EUFOREA/EPOS2020 statement on the clinical considerations for chronic rhinosinusitis with nasal polyps care.

Following the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) treatment algorithm for chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), patients suffering from severe uncontrolled CRSwNP are recommended to receive oral corticosteroids, (revision) sinus surgery, systemic biologicals and/or aspirin treatment after desensitization (ATAD). Given the major differences in indications, outcomes, practical considerations, risks and costs of these key pillars of treatment, there is a growing need to define criteria for each treatment option and list the clinically relevant and major considerations for them. This EUFOREA document therefore provides an expert panel overview of the expected outcomes, specific considerations and (contra)indications of the five major treatment arms of severe uncontrolled CRSwNP: oral corticosteroids, primary and revision sinus surgery, biological treatment and ATAD. This overview of treatment considerations is needed to allow physicians and patients to consider the different options in the context of providing optimal and personalized care for severe uncontrolled CRSwNP. In conclusion, the five major treatment options for severe uncontrolled CRSwNP have intrinsic advantages, specific indications and considerations that are of importance to the patient, the physician and the society. This EUFOREA statement supports the unmet need to define criteria for the indication of every treatment pillar of CRSwNP.

Silent Infection of B and CD8+ T Lymphocytes by Influenza A Virus in Children with Tonsillar Hypertrophy.

Influenza A viruses (IAVs) cause more than 2 million annual episodes of seasonal acute respiratory infections (ARI) and approximately 500,000 deaths worldwide. Depending on virus strain and host immune status, acute infections by IAV may reach sites other than the respiratory tract. In the present study, IAV RNA and antigens were searched for in tissues of palatine tonsils and adenoids removed from patients without ARI symptoms. A real-time reverse transcriptase PCR (RT-PCR) screening revealed that 8 tissue samples from 7 patients out of 103 were positive for IAV. Positive samples were subjected to next-generation sequencing (NGS) and 3 of 8 tissues yielded complete IAV pH1N1 genomes, whereas in 5 samples, the PB1 gene was not fully assembled. Phylogenetic analysis placed tonsil-derived IAV in clusters clearly segregated from contemporaneous Brazilian viruses. Flow cytometry of dispersed tissue fragments and serial immunohistochemistry of paraffin-embedded sections of naturally infected biopsies indicated that CD20+ B lymphocytes, CD8+ T lymphocytes, and CD11c+ cells are susceptible to IAV infection. We sought to investigate whether these lymphoid tissues could be sites of viral replication and sources of viable virus particles. MDCK cells were inoculated with tissue lysates, enabling recovery of one IAV isolate confirmed by immunofluorescence, reverse transcriptase quantitative PCR (RT-qPCR), and NGS. The data indicate that lymphoid tissues not only harbor expression of IAV proteins but also contain infectious virus. Asymptomatic long-term infection raises the possibility of IAV shedding from tonsils, which may have an impact on host-to-host transmission.IMPORTANCE Influenza A virus (IAV) infections are important threats to human health worldwide. Although extensively studied, some aspects of virus pathogenesis and tissue tropism remain unclear. Here, by different strategies, we describe the asymptomatic infection of human lymphoid organs by IAV in children. Our results indicate that IAV was not only detected and isolated from human tonsils but displayed unique genetic features in comparison with those of contemporaneous IAVs circulating in Brazil and detected in swabs and nasal washes. Inside the tissue microenvironment, immune cells were shown to be carrying IAV antigens, especially B and T CD8+ lymphocytes. Taken together, these results suggest that human lymphoid tissues can be sites of silent IAV infections with possible impact on virus shedding to the population.

Impact of early detection of acute invasive fungal rhinosinusitis in immunocompromised patients.

