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Background: With recent advancements in bronchoscopic procedures, data on the best modality to sample peripheral pulmonary lesions (PPLs) is lacking, especially comparing bronchoscopy with computed tomography-guided transthoracic biopsy or needle aspiration (CT-TBNA)., Methods: We performed a meta-analysis, pairwise meta-analysis and network meta-analysis on studies reporting diagnostic yield and complications with the use of CT-TBNA, radial endobronchial ultrasound (rEBUS), virtual bronchoscopy (VB), electromagnetic navigation (EMN) or robot-assisted bronchoscopy (RAB) to sample PPLs. The primary outcome was diagnostic yield and the secondary outcome was complications. We estimated the relative risk ratios using a random-effects model and used the frequentist approach for the network meta-analysis. We performed extensive analysis to assess the heterogeneity including reporting bias, publication bias, subgroup and meta-regressional analysis. We assessed the quality of the studies using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) and QUADAS-Comparative (QUADAS-C)., Results: We included 363 studies. The overall pooled diagnostic yield was 78.1%, the highest with CT-TBNA (88.9%), followed by RAB (84.8%) and the least with rEBUS (72%). In the pairwise meta-analysis, only rEBUS showed inferiority to CT-TBNA. The network meta-analysis ranked CT-TBNA as likely the most effective approach followed by VB, EMN and RAB, while rEBUS was the least effective, with a low-GRADE certainty. CT-TBNA had the highest rate of complications., Conclusion: Although CT-TBNA is the most effective approach to sample PPLs, RAB has a comparable diagnostic yield with a lesser complication rate. Further prospective studies are needed comparing CT-TBNA and RAB., Competing Interests: Conflict of interest: All authors have nothing to disclose., (Copyright ©The authors 2024.)

Objective  To evaluate the clinical utility of the Baveno classification in predicting incident cardiovascular mortality after five years of follow-up in a clinic-based cohort of patients with obstructive sleep apnea (OSA). Materials and Methods  We evaluated the reproducibility of the Baveno classification using data from the Santiago Obstructive Sleep Apnea (SantOSA) study. The groups were labeled Baveno A (minor symptoms and comorbidities), B (severe symptoms and minor comorbidities), C (minor symptoms and severe comorbidities), and D (severe symptoms and comorbidities). Within-group comparisons were performed using analysis of variance (ANOVA) and post hoc tests. The associations between groups and incident cardiovascular mortality were determined through the Mantel-Cox and Cox proportional hazard ratios (HRs) adjusted by covariables. Results  A total of 1,300 OSA patients were included (Baveno A: 27.7%; B: 28%; C: 16.8%; and D: 27.5%). The follow-up was of 5.4 years. Compared to Baveno A, the fully-adjusted risk of cardiovascular mortality with Baveno B presented an HR of 1.38 (95% confidence interval [95%CI]: 0.14-13.5; p  = 0.78); with Baveno C, it was of 1.71 (95%CI: 0.18-16.2; p  = 0.63); and, with Baveno D, of 1.04 (95%CI: 0.12-9.2; p  = 0.98). We found no interactions involving Baveno group, sex and OSA severity. Discussion  Among OSA patients, the Baveno classification can describe different subgroups. However, its utility in identifying incident cardiovascular mortality is unclear. Long-term follow-up studies and the inclusion of demographic variables in the classification could improve its ability to detect a high-risk phenotype associated with cardiovascular mortality. Conclusion  The Baveno classification serves as a valuable method for categorizing varying groups of patients afflicted with OSA. Nevertheless, its precision in identifying occurrence of cardiovascular mortality is still unclear., Competing Interests: Conflict of Interests The authors have no conflict of interests to declare., (Brazilian Sleep Association. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Current studies agree on the impact of sleep and circadian rest-activity rhythm alterations in acute respiratory distress syndrome (ARDS) survivors. However, research on the duration of this impact is scarce. In this study, we evaluate the impact of ARDS on the sleep and circadian rest-activity rhythm of COVID-19 survivors twelve months after hospital discharge. This is a prospective study including COVID-19 survivors with and without ARDS during hospitalization. Data was collected four and twelve months after hospital discharge. The interventions included one-week wrist actigraphy and a home sleep apnea test (HSAT), and evaluations were conducted according to the Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), and insomnia severity index (ISI). Fifty-two patients were evaluated (ARDS = 31 and non-ARDS = 21); they had a median age of 49.0 [39.0;57.2] years and 53.8% were male. After twelve months, 91.3% presented poor sleep quality, 58.7% presented insomnia, 50% presented daytime somnolence, and 37% presented comorbid insomnia and obstructive sleep apnea (COMISA). No significant improvement was observed in relation to sleep or the circadian rest-activity rhythm between four and twelve months. A tendency of poor sleep quality, insomnia, daytime somnolence, and COMISA was observed. Finally, there was no significant impact on the circadian rest-activity rhythm between four and twelve months or between the groups.

