Chronic Rhinosinusitis With Nasal Polyposis Treated With Dupilumab: Real-World Use and Outcomes.

BACKGROUND: Biologic medications are increasingly incorporated into chronic rhinosinusitis with nasal polyps (CRSwNP) management. However, little is known about prescribing patterns in real-world settings and how this relates to proposed international guidelines and outcomes. OBJECTIVES: To characterize use patterns of dupilumab for CRSwNP better in relation to proposed guidelines and explore real-world outcomes. METHODS: We used the TriNetX Web-based tool to identify patients who were prescribed dupilumab for CRSwNP. Patients prescribed dupilumab for a CRSwNP indication were included for analysis. Dupilumab initiation criteria were determined via the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 (EPOS2020). RESULTS: In total, 121 patients were identified who were prescribed dupilumab for a CRSwNP indication. Of these, 86 (71%) met EPOS2020 indications for biologic initiation and 35 (29%) did not. Overall, patients had significant improvements in the 22-item SinoNasal Outcome Test scores (mean improvement of 24.3 points) and nasal polyp scores (mean improvement of 1.0 point). However, 20 patients (30%) did not show meaningful improvement in the 22-item SinoNasal Outcome Test scores. Twenty-one patients (17%) failed a previous biologic attempt. Therapy was discontinued by six patients (5%) due to side effects, and by six (5%) owing to a lack of efficacy. CONCLUSIONS: In our experience, patients prescribed dupilumab for CRSwNP frequently may not meet EPOS2020 Guidelines. Over 25% of those who do not meet criteria may not have CRSwNP. Overall, dupilumab use among well-selected patients appears to be safe and effective. Further real-world study of biologic use for CRSwNP will help improve its judicious use and identify populations who benefit most from biologic therapies.

Adverse Events and Subsequent Management Associated With Eustachian Tube Balloon Dilation.

Objective: Eustachian tube balloon dilation is a minimally invasive technique used to improve persistent Eustachian tube dysfunction. Currently, the US Food and Drug Administration (FDA) has approved the use of balloon dilation devices produced by three manufacturers, but little is known about associated adverse events and subsequent management. Study Design: Case series. Setting: FDA Manufacturer and User Facility Device Experience (MAUDE) database. Methods: Reports submitted to the FDA using the MAUDE database searched from January 2000 to July 2022 were analyzed for adverse events and management. Results: A total of 13 adverse events were found in the database. Subcutaneous emphysema (n = 8) was the most common event. Other less frequent events included patulous Eustachian tube (n = 2), vascular dissection (n = 1), nasopharyngeal mucocele (n = 1), and tinnitus (n = 1). A majority of patients who experienced subcutaneous emphysema received antibiotics (n = 5) and were admitted to the hospital (n = 4). The patient with a carotid dissection 7 days postprocedure presented with a stroke and fully recovered after stent placement. There was limited preprocedure information in the MAUDE database. There were 2 patients who did not fully recover after a complication. Three patients underwent corrective surgical interventions. No one company had more associated adverse events reported. Conclusion: Subcutaneous emphysema is the most common adverse event after Eustachian tube dilation. Further studies exploring potential balloon dilation adverse events to allow for better patient counseling are warranted.

Ayurvedic medicine for the treatment of chronic rhinosinusitis: a systematic review of randomized and non-randomized trials.

OBJECTIVES: This article provides a comprehensive systematic review and qualitative analysis of the current research investigating Ayurveda chronic rhinosinusitis (CRS) treatment. CONTENT: PRISMA guidelines for systematic reviews was followed and our search utilized MEDLINE, Embase, Ayush Portal, and Cochrane Library databases. Articles published prior to March 2022, 10 or more patients that investigated Ayurveda as a treatment for CRS in humans were included. This resulted in thirteen articles meeting inclusion criteria. Ayurvedic treatments included herbal medications for oral consumption, nasal instillation, and steam inhalation used alone or in combination. All studies concluded that Ayurvedic therapy led to improvements in subjective CRS symptoms and objective radiographic and hematologic criteria. However, all 13 studies had a significant risk of bias due to study design and statistical methods utilized. SUMMARY: Ayurvedic therapy may be a useful CRS treatment for some patients and overall appears to be well tolerated. However, definitive recommendation for when Ayurvedic treatments would be beneficial in the treatment of CRS remains not possible. OUTLOOK: Given the overall positive effects shown in the current published evidence and growing interest in complementary and integrative therapies, Ayurvedic treatments for CRS deserve further investigation in the form of well-designed controlled trials.