BACKGROUND: Early diagnosis of acute invasive fungal rhinosinusitis (AIFRS) is vital to improving outcomes in immunocompromised patients. This study evaluated the impact of a systematic protocol with nasal endoscopy and biopsies to early detect AIFRS in immunocompromised patients. Additionally, we compared the accuracy of frozen-section biopsy and culture with formalin-fixed paraffin-embedded (FFPE) biopsy. METHODS: Retrospective cohort in a Tertiary Referral Hospital. Patients with the suspected diagnosis of AIFRS were evaluated following a standardized protocol, including serial nasal endoscopies and biopsies when necessary. The sensitivity and specificity of frozen-section biopsy and culture were also compared with FFPE. RESULTS: The mortality rate related to AIFRS of this standardized cohort (13/43) was 30.2%. Better outcomes were observed in patients with disease limited to the turbinates and in those with higher peripheral neutrophils count. Frozen-section biopsy positivity correlated with FFPE findings for fungi detection (p-value < 0.0001), with a sensitivity of 90.6%, specificity of 72.7%, and accuracy of 86.0%. CONCLUSION: Implementation of this standardized protocol was related to a considerably low mortality rate among patients with suspected AIFRS at our Institution. Frozen-section biopsy revealed high accuracy to diagnose AIFRS. The current protocol including frozen-tissue biopsy improved the evaluation and survival rates of immunocompromised patients with presumed AIFRS.

The Relationship between Colonization by Moraxella catarrhalis and Tonsillar Hypertrophy.

We sought to investigate the prevalence of potentially pathogenic bacteria in secretions and tonsillar tissues of children with chronic adenotonsillitis hypertrophy compared to controls. Prospective case-control study comparing patients between 2 and 12 years old who underwent adenotonsillectomy due to chronic adenotonsillar hypertrophy to children without disease. We compared detection of Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Pseudomonas aeruginosa, and Moraxella catarrhalis by real-time PCR in palatine tonsils, adenoids, and nasopharyngeal washes obtained from 37 children with and 14 without adenotonsillar hypertrophy. We found high frequency (>50%) of Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Pseudomonas aeruginosa in both groups of patients. Although different sampling sites can be infected with more than one bacterium and some bacteria can be detected in different tissues in the same patient, adenoids, palatine tonsils, and nasopharyngeal washes were not uniformly infected by the same bacteria. Adenoids and palatine tonsils of patients with severe adenotonsillar hypertrophy had higher rates of bacterial coinfection. There was good correlation of detection of Moraxella catarrhalis in different sampling sites in patients with more severe tonsillar hypertrophy, suggesting that Moraxella catarrhalis may be associated with the development of more severe hypertrophy, that inflammatory conditions favor colonization by this agent. Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis are frequently detected in palatine tonsils, adenoids, and nasopharyngeal washes in children. Simultaneous detection of Moraxella catarrhalis in adenoids, palatine tonsils, and nasopharyngeal washes was correlated with more severe tonsillar hypertrophy.

Facial features and hyoid bone position in preschool children with obstructive sleep apnea syndrome.

The aim of the study was to evaluate facial features and hyoid bone position in children with obstructive sleep apnea syndrome (OSAS) by cephalometric radiography. A prospective cross-sectional study was conducted in a tertiary referral hospital. Twenty-nine children in the 3-6 year age bracket were evaluated: 14 children with OSAS and 15 nasal-breathing children. All children underwent otorhinolaryngologic examination, and those with OSAS also underwent in-laboratory polysomnography for diagnostic confirmation. The children were then submitted to orthodontic evaluation and cephalometry. Lateral cephalometric radiographs from children with OSAS were compared to those of nasal-breathing children. We found no differences between the two groups regarding the linear and angular measurements of the face. However, the children with OSAS presented, already at the preschool age, with an inferiorly positioned hyoid bone, thus increasing the pharyngeal area. In children with OSAS, the hyoid bone appears to be in a significantly inferior position at an early age. Our findings provide evidence that there is a relationship between the position of the hyoid bone and OSAS in children, which could contribute to the persistence of OSAS into adulthood.

Non-antibiotic antimicrobial agents for chronic rhinosinusitis: a narrative review.