Background: Chylothorax is an uncommon medical condition for which limited data are available regarding the contemporary aetiology, management and outcomes. The goal of this study was to better define these poorly characterised features., Methods: The medical records of adult patients diagnosed with chylothorax at 12 centres across Europe, America and South Africa from 2009-2021 were retrospectively reviewed. Descriptive and inferential statistics were performed., Results: 77 patients (median age 69 years, male to female ratio 1.5) were included. Subacute dyspnoea was the most typical presenting symptom (66%). The commonest cause of chylothorax was malignancy (68.8%), with lymphoma accounting for 62% of these cases. Other aetiologies were trauma (13%), inflammatory/miscellaneous conditions (11.7%) and idiopathic cases (6.5%). At the initial thoracentesis, the pleural fluid appeared milky in 73%, was exudative in 89% and exhibited triglyceride concentrations >100 mg·dL -1 in 88%. Lymphangiography/lymphoscintigraphy were rarely ordered (3%), and demonstration of chylomicrons in pleural fluid was never ascertained. 67% of patients required interventional pleural procedures. Dietary measures were infrequently followed (36%). No patient underwent thoracic duct ligation or embolisation. Morbidity included infections (18%), and thrombosis in malignant aetiologies (16%). The 1-year mortality was 47%. Pleural fluid protein >3.5 mg·dL -1 (sub-distribution hazard ratio (SHR) 4.346) or lactate dehydrogenase <500 U·L -1 (SHR 10.21) increased the likelihood of effusion resolution. Pleural fluid protein ≤3.5 mg·dL -1 (HR 4.047), bilateral effusions (HR 2.749) and a history of respiratory disease (HR 2.428) negatively influenced survival., Conclusion: Chylothoraces have a poor prognosis and most require pleural interventions. Despite the standard recommendations, lymphatic imaging is seldom used, nor are dietary restrictions followed., Competing Interests: Conflict of interest: J.M. Porcel has received consultancy fees from Becton Dickinson and Suministros Hospitalarios SA (SH Medical Group), and is an associate editor of this journal. Conflict of interest: The remaining authors declare that they have no relevant conflicts of interest., (Copyright ©The authors 2023.)

COVID-19 continues to affect an unprecedented number of people with the emergence of new variants posing a serious challenge to global health. There is an expansion of knowledge in understanding the pathogenesis of Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the impact of the acute disease on multiple organs. In addition, growing evidence reports that the impact of COVID-19 on different organs persists long after the recovery phase of the disease, leading to long-term consequences of COVID-19. These long-term consequences involve pulmonary as well as extra-pulmonary sequelae of the disease. Noteably, recent research has shown a potential association between COVID-19 and change in the molecular cargo of extracellular vesicles (EVs). EVs are vesicles released by cells and play an important role in cell communication by transfer of bioactive molecules between cells. Emerging evidence shows a strong link between EVs and their molecular cargo, and regulation of metabolism in health and disease. This review focuses on current knowledge about EVs and their potential role in COVID-19 pathogenesis, their current and future implications as tools for biomarker and therapeutic development and their possible effects on long-term impact of COVID-19., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Long-term pulmonary dysfunction (L-TPD) is one of the most critical manifestations of long-COVID. This lung affection has been associated with disease severity during the acute phase and the presence of previous comorbidities, however, the clinical manifestations, the concomitant consequences and the molecular pathways supporting this clinical condition remain unknown. The aim of this study was to identify and characterize L-TPD in patients with long-COVID and elucidate the main pathways and long-term consequences attributed to this condition by analyzing clinical parameters and functional tests supported by machine learning and serum proteome profiling., Methods: Patients with L-TPD were classified according to the results of their computer-tomography (CT) scan and diffusing capacity of the lungs for carbon monoxide adjusted for hemoglobin (DLCOc) tests at 4 and 12-months post-infection., Results: Regarding the acute phase, our data showed that L-TPD was favored in elderly patients with hypertension or insulin resistance, supported by pathways associated with vascular inflammation and chemotaxis of phagocytes, according to computer proteomics. Then, at 4-months post-infection, clinical and functional tests revealed that L-TPD patients exhibited a restrictive lung condition, impaired aerobic capacity and reduced muscular strength. At this time point, high circulating levels of platelets and CXCL9, and an inhibited FCgamma-receptor-mediated-phagocytosis due to reduced FcγRIII (CD16) expression in CD14+ monocytes was observed in patients with L-TPD. Finally, 1-year post infection, patients with L-TPD worsened metabolic syndrome and augmented body mass index in comparison with other patient groups., Discussion: Overall, our data demonstrated that CT scan and DLCOc identified patients with L-TPD after COVID-19. This condition was associated with vascular inflammation and impair phagocytosis of virus-antibody immune complexes by reduced FcγRIII expression. In addition, we conclude that COVID-19 survivors required a personalized follow-up and adequate intervention to reduce long-term sequelae and the appearance of further metabolic diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Sanhueza, Vidal, Hernandez, Henriquez-Beltran, Cabrera, Quiroga, Antilef, Aguilar, Castillo, Llerena, Fraga Figueroa, Nazal, Castro, Lagos, Moreno, Lastra, Gajardo, Garcés, Riffo, Buchert, Sanhueza, Ormazába, Saldivia, Vargas, Nourdin, Koch, Zuñiga, Lamperti, Bustos, Guzmán-Gutiérrez, Tapia, Ferrada, Cerda, Woehlbier, Riquelme, Yuseff, Muñoz Ramirez, Lombardi, De Gonzalo-Calvo, Salomon, Verdugo, Quiñones, Colombo, Barría, Labarca and Nova-Lamperti.)

