What Is Alpha-Gal Syndrome?

This JAMA Patient Page describes alpha-gal syndrome, a type of food allergy to red meat products, and its symptoms, diagnosis, and treatment.

Enhancement of Inducible Nitric Oxide Synthase Activity by Low Molecular Weight Peptides Derived from Protamine: A Potential Therapy for Chronic Rhinosinusitis.

Nitric oxide (NO) is a key immune defense agent that is produced from l-arginine in the airways by leukocytes and airway epithelial cells, primarily via inducible nitric oxide synthase (iNOS). Deficiencies in nasal NO levels have been associated with diseases such as primary ciliary dyskinesia and chronic rhinosinusitis. Herein, we demonstrate a proof-of-concept regarding a potential new therapeutic approach for such disorders. We show that arginine-rich low molecular weight peptides (LMWPs) derived from the FDA-approved protamine (obtained from salmon sperm) are effective at significantly raising NO production in both RAW 264.7 mouse macrophage and LA4 mouse epithelial cell lines. LMWP is produced using a stable, easily produced immobilized thermolysin gel column followed by size-exclusion purification. Monomeric l-arginine induces concentration-dependent increases in NO production in stimulated RAW 264.7 and LA4 cells, as measured by stable nitrite in the cell media. In stimulated RAW 264.7 cells, LMWP significantly increases iNOS expression and total NO production 12-24 h post-treatment compared to cells given equivalent levels of monomeric l-arginine. For stimulated LA4 cells, LMWPs are effective in significantly increasing NO production compared to equivalent l-arginine monomer concentrations over 24 h but do not substantially enhance iNOS expression. The use of the arginase inhibitor S-boronoethyl-l-cysteine in combination with LMWPs results in even higher NO production by stimulated RAW 264.7 cells and LA4 cells. Increases in NO due to LMWPs, compared to l-arginine, occur only after 4 h, which may be due to iNOS elevation rather than increased substrate availability.

Improvement of Suspected Eosinophilic Otitis Media with Targeted Biologic Therapy.

OBJECTIVE: To compare the responses of suspected eosinophilic otitis media to treatment with or without a targeted biologic therapy against interleukin-4 (IL-4), IL-5, or IL-13 signaling. STUDY DESIGN: Retrospective review. SETTING: Tertiary referral center. PATIENTS: Subjects with type 2 chronic rhinosinusitis with nasal polyposis (CRSwNP), asthma, and otitis media who underwent treatment between 2005 and 2021. INTERVENTION: Treatment with targeted biologic therapy. MAIN OUTCOME MEASURES: Pre- and posttreatment nasal endoscopy, ear examination, and audiologic evaluation. RESULTS: Four hundred seventy-seven subjects with type 2 CRSwNP were treated between 2005 and 2021. Sixty-two had otitis media with pre- and posttreatment evaluation. Retrospective chart review assessed pre- and posttreatment exam findings, nasal endoscopy, audiometry, and tympanometry. Nineteen subjects received a biologic therapy, whereas 43 did not. Exam, endoscopy, and tympanometry were graded for severity and compared pre- and posttreatment. Subjective ear exam and tympanometry were significantly improved with biologic therapy (control = 0.05, biologic = 0.84, p = 9.3 × 10 -5 ; control = -0.1, biologic = 0.62, p = 0.0002). Conductive hearing loss as assessed by air-bone gaps did not change between groups (control = 1.2 dB better, biologic = 1.2 dB worse, p = 0.32). Nasal endoscopy findings improved with biologic therapy relative to the control group, although not statistically significant (control = 1.04, biologic = 1.36, p = 0.22). CONCLUSIONS: Biologic therapies targeting interleukin-4 (IL-4), IL-5, and IL-13 signaling are potential new treatments for eosinophilic otitis media. This is the largest study demonstrating improvement in subjects with suspected eosinophilic otitis media in response to biologic therapy, and immune modulation represents a novel treatment strategy for this challenging condition. PROFESSIONAL PRACTICE GAP AND EDUCATIONAL NEED: Current treatment strategies for otologic symptoms in eosinophilic disease are not tremendously effective or durable, resulting in a need for improved treatment options. LEARNING OBJECTIVE: To determine if targeted biologic therapy, often used for eosinophilic asthma and type 2 chronic rhinosinusitis with nasal polyposis, improves coexistent suspected eosinophilic otitis media. DESIRED RESULT: Treatment of suspected eosinophilic otitis media with targeted biologic therapy will result in improvement of otologic symptoms with a durable response compared with current treatment options. LEVEL OF EVIDENCE: Level IV. INDICATE IRB OR IACUC: Exempt. HUM00182703.