OBJECTIVE: This narrative review explores alternative non-antibiotic antimicrobial agents for CRS management in adults. METHODS: Alternative antimicrobial agents using EPOS 2020 guidelines as reference were selected, and articles dated from 2003 to 2022 in English, Portuguese, or Spanish using PubMed and EMBASE databases. The parameters analyzed included study design, evidence level, population characteristics, CRS characteristics, interventions, outcomes, sample size, randomization, blinding, and side effects. Reviews, unrelated contexts,in vitro experiments, and duplicates were excluded. RESULTS: 148 articles were screened; 19 articles were selected for analysis. Randomized controlled trials and cohort studies assessing non-antibiotic antimicrobial treatments for CRS were included. Xylitol demonstrated effectiveness in reducing CRS symptoms, particularly SNOT-22 scores, surpassing saline irrigation benefits. Manuka honey showed potential microbiological benefits in recalcitrant CRS, but symptomatic and endoscopic improvements remained inconclusive. Baby shampoo irrigation improved nasal mucociliary clearance and postoperative outcomes. Colloidal silver nasal irrigation showed limited efficacy in reducing CRS symptoms or endoscopic scores. Povidone-Iodine (PI) nasal irrigation yielded mixed results, with varying effects on culture negativity and SNOT-20 scores. Bacteriophage treatment exhibited promise in decreasing specific bacterial strains and cytokine levels. CONCLUSION: Non-antibiotic antimicrobial therapies, including xylitol, manuka honey, baby shampoo, colloidal silver, PI, bacteriophages, lactoferrin, and carrageenan offer potential alternatives for CRS in adult patients. Xylitol, baby shampoo, and PI presented benefits in improving symptoms and nasal endoscopic scores, however, the number of studies is limited for conclusive recommendations and safety assessments. CRS management should adopt a comprehensive approach, particularly for non-infectious or immune-related cases, moving beyond antibiotics. Antibiotics should be reserved for confirmed bacterial infections. Overall, this review shows the importance of exploring non-antibiotic therapies to enhance the management of CRS.

Brazilian guideline for the use of immunobiologicals in chronic rhinosinusitis with nasal polyps ‒ 2024 update.

INTRODUCTION: Biologics targeting type 2 inflammation have revolutionized the way we treat patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Particularly in severe and difficult-to-control cases, these drugs have provided a new reality for these patients, allowing for the effective and safe treatment of extensive diseases that were not completely managed with the typical strategy of surgery and topical medications. OBJECTIVES: The experience achieved with the approval of these medications by ANVISA for use in CRSwNP and the knowledge obtained regarding outcomes, adverse effects, and the ideal patient profile prompted the update of the previously published guideline, with a detailed review of the most recent scientific literature, the personal experiences of experts, and the adaptation to the reality of the Brazilian healthcare system, both public and private. RESULTS: We proposed a new eligibility criterion for biologics in patients with CRSwNP based on four pillars of indication: the impact of the disease on the patient's life, whether in the presence of specific symptoms or in overall quality of life; the extent of sinonasal disease; the presence of type 2 comorbidities, considering other associated diseases that may also benefit from anti-T2 biologics, and the presence of biomarkers to define type 2 inflammation, especially those associated with worse disease prognoses. CONCLUSIONS: This innovative and pioneering method has two major advantages. First, it ensures a comprehensive evaluation of patients; second, it is flexible, as advancements in our understanding of the disease and changes in cost-effectiveness can be addressed by simply adjusting the required score for indication, without the need to modify the entire evaluation scheme.

Matrix metalloproteinases and their impact on sinusal extension in chronic rhinosinusitis with nasal polyps.