Mixed Origins: HIV gp120-Specific Memory Develops from Pre-Existing Memory and Naive B Cells Following Vaccination in Humans.

The most potent and broad HIV envelope (Env)-specific antibodies often when reverted to their inferred germline versions representing the naive B cell receptor, fail to bind Env, suggesting that the initial responding B cell population not only exclusively comprises a naive population, but also a pre-existing cross-reactive antigen-experienced B cell pool that expands following Env exposure. Previously we isolated gp120-reactive monoclonal antibodies (mAbs) from participants in HVTN 105, an HIV vaccine trial. Using deep sequencing, focused on immunoglobulin G (IgG), IgA, and IgM, VH-lineage tracking, we identified four of these mAb lineages in pre-immune peripheral blood. We also looked through the ∼7 month postvaccination bone marrow, and interestingly, several of these lineages that were found in prevaccination blood were still persistent in the postvaccination bone marrow, including the CD138+ long-lived plasma cell compartment. The majority of the pre-immune lineage members included IgM, however, IgG and IgA members were also prevalent and exhibited somatic hypermutation. These results suggest that vaccine-induced gp120-specific antibody lineages originate from both naive and cross-reactive memory B cells. ClinicalTrials.gov NCT02207920.

Actinomyces Acute Rhinosinusitis Complicated by Subperiosteal Abscess in an Immunocompromised 12-Year-Old: Case Report and Literature Review.

Objective: To describe a rare case of pediatric actinomycotic rhinosinusitis with orbital subperiosteal abscess and review the current literature to assess methods of diagnosis, treatment modalities, and outcomes with appropriate treatment. Methods: A case report and a review of the literature. Results: A 12-year-old patient with Crohn's disease on infliximab presented with rhinosinusitis with orbital subperiosteal abscess formation. Endoscopic sinus surgery was performed and cultures grew actinomyces. A prolonged course of antibiotics was started, resulting in the complete resolution of the infection. In a literature review, all cases of uncomplicated and complicated actinomyces rhinosinusitis managed with appropriate surgery and prolonged antibiotics resulted in a cure. Our case is the first reported in a pediatric patient and the first taking immunosuppressive medication. Overall, only 3 cases of actinomyces rhinosinusitis in immunosuppressed individuals have been reported, each with uncontrolled diabetes and each also responded well to surgery and appropriate antibiotics. Conclusion: Actinomycosis of the paranasal sinuses poses a diagnostic challenge, with infections varying widely in presentation and extent of disease. A high index of suspicion, appropriate testing, and early aggressive treatment are critical in managing patients with this infection. Our case and prior published studies show that actinomyces rhinosinusitis can be successfully managed with endoscopic sinus surgery, abscess drainage as necessary, and a prolonged course of antibiotics, even in immunocompromised and pediatric populations.

Crenotherapy as a Complementary and Integrative Treatment for Chronic Rhinosinusitis: A Systematic Review and Discussion of Current Evidence Limitations.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common condition that affects patients' quality of life. Standard treatments for CRS have known side effects and variable efficacy rates. Thus, complementary and integrative (CIM) treatments for CRS such as crenotherapy, which utilizes high mineral content water or vapor as an inhalation therapy, are of continued interest. OBJECTIVES: To summarize and evaluate the current research investigating crenotherapy's therapeutic potential and clinical outcomes for the treatment of CRS. STUDY DESIGN: Systematic review and qualitative analysis. METHODS: A systematic review was performed, with a comprehensive search strategy applied to 6 databases from inception to March 2021: CINAHL, Cochrane, Embase, PubMed, Scopus, and Web of Science. Studies with at least 10 patients, which investigated crenotherapy as the sole or adjunctive treatment for CRS in humans were included. RESULTS: In total, 10 articles out of 756 were included. Of these, 6 were randomized controlled trials. The remaining four articles were non-randomized prospective cohort studies. Six studies assessed clinical symptoms in response to crenotherapy, and there were unanimous improvements in Visual Analog Scale (VAS), Sino-Nasal Outcome Test-20 (SNOT-20), and other quality of life metrics. The studies that assessed inflammatory markers, cytology, or other measures showed significant improvement in neutrophil count, spores, ciliary motility, IgE, and manometry. Minimal to no adverse events were reported across all 10 studies. CONCLUSION: There is limited data to support crenotherapy's effectiveness in treating patients with CRS. However, published studies suggest that for certain patients crenotherapy can both improve CRS symptoms and objective measures of nasociliary function with minimal side effects. Findings must be interpreted with caution due to study heterogeneity, inconsistent use of standard CRS definitions and outcomes measures, as well as other study design flaws. Given these results, as well as a growing interest in CIM, crenotherapy treatments for CRS deserve further investigation.