Community-acquired methicillin-resistant Staphylococcus aureus: an emerging cause of acute bacterial parotitis.

Staphylococcus aureus has long been recognized as a cause of acute bacterial parotitis. A case of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) parotitis is presented, highlighting the emergence of this increasingly important pathogen to cause a wide variety of infections. Also reviewed are the salient clinical and microbiologic features of this novel infection.

Allergic rhinitis and rhinosinusitis.

A relationship between allergic rhinitis and acute and chronic rhinosinusitis has been postulated for many years. Epidemiologic evidence suggests that such a relationship is likely. In addition, evidence of a common pathophysiologic mechanism linking these diseases is compelling and continues to evolve. Although a clear and definitive causal relationship remains to be elucidated, an increasing number of studies support the plausibility of this link. The current paradigm of the "unified airway" and evidence to support this model further strengthen this link. This article reviews the literature relating allergic rhinitis and acute and chronic rhinosinusitis.

Image-guided frontal trephination: a minimally invasive approach for hard-to-reach frontal sinus disease.

OBJECTIVES: Peripherally located frontal sinus pathology may be unreachable with standard endoscopic techniques. Patients with superiorly or laterally based lesions often undergo osteoplastic flap with or without obliteration. Image-guided frontal trephination (IGFT) can localize pathology and provide excellent exposure. We present 13 patients in whom this technique was applied. STUDY DESIGN: Medical records of 13 patients undergoing IGFT were retrospectively reviewed. RESULTS: The patients' mean age was 49.2 years, (range 14-79); follow-up time was 29.9 months (range 12-39). Indications for IGFT were superiorly or laterally based mucoceles (3), fibrous dysplasia or osteoma (3), type 4 frontal cells (3), and frontal recess stenosis or ossification (4). In five patients, IGFT was combined with endoscopic transethmoid frontal sinusotomy; eight patients were treated through a trephination approach, and three patients underwent trephination with unilateral frontal sinus obliteration. One patient required revision; all others remain symptom free. CONCLUSIONS/SIGNIFICANCE: IGFT offers an attractive alternative to osteoplastic flap.

Raeder syndrome: Paratrigeminal oculosympathetic syndrome presenting as a manifestation of chronic sinusitis.

Raeder syndrome (paratrigeminal oculosympathetic syndrome) is a rare clinical entity characterized by ipsilateral trigeminal sensory deficits, ptosis, and miosis, with an absence of anhidrosis secondary to interruption of the postganglionic oculosympathetic pathway. Going back to its original description, this constellation of physical examination findings has historically been associated with intracranial pathology involving the middle cranial fossa. Understanding this pathway is important in distinguishing Raeder syndrome from Horner syndrome, as the presentation of the former is now recognized to accompany a number of other disease entities in the head and neck region. We present an unusual case of Raeder syndrome associated with bacterial sinusitis, and we discuss its management and review the literature.

Human papillomavirus infection and biomarkers in sinonasal inverted papillomas: clinical significance and molecular mechanisms.

BACKGROUND: The role of human papillomavirus (HPV) in sinonasal inverted papillomas (IPs) is controversial. Determining the prevalence of HPV infection and its impact on the molecular biology of these tumors is critical to characterizing its role in the pathogenesis of IPs. METHODS: A total of 112 paraffin-embedded IPs from 90 patients were studied. A tissue microarray was constructed and stained for p16, p53, epidermal growth factor receptor (EGFR), and cyclin D1. HPV presence and types were determined using PGMY 09/11 primers and integration using HPV 11 detection of integrated papillomavirus sequences by ligation-mediated polymerase chain reaction (DIPS-PCR). RESULTS: HPV was detected in 11 of 90 (12%) patients. HPV 11 was found in 9 samples. HPV 6 and HPV 27 were found in 1 sample each. EGFR staining proportion was higher in HPV-positive IPs vs HPV-negative specimens (56.2% vs 23.6%; p = 0.009). Differences in p16, p53, and cyclin D1 staining were not significant. HPV-positive lesions tend to progress to malignancy (p = 0.064). Three samples were analyzed for integration. Viral integration was found in both malignant tumors but not in the precursor IP. CONCLUSION: Degradation of p53 and p16/cyclin D1 dysregulation are not important mechanisms in low-risk HPV-related IP. The low prevalence of HPV in this series indicates it is not a main etiological factor for IPs; however, when present, low-risk HPV may contribute to the biology of IPs through an increase of EGFR expression and a predisposition for malignant progression by integration into the cellular genome.

