Corrigendum: The paradigm of IL-23-independent production of IL-17F and IL-17A and their role in chronic inflammatory diseases.

[This corrects the article DOI: 10.3389/fimmu.2023.1191782.].

The paradigm of IL-23-independent production of IL-17F and IL-17A and their role in chronic inflammatory diseases.

Interleukin-17 family (IL-17s) comprises six structurally related members (IL-17A to IL-17F); sequence homology is highest between IL-17A and IL-17F, displaying certain overlapping functions. In general, IL-17A and IL-17F play important roles in chronic inflammation and autoimmunity, controlling bacterial and fungal infections, and signaling mainly through activation of the nuclear factor-kappa B (NF-κB) pathway. The role of IL-17A and IL-17F has been established in chronic immune-mediated inflammatory diseases (IMIDs), such as psoriasis (PsO), psoriatic arthritis (PsA), axial spondylarthritis (axSpA), hidradenitis suppurativa (HS), inflammatory bowel disease (IBD), multiple sclerosis (MS), and asthma. CD4+ helper T cells (Th17) activated by IL-23 are well-studied sources of IL-17A and IL-17F. However, other cellular subtypes can also produce IL-17A and IL-17F, including gamma delta (γδ) T cells, alpha beta (αß) T cells, type 3 innate lymphoid cells (ILC3), natural killer T cells (NKT), or mucosal associated invariant T cells (MAIT). Interestingly, the production of IL-17A and IL-17F by innate and innate-like lymphocytes can take place in an IL-23 independent manner in addition to IL-23 classical pathway. This would explain the limitations of the inhibition of IL-23 in the treatment of patients with certain rheumatic immune-mediated conditions such as axSpA. Despite their coincident functions, IL-17A and IL-17F contribute independently to chronic tissue inflammation having somehow non-redundant roles. Although IL-17A has been more widely studied, both IL-17A and IL-17F are overexpressed in PsO, PsA, axSpA and HS. Therefore, dual inhibition of IL-17A and IL-17F could provide better outcomes than IL-23 or IL-17A blockade.

Efficacy, safety and cost-effectiveness of methotrexate, adalimumab or their combination in non-infectious non-anterior uveitis: a protocol for a multicentre, randomised, parallel three arms, active-controlled, phase III open label with blinded outcome assessment study.

INTRODUCTION: Non-infectious uveitis include a heterogeneous group of sight-threatening and incapacitating conditions. Their correct management sometimes requires the use of immunosuppressive drugs (ISDs), prescribed in monotherapy or in combination. Several observational studies showed that the use of ISDs in combination could be more effective than and as safe as their use in monotherapy. However, a direct comparison between these two treatment strategies has not been carried out yet. METHODS AND ANALYSIS: The Combination THerapy with mEthotrexate and adalImumAb for uveitis (CoTHEIA) study is a phase III, multicentre, prospective, randomised, single-blinded with masked outcome assessment, parallel three arms with 1:1:1 allocation, active-controlled, superiority study design, comparing the efficacy, safety and cost-effectiveness of methotrexate, adalimumab or their combination in non-infectious non-anterior uveitis. We aim to recruit 192 subjects. The duration of the treatment and follow-up will last up to 52 weeks, plus 70 days follow-up with no treatment. The complete and maintained resolution of the ocular inflammation will be assessed by masked evaluators (primary outcome). In addition to other secondary measurements of efficacy (quality of life, visual acuity and costs) and safety, we will identify subjects' subgroups with different treatment responses by developing prediction models based on machine learning techniques using genetic and proteomic biomarkers. ETHICS AND DISSEMINATION: The protocol, annexes and informed consent forms were approved by the Reference Clinical Research Ethic Committee at the Hospital Clínico San Carlos (Madrid, Spain) and the Spanish Agency for Medicines and Health Products. We will elaborate a dissemination plan including production of materials adapted to several formats to communicate the clinical trial progress and findings to a broad group of stakeholders. The promoter will be the only access to the participant-level data, although it can be shared within the legal situation. TRIAL REGISTRATION NUMBER: 2020-000130-18; NCT04798755.

