Development of Oxadiazolone Activity-Based Probes Targeting FphE for Specific Detection of Staphylococcus aureus Infections.

Staphylococcus aureus (S. aureus) is a major human pathogen that is responsible for a wide range of systemic infections. Since its propensity to form biofilms in vivo poses formidable challenges for both detection and treatment, tools that can be used to specifically image S. aureus biofilms are highly valuable for clinical management. Here, we describe the development of oxadiazolone-based activity-based probes to target the S. aureus-specific serine hydrolase FphE. Because this enzyme lacks homologues in other bacteria, it is an ideal target for selective imaging of S. aureus infections. Using X-ray crystallography, direct cell labeling, and mouse models of infection, we demonstrate that oxadiazolone-based probes enable specific labeling of S. aureus bacteria through the direct covalent modification of the FphE active site serine. These results demonstrate the utility of the oxadizolone electrophile for activity-based probes and validate FphE as a target for the development of imaging contrast agents for the rapid detection of S. aureus infections.

Suppurative Thyroiditis: A Management Paradigm Based on Microbiology.

OBJECTIVE: The aim of this study was to determine if microbiological cultures can guide management of suppurative thyroiditis. DESIGN: This study is a retrospective case series set in 2 tertiary care academic hospitals. METHODS: The microbiological cultures from patients with suppurative thyroiditis who underwent incision and drainage from July 2004 to June 2018 were reviewed. Those who had confirmed pyriform sinus tracts and underwent surgical intervention were included in the study. RESULTS: Fifteen patients satisfied the criteria for inclusion. All had confirmed pyriform sinus tracts and underwent successful intervention. Endoscopic cautery was the most common intervention followed by complete open excision. Five cultures grew alpha Streptococcus, 6 had Eikenella, and 4 Prevotella. Combinations of Eikenella + Prevotella were seen in 3, and 1 sample had all 3 bacteria. Two cultured methicillin-susceptible Staphylococcus aureus alone. One culture was sterile. CONCLUSIONS: The presence of oral flora in an intrathyroidal abscess is confirmatory evidence of a pyriform sinus tract. Further investigations are not needed, and early definitive intervention can be planned.

Cigarette smoke-induced changes in the murine vocal folds: a Raman spectroscopic observation.

Raman spectroscopic methods are being projected as novel tools to study the early invisible molecular level changes in a label-free manner. In the present study, we have used Raman spectroscopy to explore the earliest biochemical changes in murine vocal folds in response to time-bound cigarette smoke exposure. Mice were exposed to cigarette smoke for 2 or 4-weeks through a customized smoke inhalation system. The larynx was collected and initial evaluations using standard methods of analysis such as histopathology and immunofluorescence was performed. Concurrent unstained sections were used for Raman imaging. Two common pathological features of vocal fold disorders including alterations in collagen content and epithelial hypercellularity, or hyperplasia, were observed. The mean spectra, principal component analysis, and Raman mapping also revealed differences in the collagen content and hypercellularity in the smoke exposed tissues. The differences in 2-week exposed tissues were found to be more prominent as compared to 4-week. This was attributed to adaptive responses and the already reported biphasic effects, which suggest that collagen synthesis is significantly reduced at higher cigarette smoke concentrations. Overall findings of the study are supportive of the prospective application of Raman imaging in monitoring changes due to cigarette smoke in the vocal folds.

Identification of early inflammatory changes in the tympanic membrane with Raman spectroscopy.

