Publications by authors named "Rakesh Chandra"

231 Publications

Impact of Biologic Therapies on Surgery for Chronic Rhinosinusitis With Nasal Polyposis.

Authors:
Rakesh Chandra

Ear Nose Throat J 2021 Sep 12;100(8):555-556. Epub 2021 Aug 12.

5718Vanderbilt University, Nashville, TN, USA.

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http://dx.doi.org/10.1177/01455613211034722DOI Listing
September 2021

Assessment of Opioid Use and Analgesic Requirements After Endoscopic Sinus Surgery: A Randomized Clinical Trial.

JAMA Otolaryngol Head Neck Surg 2021 Sep;147(9):811-819

Division of Rhinology and Endoscopic Skull Base Surgery, Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, California.

Importance: The opioid epidemic has generated interest in optimizing opioid prescribing after common surgeries. Recent studies have shown a broad range of analgesic prescription patterns following endoscopic sinus surgery (ESS).

Objective: To compare the efficacy of different analgesic regimens after ESS.

Design, Setting, And Participants: This multi-institutional, nonblinded randomized clinical trial was conducted at 6 tertiary centers across the US and Canada and included participants who underwent ESS for acute or chronic rhinosinusitis. The study was conducted from March 2019 to March 2020, and the data were analyzed in November to December 2020.

Interventions: All participants received acetaminophen, 650 mg, as the first-line analgesic. From there, patients were randomized to either oxycodone rescue (oxycodone, 5 mg, as second-line therapy) or ibuprofen rescue (ibuprofen, 600 mg, as second-line therapy, with oxycodone, 5 mg, reserved for breakthrough pain).

Main Outcomes And Measures: Baseline characteristics and disease severity were collected at enrollment. Medication logs, pain scores, and epistaxis measures were collected until postoperative day 7. The primary outcome was the postoperative visual analog scale score for pain. Brief Pain Inventory Pain Severity and Pain Interference Scores were also collected.

Results: A total of 118 patients were randomized (62 [52.5%] oxycodone rescue, 56 [47.5%] ibuprofen rescue; mean [SD] age, 46.7 [16.3] years; 44 women [44.0%]; 83 White [83.0%], 7 Black [7.0%], and 7 Asian individuals [7.0%]). After exclusions for loss to follow-up and noncompliance, 51 remained in the oxycodone rescue group and 49 in the ibuprofen rescue group. The groups had similar demographic characteristics and disease severity. Thirty-two (63%) in the oxycodone rescue group had adequate pain management with acetaminophen only, while 19 (37%) consumed at least 1 oxycodone dose. In the ibuprofen rescue group, 18 (16%) required only acetaminophen, 28 (57%) used only acetaminophen and ibuprofen, and the remaining 13 (26%) consumed 1 or more oxycodone doses. The groups had similar average acetaminophen (9.69 vs 7.96 doses; difference, 1.73; 95% CI, -1.37 to 4.83) and oxycodone (1.89 vs 0.77 doses; difference, 1.13; 95% CI, -0.11 to 2.36) use. Both groups had similar postoperative visual analog scale scores. A subanalysis that compared opioids users with nonusers showed clinically significant lower pain scores in nonusers at multiple postoperative points.

Conclusions And Relevance: In this randomized clinical trial, most patients who underwent ESS could be treated postoperatively using a nonopioid regimen of either acetaminophen alone or acetaminophen and ibuprofen. Ibuprofen as a second-line therapy did not reduce overall narcotic consumption, but the overall narcotic use was low in both groups.

Trial Registration: ClinicalTrials.gov Identifier: NCT03783702.
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http://dx.doi.org/10.1001/jamaoto.2021.1839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343514PMC
September 2021

The Effect of Timing of Surgery in Pituitary Apoplexy on Continuously Valued Visual Acuity.

J Neurol Surg B Skull Base 2021 Jul 24;82(Suppl 3):e70-e78. Epub 2020 Jan 24.

Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, Tennessee, United States.