UNLABELLED: MMPs (metalloproteinases) and their inhibitor TIMP (tissue inhibitor of metalloproteinases) are important in tissue remodeling and have been implicated in nasal polyp pathophysiology. The objective of the present study was to evaluate gene expression of MMP-1, MMP-2, MMP-9 and TIMP-1 gene expression in nasal polyps and compare them with normal nasal mucosa. Since MMPs could induce a more prominent tissue edema, we also assessed if these gene expressions could be related to a more extensive disease. For the experimental study, 30 nasal polyp samples from patients with CRSwNP (Chronic Rhinosinusitis with Nasal Polyposis) and 19 middle turbinates (MT) from controls were obtained. Gene expression of MMP-1, MMP-2, MMP-9 and TIMP-1 was assessed by qRT-PCR. The expressions of these genes were compared between nasal polyps and controls and correlated to each individual Lund-Mackay score, MMP-1, MMP-2 and MMP-9 were significantly more expressed in nasal polyps than in controls (P < 0.005, P < 0.0001 and P < 0.05 respectively). No expression of TIMP-1 mRNA was detected. There was no correlation between disease extension evaluated by the Lund-Mackay score and MMPs gene expression. The present results demonstrate that there is a significantly higher mRNA gene expression of MMP-1, MMP-2 and MMP-9 in patients with CRSwNP than controls. However, no correlation was observed between MMPs gene expression and sinonasal CT scan extension. LEVEL OF EVIDENCE: 2c.

Ciliary ultrastructure in patients with chronic rhinosinusitis and primary ciliary dyskinesia.

The Cilia represent one of the main mechanisms contributing to the clearance of microorganisms and particles from the respiratory epithelium. Primary ciliary dyskinesia (PCD) is a genetically determined disorder characterized by irreversible systemic dysmotility of the cilia. Secondary ciliary dyskinesia (SCD) differs from primary defects on the reversible ultrastructural alterations that can occur after any insult to a previously normal mucosa. Hence, this study aimed to describe and compare the main ultrastructural ciliary features in PCD and SCD through transmission electron microscopy. The most frequent PCD abnormalities were missing or short dynein arms, missing central microtubules, and displacement of one of the nine peripheral doublets. The most common changes found in SCD were compound cilia and peripheral microtubule alterations associated with modifications of the respiratory epithelium. PCD presented a higher percentage of altered cilia (>30 %) when compared to SCD (5 %), demonstrating that SCD is more limited in area than PCD. Whereas in PCD the changes in the dynein arms and in the central microtubules are fundamental for diagnostic confirmation, the diagnosis of SCD usually involves compound cilia and disarrangements in peripheral microtubules.

Which are the best murine models to study Eosinophilic Chronic Rhinosinusitis? A contemporary review.

OBJECTIVE: Mechanisms that lead to Eosinophilic Chronic Rhinosinusitis (ECRS) are not fully established in the literature. It is desirable to assess ECRS in a model that embraces most of the related events. This article reviewed the murine models for ECRS and compared them regarding eosinophilic polypoid formation. METHODS: The authors reviewed the articles that included the terms "chronic rhinosinusitis" OR "chronic sinusitis" AND "animal model". We analyzed articles in English that evaluated both the number of polyps and the number of eosinophils in the sinus mucosa of mouse models. RESULTS: We identified a total of 15 articles describing different models of ECRS that used BALB/c or C57BL/6 mice, and different triggers/stimulants such as Staphylococcus aureus Enterotoxin B (SEB) + Ovalbumin (OVA); House Dust Mite (HDM) ±â€¯Ovalbumin (OVA); and Aspergillus oryzae Protease (AP) + Ovalbumin (OVA). OVA associated with SEB was the commonest protocol to induce ECRS in both BALB/c and C57BL/6 mice, and it produced a robust response of eosinophilic nasal polyps in both. AP + OVA protocol also led to a good ECRS response. The other models were not considered adequate to produce eosinophilic polyps in mice. CONCLUSION: In conclusion, OVA associated with SEB seems to produce the most robust eosinophilic sinonasal inflammation.

Effect of rapid maxillary expansion on masticatory and swallowing functions in children with posterior crossbite.