The tympanic membrane (TM) is a dynamic structure that separates the middle ear from the external auditory canal. It is also integral for the transmission of sound waves. In this study, we demonstrate the feasibility of using Raman spectroscopy to identify early chemical changes resulting from inflammation in the TM that can serve as an indicator of acute otitis media. Bacterial lipopolysaccharide (LPS) was injected trans-tympanicaly in a murine model. Presence of inflammatory response was assessed with binocular microscopy, confirmed with histopathology and immunofluorescence staining. Successful discrimination suggesting spectral differences among the control and LPS treated groups was achieved using principal component analysis. Raman imaging revealed major differences in collagen distribution and nucleic acid content. Image segmentation analysis on the trichrome stained tissue sections was performed to corroborate the Raman spectra. The spectral co-localization study suggests changes in the expression of collagen IV specific signals in LPS treated samples. The overall findings of the study support prospective application of RS in the diagnosis and therapeutic monitoring of otitis media.

Using the shortwave infrared to image middle ear pathologies.

Visualizing structures deep inside opaque biological tissues is one of the central challenges in biomedical imaging. Optical imaging with visible light provides high resolution and sensitivity; however, scattering and absorption of light by tissue limits the imaging depth to superficial features. Imaging with shortwave infrared light (SWIR, 1-2 µm) shares many advantages of visible imaging, but light scattering in tissue is reduced, providing sufficient optical penetration depth to noninvasively interrogate subsurface tissue features. However, the clinical potential of this approach has been largely unexplored because suitable detectors, until recently, have been either unavailable or cost prohibitive. Here, taking advantage of newly available detector technology, we demonstrate the potential of SWIR light to improve diagnostics through the development of a medical otoscope for determining middle ear pathologies. We show that SWIR otoscopy has the potential to provide valuable diagnostic information complementary to that provided by visible pneumotoscopy. We show that in healthy adult human ears, deeper tissue penetration of SWIR light allows better visualization of middle ear structures through the tympanic membrane, including the ossicular chain, promontory, round window niche, and chorda tympani. In addition, we investigate the potential for detection of middle ear fluid, which has significant implications for diagnosing otitis media, the overdiagnosis of which is a primary factor in increased antibiotic resistance. Middle ear fluid shows strong light absorption between 1,400 and 1,550 nm, enabling straightforward fluid detection in a model using the SWIR otoscope. Moreover, our device is easily translatable to the clinic, as the ergonomics, visual output, and operation are similar to a conventional otoscope.

Noninvasive Monitoring of Blood Glucose with Raman Spectroscopy.

The successful development of a noninvasive blood glucose sensor that can operate reliably over sustained periods of time has been a much sought after but elusive goal in diabetes management. Since diabetes has no well-established cure, control of elevated glucose levels is critical for avoiding severe secondary health complications in multiple organs including the retina, kidney and vasculature. While fingerstick testing continues to be the mainstay of blood glucose detection, advances in electrochemical sensing-based minimally invasive approaches have opened the door for alternate methods that would considerably improve the quality of life for people with diabetes. In the quest for better sensing approaches, optical technologies have surfaced as attractive candidates as researchers have sought to exploit the endogenous contrast of glucose, notably its absorption, scattering, and polarization properties. Vibrational spectroscopy, especially spontaneous Raman scattering, has exhibited substantial promise due to its exquisite molecular specificity and minimal interference of water in the spectral profiles acquired from the blood-tissue matrix. Yet, it has hitherto been challenging to leverage the Raman scattering signatures of glucose for prediction in all but the most basic studies and under the least demanding conditions. In this Account, we discuss the newly developed array of methodologies that address the key challenges in measuring blood glucose accurately using Raman spectroscopy and unlock new prospects for translation to sustained noninvasive measurements in people with diabetes. Owing to the weak intensity of spontaneous Raman scattering, recent research has focused on enhancement of signals from the blood constituents by designing novel excitation-collection geometries and tissue modulation methods while our attempts have led to the incorporation of nonimaging optical elements. Additionally, invoking mass transfer modeling into chemometric algorithms has not only addressed the physiological lag between the actual blood glucose and the measured interstitial fluid glucose values but also offered a powerful tool for predictive measurements of hypoglycemia. This framework has recently been extended to provide longitudinal tracking of glucose concentration without necessitating extensive a priori concentration information. These findings are advanced by the results of recent glucose tolerance studies in human subjects, which also hint at the need for designing nonlinear calibration models that can account for subject-to-subject variations in skin heterogeneity and hematocrit levels. Together, the emerging evidence underscores the promise of a blood withdrawal-free optical platform-featuring a combination of high-throughput Raman spectroscopic instrumentation and data analysis of subtle variations in spectral expression-for diabetes screening in the clinic and, ultimately, for personalized monitoring.