Definition of Remission and Disease Activity Assessment in Psoriatic Arthritis: Evidence and Expert-Based Recommendations / Definición de remisión y evaluación de la actividad de la enfermedad en la artritis psoriásica: recomendaciones basadas en la evidencia y la opinión de expertos

Objective: We aimed to reach a consensus on the best instruments to monitor disease activity in patients with psoriatic arthritis (PsA) and to develop a consensus definition of remission. Methods: A modified Delphi approach was used. A scientific committee provided statements addressing the definition of remission and the monitoring of PsA in clinical practice. The questionnaire was evaluated in 2 rounds by rheumatologists with experience in managing PsA patients. Results: A panel of 77 rheumatologists reached agreement on 62 out of the 86 proposed items (72.0%). The most recommended index for monitoring disease activity was DAPSA (cut-off values: ≤4 for remission and >4–14 for low disease activity ([LDA]), MDA (at least 5/7 criteria). In cases with axial involvement, ASDAS was the preferred index (cut-off values: <1.3 for remission and <2.1 for LDA). BASDAI (cut-off values: ≤2 for remission and ≤4 for LDA) may be used as an alternative. PsAID was the preferred tool to assess disease impact. Conclusion: We propose a definition of remission in PsA as the absence of disease activity evaluated by DAPSA or MDA (ASDAS and/or BASDAI in patients with axial involvement), which would imply absence of signs or symptoms of inflammation, physical well-being, lack of disease impact, and absence of inflammation as measured by biological markers.(AU)

Objetivo: Nuestro objetivo era alcanzar un consenso sobre los mejores instrumentos para monitorizar la actividad de la enfermedad en pacientes con artritis psoriásica (AP) y desarrollar una definición consensuada de remisión. Metodología: Se utilizó una metodología Delphi modificada. Un comité científico propuso aseveraciones relacionadas con la definición de remisión y la monitorización de la AP en la clínica. El cuestionario fue evaluado en 2 rondas por reumatólogos con experiencia en el manejo de la AP. Resultados: Un panel de 77 reumatólogos alcanzó un acuerdo en 62 de los 86 ítems propuestos (72,0%). El índice más recomendado para monitorizar la actividad de la enfermedad fue DAPSA (valores de corte: ≤4 para la remisión y >4-14 para baja actividad de la enfermedad ([LDA]), MDA (al menos 5/7 criterios). En los casos con afectación axial, el índice preferido fue ASDAS (valores de corte: <1,3 para remisión y <2,1 para LDA). Como alternativa puede usarse BASDAI (valores de corte: ≤2 para remisión y ≤4 para LDA). PsAID fue la herramienta preferida para evaluar el impacto de la enfermedad. Conclusión: Proponemos una definición de remisión en pacientes con AP como la ausencia de actividad de la enfermedad evaluada mediante DAPSA o MDA (ASDAS y/o BASDAI en pacientes con afectación axial), lo que implicaría ausencia de signos o síntomas de inflamación, bienestar físico, ausencia de impacto de la enfermedad y ausencia de inflamación medida por marcadores biológicos.(AU)

Definition of Remission and Disease Activity Assessment in Psoriatic Arthritis: Evidence and Expert-Based Recommendations.

OBJECTIVE: We aimed to reach a consensus on the best instruments to monitor disease activity in patients with psoriatic arthritis (PsA) and to develop a consensus definition of remission. METHODS: A modified Delphi approach was used. A scientific committee provided statements addressing the definition of remission and the monitoring of PsA in clinical practice. The questionnaire was evaluated in 2 rounds by rheumatologists with experience in managing PsA patients. RESULTS: A panel of 77 rheumatologists reached agreement on 62 out of the 86 proposed items (72.0%). The most recommended index for monitoring disease activity was DAPSA (cut-off values: ≤4 for remission and >4-14 for low disease activity ([LDA]), MDA (at least 5/7 criteria). In cases with axial involvement, ASDAS was the preferred index (cut-off values: <1.3 for remission and <2.1 for LDA). BASDAI (cut-off values: ≤2 for remission and ≤4 for LDA) may be used as an alternative. PsAID was the preferred tool to assess disease impact. CONCLUSION: We propose a definition of remission in PsA as the absence of disease activity evaluated by DAPSA or MDA (ASDAS and/or BASDAI in patients with axial involvement), which would imply absence of signs or symptoms of inflammation, physical well-being, lack of disease impact, and absence of inflammation as measured by biological markers.