Study Objectives: There is uncertainty on best approaches for defining apnea-hypopnea events. To clarify the contributions of desaturation vs arousal to defining hypopneas, we examined the associations of events with desaturation (≥ 3%) but not arousal (apnea-hypopnea index [AHI] ≥3%Only ) vs events with arousals but no desaturation (AHI ArOnly ) with obstructive sleep apnea-related comorbidities and incident cardiovascular disease across multiple cohorts., Methods: In the Sleep Heart Health Study (n = 5,473), the Multi-Ethnic Study of Atherosclerosis (n = 1,904), and the Osteoporotic Fractures in Men Study (n = 2,685), we examined the independent associations of AHI ≥3%Only and AHI ArOnly with hypertension, diabetes, and daytime sleepiness, and incident cardiovascular disease., Results: After adjusting for covariates and AHI based on events with electroencephalogram arousal (regardless of desaturation), AHI ≥3%Only was associated with hypertension in Sleep Heart Health Study (odds ratio: 1.12; 95% confidence interval: 1.04,1.21), per 1 standard deviation increase). Similar associations were observed in the Multi-Ethnic Study of Atherosclerosis and Osteoporotic Fractures in Men Study, as well as for associations with diabetes (odds ratio: 1.30; 1.09,1.54, and 1.25; 1.07,1.47, respectively), sleepiness (odds ratio: 1.19; 1.00,1.41; and 1.17; 1.01-1.35), and incident cardiovascular disease (hazard ratio: 1.37; 1.05,1.77 and 1.14; 1.00,1.29). In contrast, after adjusting for events with desaturation (regardless of arousal), AHI ArOnly was unassociated with these outcomes. In Sleep Heart Health Study, greater baseline obstructive sleep apnea severity was associated with a reduction in arousal frequency over 5 years ( P < .0001)., Conclusions: In middle-aged and older individuals, addition of events with arousals does not improve the strength of associations with comorbidities or incident cardiovascular disease. Research is needed to understand generalizability to younger individuals and the mechanistic role of arousals in obstructive sleep apnea., Citation: Azarbarzin A, Sands SA, Han S, et al. Relevance of cortical arousals for risk stratification in sleep apnea: a 3 cohort analysis. J Clin Sleep Med . 2023;19(8):1475-1484., (© 2023 American Academy of Sleep Medicine.)

Sleep is essential for life, and inappropriate sleep duration patterns may lead to chronic consequences regarding human health. Several studies have confirmed the presence of a U-shaped association between sleep duration and mortality. Moreover, many consequences related to cardiometabolic aspects have been suggested in patients with abnormal sleep durations. In this study, we analyzed the associations between sleep duration, total sleep time (TST), the risk of all-cause mortality, and 10-year cardiovascular risk in a cohort of patients at a sleep medicine center in Santiago, Chile. We conducted a prospective cohort study of patients (SantOSA). A short TST was defined as ≤6 h, a normal TST as 6 to 9 h, and a long TST as ≥9 h. Adjusted hazard ratios (aHRs) for all-cause mortality were calculated. A cross-sectional analysis between TST and 10-year cardiovascular risk (calculated using the Framingham 2008 formula) was determined using logistic regression models. A total of 1385 subjects were included in the results (78% male; median age: 53, interquartile range (IQR): 42-64 years; median BMI: 29.5, IQR: 16.7-33.1). A total of 333 subjects (24%) reported short TSTs, 938 (67.7%) reported normal TSTs, and 114 (8.3%) reported long TSTs. In the fully adjusted model, the association remained significant for short (aHR: 2.51 (1.48-4.25); p -value = 0.01) and long TSTs (aHR: 3.97 (1.53-10.29); p -value = 0.04). Finally, a U-shaped association was found between short and long TSTs, with an increase in cardiovascular risk at 10 years. Compared with normal TSTs, short (≤6 h) and long (≥9 h) TSTs were significantly associated with all-cause mortality and increased 10-year cardiovascular risk.

Purpose: Robust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness., Methods: We conducted a multi-cohort observational study to investigate the biology and the prognostic role of interferon alpha-inducible protein 27 ( IFI27 ) in COVID-19 patients., Results: We show that IFI27 is expressed in the respiratory tract of COVID-19 patients and elevated IFI27 expression in the lower respiratory tract is associated with the presence of a high viral load. We further demonstrate that the systemic host response, as measured by blood IFI27 expression, is associated with COVID-19 infection. For clinical outcome prediction (e.g., respiratory failure), IFI27 expression displays a high sensitivity (0.95) and specificity (0.83), outperforming other known predictors of COVID-19 outcomes. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For example, in the pandemic H1N1/09 influenza virus infection, IFI27- like genes were highly upregulated in the blood samples of severely infected patients., Conclusion: These data suggest that prognostic biomarkers targeting the family of IFI27 genes could potentially supplement conventional diagnostic tools in future virus pandemics, independent of whether such pandemics are caused by a coronavirus, an influenza virus or another as yet-to-be discovered respiratory virus., Competing Interests: FS-F-G is a consultant for Biotheus Inc. KS is a consultant for Sanofi, Roche and NovoNordisk. The opinions and data presented in this manuscript are of the authors and are independent of these relationships. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shojaei, Shamshirian, Monkman, Grice, Tran, Tan, Teo, Rodrigues Rossi, McCulloch, Nalos, Raei, Razavi, Ghasemian, Gheibi, Roozbeh, Sly, Spann, Chew, Zhu, Xia, Wells, Senegaglia, Kuniyoshi, Franck, dos Santos, Noronha, Motamen, Valadan, Amjadi, Gogna, Madan, Alizadeh-Navaei, Lamperti, Zuñiga, Nova-Lamperti, Labarca, Knippenberg, Herwanto, Wang, Phu, Chew, Kwan, Kim, Teoh, Pelaia, Kuan, Jee, Iredell, O’Byrne, Fraser, Davis, Belz, Warkiani, Gallo, Souza-Fonseca-Guimaraes, Nguyen, Mclean, Kulasinghe, Short and Tang.)