Activity in the dorsal cochlear nucleus of hamsters previously tested for tinnitus following intense tone exposure.

Chronic increases in spontaneous multiunit activity can be induced in the dorsal cochlear nucleus (DCN) of hamsters by intense sound exposure (Kaltenbach and McCaslin, 1996). It has been hypothesized that this hyperactivity may represent a neural code that could underlie the sound percepts of tinnitus. The goal of the present study was to determine whether hyperactivity could be demonstrated in animals that had previously been tested for tinnitus, and, if so, whether animals differing in their behavioral evidence for tinnitus also differ in their levels of spontaneous activity. The results showed not only that levels of activity in exposed animals were higher than those in control animals, but the degree to which the activity was increased was related to the strength of the behavioral evidence for tinnitus. These findings are consistent with the hypothesis that hyperactivity in the DCN may be a physiological correlate of noise-induced tinnitus.

Effects of cochlear ablation on noise induced hyperactivity in the hamster dorsal cochlear nucleus: implications for the origin of noise induced tinnitus.

Chronic increases in multiunit spontaneous activity are induced in the dorsal cochlear nucleus (DCN) following exposures to intense sound. This hyperactivity has been implicated as a neurophysiological correlate of noise induced tinnitus. However, it is not known whether this hyperactivity originates centrally, or instead, reflects an increase in the level of spontaneous input from the auditory nerve. In the present study we addressed this issue by testing whether hyperactivity, induced in the DCN by previous exposure to intense sound, persists after ipsilateral cochlear input to the DCN has been removed. To induce hyperactivity, Syrian golden hamsters were exposed under anesthesia to an intense pure tone (122-127 dB SPL at 10 kHz) for 4 h. Additional hamsters, which were anesthetized for 4 h, but not tone exposed, served as controls. Electrophysiological recordings of spontaneous activity were performed on the surface of the left DCN in animals in which the ipsilateral cochlea was either intact or ablated. The degree of cochlear removal was determined by microdissection and histologic evaluation of the cochlea after completion of each recording session. Comparisons between the levels of activity recorded in animals with and without intact cochleas revealed that the induced hyperactivity in the DCN persisted after both partial and complete cochlear ablations. These results indicate that the maintenance of hyperactivity is not dependent on input from the ipsilateral cochlea, implying that hyperactivity originates centrally.

The role of allergy in chronic rhinosinusitis.

Issues surrounding the cause and pathogenesis of chronic rhinosinusitis (CRS) remain controversial. Various models involving physiologic factors and anatomic obstruction have been offered to explain the pathogenesis of this common disease. More recently, the role of chronic inflammatory processes has been demonstrated. These findings may modify the current paradigm of this disease and transform the diagnosis and management of patients with CRS. This review focuses on the role of allergy and inflammation in the pathogenesis of CRS.

Voice and deglutition functions after the supracricoid and total laryngectomy procedures for advanced stage laryngeal carcinoma.

OBJECTIVES: This investigation compared speech and deglutition functions after alternative surgical treatments for advanced stage laryngeal carcinoma: the supracricoid laryngectomy (SCL) versus the total laryngectomy (TL). Study design and setting Cohort investigation at Wayne State University School of Medicine. METHODS: Quantitative studies of laryngeal biomechanics, acoustic and speech aerodynamic features, and deglutition skills of these individuals were coupled to listener and patient self-impressions of speech and voice characteristics for group comparative analyses. RESULTS: Results revealed that patients from each subgroup performed comparably relative to speech intelligibility and voice quality disturbances. Videostroboscopy of the neoglottal mechanisms in these two populations helped to explain these outcomes. Acoustic and speech aerodynamic testing demonstrated variably abnormal features in both surgical subgroups. Whereas the SCL patients eventually achieved full oral diets, they required many sessions of swallowing therapy to obtain this objective and eliminate tube feeding supplementation. The TL patients did not evidence protracted swallowing difficulties or the need for specific exercises in order to remove their feeding tubes postoperatively. References to organ preservation strategies in lieu of surgical management are included for completeness purposes. CONCLUSIONS: The SCL and TL surgical procedures for advanced stage laryngeal carcinoma resulted in equivalent speech and swallowing functional outcomes.

The office management of recalcitrant rhinosinusitis.

The patient referred to the otolaryngologist for the treatment of CRS has received many therapies for the condition. Newer therapies available focus on the anti-inflammatory therapies and local application of antimicrobial and antifungal agents to the sinus cavities. Much clinical work remains to be done to prove the efficacy of currently available treatments. The recent advances in the understanding of allergic and immune mechanisms may allow eventual intervention at the level of cytokines and other immunomodulators of inflammation. The complex cascade of interleukins and proinflammatory agents in CRS patients may some day allow "silver bullet" therapies in the properly selected patient. Until then, a systematic approach to the evaluation of these patients and management with the currently available treatment modalities may help relieve the symptoms in patients with CRS.