OBJECTIVE: Investigate the influence of posterior crossbite on masticatory and swallowing functions by videofluoroscopy examination and to analyze the effects of Rapid Maxillary Expansion (RME) on the same functions. METHODS: A prospective longitudinal study was conducted on 32 children, 21 of them with posterior crossbite (10 girls and 11 boys, mean age 9.2 years, study group) and 11 children with no occlusal changes (6 girls and 5 boys, mean age 9.3 years, control group). The children were evaluated by an orthodontist for diagnosis, group characterization and occlusal treatment, by the otorhinolaryngology team for the assessment of respiratory symptoms, and by a speech therapist for videofluoroscopic evaluation of masticatory and swallowing parameters. The children with posterior crossbite were treated orthodontic ally using the Haas disjunctor for approximately six months and re-evaluated 5-months after removal of the appliance. Data were analyzed statistically by the Studentt-test for independent samples for comparison of the crossbite and control groups before and after treatment. RESULTS: There was no significant difference in oral preparatory and oral transit times, nor in cycles and masticatory frequency, between the pre and post orthodontic treatment groups and the control group. CONCLUSION: Rapid maxillary expansion did not influence the masticatory and swallowing variables studied by videofluoroscopy. However, the data require caution in interpretation.

Revisiting the orbital complications of acute rhinosinusitis.

OBJECTIVE: The present study revisited three classification systems of orbital complications of acute rhinosinusitis (ARS) (Chandler, Mortimore & Wormald, and Velasco e Cruz & Anselmo-Lima) and observed which of them presented the best clinical applicability. METHODS: Clinical data and CT scan findings of patients with orbital infection were retrospectively collected. To compare the three classification systems, we revised and graded all CT images accordingly, and divided the patients into four groups: Eyelid cellulitis (EC), orbital cellulitis (OC), subperiosteal abscess (SA), and orbital abscess (OA). The groups were compared regarding the presence of sinus opacification, the need for hospitalization and/or surgical treatment, and the presence of further complications/sequelae. RESULTS: 143 patients were included. The median number of sinuses involved in patients in the OC, SA, and OA groups was 2.0. ARS was rarely associated with signs of EC (present in both Chandler's and Mortimore & Wormald's classifications. The hospitalization rate was significantly lower in the EC group compared to the other three groups. Surgery was performed in all cases in the OA group, in 58.1% in the SA group, 19.4% in the OC group, and 12.5% in the EC group (p-value < 0.0001). Complications were present at higher rates in the OA group compared to the other three groups. CONCLUSIONS: ARS was rarely associated with Eyelid Cellulitis. The stratification in the other three groups showed to be clinically relevant. Velasco e Cruz & Anselmo-Lima's classification system proved valid, simple, and effective for categorizing orbital complications of ARS.

Suppression of inflammatory cytokine secretion by an NF-ĸB inhibitor DHMEQ in nasal polyps fibroblasts.

BACKGROUND: NF-ĸB is an essential transcription factor strongly associated to inflammatory response in chronic rhinosinusitis with nasal polyps (CRSwNP). DHMEQ is a NF-ĸB inhibitor that has been previously described with a greatpotential indecreasing inflammation in diseases other than CRSwNP. The aim of study isto evaluate the ability of DHMEQ to reducethe inflammatory recruiters on CRSwNP and to compare its anti-inflammatory profile as a single-agent or in association with fluticasone propionate (FP). METHODS: nasal polyp fibroblasts were cultured in TNF-α enriched media. Cells were submitted to three different concentrations (1, 10 and 100nM) of either FP, DHMEQ or both. Inflammatory response was accessed by VCAM-1, ICAM-1 and RANTES expression (by RTQ-PCR) and protein levels by ELISA. Nuclear translocation of NF-ĸB was also evaluated. RESULTS: both FP and DHMEQ inhibited inflammatory recruiters' production and NF-ĸB nuclear translocation. Interestingly, the anti-inflammatory effect from the association steroids plus DHMEQ was more intense than of each drug in separate. CONCLUSION: DHMEQ seems efficient in modulating the inflammatory process in CRSwNP. The synergic anti-inflammatory effect of DHMEQ and steroids may be a promising strategy to be explored, particularly in the setting of steroid-resistant NP.