The long-term clinical management and evolution of a cohort of critical COVID-19 survivors have not been described in detail. We report a prospective observational study of COVID-19 patients admitted to the ICU between March and August 2020. The follow-up in a post-COVID consultation comprised symptoms, pulmonary function tests, the 6-minute walking test (6MWT), and chest computed tomography (CT). Additionally, questionnaires to evaluate the prevalence of post-COVID-19 syndrome were administered at 1 year. A total of 181 patients were admitted to the ICU during the study period. They were middle-aged (median [IQR] of 61 [52;67]) and male (66.9%), with a median ICU stay of 9 (5-24.2) days. 20% died in the hospital, and 39 were not able to be included. A cohort of 105 patients initiated the follow-up. At 1 year, 32.2% persisted with respiratory alterations and needed to continue the follow-up. Ten percent still had moderate/severe lung diffusion (DLCO) involvement (<60%), and 53.7% had a fibrotic pattern on CT. Moreover, patients had a mean (SD) number of symptoms of 5.7 ± 4.6, and 61.3% met the criteria for post-COVID syndrome at 1 year. During the follow-up, 46 patients were discharged, and 16 were transferred to other consultations. Other conditions, such as emphysema (21.6%), COPD (8.2%), severe neurocognitive disorders (4.1%), and lung cancer (1%) were identified. A high use of health care resources is observed in the first year. In conclusion, one-third of critically ill COVID-19 patients need to continue follow-up beyond 1 year, due to abnormalities on DLCO, chest CT, or persistent symptoms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 González, Zuil, Benítez, de Gonzalo-Calvo, Aguilar, Santisteve, Vaca, Minguez, Seck, Torres, de Batlle, Gómez, Barril, Moncusí-Moix, Monge, Gort-Paniello, Ferrer, Ceccato, Fernández, Motos, Riera, Menéndez, Garcia-Gasulla, Peñuelas, Labarca, Caballero, Barberà, Torres and Barbé.)

Objective: To determine the association between Obstructive Sleep Apnea (OSA) with long-term symptoms and inflammatory cytokines, exploring the changes between 4-months and 1-year after COVID-19 infection., Methods: We conducted an observational, prospective cohort study, including patients ≥18 years old with confirmed diagnosis of COVID-19 between April to July 2020. All participants underwent two clinical follow-up visits, the first at 4-months (Visit 1) and the second at 1 year, after SARS-CoV-2 infection (Visit 2). Plasma glucose, total cholesterol, HDL, and triglycerides. Regarding pulmonary function, spirometry and lung diffusion capacity tests were assessed. For mental and neurocognitive evaluation, a short-form (SF-12), Beck depression and Hospital-Anxiety depression questionnaires were conducted at both time-points, whereas the Montreal Cognitive assessment was conducted during the second follow-up. Regarding to sleep evaluation, Epworth Sleepiness Scale, Insomnia Severity index and STOP-BANG questionnaire were conducted. Additionally, a home sleep apnea test and 7-day wrist actigraphy were performed in all participants. Inflammatory cytokines were measured using an inflammatory cytokine bead array kit. p- values < 0.05 were considered statistically significant and statistical analyses were performed using R software., Results: A total of 60 patients were included in the first follow-up, from which 57 completed the second follow-up. The mean age was 46.4 years-old (SD ± 13.1) and 53.3% were male. 30% of cases reported mild COVID-19 infection, 28.3% with moderate illness, and 41.6% with severe illness. Moreover, 56.6% of them were admitted to the ICU. Regarding to metabolic values, the OSA group showed higher values of insulin resistance (IR) (27%), systolic blood pressure (SBP) 135.2 (±19.1), dyslipidemia (67.5%), total cholesterol 202.1 (±60.5), triglycerides 176.1 (±119.0) and HOMA-IR 9.0 (±18.8) in comparison with the non-OSA group. 1 year after COVID-19 infection, DLCO test remains abnormal in OSA patients (25% OSA vs. 3.6% non-OSA, p = 0.02). Finally, those participants with OSA who develop ARDS reported an adjusted OR 20.4 (95%-CI, 1.04-504) risk of neurocognitive impairment., Discussion: Among patients with previous COVID-19, OSA impact the development of incident glycemic, neurocognitive impairment, and abnormal functional pulmonary changes that persist up to 1 year since acute phase., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Labarca, Henríquez-Beltrán, Lamperti, Nova-Lamperti, Sanhueza, Cabrera, Quiroga, Antilef, Ormazábal, Zúñiga, Castillo, Horta, Enos, Lastra, Gonzalez, Targa and Barbe.)

Objective: To describe the prevalence and severity of sleep disorders and circadian alterations in COVID-19 patients four months after the acute phase of the disease., Methods: This was a cross-sectional observational prospective study of patients with mild COVID-19, moderate COVID-19 (requiring hospitalization but no mechanical ventilation), or severe COVID-19 (with ARDS) four months after the acute phase of the disease. All patients underwent a home sleep apnea test and seven-day wrist actigraphy, as well as completing questionnaires to assess sleep quality and mental health. Differences among the three groups of patients were evaluated by ANOVA and the chi-square test., Results: A total of 60 patients were included in the study. Of those, 17 were in the mild COVID-19 group, 18 were in the moderate COVID-19 group, and 25 were in the severe COVID-19 group. Sleep quality, as assessed by satisfaction, alertness, timing, efficiency, and duration scale scores, was found to be impaired in all three groups, which also had a high prevalence of unhealthy sleep, as assessed by the Pittsburgh Sleep Quality Index. The prevalence of insomnia was increased in all three groups, as assessed by the Insomnia Severity Index. The home sleep apnea test showed that the overall prevalence of obstructive sleep apnea was 60%, and seven-day wrist actigraphy showed that total sleep time was < 7 h in all three groups. Changes in quality of life and in the circadian rest-activity pattern were observed in all three groups., Conclusions: Sleep-related symptoms, changes in the circadian rest-activity pattern, and impaired mental health appear to be common in COVID-19 patients four months after the acute phase of the disease, severe COVID-19 being associated with a higher prevalence of obstructive sleep apnea.