Multi-color reflectance imaging of middle ear pathology in vivo.

Otoscopic examination using white-light illumination has remained virtually unchanged for well over a century. However, the limited contrast of white-light otoscopy constrains the ability to make accurate assessment of middle ear pathology and is subject to significant observer variability. Here, we employ a modified otoscope with multi-color imaging capabilities for superior characterization of the middle ear constituents in vivo and for enhanced diagnosis of acute otitis media and cholesteatoma. In this pilot study, five patients undergoing surgery for tympanostomy tube placement and congenital cholesteatoma excision were imaged using the custom-designed multi-color video-rate reflectance imaging system. We show that the multi-color imaging approach offers an increase in image contrast, thereby enabling clear visualization of the middle ear constituents, especially of the tympanic membrane vascularity. Differential absorption at the multiple wavelengths provides a measure of biochemical and morphological information, and the rapid acquisition and analysis of these images aids in objective evaluation of the middle ear pathology. Our pilot study shows the potential of using label-free narrow-band reflectance imaging to differentiate middle ear pathological conditions from normal middle ear. This technique can aid in obtaining objective and reproducible diagnoses as well as provide assistance in guiding excisional procedures.

Nasal vestibulitis due to targeted therapies in cancer patients.

BACKGROUND AND PURPOSE: Cancer patients treated with targeted therapies (e.g., epidermal growth factor receptor inhibitors) are susceptible to dermatologic adverse events (AEs) including secondary skin infections. Whereas infections such as paronychia and cellulitis have been reported, nasal vestibulitis (NV) has not been described with the use of these agents. The aim of our study was to characterize NV in cancer patients treated with targeted therapies. METHODS: We utilized a retrospective chart review of cancer patients who had been referred to dermatology and were diagnosed with NV. We recorded data including demographics, referral reason, underlying malignancy, targeted anticancer regimen, NV treatment, and nasal bacterial culture results. RESULTS: One Hundred Fifteen patients were included in the analysis, of which 13 % experienced multiple NV episodes. Skin rash was the most common reason (90 %) for a dermatology referral. The most common underlying malignancies were lung (43 %), breast (19 %), and colorectal (10 %) cancer. Sixty-eight percent of patients had been treated with an EGFRI-based regimen. Nasal cultures were obtained in 60 % of episodes, of which 94 % were positive for one or more organisms. Staphylococcus aureus was the most commonly isolated organism [methicillin-sensitive S. aureus 43 %; methicillin-resistant S. aureus 3 %]. CONCLUSIONS: We report the incidence and characteristics of an unreported, yet frequent dermatologic condition in cancer patients treated with targeted therapies. These findings provide the basis for additional studies to describe the incidence, treatment, and consequences of this event. A better understanding of NV would mitigate its impact on patients' quality of life and risk for additional dermatologic AEs.

Multiwavelength fluorescence otoscope for video-rate chemical imaging of middle ear pathology.