 Pituitary apoplexy is often treated urgently, but this is based on studies which assess vision categorically and dichotomizes the time interval between symptom onset and surgery which may introduce bias in measuring an association between the two.  This study was aimed to assess for a relationship between continuously valued surgery delay and visual acuity recovery after pituitary apoplexy.  In this retrospective study, all patients presenting with symptomatic pituitary apoplexy between 2004 and 2016 were identified from an institutional database. The primary endpoint was visual acuity improvement, measured as the difference in acuity from the pre- to postoperative period, and measured in Logarithm of the Minimal Angle of Resolution (LogMAR) units. Analysis was performed using continuous values of time delay and visual acuity to assess for an underlying association.  Thirty-two pituitary apoplexy patients were identified. Visual acuity deficits were reported in 81%. The median visual acuity was 0.35 LogMAR (Snellen's fraction 20/40) preoperatively, and 0.1 (20/25) postoperatively (  < 0.01). The time between symptom onset and surgery was not associated with improvement in visual acuity (  = 0.46). When the time delay and visual outcome were intentionally dichotomized, patients undergoing surgery within 2 days of symptom onset had 0.21 times the odds of a good visual outcome (95% confidence interval [CI]: 0.04-1.05).  When assessed as continuously valued measures, the time from symptom onset to surgical intervention and the improvement in visual acuity are not associated, although intentional dichotomization of data produced conflicting results.
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http://dx.doi.org/10.1055/s-0040-1701217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289513PMC
July 2021

Differential olfactory outcomes in COVID-19: A large healthcare system population study.

Int Forum Allergy Rhinol 2021 Jul 21. Epub 2021 Jul 21.

Department of Otolaryngology - Head and Neck Surgery, Division of Rhinology/Skull Base Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

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http://dx.doi.org/10.1002/alr.22870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426833PMC
July 2021

Evolution of Topic Corticosteroid Therapy for the Management of Sinonasal Inflammatory Disease.

Ear Nose Throat J 2021 Jun;100(5):293-294

Department of Otolaryngology-Head & Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.

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http://dx.doi.org/10.1177/01455613211015746DOI Listing
June 2021

The Utility of Preoperative Phone Calls for Endoscopic Sinus Surgery Procedures.

Am J Rhinol Allergy 2021 Jun 1:19458924211020550. Epub 2021 Jun 1.

Vanderbilt University School of Medicine, Nashville, Tennessee.

Objective: Perioperative patient education improves patient satisfaction, surgical outcomes, and can reduce postoperative call volume. Here, we investigate whether the use of standardized preoperative phone calls elicits similar results in patients undergoing endoscopic sinus surgery (ESS).

Methods: Patients undergoing ESS at a tertiary rhinology center were identified prospectively through the electronic medical record (EMR). In the intervention cohort, a standardized preoperative educational phone call was performed. A postoperative survey was utilized to collect self-assessment of satisfaction and understanding in all patients. Postoperative call rates were obtained from the EMR. Wilcoxon rank sum and chi-squared analyses were conducted to compare results. Demographics of the otology and rhinology cohorts were compared with a Mann Whitney U-test.

Results: Data from 43 cases and 58 controls were collected. Patients receiving the intervention were similar to controls with regard to patient-reported understanding (case:9.1 ± 1.1 vs control:9.0 ± 1.4,  = 0.801) and satisfaction (case:9.4 ± 1.1 vs 8.9 ± 1.4,  = 0.155). Both cases and controls called the clinic regarding surgical outcomes more often than for postoperative medications or administrative concerns. Independent of receiving the intervention, patients that did not call clinic postoperatively had significantly better understanding of their procedures (call:8.6 ± 1.6 vs no-call:9.5 ± 1.0,  < 0.015) and satisfaction with their experience (call:8.8 ± 1.4 vs no-call:9.5 ± 1.1,  < 0.028). Patient age may contribute to lack of impact in the rhinology cohort, as compared to the otology group, but socioeconomic status does not seem to differentiate the two samples.

Conclusion: Though shown in other settings, a significant impact of educational phone calls prior to surgery was not observed in this sample. Patient education calls prior to endoscopic sinus surgery were not associated with changes in postoperative call volume to the clinic. Patient understanding and satisfaction may be related to other factors, such as patient selection or demographics. Future studies may target such patients prior to ESS.
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http://dx.doi.org/10.1177/19458924211020550DOI Listing
June 2021

Bilateral Longus Colli Abscesses as a Complication of Advanced Bacterial Rhinosinusitis.

Ear Nose Throat J 2021 May 27:1455613211018563. Epub 2021 May 27.

Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.

Known complications of acute bacterial rhinosinusitis include retropharyngeal abscess, cavernous sinus thrombosis, intracranial abscess, and associated sequelae. We describe the case of a patient with longus colli abscess formation resulting from acute pansinusitis, complicated by bilateral cavernous sinus thrombosis in the setting of concurrent viral pneumonitis, severe sepsis, and a large area cerebral infarction. The bilateral longus colli abscesses were drained via stereotactic image-guided endonasal sinus surgery, yielding in culture. The described disease progressed rapidly over a 2-week course amid the COVID-19 pandemic.
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http://dx.doi.org/10.1177/01455613211018563DOI Listing
May 2021

Evaluation of triazophos induced immunotoxicity of spleen and head kidney in fresh water teleost, Channa punctata.

