Ng and Nm. For this study, we then performed PCR-based genogrouping on confirmed Nm isolates. Results Between July 2018 and March 2019, oropharyngeal screening occurred at 5,015 patient visits and oropharyngeal Nm was detected at 163 visits (3.3%). Nm-positive individuals were primarily male (69.9%), Caucasian (62.6%), with non-Hispanic ethnicity (98.8%). The median age was 27 years and 5.5% were HIV-positive. Among male cases, 49.1% reported sex with men; among women, 98.0% reported sex with men. Meningococcal vaccination status was unknown for 71.2%, but 26.4% had documentation of prior MenACWY vaccination and 2.3% had prior MenB vaccination. Among the 163 cases, genogroup distribution was 23.9% B, 10.4% E, 9.8% Z, 3.1% C, 0.0% W, 0.0% Y, and 39.3% capsule null locus. For 13.5%, the selected screening approach could not determine genogroup. Conclusion In STD clinic patients reporting recent oral sex, we found a much lower prevalence of oropharyngeal Nm carriage compared with what has been reported historically for similar populations. While NmB was the most common capsular type identified by genogrouping, almost 40% of Nm isolates contained the capsule null locus, making them unable to express capsule. Additional studies should evaluate the effect of Nm vaccination programs on carriage among STD-clinic attendees. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background In people over 65, there are on average 177,000 hospitalizations and 14,000 deaths because of respiratory syncytial virus (RSV) each year. Elderly patients infected with RSV can suffer serious infections leading to pneumonia and congestive heart failure. RSV vaccines have failed in the elderly in part because they have been unable to mount a robust cellular immune response. Methods RSV-MinL4.0 is a live-attenuated intranasal vaccine candidate that was generated by codon pair deoptimization of the L gene followed by the addition of four stabilizing mutations found via stress passaging. Four African Green Monkeys (AGMs) per group were vaccinated with RSV-MinL4.0 or wild-type (WT) RSV at 2 × 106 PFU, boosted on day 28 and challenged with wild-type (WT) RSV on day 104. Oropharyngeal swabs and tracheal lavage were collected daily and every other day, respectively, to evaluate virus shedding (qPCR) and blood was drawn on days 1, 14, 21, 28, and 49 for antibody titers (PRNT50), and PBMC activation (IFNγ ELISPOT with whole inactivated virus). Results MinL4.0 was 2 to 3 log10 attenuated when compared with WT RSV in AGMs. Despite the presence of antibodies on day 28, there was a "take" of the boost indicating the potential for this vaccine to be immunogenic in the elderly with pre-existing circulating antibodies (Figure 1A). MinL4.0 led to robust activation of PBMCs comparable to WT RSV (> 2,000 spots per 106 total cells, Figure 1B). Shedding of the vaccine and challenge viruses was minimal (data not shown). Conclusion MinL4.0 led to robust activation of cellular and humoral immune responses, which are critical for induction of protective immunity in the elderly. Animals were protected from WT challenge. Preliminary data in AGMs with pre-existing antibodies to RSV indicate that circulating antibodies do not prevent vaccine "take," critical for a vaccine targeting sero-positive elderly individuals. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]