A common motif in otolaryngology is the lack of certainty regarding diagnosis for middle ear conditions, resulting in many patients being overtreated under the worst-case assumption. Although pneumatic otoscopy and adjunctive tests offer additional information, white light otoscopy has been the main tool for diagnosis of external auditory canal and middle ear pathologies for over a century. In middle ear pathologies, the inability to avail high-resolution structural and/or molecular imaging is particularly glaring, leading to a complicated and erratic decision analysis. Here, we propose a novel multiwavelength fluorescence-based video-rate imaging strategy that combines readily available optical elements and software components to create a novel otoscopic device. This modified otoscope enables low-cost, detailed and objective diagnosis of common middle ear pathological conditions. Using the detection of congenital cholesteatoma as a specific example, we demonstrate the feasibility of fluorescence imaging to differentiate this proliferative lesion from uninvolved middle ear tissue based on the characteristic autofluorescence signals. Availability of real-time, wide-field chemical information should enable more complete removal of cholesteatoma, allowing for better hearing preservation and substantially reducing the well-documented risks, costs and psychological effects of repeated surgical procedures.

Artificial Intelligence and Pediatric Otolaryngology.

Artificial intelligence (AI) studies show how to program computers to simulate human intelligence and perform data interpretation, learning, and adaptive decision-making. Within pediatric otolaryngology, there is a growing body of evidence for the role of AI in diagnosis and triaging of acute otitis media and middle ear effusion, pediatric sleep disorders, and syndromic craniofacial anomalies. The use of automated machine learning with robotic devices intraoperatively is an evolving field of study, particularly in the realms of pediatric otologic surgery and computer-aided planning for maxillofacial reconstruction, and we will likely continue seeing novel applications of machine learning in otolaryngologic surgery.

Label-Free Optical Technologies for Middle-Ear Diseases.

Medical applications of optical technology have increased tremendously in recent decades. Label-free techniques have the unique advantage of investigating biological samples in vivo without introducing exogenous agents. This is especially beneficial for a rapid clinical translation as it reduces the need for toxicity studies and regulatory approval for exogenous labels. Emerging applications have utilized label-free optical technology for screening, diagnosis, and surgical guidance. Advancements in detection technology and rapid improvements in artificial intelligence have expedited the clinical implementation of some optical technologies. Among numerous biomedical application areas, middle-ear disease is a unique space where label-free technology has great potential. The middle ear has a unique anatomical location that can be accessed through a dark channel, the external auditory canal; it can be sampled through a tympanic membrane of approximately 100 microns in thickness. The tympanic membrane is the only membrane in the body that is surrounded by air on both sides, under normal conditions. Despite these favorable characteristics, current examination modalities for middle-ear space utilize century-old technology such as white-light otoscopy. This paper reviews existing label-free imaging technologies and their current progress in visualizing middle-ear diseases. We discuss potential opportunities, barriers, and practical considerations when transitioning label-free technology to clinical applications.

Cough Sounds in Screening and Diagnostics: A Scoping Review.

OBJECTIVE: The aim of the study was to examine applications of cough sounds towards screening tools and diagnostics in the biomedical and engineering literature, with particular focus on disease types, acoustic data collection protocols, data processing and analytics, accuracy, and limitations. DATA SOURCES: PubMed, EMBASE, Web of Science, Scopus, Cochrane Library, IEEE Xplore, Engineering Village, and ACM Digital Library were searched from inception to August 2021. REVIEW METHODS: A scoping review was conducted on screening and diagnostic uses of cough sounds in adults, children, and animals, in English peer-reviewed and gray literature of any design. RESULTS: From a total of 438 abstracts screened, 108 articles met inclusion criteria. Human studies were most common (77.8%); the majority focused on adults (57.3%). Single-modality acoustic data collection was most common (71.2%), with few multimodal studies, including plethysmography (15.7%) and clinico-demographic data (7.4%). Data analytics methods were highly variable, with 61.1% using machine learning, the majority of which (78.8%) were published after 2010. Studies commonly focused on cough detection (41.7%) and screening of COVID-19 (11.1%); among pediatric studies, the most common focus was diagnosis of asthma (52.6%). CONCLUSION: Though the use of cough sounds in diagnostics is not new, academic interest has accelerated in the past decade. Cough sound offers the possibility of an accessible, noninvasive, and low-cost disease biomarker, particularly in the era of rapid development of machine learning capabilities in combination with the ubiquity of cellular technology with high-quality recording capability. However, most cough sound literature hinges on nonstandardized data collection protocols and small, nondiverse, single-modality datasets, with limited external validity. Laryngoscope, 134:1023-1031, 2024.