Association between the intensity of obstructive sleep apnea and skeletal alterations in the face and hyoid bone.

INTRODUCTION: The association between the intensity of obstructive sleep apnea and skeletal alterations in the face and hyoid bone is still scarcely addressed in the literature. OBJECTIVE: To evaluate whether the intensity of obstructive sleep apnea is associated with craniofacial alterations and the position of the hyoid bone in children with mixed dentition. METHODS: 76 children aged 7 to 10 years old were examined by otorhinolaryngological evaluation, polysomnography, and orthodontic assessment, including cephalometry. The participants were divided in 3 groups: primary snoring, mild obstructive sleep apnea and moderate to severe obstructive sleep apnea. Cephalometric measures of the face and hyoid bone were assessed. These measures were compared among the different groups by unpaired Student's t test. Moreover, these measures were correlated with the patient's obstructive apnea and hypopnea index variable using Pearson's correlation test. RESULTS: Of the 76 children, 14 belonged to group 1, with primary snoring; 46 to group 2, with mild obstructive sleep apnea; and 16 to group 3, with moderate-severe obstructive sleep apnea. There was no difference between the groups regarding the craniofacial variables. Children with obstructive sleep apnea showed a longer distance from the hyoid bone to the mandibular plane when compared to the primary snoring group (p<0.05). Between the two obstructive sleep apnea subgroups, patients with moderate or severe disease showed significantly shorter horizontal distance between the hyoid bone and the posterior pharyngeal wall (p<0.05), when compared to the groups with mild obstructive sleep apnea. We also observed a significant positive correlation between obstructive apnea and hypopnea index and the distance from the hyoid to the mandibular plane (p<0.05) as well as a significant negative association between obstructive apnea and hypopnea index and the horizontal distance from the hyoid to the posterior pharyngeal wall (p<0.01). CONCLUSION: We did not observe any association between obstructive sleep apnea and linear lateral alterations of the face. In contrast, there is a direct association between obstructive sleep apnea severity and the inferior and posterior position of the hyoid bone in children aged 7 to 10 years old.

Validation of the Connecticut olfactory test (CCCRC) adapted to Brazil.

INTRODUCTION: Olfactory changes are quite common in the population, causing a significant impact on the quality of life. Documentation of the olfactory function is essential for the diagnosis, treatment and follow-up of patients with inflammatory diseases of the upper airways, neurodegenerative diseases or viral infections. Among the different existing smell tests, the CCCRC is an inexpensive test, easy to apply, but it has not yet been evaluated on a large scale in the Brazilian population. OBJECTIVE: To validate the CCCRC smell test, after adaptation for the Brazilian population, evaluating the performance of healthy volunteers and the stability of the test in retests. METHODS: In this study, we carried out a cultural adaptation of the CCCRC test to Brazil. To validate and determine the normality scores, we applied the test to 334 healthy volunteers, aged >18 years of age. The retest was also carried out in up to four weeks on 34 additional volunteers to assess validity of the results. RESULTS: When evaluating the participants' performance, normosmia and mild hyposmia values were obtained in more than 95% of them. Women (58.4%) showed better accuracy than men (41.6%): p<0.02, and individuals over 60 years of age showed worse performance (median: 6; 75th percentile: 6.5; 25th percentile). The test and retest of the 34 volunteers demonstrated that there was agreement (ICC, intraclass correlation coefficient) considered good in the left nostril (ICC=0.65) and excellent in the right nostril (ICC=0.77) in the combined score. CONCLUSION: The CCCRC test adapted to Brazil showed normal values, similar to the originally-described test and validations in other countries, with a high reproducibility rate. Considering the highly favorable cost-benefit ratio, the adapted CCCRC is a very useful tool for measuring olfactory function in the Brazilian population.