Lateral-Expansion Pharyngoplasty: Combined Technique for the Treatment of Obstructive Sleep Apnea Syndrome

Abstract Introduction Obstructive sleep apnea syndrome (OSAS) is a multifactorial disease characterized by episodes of partial or complete collapse during sleep of different regions of the upper airway. Surgery for OSAS evolved with the introduction of different techniques, considering new surgical concept of reconstruction of the upper airway. Objective To retrospectively evaluate the effectiveness of a new approach aimed at reducing pharyngeal collapse by combining two surgical techniques: lateral and expansion pharyngoplasty. Methods We reviewed the medical records of 38 patients with OSAS undergoing lateral/expansion pharyngoplasty from January 2012 to December 2016. The following data were collected: patient age, gender, and pre- and postoperative body mass index (BMI), Epworth sleepiness scale (ESS) scores, snoring visual analogue scale (VAS) scores, and polysomnography (PSG) results. Results The PSG results showed a significant reduction in the apnea/hypopnea index (AHI) from 22.4 ± 27.3 events/h preoperatively to 13.6 ± 17.9 events/h postoperatively (p = 0.009), with postoperative AHI reduction greater than 50% in 63.2% of the patients. There was also a significant reduction in the microarousal index (19.5 ± 22.6 vs 11.0 ± 13.4 events/h; p = 0.001) and in the minimum oxygen saturation (82.6 ± 10.3 vs 86.9 ± 11.1; p = 0.007). Conclusions Lateral-expansion pharyngoplasty represents a new surgical strategy for the treatment of OSAS in patients with palatal collapse by combining two different techniques: lateral and expansion pharyngoplasty. The two techniques, performed as a one-stage procedure, led to improvements in excessive daytime sleepiness, snoring, and PSG respiratory parameters by acting on lateral and retropalatal collapse, produc- ing favorable results with good applicability in otolaryngology clinical practice.

Lateral-Expansion Pharyngoplasty: Combined Technique for the Treatment of Obstructive Sleep Apnea Syndrome.

Introduction Obstructive sleep apnea syndrome (OSAS) is a multifactorial disease characterized by episodes of partial or complete collapse during sleep of different regions of the upper airway. Surgery for OSAS evolved with the introduction of different techniques, considering new surgical concept of reconstruction of the upper airway. Objective To retrospectively evaluate the effectiveness of a new approach aimed at reducing pharyngeal collapse by combining two surgical techniques: lateral and expansion pharyngoplasty. Methods We reviewed the medical records of 38 patients with OSAS undergoing lateral/expansion pharyngoplasty from January 2012 to December 2016. The following data were collected: patient age, gender, and pre- and postoperative body mass index (BMI), Epworth sleepiness scale (ESS) scores, snoring visual analogue scale (VAS) scores, and polysomnography (PSG) results. Results The PSG results showed a significant reduction in the apnea/hypopnea index (AHI) from 22.4 ± 27.3 events/h preoperatively to 13.6 ± 17.9 events/h postoperatively ( p = 0.009), with postoperative AHI reduction greater than 50% in 63.2% of the patients. There was also a significant reduction in the microarousal index (19.5 ± 22.6 vs 11.0 ± 13.4 events/h; p = 0.001) and in the minimum oxygen saturation (82.6 ± 10.3 vs 86.9 ± 11.1; p = 0.007). Conclusions Lateral-expansion pharyngoplasty represents a new surgical strategy for the treatment of OSAS in patients with palatal collapse by combining two different techniques: lateral and expansion pharyngoplasty. The two techniques, performed as a one-stage procedure, led to improvements in excessive daytime sleepiness, snoring, and PSG respiratory parameters by acting on lateral and retropalatal collapse, producing favorable results with good applicability in otolaryngology clinical practice.

Otitis Media with Effusion in Aircrew Members.

BACKGROUND: Middle-ear barotrauma is a common problem reported by aircrew members and passengers. Studies have shown that 20-50% of passengers report ear complaints during the flight or after landing. The aim of this study is to determine the prevalence of otitis media with effusion in aircrew members and describe the time to resolution of the condition.METHODS: All aircrew members presenting at Civil Aviation Center at Congonhas Airport at São Paulo for annual flight medical examinations from September 2014 to May 2015 were reviewed retrospectively for the presence of otologic disorders. Eligible participants were all pilots, copilots, and flight attendants with a diagnosis of otitis media with effusion confirmed by immittance testing.RESULTS: Of 1607 aircrew members, 155 (9.65%) were diagnosed as having otitis media with effusion. Most participants were men (51.6%). Regarding aircrew position, 81.9% were flight attendants, 11.6% were copilots, and 6.5% were pilots. The mean time to resolution of the otitis media was 8.23 (± 3.02) days.DISCUSSION: Otolaryngologists must be aware of the effects of gas expansion in the middle ear at higher altitudes for the appropriate treatment of diseases related to pressure changes. The recommendation for an aircrew member to return to flying duties should occur only after the individual has been treated and complete resolution, confirmed by immittance testing, has been documented.Pinto JA, dos Santos Sobreira Nunes H, dos Santos RS, Cavallini A, Freitas G, Knoll D, Duarte C. Otitis media with effusion in aircrew members. Aerosp Med Hum Perform. 2019; 90(5):462-465.