Question: We evaluated whether the time between first respiratory support and intubation of patients receiving invasive mechanical ventilation (IMV) due to COVID-19 was associated with mortality or pulmonary sequelae., Materials and Methods: Prospective cohort of critical COVID-19 patients on IMV. Patients were classified as early intubation if they were intubated within the first 48 h from the first respiratory support or delayed intubation if they were intubated later. Surviving patients were evaluated after hospital discharge., Results: We included 205 patients (140 with early IMV and 65 with delayed IMV). The median [p 25 ;p 75 ] age was 63 [56.0; 70.0] years, and 74.1% were male. The survival analysis showed a significant increase in the risk of mortality in the delayed group with an adjusted hazard ratio (HR) of 2.45 (95% CI 1.29-4.65). The continuous predictor time to IMV showed a nonlinear association with the risk of in-hospital mortality. A multivariate mortality model showed that delay of IMV was a factor associated with mortality (HR of 2.40; 95% CI 1.42-4.1). During follow-up, patients in the delayed group showed a worse DLCO (mean difference of - 10.77 (95% CI - 18.40 to - 3.15), with a greater number of affected lobes (+ 1.51 [95% CI 0.89-2.13]) and a greater TSS (+ 4.35 [95% CI 2.41-6.27]) in the chest CT scan., Conclusions: Among critically ill patients with COVID-19 who required IMV, the delay in intubation from the first respiratory support was associated with an increase in hospital mortality and worse pulmonary sequelae during follow-up., (© 2022. The Author(s).)

Objective: To describe baseline characteristics of outpatients with a positive RT-PCR for SARS-CoV-2 and to define whether "red flags" (new-onset fever, dyspnea, and chest pain) can predict clinical worsening during the isolation period., Methods: This was an epidemiological, observational, descriptive study. Between March and September of 2020, all outpatients who tested positive for SARS-CoV-2 at a tertiary medical center located in Santiago de Chile were included. Demographic variables, comorbidities, red flags, and other symptoms were compiled using follow-up surveys at specific time points. The risk of clinical worsening (hospitalization) and adjusted hazard ratios (HRs) were calculated., Results: A total of 7,108 patients were included. The median age was 38 years (range, 0-101), and 52% were men. At baseline, 77% of the patients reported having characteristic symptoms of SARS-CoV-2 infection. The most prevalent onset symptoms were headache (53%), myalgia (47%), and fever (33%). According to the follow-up surveys, the incidence of symptoms decreased during the isolation period; however, 28% of the patients still presented with symptoms on day 14. The risk of hospitalization for patients with new-onset fever and dyspnea during the follow-up period was HR = 7.43 (95% CI, 3.85-14.3, p<0.01) and HR = 5.27 (95% CI, 1.52-18.30; p < 0.01 for both), respectively. New-onset chest pain showed no association with clinical worsening., Conclusions: In this sample of outpatients with a recent diagnosis of SARS-CoV-2 infection, a survey-based monitoring of symptoms was useful to identify those at risk of clinical worsening. New-onset fever and dyspnea during the isolation period were considered as red flags associated with clinical worsening and warrants prompt medical evaluation.

Objective: Obstructive sleep apnea (OSA) is associated with an increased risk of mortality and cardiometabolic diseases. The STOP-Bang questionnaire is a tool to screen populations at risk of OSA and prioritize complementary studies. Our objective was to evaluate the clinical utility of this questionnaire in identifying patients at an increased risk of mortality after discharge in a cohort of hospitalized patients., Methods: This was a prospective cohort study involving consecutive patients admitted to an internal medicine unit between May and June of 2017 who were reevaluated three years after discharge. At baseline, we collected data on comorbidities (hypertension, obesity, diabetes, and fasting lipid profile) and calculated STOP-Bang scores, defining the risk of OSA (0-2 score, no risk; ≥ 3 score, risk of OSA; and ≥ 5 score, risk of moderate-to-severe OSA), which determined the study groups. We also recorded data regarding all-cause and cardiovascular mortality at the end of the follow-up period., Results: The sample comprised 435 patients. Of those, 352 (80.9%) and 182 (41.8%) had STOP-Bang scores ≥ 3 and ≥ 5, respectively. When compared with the group with STOP-Bang scores of 0-2, the two groups showed higher prevalences of obesity, hypertension, diabetes, and dyslipidemia. Multivariate analysis showed an independent association between cardiovascular mortality and STOP-Bang score ≥ 5 (adjusted hazard ratio = 3.12 [95% CI, 1.39-7.03]; p = 0.01). Additionally, previous coronary heart disease was also associated with cardiovascular mortality., Conclusions: In this cohort of hospitalized patients, STOP-Bang scores ≥ 5 were able to identify patients at an increased risk of cardiovascular mortality three years after discharge.

The immune system plays a key role in the protective response against oral cancer; however, the tumor microenvironment (TME) impairs this anti-cancer response by modulating T helper (Th) responses and promoting an anti-inflammatory environment. Regulatory T cells (Tregs) and Th2 effector cells (Teff) are associated with poor prognosis in oral squamous cell carcinoma (OSCC). However, the main immunomodulatory mechanisms associated with the enrichment of these subsets in OSCC remain unknown. We characterized Th-like lineages in Tregs and Teff and evaluated immunomodulatory changes induced by the TME in OSCC. Our phenotypic data revealed a higher distribution of tumour-infiltrating CCR8 + and Th2-like Treg in OSCC compared with non-malignant samples, whereas the percentages of Th1 cells were reduced in cancer. We then analyzed the direct effect of the TME by exposing T cell subsets to cancer secretomes and observed the OSCC secretome induced CCR8 expression and reduced cytokine production from both subsets. Transcriptomic analysis showed that the co-culture with OSCC secretome induced several gene changes associated with the vitamin D (VitD) signaling pathway in T cells. In addition, proteomic analysis identified the presence of several proteins associated with prostaglandin E2 (PGE2) production by rapid membrane VitD signaling and a reduced presence of the VitD binding protein. Thus, we analyzed the effect of VitD and PGE2 and observed that VitD promotes a regulatory Th2-like response with CCR8 expression whilst PGE2 also modulated CCR8 but inhibited cytokine production in combination with VitD. Finally, we evaluated the presence of CCR8 ligand in OSCC and observed increased chemokine CCL18, which was also able to upregulate CCR8 in activated Th cells. Overall, our data showed the immunomodulatory changes induced by the TME involving CCR8 expression and regulatory Th2 phenotypes, which are associated with PGE2 mediated VitD signaling pathway and CCL18 expression in OSCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fraga, Yáñez, Sherman, Llerena, Hernandez, Nourdin, Álvarez, Urrizola, Rivera, Lamperti, Nova, Castro, Zambrano, Cifuentes, Campos, Moya, Pastor, Nuñez, Gatica, Figueroa, Zúñiga, Salomón, Cerda, Puentes, Labarca, Vidal, McGregor and Nova-Lamperti.)