Guideline for the use of immunobiologicals in chronic rhinosinusitis with nasal polyps (CRSwNP) in Brazil.

INTRODUCTION: Severe uncontrolled chronic rhinosinusitis with nasal polyps has a negative impact on an individual's quality of life. Therefore, new biologics have emerged for use in specific phenotypes of chronic rhinosinusitis, changing the paradigms of its treatment. OBJECTIVE: To review the current status of biologic treatment indications in chronic rhinosinusitis. METHODS: The Brazilian Academy of Rhinology brought together different specialists to suggest a course of action, considering its particularities and aspects related to the national reality. RESULTS: Of particular interest for decision making will be the identification of subgroups of patients refractory to pre-existing treatment options and the construction of a strategy that improves their quality of life, with the best cost-benefit ratio. CONCLUSION: The use of biologics is a valid option for treatment in more severe cases. This strategy must be better understood and improved in the future, with more studies and greater clinical experience.

Changes in facial morphology after adenotonsillectomy in mouth-breathing children.

BACKGROUND: Morphological and dentofacial alterations have been attributed to impaired respiratory function. OBJECTIVE: To examine the influence of mouth breathing (MB) on children facial morphology before and after adenoidectomy or adenotonsillectomy. METHODS: Thirty-three MB children who restored nasal breathing (NB) after surgery and 22 NB children were evaluated. Both groups were submitted to lateral cephalometry, at time 1 (T1) before and at time 2 (T2) 28 months on average postoperatively. RESULTS: Comparison between the MB and NB groups at T1 showed that mouth breathers had higher inclination of the mandibular plane; more obtuse gonial angle; dolichofacial morphology; and a decrease in the total and inferior posterior facial heights. Twenty-eight months after the MB surgical intervention, they still presented a dolichofacial morphologic pattern. During this period, MB altered the face growth direction and decreased their mandible plane inclination, with reduction in the SN.GoGn, PP.MP, SNGn, and ArGo.GoMe parameters as well as an increase in BaN.PtGn. CONCLUSION: After the MB rehabilitation, children between 3 and 6 years old presented significant normalization in the mandibular growth direction, a decrease in the mandible inclination, and an increase in the posterior facial height. Instead, they still persisted with a dolichofacial pattern when compared with nasal breathers.

Association of interleukin 22 receptor subunit alpha 1 gene polymorphisms with chronic rhinosinusitis.

INTRODUCTION: Chronic rhinosinusitis is a multifactorial disease whose pathogenesis, influenced by both genetic and environmental factors, is still unclear. Previous genetic studies have shown that patients with chronic rhinosinusitis have reduced expression of the Interleukin-22 (IL-22) gene. OBJECTIVE: Identify and compare the frequency of polymorphisms in the IL22RA1 gene (IL22 alpha-1 subunit receptor) among chronic rhinosinusitis patients - either with or without nasal polyps. METHODS: Peripheral blood samples were collected from 70 chronic rhinosinusitis with polyps patients, 14 chronic rhinosinusitis without polyps patients and 68 subjects without chronic rhinosinusitis, followed by DNA extraction and IL22RA1 gene sequence analysis. RESULTS: Among ten polymorphisms identified in the IL22RA1 gene, three were not found in any of the genetic databases analyzed. Chronic rhinosinusitis patients displayed higher frequency of the c.113_114insA frameshift insertion, possibly pathogenic. Conversely, in the control group, polymorphism c.435A > C had a significant predominance of the mutated allele, perhaps related to a potential protection against the chronic rhinosinusitis phenotype. Polymorphism c.770C > T, characterized as a non-synonymous variant, was exclusively found in Black chronic rhinosinusitis with polyps patients. CONCLUSIONS: Although no direct causal relationship could be established between IL22RA1 gene polymorphisms and the pathophysiology of chronic rhinosinusitis, genetic variations such as c.113_114insA and c.435A > C may be involved in the susceptibility to or protection against the chronic rhinosinusitis phenotype, respectively. Testing this hypothesis will require studies with larger cohorts.