PET-CT has low specificity for mediastinal staging of non-small-cell lung cancer in an endemic area for tuberculosis: a diagnostic test study (LACOG 0114).

BACKGROUND: The present study aims to assess the performance of 18F-FDG PET-CT on mediastinal staging of non-small cell lung cancer (NSCLC) in a location with endemic granulomatous infectious disease. METHODS: Diagnostic test study including patients aged 18 years or older with operable stage I-III NSCLC and indication for a mediastinal lymph node biopsy. All patients underwent a 18F-FDG PET-scan before invasive mediastinal staging, either through mediastinoscopy or thoracotomy, which was considered the gold-standard. Surgeons and pathologists were blinded for scan results. Primary endpoint was to evaluate sensitivity, specificity and positive and negative predictive values of PET-CT with images acquired in the 1st hour of the exam protocol, using predefined cutoffs of maximal SUV, on per-patient basis. RESULTS: Overall, 85 patients with operable NSCLC underwent PET-CT scan followed by invasive mediastinal staging. Mean age was 65 years, 49 patients were male and 68 were white. One patient presented with active tuberculosis and none had HIV infection. Using any SUV_max > 0 as qualitative criteria for positivity, sensitivity and specificity were 0.87 and 0.45, respectively. Nevertheless, even when the highest SUV cut-off was used (SUV_max ≥5), specificity remained low (0.79), with an estimated positive predictive value of 54%. CONCLUSIONS: Our findings are in line with the most recent publications and guidelines, which recommend that PET-CT must not be solely used as a tool to mediastinal staging, even in a region with high burden of tuberculosis. TRIAL REGISTRATION: The LACOG 0114 study was registered at ClinicalTrials.gov , before study initiation, under identifier NCT02664792.

Genetic variation at the glycosaminoglycan metabolism pathway contributes to the risk of psoriatic arthritis but not psoriasis.

OBJECTIVE: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis (Ps). To date, most of the known risk loci for PsA are shared with Ps, and identifying disease-specific variation has proven very challenging. The objective of the present study was to identify genetic variation specific for PsA. METHODS: We performed a genome-wide association study in a cohort of 835 patients with PsA and 1558 controls from Spain. Genetic association was tested at the single marker level and at the pathway level. Meta-analysis was performed with a case-control cohort of 2847 individuals from North America. To confirm the specificity of the genetic associations with PsA, we tested the associated variation using a purely cutaneous psoriasis cohort (PsC, n=614) and a rheumatoid arthritis cohort (RA, n=1191). Using network and drug-repurposing analyses, we further investigated the potential of the PsA-specific associations to guide the development of new drugs in PsA. RESULTS: We identified a new PsA risk single-nucleotide polymorphism at B3GNT2 locus (p=1.10e-08). At the pathway level, we found 14 genetic pathways significantly associated with PsA (pFDR<0.05). From these, the glycosaminoglycan (GAG) metabolism pathway was confirmed to be disease-specific after comparing the PsA cohort with the cohorts of patients with PsC and RA. Finally, we identified candidate drug targets in the GAG metabolism pathway as well as new PsA indications for approved drugs. CONCLUSION: These findings provide insights into the biological mechanisms that are specific for PsA and could contribute to develop more effective therapies.

Lung cancer: changes in histology, gender, and age over the last 30 years in Brazil.

OBJECTIVE: To describe the trends in tumor histology, gender and age among patients with non-small cell lung cancer (NSCLC) treated with lung resection. The histology of lung cancer has changed in developed countries, and there is still little information available on the topic for developing countries. METHODS: This was a retrospective study of 1,030 patients with NSCLC treated with lung resection between 1986 and 2015 at a university hospital in southern Brazil. Differences in histology, stage, and type of surgery were analyzed by gender and for three periods (1986-1995, 1996-2005, and 2006-2015). RESULTS: Most (64.5%) of the patients were males, and the main histological types were squamous cell carcinoma (in 40.6%) and adenocarcinoma (in 44.5%). The mean age at surgery during the first period was 56.4 years for women and 58.9 years for men, compared with 62.2 for women and 64.6 for men in the third period (p < 0.001). The proportion of females increased from 26.6% in the first period to 44.1% in the third. From the first to the third period, the proportion of patients with squamous cell carcinoma decreased from 49.6% to 34.8% overall (p < 0.001), decreasing to an even greater degree (from 38.9% to 23.2%) among men. Among the NSCLC patients in our sample, females with adenocarcinoma accounted for 11.9% in the first period and 24.0% in the third period (p < 0.001). CONCLUSIONS: As has been seen in developed countries, the rates of lung cancer in females in southern Brazil have been rising over the last three decades, although they have yet to surpass those observed for males in the region. The incidence of squamous cell carcinoma has decreased in males, approaching adenocarcinoma rates, whereas adenocarcinoma has significantly increased among women.