The association between Takayasu's arteritis and membranous nephropathy is uncommon. We present the case of a 46-year-old man with Takayasu's arteritis treated over 10 years by a multidisciplinary medical team. He had an atrophic left kidney due to arterial stenosis, with a basal creatinine of 1.59 mg/dL (140.55 µmol/l). Three years ago, he presented with full nephrotic syndrome, uncontrolled blood pressure, creatinine increases to 4.5 mg/dL (basal: 1.59 mg/dL), severe hypoalbuminaemia (1.4 g/dL) and albuminuria of 24.6 g per day. He underwent percutaneous biopsy of the right kidney that showed membranous nephropathy with negative PLA2R1 and positive IgG 1, 3 and 4 subclasses. After therapy with oral prednisone and cyclophosphamide, the patient's kidney function improved, without recurrence of disease after 3 years of follow-up. Here, we present this extremely uncommon association of Takayasu's arteritis and membranous nephropathy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Abatacept is a biological agent that modulates T-cell costimulation by blocking CD28 signalling. This cytotoxic T-lymphocyte-associated antigen-4-Ig fusion protein was approved for treatment of rheumatoid arthritis (RA). However, a few case reports have revealed respiratory failure after abatacept treatment. In this report, we present a patient with RA who developed severe acute respiratory distress syndrome (ARDS) and who passed away 2 months after starting abatacept. A comprehensive analysis including radiology, blood examinations, infectious panel and flow cytometry lymphocyte analysis was done to determine the cause of respiratory failure. Since no infection was detected in this patient, an association between ARDS and abatacept is a strong possibility due to significant adverse reactions to the biological agent. Considering the rapid progression of respiratory failure after abatacept treatment in this report, we suggest that pulmonary function testing and lung structure evaluation be regarded throughout the early stage of treatment of patients with RA., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: There is evidence of an association between inflammatory bowel disease (IBD) and lung conditions such as chronic obstructive pulmonary disease (COPD). This systematic review and meta-analysis explored the risk of new onset IBD in patients with COPD and new onset COPD in IBD patients., Methods: We performed a systematic review of observational studies exploring the risk of both associations. Two independent reviewers explored the EMBASE, MEDLINE, LILACS and DOAJ databases, and the risk of bias was evaluated using the ROBBINS-I tool. Data from included studies was pooled in a random effect meta-analysis following a DerSimonian-Laird method. The quality of the evidence was ranked using GRADE criteria., Results: Four studies including a pooled population of 1355 new cases were included. We found association between new onset IBD in COPD population. The risk of bias was low in most of them. Only one study reported tobacco exposure as a potential confounding factor. The pooled risk ratio (RR) for a new diagnosis of IBD in COPD patients was 2.02 (CI, 1.56 to 2.63), I 2  = 72% (GRADE: low). The subgroup analyses for Crohn's disease and ulcerative colitis yielded RRs of 2.29 (CI, 1.51 to 3.48; I 2  = 62%), and 1.79 (CI, 1.39 to 2.29; I 2  = 19%.), respectively., Discussion: According to our findings, the risk of new onset IBD was higher in populations with COPD compared to the general population without this condition. Based on our analysis, we suggest a potential association between IBD and COPD; however, further research exploring the potential effect of confounding variables, especially cigarette smoking, is still needed. REVIEW REGISTER: (PROSPERO: CRD42018096624).

Background: Snoring is a main concern in patients who consult an otolaryngologist (ENT physicians) and patients who have cardiovascular comorbidities or excessive daytime sleepiness who usually consult with other specialists. The aim of this study was to describe the clinical differences in patients with obstructive sleep apnea (OSA) referred from ENT or other specialists., Methods: A prospective study was carried out between June 2015 and July 2018 in a tertiary center. We included patients with suspected OSA referred by the Home Sleep Apnea Test (HSAT) from different specialties such as ENT or other specialties. The main outcome measures of our study were demographic characteristics, clinical characteristics, sleep questionnaire results and HSAT results between OSA patients referred from ENT or other specialists. We used a t-test and chi-squared test for analysis. The diagnostic accuracy of the sleep questionnaires was achieved using receiver operating characteristic (ROC) curve and the area under the curve (AUC)., Results: A total of 481 patients were included. OSA was occurred in 82.4% of the subjects (90 in ENT and 306 in other specialties). Patients with OSA referred from other specialists were older than ENT patients (55 ± 13 vs 44 ± 12; p < 0.001), there was more obesity (IMC 31 ± 5.0 vs 28.7 ± 3.8; p < 0,001), a larger neck circumference (42.2 cm ± 3.7 vs 40.6 cm ± 3.0; p < 0.001) and more reported comorbidities (p < 0.001). ENT patients reported mild OSA (46% vs 31%, p = 0.015) and more positional apnea (62% vs 39%, p = 0.002). In this group, the STOP-BANG questionnaire showed an AUC 0.695 vs AUC 0.804, and for sensitivity, the best cutoff was 4 points. Patients referred from otorhinolaryngology are different from those referred from other specialties. Clinical evaluation and screening of OSA should be patient-centered according to these clinical findings.