Tympanostomy Tube Insertion With and Without Adenoidectomy.

Importance: The benefit of adenoidectomy on otologic outcomes after tympanostomy tube (TT) insertion is unclear. Results from prior work are challenging to interpret due to small sample sizes, heterogeneous study designs, and varying outcome measures. Objective: To evaluate the association between adenoidectomy and otologic outcomes using a US population-level sample of children who received TTs, producing generalizable results for widespread clinical application. Design, Setting, and Participants: A matched cohort study was conducted using claims data from the Merative MarketScan Research Databases. The study included 601 848 children who received TTs between January 1, 2007, and December 31, 2021. Children who received adenoidectomy and TTs simultaneously (Ad+TT) were identified irrespective of the number of prior TTs. Control participants who received TTs without adenoidectomy were matched based on sex, age at the time of the procedure, and the number of prior TT procedures. Exposures: Adenoidectomy without tonsillectomy was the primary exposure. Main Outcomes and Measures: The primary outcomes were repeat TT insertion and subsequent oral antibiotic prescriptions after TT insertions. Multivariable logistic regression was used to quantify the effects of adenoidectomy and covariates on each outcome. Stratified analyses were performed in children younger than 4 years and 4 years or older. Results: Overall, 601 848 children (median [IQR] age, 2 [1-4] years; range, 0-11 years; 351 078 [58.3%] male) who received TTs were identified. The Ad+TT cohort included 201 932 children, with an equal number in the matched cohort. In children younger than 4 years, Ad+TT was common and was associated with lower odds of subsequent oral antibiotics (odds ratio [OR], 0.59; 95% CI, 0.58-0.60) but higher odds of repeat TT insertions (OR, 1.24; 95% CI, 1.22-1.27). In children 4 years or older, Ad+TT was associated with lower odds of repeat TT insertions (OR, 0.78; 95% CI, 0.75-0.81) and subsequent oral antibiotics (OR, 0.63; 95% CI, 0.62-0.65). Conclusions and Relevance: This study found that in children younger than 4 years, Ad+TT was commonly performed and may have had a secondary benefit of reducing subsequent oral antibiotic courses; however, it was not associated with a reduction in the risks of repeat TT insertions. In children 4 years or older, Ad+TT was associated with a reduction in the risk of repeat TT insertions and subsequent oral antibiotics. Given these findings, Ad+TT may be offered in children 4 years or older to improve otologic outcomes.

Advancing neonatal hearing screening in Latin America: Insights from pediatric otolaryngologists.

OBJECTIVE: To assess the real-world application of legislative measures and regulations governing newborn hearing testing in Latin America. METHODS: An online survey was sent to the Interamerican Association of Pediatric Otorhinolaryngology (IAPO) network to investigate neonatal hearing screening practices. Twelve questions were asked about legislation, implementation, and barriers to neonatal hearing screening. RESULTS: A total of 89 pediatric otolaryngologists representing 20 Latin American nations participated in this survey. The majority of respondents (64 %) indicated the existence of neonatal hearing laws within their respective countries and correctly named the specific legislation. However, it is noteworthy that over half (58 %) of pediatric ear, nose, and throat specialists reported that these laws are not consistently put into practice in their daily clinical routines. Respondents from five countries disclosed that neonatal hearing screening is not conducted within the first month of an infant's life. CONCLUSIONS: While the majority of Latin American nations have established legislation concerning neonatal hearing screening, its application in clinical practice is lacking due to economic obstacles. Marked disparities across Latin America persist for neonatal hearing screening. Our study provides key insights and recommendations aimed at addressing these issues, including the need for stronger legislative enforcement, increased funding, improved infrastructure, targeted professional training, and expanded public education to strengthen this vital aspect of healthcare in Latin America.