Does ibuprofen, prednisolone, or amoxicillin reduce post-tonsillectomy pain in children? A prospective randomized controlled trial.

OBJECTIVE: To evaluate whether the use of anti-inflammatory or antibiotic in the postoperative period modifies pain in children undergoing tonsillectomy. METHODS: 225 children who underwent cold knife tonsillectomy ± adenoidectomy were randomized into five groups, receiving #1 metamizole/acetaminophen, #2 amoxicillin, #3 ibuprofen, #4 prednisolone, or #5 amoxicillin plus prednisolone. All groups received oral analgesics (metamizole/acetaminophen) to use as needed. Pain was monitored during the 7 days following surgery using the Parents' Postoperative Pain Measurement (PPPM) and the Faces Pain Scale - Revised (FPS-R). Pain was also indirectly evaluated by the dose of analgesics administered on each day and by the time needed to return to a solid diet. RESULTS: After losses (24%), 170 individuals were submitted for analysis. Multiple comparisons demonstrated that the evolution of pain between the different groups, as matched day-per-day, was not significantly different by either PPPM or FPS-R (p > 0.05). The instances of analgesic intake were also similar in all the groups (p > 0.05), as was the return to solid food ingestion (p = 0.41). All groups presented a similar standard of clinical improvement at intervals of 2 days (p < 0.01). Independent of postoperative pain management, patients developed significant pain up to the day 4 following surgery. CONCLUSION: The addition of amoxicillin, ibuprofen, prednisolone, or amoxicillin and prednisolone does not modify postoperative pain in children undergoing cold-knife tonsillectomy. Special pain control should be performed on the first 4 days following tonsillectomy in children.

Biofilm and Planktonic Antibiotic Resistance in Patients With Acute Exacerbation of Chronic Rhinosinusitis.

INTRODUCTION: The recalcitrant nature of patients with acute exacerbation of chronic rhinosinusitis (AECRS) potentially involves persisting colonization of the sinonasal mucosa by bacterial biofilms. Biofilms are known to be highly resistant to antibiotics, which may trigger or maintain chronic inflammation in the sinonasal mucosa. However, little is known about the relationship between the minimum inhibitory concentration (MIC) and antibiofilm concentrations of bacteria obtained from AECRS patients. MATERIAL AND METHODS: Thirty bacterial strains from 25 patients with AECRS were identified and underwent MIC determination (VITEK® 2). The planktonic isolates were submitted to an in vitro formation of biofilms (Modified Calgary Biofilm Device) and determination of minimum biofilm inhibitory concentration (MBIC) and minimum biofilm eradication concentration (MBEC) for amoxicillin, amoxicillin/clavulanic acid, clarithromycin, and levofloxacin. MIC of the planktonic forms was compared with MBIC and MBEC levels, according to the breakpoints established by the Clinical Laboratory Standards Institute guidelines. RESULTS: The main bacteria retrieved was S. aureus (60%), followed by other Gram-positive and Gram-negative bacteria in lower frequencies. 76.7% of strains formed biofilm in vitro (n=23/30). The planktonic isolates presented high rates of resistance for amoxicillin (82.6%) and clarithromycin (39.1%), and lower rates for amoxicillin/clavulanic acid (17.4%). The biofilm-forming bacteria counterparts presented higher levels of MBIC and MBEC compared to the MIC levels for amoxicillin, amoxicillin/clavulanic acid, and clarithromycin. Levofloxacin was highly effective against both planktonic and biofilm forms. Planktonic resistant forms were associated with levels of antibiofilm concentrations (MBIC and MBEC). CONCLUSIONS: Biofilm-forming bacteria from AECRS patients are prevalent, and biofilm forms are highly resistant to antibiotics compared to their planktonic counterparts. Antibiotic resistance observed in planktonic forms is a good indicator of biofilm resistance, although near 20% of susceptible planktonic bacteria can produce antibiotic tolerant biofilms.