Comp Biochem Physiol C Toxicol Pharmacol 2021 Jul 17;245:109029. Epub 2021 Mar 17.

Department of Zoology, School of Life Sciences, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur, Chhattisgarh, India. Electronic address:

The utilization of pesticides has increased for destroying pests and protecting crops in the agriculture field. Triazophos is a commonly used organophosphorous insecticide that causes alterations in haematological and histological parameters in fish. The present study was designed to evaluate the effect of triazophos induced innate and cell mediated immunotoxicity in freshwater teleost, Channa punctata. Fishes were exposed to triazophos at concentrations 5 and 10% of LC value for 10 and 20 days. Splenic and head kidney macrophage phagocytosis, nitric oxide production and superoxide production were assayed to evaluate the innate immunity. Cell-mediated immunity was measured through splenic and head kidney lymphocyte proliferation in presence of T and B cell mitogens. Results of the present study revealed that macrophage phagocytosis was significantly reduced after in vivo triazophos treatment. Differential suppressive effect of triazophos was also observed where mitogen induced splenic and head kidney lymphocyte proliferations were reduced after 10 and 20 days treatment. Concentration dependent effect of triazophos was observed in in vivo studies where the production of reactive oxygen and nitrogen intermediates were suppressed. This study describes the first investigation of the effect of triazophos on immune functions and will help to determine appropriate ecotoxicity and immunotoxicity in freshwater teleosts.
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http://dx.doi.org/10.1016/j.cbpc.2021.109029DOI Listing
July 2021

Analysis of suppressive effects of pesticide triazophos on leucocyte immune responses in a teleost, .

Drug Chem Toxicol 2021 Feb 18:1-8. Epub 2021 Feb 18.

Department of Zoology, School of Studies in Life Sciences, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur, India.

Triazophos is a commonly used organophosphate insecticide, which inhibits the acetylcholinesterase enzyme and causes paralysis and death of insects. Impact of the pesticides on immunity has scarcely been investigated, especially in fishes. The present study was designed to analyze the immunotoxic role of triazophos exposure to the leucocytes in freshwater teleost, . Triazophos, at concentrations of 0.1, 0.5, and 1 µg ml, was used to study leucocyte phagocytosis, superoxide production, nitrite release, and lymphocyte proliferation. Dose-dependent suppression of various immune responses was observed. Nitrite release and superoxide production by leucocytes were reduced in cultures incubated with triazophos. Mitogen-induced lymphocyte proliferation was significantly reduced at 0.5 and 1 µg ml but not at 0.1 µg ml concentration of pesticide. The biphasic suppressive effect was also discovered while evaluating phagocytic response. These investigations describe the effects of pesticide on immune responses in , which are helpful in understanding the immunotoxicity in fish. Substantially more researches are required to help design the measures to combat ecotoxicity in freshwater bodies.
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http://dx.doi.org/10.1080/01480545.2021.1886306DOI Listing
February 2021

Is there still a role for cranialization in modern sinus surgery?

Curr Opin Otolaryngol Head Neck Surg 2021 Feb;29(1):53-58

Vanderbilt Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Purpose Of Review: To give an overview of recently published literature on the indications and use of cranialization of the frontal sinuses.

Recent Findings: Recent studies on cranialization have evaluated its role in frontal sinus fractures, inflammatory disease, and tumors involving both the frontal sinus and anterior cranial fossa. Currently, a more conservative approach is favored with traumatic injury to the frontal sinus outflow tract, with multiple studies demonstrating outflow recanalization with observation alone. Similarly, advancements in endoscopic sinus surgical approaches allow the many posterior table fractures to be managed without cranialization. Severe inflammatory disease of the frontal sinus including giant mucoceles with frontal lobe compression have successfully been managed without cranialization in multiple studies suggesting an endoscopic surgical approach can be favored in these settings. Both benign and malignant tumors of the frontal sinus are managed without cranialization with select cases favoring an open approach with cranialization depending on tumor location. Malignant tumors of the frontal sinus are more likely to require cranialization as oncologic resection including margins can lead to large dural defects with significant tissue loss, which is unfavorable for more conservative reconstructive options.