Bridging the Translation of ICG-1-Maltotriose: A Multimodal Sensor for Monitoring and Detecting Bacterial Infections.

Bacterial infections lack reliable, specific, and quick detection methods, which incur substantial costs to patients and caretakers. Our team conjugated the FDA-approved fluorescent dye indocyanine green (ICG) with a maltotriose sugar, resulting in two highly specific imaging agents (ICG-DBCO-1-Maltotriose and ICG-Amide-1-Maltotriose) for detecting bacterial infections. We then evaluated the two derivatives using fluorescence imaging (FLI), bioluminescence imaging (BLI), and photoacoustic imaging (PAI) in bacterial infection murine models. Our findings indicate that both imaging agents can correlate with and reliably detect the infection site using FLI and PAI for both Gram-negative and Gram-positive strains, with various bacterial loads. Furthermore, the differences in pharmacokinetic (PK) properties between the two agents allow for one to be used for immediate imaging (2-4 h postinjection), while the other is more effective for longitudinal studies (18-40 h postinjection).

Executive Summary of Clinical Practice Guideline on Immunotherapy for Inhalant Allergy.

OBJECTIVE: Allergen immunotherapy (AIT) is the therapeutic exposure to an allergen or allergens selected by clinical assessment and allergy testing to decrease allergic symptoms and induce immunologic tolerance. Inhalant AIT is administered to millions of patients for allergic rhinitis (AR) and allergic asthma (AA) and is most commonly delivered as subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT). Despite its widespread use, there is variability in the initiation and delivery of safe and effective immunotherapy, and there are opportunities for evidence-based recommendations for improved patient care. PURPOSE: The purpose of this clinical practice guideline is to identify quality improvement opportunities and provide clinicians trustworthy, evidence-based recommendations regarding the management of inhaled allergies with immunotherapy. Specific goals of the guideline are to optimize patient care, promote safe and effective therapy, reduce unjustified variations in care, and reduce risk of harm. The target patients for the guideline are any individuals aged 5 years and older with AR, with or without AA, who are either candidates for immunotherapy or treated with immunotherapy for their inhalant allergies. The target audience is all clinicians involved in the administration of immunotherapy. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group. It is not intended to be a comprehensive, general guide regarding the management of inhaled allergies with immunotherapy. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. ACTION STATEMENTS: The guideline development group made a strong recommendation that (Key Action Statement [KAS] 10) the clinician performing allergy skin testing or administering AIT must be able to diagnose and manage anaphylaxis. The guideline development group made recommendations for the following KASs: (KAS 1) Clinicians should offer or refer to a clinician who can offer immunotherapy for patients with AR with or without AA if their patients' symptoms are inadequately controlled with medical therapy, allergen avoidance, or both, or have a preference for immunomodulation. (KAS 2A) Clinicians should not initiate AIT for patients who are pregnant, have uncontrolled asthma, or are unable to tolerate injectable epinephrine. (KAS 3) Clinicians should evaluate the patient or refer the patient to a clinician who can evaluate for signs and symptoms of asthma before initiating AIT and for signs and symptoms of uncontrolled asthma before administering subsequent AIT. (KAS 4) Clinicians should educate patients who are immunotherapy candidates regarding the differences between SCIT and SLIT (aqueous and tablet) including risks, benefits, convenience, and costs. (KAS 5) Clinicians should educate patients about the potential benefits of AIT in (1) preventing new allergen sensitization, (2) reducing the risk of developing AA, and (3) altering the natural history of the disease with continued benefit after discontinuation of therapy. (KAS 6) Clinicians who administer SLIT to patients with seasonal AR should offer pre- and co-seasonal immunotherapy. (KAS 7) Clinicians prescribing AIT should limit treatment to only those clinically relevant allergens that correlate with the patient's history and are confirmed by testing. (KAS 9) Clinicians administering AIT should continue escalation or maintenance dosing when patients have local reactions to AIT. (KAS 11) Clinicians should avoid repeat allergy testing as an assessment of the efficacy of ongoing AIT unless there is a change in environmental exposures or a loss of control of symptoms. (KAS 12) For patients who are experiencing symptomatic control from AIT, clinicians should treat for a minimum duration of 3 years, with ongoing treatment duration based on patient response to treatment. The guideline development group offered the following KASs as options: (KAS 2B) Clinicians may choose not to initiate AIT for patients who use concomitant beta-blockers, have a history of anaphylaxis, have systemic immunosuppression, or have eosinophilic esophagitis (SLIT only). (KAS 8) Clinicians may treat polysensitized patients with a limited number of allergens.