Study Objectives: Several studies have reported an association between obstructive sleep apnea (OSA) and several extra-pulmonary issues, such as arterial hypertension and insulin resistance. In recent years, the associations between OSA, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis (NASH) have been published; however, there is a gap between experimental and clinical studies regarding the efficacy of continuous positive airway pressure (CPAP) treatment in patient populations with these conditions. This issue should be considered when deciding on CPAP treatment in patients with OSA, especially in patients with moderate OSA., Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) using the following databases: MEDLINE, Lilacs, and CENTRAL. Two independent reviewers performed the search, analysis, data extraction, and critical analysis., Results: From 622 identified studies, we included 5 RCTs that involved patients with OSA and NASH and who were treated with a CPAP device. After CPAP treatment, no changes in liver steatosis, liver fibrosis, and aminotransferase levels (alanine aminotransferase and aspartate aminotransferase) were found. Finally, the quality of evidence using the GRADE approach was low and very low for several outcomes., Conclusions: According to the current analysis, no data regarding the efficacy of CPAP in patients with NASH are available to make recommendations., Systematic Review Registration: PROSPERO; ID: CRD42015027981; URL: https://www.crd.york.ac.uk/PROSPERO/display&#95;record.php?ID=CRD42015027981., (© 2018 American Academy of Sleep Medicine)

Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the intra-alveolar accumulation of a proteinaceous phospholipid-laden material called surfactant. Clinically, this disease should be suspected with respiratory failure in association with a crazy paving pattern on high-resolution chest computed tomography. We report a 24-year-old gentleman who was referred to us for a history of respiratory failure, treatment with invasive ventilation and tracheostomy. His blood exams and biochemistry were normal. His infectious and rheumatological panel was negative for a secondary disease. A flexible bronchoscopy with a transbronchial biopsy through a CryoProbe was performed. An anatomopathological analysis was periodic acid-Schiff positive for PAP. A CryoProbe is a recently developed diagnostic tool that improves the diagnostic yield in diffuse lung diseases compared to bronchoscopy with transbronchial biopsy. This method should be considered for patients with diffuse lung disease and PAP.

Introduction: Clinical onset of chronic obstructive pulmonary disease (COPD) is the point at which the disease is first identifiable by physicians. It is a poorly defined stage which seems to include both mild spirometric and non-spirometric disease, and could be described as early grade COPD, for practical purposes. While dyspnoea; chronic bronchitis and CT imaging evidence of emphysema and airway disease may be present very early, the lone significance of dyspnoea, the most relevant symptom in COPD in identifying these individuals, has been scarcely assessed.The Searching Clinical COPD Onset (SOON) Study was designed primarily to detect clinical, physiological and structural differences between dyspnoeic and non-dyspnoeic individuals with early grade COPD. It is hypothesised that presence of dyspnoea in early disease may identify a subtype of individuals with reduced exercise capacity, notwithstanding of their spirometry results. In addition, dyspnoeic individuals will share worse quality of life, lower physical activity, greater lung hyperinflation greater emphysema and airway thickness and reduced peripheral muscle mass than their non-dyspnoeic counterpart., Methods and Analysis: SOON is a monocentric study, with a cross sectional design aimed at obtaining representative samples of current or ex-smoker-adults aged ≥45 and ≤80 years. Two hundred and forty participants will be enrolled into four strata, according to normal spirometry or mild spirometric obstruction and presence or not of dyspnoea modified Medical Research Council score ≥1. The primary outcome will be the difference between dyspnoeic and non-dyspnoeic individuals on the 6-min walk test performance, regardless of their spirometry results. To account for the confounding effect of heart failure on dyspnoea, stress echocardiography will be also performed. Secondary outcomes will include clinical (quality of life, physical activity), physiological (exercise testing) and structural characteristics (emphysema, airway disease and peripheral muscle mass by CT imaging)., Ethics and Dissemination: The Institutional Ethics Committee from Pontificia Universidad Católica de Chile has approved the study protocol and signed informed consent will be obtained from all participants. The findings of the trial will be disseminated through relevant peer-reviewed journals and international conference presentations., Trial Registration Number: NCT03026439., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Fibroepithelial polyps are benign lesions, frequently found in the skin and genitourinary tract. Airway involvement is rare, and few case reports have been published. Our patient was a 79 y.o. male smoker, who was referred to us with a 3-month history of dry cough. At physical examination, the patient looked well, but a chest CT showed a 6-mm polyp lesion in his trachea. A flexible bronchoscopy confirmed this lesion, and forceps biopsies were performed. Argon plasma coagulation was used to completely resect and treat the lesion. Pathological analysis revealed a fibroepithelial polyp (FP). The aim of this manuscript is to report a case of FP with bronchoscopic management and to review the current literature about this condition.