Summary: Cranialization remains a necessary and indicated procedure in the appropriate clinical circumstances. A more conservative approach to frontal sinus fractures is warranted, with recent literature supporting similar outcomes and less morbidity. Inflammatory disease of the frontal sinus including giant mucoceles with frontal lobe compression can be managed without cranialization. Although most benign tumors can be resected via endoscopic approaches, cranialization remains a mainstay as part of the reconstructive plan after oncologic resection of malignant tumors involving the frontal sinus.
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http://dx.doi.org/10.1097/MOO.0000000000000691DOI Listing
February 2021

International consensus statement on allergy and rhinology: rhinosinusitis 2021.

Int Forum Allergy Rhinol 2021 03;11(3):213-739

Rutgers New Jersey Medical School, Newark, NJ.

I.

Executive Summary: BACKGROUND: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR-RS-2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence-based findings of the document.

Methods: ICAR-RS presents over 180 topics in the forms of evidence-based reviews with recommendations (EBRRs), evidence-based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary.

Results: ICAR-RS-2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence-based management algorithm is provided.

Conclusion: This ICAR-RS-2021 executive summary provides a compilation of the evidence-based recommendations for medical and surgical treatment of the most common forms of RS.
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http://dx.doi.org/10.1002/alr.22741DOI Listing
March 2021

Inflammatory heterogeneity in aspirin-exacerbated respiratory disease.

J Allergy Clin Immunol 2021 04 12;147(4):1318-1328.e5. Epub 2020 Nov 12.

Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tenn. Electronic address:

Background: Aspirin-exacerbated respiratory disease (AERD) is a mechanistically distinct subtype of chronic rhinosinusitis with nasal polyps (CRSwNP). Although frequently associated with type 2 inflammation, literature characterizing the milieu of inflammatory cytokines and lipid mediators in AERD has been conflicting.

Objective: We sought to identify differences in the upper airway inflammatory signature between CRSwNP and AERD and determine whether endotypic subtypes of AERD may exist.

Methods: Levels of 7 cytokines representative of type 1, type 2, and type 3 inflammation, and 21 lipid mediators were measured in nasal mucus from 109 patients with CRSwNP, 30 patients with AERD, and 64 non-CRS controls. Differences in inflammatory mediators were identified between groups, and patterns of inflammation among patients with AERD were determined by hierarchical cluster analysis.

Results: AERD could be distinguished from CRSwNP by profound elevations in IL-5, IL-6, IL-13, and IFN-γ; however, significant heterogeneity existed between patients. Hierarchical cluster analysis identified 3 inflammatory subendotypes of AERD characterized by (1) low inflammatory burden, (2) high type 2 cytokines, and (3) comparatively low type 2 cytokines and high levels of type 1 and type 3 cytokines. Several lipid mediators were associated with asthma and sinonasal disease severity; however, lipid mediators showed less variability than cytokines.

Conclusions: AERD is associated with elevations in type 2 cytokines (IL-5 and IL-13) and the type 1 cytokine, IFN-γ. Among patients with AERD, the inflammatory signature is heterogeneous, supporting subendotypes of the disease. Variability in AERD immune signatures should be further clarified because this may predict clinical response to biologic medications that target type 2 inflammation.
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http://dx.doi.org/10.1016/j.jaci.2020.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035132PMC
April 2021

Sinonasal Small Cell Carcinoma-Case Series of a Rare Malignancy.

Ear Nose Throat J 2020 Oct 22:145561320964640. Epub 2020 Oct 22.

Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.

Sinonasal small cell neuroendocrine carcinoma (SNEC) is an extremely rare and aggressive neoplasm that can arise in the sinonasal region. These tumors are associated with high morbidity and mortality, are difficult to diagnose, and are hard to treat. We describe 2 cases of this poorly understood malignancy and review imaging, pathology, and treatment decisions. A 41-year-old male and a 64-year-old female presented to a tertiary center in 2019 after developing nasal obstruction and were found to have sinonasal masses on imaging. Both biopsies showed strong expression of pancytokeratin with dot-like reactivity and expression of neuroendocrine markers chromogranin and synaptophysin. The findings were diagnostic of SNEC. Staging positron emission tomography/computed tomography and brain MRI were performed, and patients were discussed at a multidisciplinary tumor board. Neither had distant metastatic disease at presentation. One patient had no intracranial or orbital disease and underwent a subtotal endoscopic resection with adjuvant chemoradiation. The other patient demonstrated middle cranial fossa, dural, and orbital involvement as well as cranial nerve V palsy. This patient was treated with induction chemotherapy, followed by concurrent chemoradiation. Both patients are presently alive at 4 months follow-up, but one with persistent local disease and the other distant metastasis. Sinonasal small cell neuroendocrine carcinoma is a rare and poorly understood malignancy with an aggressive clinical course. Continued careful review of pathology and study of molecular features are needed for improved understanding of SNEC, and particularly for head and neck SNEC, to establish a staging system and better formulate treatment protocols.
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http://dx.doi.org/10.1177/0145561320964640DOI Listing
October 2020

Crustal deformation rates in Kashmir valley and adjoining regions from continuous GPS measurements from 2008 to 2019.