Clinical Practice Guideline: Immunotherapy for Inhalant Allergy.

OBJECTIVE: Allergen immunotherapy (AIT) is the therapeutic exposure to an allergen or allergens selected by clinical assessment and allergy testing to decrease allergic symptoms and induce immunologic tolerance. Inhalant AIT is administered to millions of patients for allergic rhinitis (AR) and allergic asthma (AA) and is most commonly delivered as subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT). Despite its widespread use, there is variability in the initiation and delivery of safe and effective immunotherapy, and there are opportunities for evidence-based recommendations for improved patient care. PURPOSE: The purpose of this clinical practice guideline (CPG) is to identify quality improvement opportunities and provide clinicians trustworthy, evidence-based recommendations regarding the management of inhaled allergies with immunotherapy. Specific goals of the guideline are to optimize patient care, promote safe and effective therapy, reduce unjustified variations in care, and reduce the risk of harm. The target patients for the guideline are any individuals aged 5 years and older with AR, with or without AA, who are either candidates for immunotherapy or treated with immunotherapy for their inhalant allergies. The target audience is all clinicians involved in the administration of immunotherapy. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group (GDG). It is not intended to be a comprehensive, general guide regarding the management of inhaled allergies with immunotherapy. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. ACTION STATEMENTS: The GDG made a strong recommendation that (Key Action Statement [KAS] 10) the clinician performing allergy skin testing or administering AIT must be able to diagnose and manage anaphylaxis. The GDG made recommendations for the following KASs: (KAS 1) Clinicians should offer or refer to a clinician who can offer immunotherapy for patients with AR with or without AA if their patients' symptoms are inadequately controlled with medical therapy, allergen avoidance, or both, or have a preference for immunomodulation. (KAS 2A) Clinicians should not initiate AIT for patients who are pregnant, have uncontrolled asthma, or are unable to tolerate injectable epinephrine. (KAS 3) Clinicians should evaluate the patient or refer the patient to a clinician who can evaluate for signs and symptoms of asthma before initiating AIT and for signs and symptoms of uncontrolled asthma before administering subsequent AIT. (KAS 4) Clinicians should educate patients who are immunotherapy candidates regarding the differences between SCIT and SLIT (aqueous and tablet) including risks, benefits, convenience, and costs. (KAS 5) Clinicians should educate patients about the potential benefits of AIT in (1) preventing new allergen sensitizations, (2) reducing the risk of developing AA, and (3) altering the natural history of the disease with continued benefit after discontinuation of therapy. (KAS 6) Clinicians who administer SLIT to patients with seasonal AR should offer pre- and co-seasonal immunotherapy. (KAS 7) Clinicians prescribing AIT should limit treatment to only those clinically relevant allergens that correlate with the patient's history and are confirmed by testing. (KAS 9) Clinicians administering AIT should continue escalation or maintenance dosing when patients have local reactions (LRs) to AIT. (KAS 11) Clinicians should avoid repeat allergy testing as an assessment of the efficacy of ongoing AIT unless there is a change in environmental exposures or a loss of control of symptoms. (KAS 12) For patients who are experiencing symptomatic control from AIT, clinicians should treat for a minimum duration of 3 years, with ongoing treatment duration based on patient response to treatment. The GDG offered the following KASs as options: (KAS 2B) Clinicians may choose not to initiate AIT for patients who use concomitant beta-blockers, have a history of anaphylaxis, have systemic immunosuppression, or have eosinophilic esophagitis (SLIT only). (KAS 8) Clinicians may treat polysensitized patients with a limited number of allergens.