Sinonasal inverted papilloma: prognostic factors with emphasis on resection margins.

Objective We review our institution's experience with the treatment of inverted papilloma (IP) with emphasis on the implications of surgical margins for disease control. Design Retrospective chart review of patients with IP treated at the University of Michigan from 1996 to 2011. Setting Tertiary care center. Participants Patients undergoing surgical resection with curative intent for IP. Main Outcome Measures Overall survival, disease-specific survival, and locoregional control were used as main outcome measures. Results We studied 129 patients including 19 with carcinoma arising from IP. Disease-free rates at 2, 3, and 5 years were 79.7%, 77.9%, and 61%, respectively. Overall, 10 of 18 recurrences were detected > 2 years from follow-up, with recurrences detected up to 8 years from surgery. For benign disease, obtaining tissue margins outside of the primary specimen for margin control did not affect disease control rates. Conclusion IP is a disease that requires significant follow-up periods beyond 2 years. For IP without carcinogenesis, acquiring margins outside of the tumor specimen did not appear to affect disease control rates in this study. No clear predictors of malignancy were seen in this study, which highlights the need for further research to predict this phenomenon.

Epidermal growth factor receptor, p16, cyclin D1, and p53 staining patterns for inverted papilloma.

BACKGROUND: The aim of this study was better characterize the staining patterns of inverted papilloma (IP) with and without carcinoma by performing immunohistochemistry for p16, epidermal growth factor receptor (EGFR), p53, and cyclin D1 antibodies in a large patient cohort. METHODS: A total of 162 IP specimens were collected from 147 patients treated at the University of Michigan between 1996 and 2011. Twenty-two specimens contained carcinoma. Tumor was extracted for construction of 2 tissue microarrays and stained for p16, EGFR, p53, and cyclin D1. Tumor staining intensity and percentage staining were scored. RESULTS: Benign disease was positive for p16 in 64%, EGFR in 50%, p53 in 30%, and cyclin D1 in 76%. IP with carcinomatous degeneration was positive for p16 in 14%, EGFR in 71%, p53 in 62%, and cyclin D1 in 76%. The differences in staining positivity between benign and malignant disease reached significance for p16 and p53 only. Mean percentage staining by tumor surface area for IP and IP with carcinoma was 12% vs 7% for p16 (no statistical significance [NS]), 20% vs 34% for EGFR (NS), 4% vs 24% for p53 (p < 0.001), and 17% vs 21% for cyclin D1 (NS). CONCLUSION: Important characteristic staining pattern for IP with and without carcinoma are highlighted in this study. Unlike recent trends in human papilloma virus (HPV)-related head and neck malignancies, low expression of p16 is a marker for malignancy in this series. Positive staining for p53 correlates with the development of carcinoma in IP.

Climate change and its impact on allergic rhinitis and other allergic respiratory diseases.

PURPOSE OF REVIEW: To discuss current evidence of global climate change and its implications for allergic rhinitis and other allergic respiratory diseases. RECENT FINDINGS: Global climate change is evidenced by increasing average earth temperature, increasing anthropogenic greenhouse gas levels, and elevated pollen levels. Pollutants of interest include carbon dioxide (CO2), ozone (O3), and nitrous oxide (NO2) because they can enhance the allergic response and lead to increased symptoms of allergic respiratory diseases. Heightened CO2 levels stimulate pollen production via photosynthesis and increased growth in multiple plant species investigated. Although worsened air quality appears to increase prevalence of allergic rhinitis, the effects of increased temperature are less certain. The findings of increased aeroallergen levels likely contribute to increases in presentation of allergic diseases, although more healthcare impact studies are necessary. SUMMARY: Although recent literature indicates and strongly supports changes in temperature, pollution levels, and aeroallergen levels, more longitudinal epidemiologic surveillance of allergic diseases in relation to climate change as well as pathophysiologic studies on changing aeroallergen effects on allergic diseases are needed.

Vitamin D and chronic rhinitis.