Microbiomics of irrigation with xylitol or Lactococcus lactis in chronic rhinosinusitis.

OBJECTIVE: Topical sinonasal rinse therapies may alter the local microbiome and improve disease control in chronic rhinosinusitis (CRS). The objective of this study was to examine microbiome changes in post-surgical CRS patients when rinsing with commercially available products containing xylitol or Lactococcus lactis. METHODS: A crossover-type protocol with a washout period was designed. Swab samples from anterior ethmoid cavities of CRS patients were collected prospectively at baseline. Subjects were provided packets containing either L. lactis W136 or xylitol in non-blinded fashion and instructed to add it to their rinse bottles daily for 28 days, after which another swab was taken. A saline wash-out period was completed and a third swab taken. A final 28-day regimen of the opposite product was followed by a final swab. DNA extraction and sequencing of the 16S rRNA gene allowed for global microbiome analysis. RESULTS: We enrolled 25 subjects with CRS and 10 controls resulting in 70 adequate samples. Increased detection of Lactococcus was observed after use of L. lactis. No significant trends in alpha or beta diversity as a result of treatment were observed. SNOT-22 score did not change significantly following treatment with xylitol, L. lactis, or saline. CONCLUSION: We did not detect any major clinical or microbiome-level effect due to treatment with two topical rinse products. Further research is needed to elucidate their clinical utility and possible probiotic effect. LEVEL OF EVIDENCE: 3.

Utilization of Invasive Procedures for Adult Eustachian Tube Dysfunction.

OBJECTIVE: Eustachian tube dysfunction (ETD) is a common diagnosis among adults presenting for outpatient care. We sought to determine national utilization and the associated cost of invasive procedures for adult ETD. STUDY DESIGN: Cross-sectional study. SETTING: National health care database. SUBJECTS AND METHODS: The Truven Health MarketScan Databases (2010-2014) analytic cohort included health care encounters of patients ≥18 years of age with a diagnosis of ETD or related conditions of otitis media with effusion (OME) or tympanic membrane retraction (TMR). Visits associated with recent diagnoses of acute upper respiratory infection, head and neck cancer, or radiation therapy were excluded. Invasive procedure usage was subdivided into nasal and otologic procedures. RESULTS: ETD, OME, or TMR was diagnosed in 1,298,987 patients, 11.1% of which were chronic. The most common procedure was diagnostic endoscopy (including nasal endoscopy and laryngopharyngoscopy), which was used most frequently in the first 3 months after diagnosis, during which it was performed in 120,971 (9.3%) patients. The most frequent therapeutic nasal procedure was eustachian tube inflation without catheterization, performed in 11,412 patients over 5 years at a total cost of $1,210,939 ($106 per person annually). The most common therapeutic otologic procedure was myringotomy with tympanostomy, performed on 56,137 patients over 5 years at a total cost of $47,713,708 ($810 per person annually). CONCLUSION: Several nasal and otologic procedures are associated with a diagnosis of adult ETD at substantial cost. Development of therapeutic alternatives should be sought to mitigate the need for invasive procedures to treat this condition.

Health Care Utilization and Prescribing Patterns for Adult Eustachian Tube Dysfunction.