Lung cancer: changes in histology, gender, and age over the last 30 years in Brazil / Câncer de pulmão: mudanças na histologia, sexo e idade nos últimos 30 anos no Brasil

ABSTRACT Objective: To describe the trends in tumor histology, gender and age among patients with non-small cell lung cancer (NSCLC) treated with lung resection. The histology of lung cancer has changed in developed countries, and there is still little information available on the topic for developing countries. Methods: This was a retrospective study of 1,030 patients with NSCLC treated with lung resection between 1986 and 2015 at a university hospital in southern Brazil. Differences in histology, stage, and type of surgery were analyzed by gender and for three periods (1986-1995, 1996-2005, and 2006-2015). Results: Most (64.5%) of the patients were males, and the main histological types were squamous cell carcinoma (in 40.6%) and adenocarcinoma (in 44.5%). The mean age at surgery during the first period was 56.4 years for women and 58.9 years for men, compared with 62.2 for women and 64.6 for men in the third period (p < 0.001). The proportion of females increased from 26.6% in the first period to 44.1% in the third. From the first to the third period, the proportion of patients with squamous cell carcinoma decreased from 49.6% to 34.8% overall (p < 0.001), decreasing to an even greater degree (from 38.9% to 23.2%) among men. Among the NSCLC patients in our sample, females with adenocarcinoma accounted for 11.9% in the first period and 24.0% in the third period (p < 0.001). Conclusions: As has been seen in developed countries, the rates of lung cancer in females in southern Brazil have been rising over the last three decades, although they have yet to surpass those observed for males in the region. The incidence of squamous cell carcinoma has decreased in males, approaching adenocarcinoma rates, whereas adenocarcinoma has significantly increased among women.

RESUMO Objetivo: Descrever as tendências da histologia do tumor, do gênero e da idade em pacientes com câncer de pulmão de células não pequenas (CPCNP) tratados com ressecção pulmonar. A histologia do câncer de pulmão mudou em países desenvolvidos, e ainda há pouca informação disponível sobre o tema em países em desenvolvimento. Métodos: Estudo retrospectivo com 1.030 pacientes com CPCNP tratados através de ressecção pulmonar entre 1986 e 2015 em um hospital universitário no sul do Brasil. As diferenças em histologia, estádio e tipo de cirurgia foram analisadas por gênero e em três períodos (1986-1995, 1996-2005 e 2006-2015). Resultados: A maioria dos pacientes (64,5%) era do sexo masculino, e os principais tipos histológicos foram carcinoma de células escamosas (40,6%) e adenocarcinoma (44,5%). A média de idade à cirurgia durante o primeiro período foi de 56,4 anos para mulheres e de 58,9 anos para homens, enquanto essa foi de 62,2 para mulheres e 64,6 para homens no terceiro período (p < 0,001). A proporção de mulheres aumentou de 26,6% no primeiro período para 44,1% no terceiro. Do primeiro ao terceiro período, a proporção de pacientes com carcinoma de células escamosas diminuiu de 49,6% para 34,8% no total (p < 0,001), diminuindo para um grau ainda maior (de 38,9% para 23,2%) entre os homens. Entre os pacientes com CPCNP em nossa amostra, mulheres com adenocarcinoma representaram 11,9% no primeiro período e 24,0% no terceiro período (p < 0,001). Conclusões: Como se observa em países desenvolvidos, as taxas de câncer de pulmão em mulheres no sul do Brasil têm aumentado nas últimas três décadas, embora ainda não tenham superado as observadas em homens na região. Entre homens no sul do Brasil, a incidência de carcinoma de células escamosas diminuiu, aproximando-se a de adenocarcinoma. A incidência de adenocarcinoma entre mulheres no sul do Brasil aumentou significativamente.