PURPOSE OF REVIEW: To discuss the role of vitamin D in chronic rhinitis and chronic rhinosinusitis (CRS). RECENT FINDINGS: Vitamin D has been shown to have an immunomodulatory effect with a significant impact on immune function. Specifically, vitamin D regulates the mechanisms which suppress the inflammatory response and direct the differentiation fate of immune cells. Vitamin D has been shown to play an important role in asthma, and the concept of the unified airway model allows the extrapolation of vitamin D as a critical player in chronic rhinitis and rhinosinusitis. SUMMARY: Recent findings on the function of vitamin D may explain aspects of the pathophysiology of chronic rhinitis and CRS, and may help direct future treatment of these diseases.

Vitamin D: immunomodulation of asthma, allergic rhinitis, and chronic rhinosinusitis.

PURPOSE OF REVIEW: To discuss the role of vitamin D in asthma, allergic rhinitis, and chronic rhinosinusitis (CRS). RECENT FINDINGS: Over the last several years, the role of vitamin D in immunomodulation has been studied and shown to have a significant impact on immune function. A causal relationship exists between vitamin D function and innate and adaptive immunity to infections. The mechanisms underlying vitamin D immune actions could be attributed to a paracrine feedback loop that reduces inflammation as well as influencing the differentiation fate of activated CD4 T cells, or the enhancement of suppressor T-cell function; indeed, a combination of these factors may underlie the actions of vitamin D. SUMMARY: Recent findings on the function of vitamin D may explain aspects of the pathophysiology of allergic rhinitis and CRS and may help direct future interventions and treatment of these diseases.

Three-dimensional volumetric measurements and analysis of the maxillary sinus.

BACKGROUND: Multiple chronic rhinosinusitis (CRS) staging systems have been developed in an attempt to correlate symptoms with radiological imaging results. Currently, no perfect system exists. We sought to analyze the maxillary sinus (MS) using three-dimensional volumetric measurements and advanced high-resolution CT imaging. METHODS: We reviewed MS CT scans from 50 control subjects and 50 subjects with documented CRS involving at least one MS. The following measurements were recorded: (1) volume of MS free air, (2) MS mucosal thickening, and (3) MS lateral wall bony thickness. Average Hounsfield unit (HU) values for mucosal thickening among CRS subjects were also recorded. Values are expressed as mean ± SD and median. Values from the CRS patients were compared with healthy controls using Student's t-tests. RESULTS: Among controls (n = 50), volumes (mL) of right and left MS were 24.1 ± 9.7 and 24.7 ± 9.0, respectively. Among CRS patients (n = 50), the portion of mucosal disease to total sinus volume was 51.8% (right) and 50.7% (left). Mean bony thickness (mm) in controls was 0.98 ± 0.2 (right) and 1.0 ± 0.3 (left). CRS patients had significantly greater bony thickness 1.9 ± 0.8 (right) and 2.0 ± 0.9 (left; p = 0.0001). HU for diseased MS were 30.1 ± 18.7 (right) and 35.7 ± 22.1 (left). CONCLUSION: Three-dimensional volumetric analysis combined with HU calculations and bony thickness measurements represents a new and unique way to evaluate CT scans in patients with CRS. Additional studies correlating symptoms with imaging findings as well as analysis of all paranasal sinuses is the next step toward a novel staging system.

Wound healing in the paranasal sinuses after Coblation, Part II: evaluation for endoscopic sinus surgery using a sheep model.

BACKGROUND: A previous study on wound healing with a rabbit model showed thermal injury to sinus mucosa with complete respiratory re-epithelialization by postoperative day (POD) 29. This study was designed to further understand the pattern of injury using the bipolar radiofrequency plasma process used by the Coblator and evaluate postprocedure healing. METHODS: Based on experience with our rabbit model, three sheep underwent endoscopic sinus surgery. Coblation was applied to inferior turbinate mucosa in three areas for 2, 4, or 6 seconds. After resection of the contralateral middle turbinate and ethmoidectomy, Coblation was applied to the lateral wall or lamina papyracea for 2 seconds. The ethmoid and turbinate specimens were resected en bloc during necropsy immediately for the first sheep and on POD 14 for the others. RESULTS: Coblation resulted in immediate loss of surface respiratory epithelium and thermal-type injury to the underlying seromucinous glands. On POD 14, the Coblation site showed re-epithelialization with respiratory epithelium. The underlying seromucinous glands were replaced by mild fibrosis. A small, well-defined zone of injury was shown. Longer use did not result in a deeper injury. Rather, the depth of injury was dependent on the type of submucosal tissue present. Underlying bone was associated with reactive, regenerative changes. No histological changes were shown in the orbit. CONCLUSION: The effects of Coblation on sheep mucosa show a similar injury and healing pattern to that shown on rabbit mucosa. Based on this work and the previous rabbit study, the Coblator may be an additional tool for use in endoscopic sinus surgery.