OBJECTIVE: Eustachian tube dysfunction (ETD) prompts >2 million adult visits in the United States annually. While disease prevalence and health care utilization are established for children, practice patterns for adults remain unknown. Our objective was to determine national resource utilization for adult ETD. STUDY DESIGN: Cross-sectional study. SETTING: National database sample. SUBJECTS AND METHODS: The Truven Health MarketScan Databases (2010-2014) analytic cohort included health care encounters of patients ≥18 years of age with a diagnosis of ETD, otitis media with effusion, or tympanic membrane retraction. Visits associated with recent diagnoses of acute upper respiratory infection, head and neck cancer, or radiation therapy were excluded. Acute ETD (<3 months) and chronic ETD (≥3 months) were subgroups. Medication usage was quantified by class. RESULTS: ETD was diagnosed for 1,298,987 patients, 11% of which was chronic. Over 92% of patients were seen in outpatient clinics, most often by otolaryngology (57%) for chronic ETD and by general medicine (49%) for acute ETD. Medications were frequently utilized, as 530,146 (53.7%) patients received ≥1 prescription. Top prescriptions for chronic ETD included intranasal corticosteroids (22%), antibiotics (22%), oral corticosteroids (13%), and analgesics (6%). The overall annual cost of prescribed medications associated with visits in which either acute or chronic ETD was diagnosed exceeded $8.5 million for a mean of $80.78 per patient who filled a prescription. CONCLUSION: Adult ETD is frequently treated with several medication classes by a variety of provider types. Understanding the potential adverse effects and cost associated with these practices should be a priority.

Evaluating metrics of responsiveness using patient-reported outcome measures in chronic rhinosinusitis.

BACKGROUND: Responsiveness, or sensitivity to clinical change, is important when selecting patient-reported outcome measures (PROMs) for research and clinical applications. This study compares responsiveness of PROMs used in chronic rhinosinusitis (CRS) to inform the future development of a highly responsive instrument that accurately portrays CRS patients' symptom experiences. METHODS: Adult CRS patients initiating medical therapy (MT; n = 143) or undergoing endoscopic sinus surgery after failing MT (ESS; n = 123) completed the 22-item Sino-Nasal Outcome Test (SNOT-22), European Position Statement on Rhinosinusitis (EPOS) visual analog scale (VAS), and 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29) at baseline and 3 months after treatment. Cohen's d and paired t statistics were used to evaluate the responsiveness of each measure. RESULTS: Fifty-two (36.4%) subjects and 42 (34.1%) subjects in the MT and ESS groups, respectively, completed baseline and 3-month questionnaires. Subjects with and without 3-month data were similar with respect to baseline demographics, VAS scores, and SNOT-22 scores (p > 0.05). In MT patients, CRS-specific measures, like VAS (d = -0.58, p < 0.01; t = -1.81, p > 0.05) and SNOT-22 (d = -0.70, p < 0.01; t = -3.29, p < 0.05) scores, were more responsive than PROMIS-29 general health domains (p > 0.05 for Cohen's d). In ESS patients, VAS (d = -1.97; t = -9.63, both p < 0.01) and SNOT-22 (d = -1.56; t = -9.99, both p < 0.01) scores were similarly more responsive, although changes in PROMIS-29 domains of Fatigue (d = -0.82, p = 0.01; t = -4.63, p < 0.01), Sleep Disturbance (d = -0.83; t = -3.77, both p < 0.01), and Pain Intensity (d = -1.0; t = -5.67, both p < 0.01) were significant. All 22 individual SNOT-22 items differed significantly after surgery, whereas only 8 items were consistently responsive after MT. CONCLUSIONS: For both MT and ESS patients, CRS-specific PROMs are more responsive to posttreatment clinical changes than general health measures. Still, the SNOT-22 contains items that likely decrease its overall responsiveness. Our findings also indicate that existing PROMs had a greater response to ESS than MT.

The effect of antibiotics on the microbiome in acute exacerbations of chronic rhinosinusitis.