Imaging guidance for cholesteatoma surgery using tissue autofluorescence.

Significance: Cholesteatoma is an expansile destructive lesion of the middle ear and mastoid, which can result in significant complications by eroding adjacent bony structures. Currently, there is an inability to accurately distinguish cholesteatoma tissue margins from middle ear mucosa tissue, causing a high recidivism rate. Accurately differentiating cholesteatoma and mucosa will enable a more complete removal of the tissue. Aim: Develop an imaging system to enhance the visibility of cholesteatoma tissue and margins during surgery. Approach: Cholesteatoma and mucosa tissue samples were excised from the inner ear of patients and illuminated with 405, 450, and 520 nm narrowband lights. Measurements were made with a spectroradiometer equipped with a series of different longpass filters. Images were obtained using a red-green-blue (RGB) digital camera equipped with a long pass filter to block reflected light. Results: Cholesteatoma tissue fluoresced under 405 and 450 nm illumination. Middle ear mucosa tissue did not fluoresce under the same illumination and measurement conditions. All measurements were negligible under 520 nm illumination conditions. All spectroradiometric measurements of cholesteatoma tissue fluorescence can be predicted by a linear combination of emissions from keratin and flavin adenine dinucleotide. We built a prototype of a fluorescence imaging system using a 495 nm longpass filter in combination with an RGB camera. The system was used to capture calibrated digital camera images of cholesteatoma and mucosa tissue samples. The results confirm that cholesteatoma emits light when it is illuminated with 405 and 450 nm, whereas mucosa tissue does not. Conclusions: We prototyped an imaging system that is capable of measuring cholesteatoma tissue autofluorescence.

Post-tonsillectomy outcomes in children with mucopolysaccharidosis and obstructive sleep apnea.

OBJECTIVE: To describe the incidence of respiratory complications, postoperative hemorrhage, length of stay, and cost of care in children with mucopolysaccharidosis (MPS) undergoing adenotonsillectomy (AT). METHODS: Analysis of the 2009, 2012, and 2016 editions of the Healthcare Cost and Utilization Project Kids' Inpatient Database (HCUP KID) identified 24,700 children who underwent AT (40 children with MPS). Demographics, respiratory complications, postoperative hemorrhage, length of stay, and total cost were compared across children with and without MPS. RESULTS: Children with MPS had a higher likelihood of being male (P < 0.017). There was a higher rate of respiratory complications in children with MPS compared with children without MPS [6/40 (15%) vs. 586/24,660 (2.4%), P < 0.001], which remained significant after adjusting for sex [adjusted odds ratio 6.88 (95% CI 2.87-16.46)]. There was also a higher risk of postoperative hemorrhage [4/40 (10%) vs. 444/24,660 (1.8%), P < 0.001), with sex-adjusted odds ratio of 5.97 (95% CI 2.12-16.86). Median (IQR) length of stay was increased in children with MPS (3 days, 1-4) compared with children without MPS (1 day, 1-2, P < 0.001). There was an increase in median (IQR) charges for hospital stay in children with MPS compared with their peers [$33,016 ($23,208.50-$72,280.50 vs. $15,383 ($9937-$24,462), P < 0.001]. CONCLUSIONS: Children with MPS undergoing AT had an increased risk of respiratory complications, postoperative hemorrhage, longer length of stay, and a higher cost of treatment when compared with children without MPS. This information may help inform interventional, perioperative, and postoperative decision making.