Sci Rep 2020 Oct 21;10(1):17927. Epub 2020 Oct 21.

CSIR-4PI, CSIR Fourth Paradigm Institute (Formerly CSIR-CMMACS), Wind Tunnel Road, Bangalore, India.

We present GPS velocities in Kashmir valley and adjoining regions from continuous Global Positioning System (cGPS) network during 2008 to 2019. Results indicate total arc normal shortening rates of ~ 14 mm/year across this transect of Himalaya that is comparable to the rates of ~ 10 to 20 mm/year reported else-where in the 2500 km Himalaya Arc. For the first time in Himalayas, arc-parallel extension rate of ~ 7 mm/year was recorded in the Kashmir valley, pointing to oblique deformation. Inverse modeling of the contemporary deformation rates in Kashmir valley indicate oblique slip of ~ 16 mm/year along the decollement with locking depth of ~ 15 km and width of ~ 145 km. This result is consistent with the recorded micro-seismicity and low velocity layer at a depth of 12 to 16 km beneath the Kashmir valley obtained from collocated broadband seismic network. Geodetic strain rates are consistent with the dislocation model and micro-seismic activity, with high strain accumulation (~ 7e-08 maximum compression) to the north of Kashmir valley and south of Zanskar ranges. Assuming the stored energy was fully released during 1555 earthquake, high geodetic strain rate since then and observed micro-seismicity point to probable future large earthquakes of Mw ~ 7.7 in Kashmir seismic gap.
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http://dx.doi.org/10.1038/s41598-020-74776-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577991PMC
October 2020

In Reply: Central compartment atopic disease: the missing link in the allergy and CRSwNP saga.

Authors:
Rakesh K Chandra

Int Forum Allergy Rhinol 2020 10 24;10(10):1193-1194. Epub 2020 Jul 24.

Department of Otolaryngology-Head & Neck Surgery, Vanderbilt University Medical Center, Nashville, TN.

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http://dx.doi.org/10.1002/alr.22662DOI Listing
October 2020

Elevated mucus interleukin-17A levels are associated with increased prior sinus surgery for chronic rhinosinusitis.

Int Forum Allergy Rhinol 2021 02 23;11(2):120-127. Epub 2020 Jul 23.

Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.

Background: Recent advances in molecular biology have enabled the identification of potential inflammatory endotypes of chronic rhinosinusitis (CRS), with prior work suggesting differential short-term surgical outcome trajectories based on cytokine signatures. However, there is a paucity of data assessing long-term treatment failure and need for revision surgery based on inflammatory biomarkers.

Methods: Retrospective analysis of prospectively collected cross-sectional data from 231 patients electing surgical therapy for CRS. Intraoperative mucus specimens were quantitatively sampled for inflammatory cytokines using a multiplex flow cytometric bead assay. Univariate Spearman correlations between cytokine levels and prior number of surgeries were assessed. A stepwise adjusted multivariate Poisson regression analysis was used to model patient-reported prior sinus surgery counts as a function of cytokine levels.

Results: Several cytokines (interleukin [IL]-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17A, tumor necrosis factor α [TNF-α], interferon γ [IFN-γ], and eotaxin) demonstrated significant positive correlations with number of prior surgeries. However, only higher IL-17A levels were independently associated with a higher number of prior sinus surgeries (β = 0.345, p = 0.0003) after adjusting for the significant covariates of age (β = 0.018, p = 0.0036), Lund-Mackay score (β = -0.046, p = 0.02), history of aspirin-exacerbated respiratory disease (β = 1.01, p < 0.0001) and allergic fungal rhinosinusitis (β = 1.08, p < 0.0001). Higher levels of regulated on activation, normal T-cell expressed and secreted (RANTES) were conversely associated with a lower number of prior surgeries (β = -0.17, p = 0.048).

Conclusion: An IL-17A-predominant cytokine profile is linked to an increased number of prior sinus surgeries. Thus, type 3 inflammatory markers may indicate a particularly difficult-to-treat, recalcitrant CRS endotype.
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http://dx.doi.org/10.1002/alr.22652DOI Listing
February 2021
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