BACKGROUND: Current treatment of acute exacerbations of chronic rhinosinusitis (CRS) is driven by identification of predominant bacteria using culture-based methods and determination of antibiotic sensitivities. The objective of this study was to evaluate the response of the sinonasal microbiome to antibiotic therapy in the setting of an acute exacerbation of CRS. METHODS: Aspirate and swab samples for culture and DNA analysis were collected bilaterally from 8 CRS patients presenting with acute exacerbations. Patients were started on a 2-week course of a culture-directed antibiotic after sensitivities were determined. Repeat samples were taken immediately on the completion of treatment. DNA was extracted from each sample, amplified using bacterial 16S primers and sequenced. Bacterial abundance was determined by quantitative polymerase chain reaction (qPCR). Diversity metrics of the microbiota between pretreatment and posttreatment samples were calculated. RESULTS: There was significantly more bacterial DNA present in the pretreatment group than in the posttreatment group. An increase in α-diversity was found in the posttreatment group relative to the pretreatment group (p < 0.05 in each comparison) with swab sampling, but not by aspirate sampling. The predominant organism identified by 16S sequencing correlated with the culture-identified bacteria genus in each patient. CONCLUSION: Significant differences exist in the diversity of bacteria populations during acute exacerbations of CRS and after antimicrobial treatment. After therapy, the increase in diversity is accompanied by a decrease in the total of abundance of the bacterial population.

Melkersson-Rosenthal syndrome: a facial nerve center perspective.

OBJECTIVES: Melkersson-Rosenthal syndrome (MRS) is a rare neuro-mucocutaneous granulomatous disorder of unknown etiology, characterized by the triad of facial palsy, lingua plicata (fissured tongue), and orofacial edema. Few articles in the literature report series with more than 20 patients or focus on the facial nerve dominant presentation of MRS. METHODS: We performed a retrospective review of the patients diagnosed with MRS at a university-based Facial Nerve Center. RESULTS: Twenty-one patients were identified from 1971 to 2010. The age of presentation ranged from 22 to 67 years (mean 44.1). Seven (33.3%) were male and 14 (66.7%) were female. All (100%) patients had facial paralysis. Fourteen (66.7%) patients who initially presented with unilateral paralysis subsequently developed metachronous contralateral paralysis (alternating unilateral facial paralysis). One (4.7%) patient had simultaneous bilateral facial paralysis. The number of episodes per patient ranged from 1 to 8 (mean 3.1). Laterality was relatively equal: 35 episodes occurred on the right side and 31 on the left. The patient with most episodes of facial paralysis had four on the left and four on the right (metachronous). This was followed by three patients with six episodes each. The age of first incidence of facial paralysis ranged from 2 to 60 years (mean 34.4, median of 39). The mean interval between episodes was 4.7 years (range 0-30, median 3). Six (28.5%) of the patients reported a family history of MRS. CONCLUSIONS: MRS is a rare disease of unknown pathogenesis in which oligosymptomatic forms predominate. Patients with this disease may present to different specialties complaining of different symptoms, and frequently, not all the classic features of the triad will be present. In our series of facial paralysis patients diagnosed with MRS, a higher proportion had the full triad of symptoms than has been previously reported in the literature.

The effect of intranasal fluticasone propionate irrigations on salivary cortisol, intraocular pressure, and posterior subcapsular cataracts in postsurgical chronic rhinosinusitis patients.

BACKGROUND: Intranasal corticosteroid irrigations, especially budesonide, are used increasingly in the management of chronic rhinosinusitis. In post-endoscopic sinus surgery patients, irrigations may offer improved delivery at higher doses to the paranasal sinuses than intranasal spray preparations. Fluticasone propionate may have higher potency and lower systemic bioavailability than budesonide, but there is little data on its effects as an intranasal irrigation on the hypothalamic-pituitary-adrenal axis or on ocular findings. METHODS: Adult patients who had previously undergone bilateral endoscopic sinus surgery and had not taken systemic corticosteroids in the last 6 months were prospectively enrolled. Subjects irrigated with 3 mg of fluticasone propionate in 240 mL saline solution twice daily. Salivary cortisol, intraocular pressure, and the presence of posterior subcapsular cataracts were measured before drug administration and after 6 weeks of continuous use. RESULTS: Twenty-three subjects completed the study. No subjects had salivary cortisol levels below the normal range before or after therapy, and there was no statistical difference in mean salivary cortisol levels pretreatment and posttreatment (0.294 vs 0.392 µg/dL; p = 0.27). There was no clinical or statistical difference in mean intraocular pressure before or after therapy (13.3 vs 13.3 mmHg; p = 0.86). No subjects developed a posterior subcapsular cataract. CONCLUSION: Fluticasone propionate irrigations did not suppress salivary cortisol levels or result in ocular changes. Irrigation with fluticasone propionate 3 mg in 240 mL saline twice daily may be a safe alternative to other intranasal or systemic corticosteroid treatments for chronic rhinosinusitis patients.