Comparison between the Reflux Finding Score and the Reflux Symptom Index in the Practice of Otorhinolaryngology

Abstract Introduction The Gastroesophageal Reflux Disease has a prevalence of 12% of the urban population in Brazil. Koufman proposed the term to designate Laryngeal Pharyngeal Reflux (LPR) symptoms, signs or tissue damage resulting from aggression of the gastrointestinal contents in the upper aerodigestive tract. Belafsky et al proposed a score that points to inflammatory laryngeal signs through videolaryngoscopic findings, the Reflux Finding Score (RFS). Moreover, in 2002, they published the Reflux Symptom Index (RSI). Objective The objective of this study is to provide a comparison between the Reflux Finding Score and the Reflux Symptom Index in the practice of Otorhinolaryngology. Methods Our study involved a total of 135 patients who visited the Ear, Nose, and Throat (ENT) clinic Núcleo de Otorrinolaringologia e Cirurgia de Cabeça e Pescoço de São Paulo between April 2014 and May 2015 with suspected LPR.We excluded nine patients and the study group was 126 patients. All patients were ranked by their RSI and RFS scores. Results The study group consisted of 126 patients (88 women and 38 men). Their main complaints were cough (40.4%), globus (21.4%), dysphonia (19.8%), throat clearing (15.8%), postnasal drip (3.17%), snoring (1.5%), dysphagia (1.5%), cacosmia (0.7%), and regurgitation (1.5%). The RSI ranges from 13 to 42 with a mean of 20.7 (SD = 6.67). The RFS ranged from 3 to 19 with a mean of 9.53 (SD = 2.64). Conclusion The RSI and RFS can easily be included in ENT routines as objective parameters,with low cost and high practicality. Based on the clinical index, the specialist can evaluate the need for further tests.

Comparison between the Reflux Finding Score and the Reflux Symptom Index in the Practice of Otorhinolaryngology.

INTRODUCTION: The Gastroesophageal Reflux Disease has a prevalence of ∼12% of the urban population in Brazil. Koufman proposed the term to designate Laryngeal Pharyngeal Reflux (LPR) symptoms, signs or tissue damage resulting from aggression of the gastrointestinal contents in the upper aerodigestive tract. Belafsky et al proposed a score that points to inflammatory laryngeal signs through videolaryngoscopic findings, the Reflux Finding Score (RFS). Moreover, in 2002, they published the Reflux Symptom Index (RSI). OBJECTIVE: The objective of this study is to provide a comparison between the Reflux Finding Score and the Reflux Symptom Index in the practice of Otorhinolaryngology. METHODS: Our study involved a total of 135 patients who visited the Ear, Nose, and Throat (ENT) clinic Núcleo de Otorrinolaringologia e Cirurgia de Cabeça e Pescoço de São Paulo between April 2014 and May 2015 with suspected LPR. We excluded nine patients and the study group was 126 patients. All patients were ranked by their RSI and RFS scores. RESULTS: The study group consisted of 126 patients (88 women and 38 men). Their main complaints were cough (40.4%), globus (21.4%), dysphonia (19.8%), throat clearing (15.8%), postnasal drip (3.17%), snoring (1.5%), dysphagia (1.5%), cacosmia (0.7%), and regurgitation (1.5%). The RSI ranges from 13 to 42 with a mean of 20.7 (SD = 6.67). The RFS ranged from 3 to 19 with a mean of 9.53 (SD = 2.64). CONCLUSION: The RSI and RFS can easily be included in ENT routines as objective parameters, with low cost and high practicality. Based on the clinical index, the specialist can evaluate the need for further tests.

A Single Nucleotide Polymorphism in the Il17ra Promoter Is Associated with Functional Severity of Ankylosing Spondylitis.

The aim of this study was to identify new genetic variants associated with the severity of ankylosing spondylitis (AS). We sequenced the exome of eight patients diagnosed with AS, selected on the basis of the severity of their clinical parameters. We identified 27 variants in exons and regulatory regions. The contribution of candidate variants found to AS severity was validated by genotyping two Spanish cohorts consisting of 180 cases/300 controls and 419 cases/656 controls. Relationships of SNPs and clinical variables with the Bath Ankylosing Spondylitis Disease Activity and Functional Indices BASDAI and BASFI were analyzed. BASFI was standardized by adjusting for the duration of the disease since the appearance of the first symptoms. Refining the analysis of SNPs in the two cohorts, we found that the rs4819554 minor allele G in the promoter of the IL17RA gene was associated with AS (p<0.005). This variant was also associated with the BASFI score. Classifying AS patients by the severity of their functional status with respect to BASFI/disease duration of the 60th, 65th, 70th and 75th percentiles, we found the association increased from p60 to p75 (cohort 1: p<0.05 to p<0.01; cohort 2: p<0.01 to p<0.005). Our findings indicate a genetic role for the IL17/ILRA axis in the development of severe forms of AS.

Comorbidities Associated with Obstructive Sleep Apnea: a Retrospective Study

Abstract Introduction Obstructive sleep apnea (OSA) is characterized by partial or complete recurrent upper airway obstruction during sleep. OSA brings many adverse consequences, such as hypertension, obesity, diabetes mellitus, cardiac and encephalic alterations, behavioral, among others, resulting in a significant source of public health care by generating a high financial and social impact. The importance of this assessment proves to be useful, because the incidence of patients with comorbidities associated with AOS has been increasing consistently and presents significant influence in natural disease history. Objective The objective of this study is to assess major comorbidities associated with obstructive sleep apnea (OSA) and prevalence in a group of patients diagnosed clinically and polysomnographically with OSA. Methods This is a retrospective study of 100 charts from patients previously diagnosed with OSA in our service between October 2010 and January 2013. Results We evaluated 100 patients with OSA (84 men and 16 women) with a mean age of 50.05 years (range 19-75 years). The prevalence of comorbidities were hypertension (39%), obesity (34%), depression (19%), gastroesophageal reflux disease (GERD) (18%), diabetes mellitus (15%), hypercholesterolemia (10%), asthma (4%), and no comorbidities (33%). Comorbidities occurred in 56.2% patients diagnosed with mild OSA, 67.6% with moderate OSA, and 70% of patients with severe OSA. Conclusion According to the current literature data and the values obtained in our paper, we can correlate through expressive values obesity with OSA and their apnea hypopnea index (AHI) values. However, despite significant prevalence of OSA with other comorbidities, our study could not render expressive significance values able to justify their correlations.

Comorbidities Associated with Obstructive Sleep Apnea: a Retrospective Study.

Introduction Obstructive sleep apnea (OSA) is characterized by partial or complete recurrent upper airway obstruction during sleep. OSA brings many adverse consequences, such as hypertension, obesity, diabetes mellitus, cardiac and encephalic alterations, behavioral, among others, resulting in a significant source of public health care by generating a high financial and social impact. The importance of this assessment proves to be useful, because the incidence of patients with comorbidities associated with AOS has been increasing consistently and presents significant influence in natural disease history. Objective The objective of this study is to assess major comorbidities associated with obstructive sleep apnea (OSA) and prevalence in a group of patients diagnosed clinically and polysomnographically with OSA. Methods This is a retrospective study of 100 charts from patients previously diagnosed with OSA in our service between October 2010 and January 2013. Results We evaluated 100 patients with OSA (84 men and 16 women) with a mean age of 50.05 years (range 19-75 years). The prevalence of comorbidities were hypertension (39%), obesity (34%), depression (19%), gastroesophageal reflux disease (GERD) (18%), diabetes mellitus (15%), hypercholesterolemia (10%), asthma (4%), and no comorbidities (33%). Comorbidities occurred in 56.2% patients diagnosed with mild OSA, 67.6% with moderate OSA, and 70% of patients with severe OSA. Conclusion According to the current literature data and the values obtained in our paper, we can correlate through expressive values obesity with OSA and their apnea hypopnea index (AHI) values. However, despite significant prevalence of OSA with other comorbidities, our study could not render expressive significance values able to justify their correlations.

Accuracy of peripheral arterial tonometry in the diagnosis of obstructive sleep apnea / Acurácia da tonometria arterial periférica no diagnóstico da apneia obstrutiva do sono

ABSTRACT INTRODUCTION: The use of handheld devices that assess peripheral arterial tonometry has emerged as an auxiliary method for assessment and diagnosis of obstructive sleep apnea syndrome. OBJECTIVE: To evaluate the accuracy of peripheral arterial tonometry in the diagnosis of obstructive sleep apnea. METHODS: Contemporary cohort cross-sectional study. Thirty patients with suspected obstructive sleep apnea underwent peripheral arterial tonometry and assisted nocturnal polysomnography concomitantly. RESULTS: The mean apnea/hypopnea index by peripheral arterial tonometry was significantly higher than that by polysomnography (p < 0.001), but the values of both sleep studies were significantly correlated (r = 0.762). There was a high correlation between variables: minimum oxygen saturation (r = 0.842,p < 0.001), oxygen saturation < 90% (r = 0.799, p < 0.001), and mean heart rate (r = 0.951, p < 0.001). Sensitivity and specificity were 60% and 96.2% (AUC: 0.727;p = 0.113), respectively, when at a threshold value of 5 events/h. In severe cases (≥30 events/h), the result was a sensitivity of 77.8% and a specificity of 86.4% (AUC: 0.846, p = 0.003). CONCLUSION: Peripheral arterial tonometry is a useful portable device for the diagnosis of obstructive sleep apnea; its accuracy is higher in moderate and severe cases.