Endoscopic trans(naso)orbital management of supraorbital mucoceles with biliary T-tube stenting.

The objective of this article is to describe our surgical technique for accessing orbital and supraorbital ethmoid sinus mucoceles and the novel application of a biliary T-tube to stent and redirect mucociliary flow into the frontal recess. We describe in technical terms our surgical approach and the use of an 8-Fr pediatric biliary T-tube as a paranasal sinus stent with demonstrative case reports. Four patients have been successfully managed employing the endoscopic trans(naso)orbital approach to access and marsupialize supraorbital and superiorly located orbital mucoceles without egress to the frontal recess. Patency of drainage was maintained by utilizing a flexible, pediatric, biliary T-tube that is inserted via an above (trephination) and below (endoscopic) approach in three patients, and without the need for stenting in one patient (median follow-up, 14.5 months). The presented surgical strategy is safe and effective in accessing and maintaining long-term patency of problematic supraorbital and superiorly located intraorbital mucoceles without communication to the frontal recess.

Pilot study comparing total intravenous anesthesia to inhalational anesthesia in endoscopic sinus surgery: novel approach of blood flow quantification.

OBJECTIVES: We compared anesthesia with sevoflurane-remifentanil hydrochloride (SR) to total intravenous anesthesia with propofol-remifentanil hydrochloride (PR) in patients undergoing endoscopic sinus surgery for chronic rhinosinusitis in terms of sinonasal mucosal blood flow, the surgical field visualization score, and blood loss. METHODS: We performed a double-blinded prospective study at a tertiary care center in 23 adults scheduled to undergo endoscopic sinus surgery for chronic rhinosinusitis. The patients were randomized to receive SR or PR. The sinonasal mucosal blood flow was measured by optical rhinometry. The surgical field visualization score was based on the Boezaart scale. RESULTS: The groups had similar clinical characteristics. During the 60- to 90-minute and 90- to 120-minute operative time windows, the blood flow was significantly greater in the PR group than in the SR group (p = 0.04 and p = 0.03, respectively). The amounts of blood loss in the PR and SR groups were 152.9 +/- 161.3 mL and 355.9 +/- 393.4 mL, respectively (p = 0.12). The median ratios of the surgical field visualization score to the number of sinuses operated on in the PR and SR groups were 2.1 and 1.8, respectively (p = 0.52). CONCLUSIONS: The intraoperative blood flow, as determined by optical rhinometry, was significantly greater with anesthesia with PR than with anesthesia with SR, 1 hour into the procedure; however, this difference did not translate into differences in the amounts of operative blood loss or in the surgical field visualization scores.

Antibiotic prophylaxis in uncontaminated neck dissection.

OBJECTIVES/HYPOTHESIS: To describe our institution's experience with antibiotic prophylaxis in uncontaminated neck dissection and to identify risk factors associated with postoperative wound infection. STUDY DESIGN: Retrospective chart review. METHODS: Between April 2006 and June 2010, 244 patients underwent 273 uncontaminated neck dissections at a single tertiary care center. Patient factors, operative details, and postoperative complications were recorded. Patients were separated into three groups: no prophylactic antibiotics, intraoperative antibiotics only, and intra- and postoperative antibiotics. RESULTS: Wound infections occurred after nine of the 273 procedures (3.3%). All of the wound infections occurred in patients receiving intraoperative antibiotics only (4 of 157) or intra- and postoperative antibiotics (5 of 75) (P = .11). The development of a wound infection was not associated with age, sex, history of tobacco and alcohol use, history of head and neck surgery, or history of radiation or chemotherapy. Wound infection was independently associated with operative time (adjusted odds ratio, 1.35; 95% confidence interval, 1.07-1.71; P = .011, for each additional hour of surgery) and with radical or extended neck dissection (adjusted odds ratio, 14.61; 95% confidence interval, 2.37-90.01, P = .004). CONCLUSIONS: Our data did not support the use of antibiotic prophylaxis in routine uncontaminated neck dissection. Prophylactic antibiotics, however, may be indicated for more extensive lymphadenectomy procedures.