RESUMO Introdução: A utilização de dispositivos portáteis, que avaliam a tonometria arterial periférica, surge como método adjuvante para avaliação e diagnóstico da síndrome da apneia obstrutiva do sono. Objetivo: Avaliar a acurácia da tonometria arterial periférica no diagnóstico da apneia obstrutiva do sono. Método: Estudo de coorte contemporânea com corte transversal. Trinta pacientes com suspeita de apneia obstrutiva do sono foram submetidos a tonometria arterial periférica e a polissonografia noturna assistida simultaneamente. Resultados: A média do índice de apneia/hipopneia pela tonometria arterial periféricafoi significativamente maior do que a da polissonografia (p < 0,001), porém os valores de ambos os estudos do sono foram significativamente correlacionados (r = 0,762). Houve alta correlação entre as variáveis: saturação mínima de oxigênio (r = 0,842, p < 0,001), saturação de oxigênio < 90% (r = 0,799, p < 0,001) e média de frequência cardíaca (r = 0,951, p < 0,001). A sensibilidade e especificidade foram 96,2% e 60% (AUC: 0,727, p = 0,113), respectivamente, quando limiar de 5 eventos/hora. Nos casos graves (≥ 30 eventos/hora), o resultado foi uma sensibilidade de 77,8% e uma especificidade de 86,4% (AUC: 0,846, p = 0,003). Conclusão: A tonometria arterial periférica é um dispositivo portátil útil no diagnóstico da apneia obstrutiva do sono e sua acurácia é maior nos casos moderados e graves.

Accuracy of peripheral arterial tonometry in the diagnosis of obstructive sleep apnea.

INTRODUCTION: The use of handheld devices that assess peripheral arterial tonometry has emerged as an auxiliary method for assessment and diagnosis of obstructive sleep apnea syndrome. OBJECTIVE: To evaluate the accuracy of peripheral arterial tonometry in the diagnosis of obstructive sleep apnea. METHODS: Contemporary cohort cross-sectional study. Thirty patients with suspected obstructive sleep apnea underwent peripheral arterial tonometry and assisted nocturnal polysomnography concomitantly. RESULTS: The mean apnea/hypopnea index by peripheral arterial tonometry was significantly higher than that by polysomnography (p<0.001), but the values of both sleep studies were significantly correlated (r=0.762). There was a high correlation between variables: minimum oxygen saturation (r=0.842, p<0.001), oxygen saturation<90% (r=0.799, p<0.001), and mean heart rate (r=0.951, p<0.001). Sensitivity and specificity were 60% and 96.2% (AUC: 0.727; p=0.113), respectively, when at a threshold value of 5 events/h. In severe cases (≥30 events/h), the result was a sensitivity of 77.8% and a specificity of 86.4% (AUC: 0.846, p=0.003). CONCLUSION: Peripheral arterial tonometry is a useful portable device for the diagnosis of obstructive sleep apnea; its accuracy is higher in moderate and severe cases.

A deletion at ADAMTS9-MAGI1 locus is associated with psoriatic arthritis risk.

OBJECTIVE: Copy number variants (CNVs) have been associated with the risk to develop multiple autoimmune diseases. Our objective was to identify CNVs associated with the risk to develop psoriatic arthritis (PsA) using a genome-wide analysis approach. METHODS: A total of 835 patients with PsA and 1498 healthy controls were genotyped for CNVs using the Illumina HumanHap610 BeadChip genotyping platform. Genomic CNVs were characterised using CNstream analysis software and analysed for association using the χ(2) test. The most significant genomic CNV associations with PsA risk were independently tested in a validation sample of 1133 patients with PsA and 1831 healthy controls. In order to test for the specificity of the variants with PsA aetiology, we also analysed the association to a cohort of 822 patients with purely cutaneous psoriasis (PsC). RESULTS: A total of 165 common CNVs were identified in the genome-wide analysis. We found a highly significant association of an intergenic deletion between ADAMTS9 and MAGI1 genes on chromosome 3p14.1 (p=0.00014). Using the independent patient and control cohort, we validated the association between ADAMTS9-MAGI1 deletion and PsA risk (p=0.032). Using next-generation sequencing, we characterised the 26 kb associated deletion. Finally, analysing the PsC cohort we found a lower frequency of the deletion compared with the PsA cohort (p=0.0088) and a similar frequency to that of healthy controls (p>0.3). CONCLUSIONS: The present genome-wide scan for CNVs associated with PsA risk has identified a new deletion associated with disease risk and which is also differential from PsC risk.