Introduction: Obstructive sleep apnoea (OSA) is associated with both pulmonary and extrapulmonary consequences. Continuous positive airway pressure (CPAP) is an effective treatment for pulmonary symptoms. However, it is not clear if CPAP modifies extrapulmonary symptoms, especially in the long term. To date, several studies addressing this issue have been performed, but the evidence is scattered across different reviews that address each outcome separately. Therefore, we will conduct an overview to assess and summarise all systematic reviews on the extrapulmonary effects of this intervention in patients with OSA., Methods: This is a protocol for a systematic overview of reviews that will follow the guidelines from the Cochrane Handbook of Systematic Reviews of Interventions and PRISMA-P. We will conduct comprehensive literature searches using MEDLINE, EMBASE, Cochrane, CINAHL, DARE and Epistemonikos. We will consider systematic reviews and meta-analyses of randomised controlled trials evaluating the extrapulmonary effects of CPAP on OSA. Two reviewers will independently screen articles for inclusion using criteria that are determined a priori, assessing the quality of included reviews and extracting relevant information. We will create matrices of evidence in the Epistemonikos database, including all systematic reviews addressing a similar question and all studies addressing the question in those reviews. We will try to explain why studies are not included in individual reviews using the inclusion criteria, and we will estimate the overlap between different reviews in the same matrix of evidence., Ethics and Dissemination: This review will be published in a peer-reviewed journal., Trial Registration Number: CRD42014013036., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Idiopathic pulmonary fibrosis has poor prognosis and effective therapies are scarce. In the search for treatments that can modify the course of the disease, nintedanib (BIBF 1120), a tyrosine kinase inhibitor, has emerged as an alternative. However, its role is still unclear. To answer this question, we searched in Epistemonikos database, which is maintained by screening multiple sources of information. We identified seven systematic reviews including seven randomized trials overall. We extracted data, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. We concluded nintedanib probably decreases the risk of acute exacerbations, and might reduce mortality in idiopathic pulmonary fibrosis. On the other hand, it is probably not associated with serious adverse events.

Idiopathic pulmonary fibrosis has an ominous prognosis and there are virtually no effective therapies. It has been suggested that pirfenidone, an antifibrotic agent, could change its course. Searching in Epistemonikos database, which is maintained by screening multiple databases, we identified 13 systematic reviews comprising nine trials addressing the question of this article, seven of which are randomized and whose results were analyzed in this summary. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded pirfenidone decreases disease progression and mortality in idiopathic pulmonary fibrosis. Although it is associated with frequent gastrointestinal and cutaneous adverse effects, these are generally not severe.

Idiopathic pulmonary fibrosis is a progressive chronic respiratory disease that in final stages carries high mortality. Several treatment options have been proposed, including N-acetylcysteine, but its role is not clearly established. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified eight systematic reviews including 16 trials addressing the question of this article. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded N-acetylcysteine might increase the risk of hospitalizations and exacerbations. While it is unclear whether this leads to increased mortality because the certainty of the evidence is very low, in general there is consensus that it should not be used except in the context of a new clinical trial.

Hydrocephalus is an uncommon presentation of neurosarcoidosis. We discuss the case of a 67-year-old woman with a prior diagnosis of hypothyroidism, systemic hypertension, and lung sarcoidosis who presented with a 1-month history of progressive impairment of consciousness leading to prostration and loss of sphincter control. At admission, patient was febrile with altered speech and without focalization. Laboratory results showed leucocytosis and mild anaemia. Cerebrospinal fluid (CSF) analysis was characterized by mild elevated protein level, increased cell count, normal glucose and adenosine deaminase (ADA), negative cytology, and no bacterial isolations. Electroencephalogram showed toxic-metabolic encephalopathy. Computed tomography (CT) of the brain revealed hydrocephalus without structural damage, and magnetic resonance imaging of the brain demonstrated non-specific diffuse meningeal enhancement and periventricular changes supporting normal pressure hydrocephalus. Chest X-ray showed mediastinal adenopathy and parenchymatous lesions, consistent with stage II lung sarcoidosis. A ventriculoperitoneal shunt was installed, and the patient experienced rapid improvement in her symptoms.

Introduction . Endobronchial ultrasound (EBUS) is a procedure that provides access to the mediastinal staging; however, EBUS cannot be used to stage all of the nodes in the mediastinum. In these cases, endoscopic ultrasound (EUS) is used for complete staging. Objective . To provide a synthesis of the evidence on the diagnostic performance of EBUS + EUS in patients undergoing mediastinal staging. Methods . Systematic review and meta-analysis to evaluate the diagnostic yield of EBUS + EUS compared with surgical staging. Two researchers performed the literature search, quality assessments, data extractions, and analyses. We produced a meta-analysis including sensitivity, specificity, and likelihood ratio analysis. Results . Twelve primary studies (1515 patients) were included; two were randomized controlled trials (RCTs) and ten were prospective trials. The pooled sensitivity for combined EBUS + EUS was 87% (CI 84-89%) and the specificity was 99% (CI 98-100%). For EBUS + EUS performed with a single bronchoscope group, the sensitivity improved to 88% (CI 83.1-91.4%) and specificity improved to 100% (CI 99-100%). Conclusion . EBUS + EUS is a highly accurate and safe procedure. The combined procedure should be considered in selected patients with lymphadenopathy noted at stations that are not traditionally accessible with conventional EBUS.

Unlabelled: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis. In the last decades pirfenidone an anti-inflammatory and anti-fibrotic agent has shown benefit in inhibit collagen production and has also demonstrated benefit in decline progression in IPF in physiological outcomes as Forced vital capacity (FVC), in clinical outcomes such as progression free survival (PFS) and a benefit in mortality but no in clinically relevant outcomes as exacerbations or worsening of IPF., Methods: We conducted a systematic review to evaluate the effectiveness of physiological and clinical outcomes of pirfenidone compared to placebo in IPF. We performed a search with no language restriction. Two researchers performed literature search, quality assessment, data extraction and analysis. And was performed a summary of findings table following the GRADE approach., Results: We included 5 RCTs (Randomized controlled trials) in analysis. The meta-analysis resulted in a decrease in all cause-mortality (RR 0.52 IC 0.32-0.88) and IPF related mortality (RR 0.32 IC 0.14-0.75); other outcomes evaluated were worsening of IPF (RR 0.64 IC 0.50-0.83) and acute exacerbation (RR: 0.72 IC 0.30-1.66 respectively). Also there was a decrease in the risk of progression (RR of PFS: 0.82 IC 0.73–0.92) compared to placebo. Conclusions: We observed significant differences in physiologic and clinically relevant outcomes such as reduction in all-cause mortality, IPF related mortality, worsening of IPF and improvement of PFS. So pirfenidone treatment should be considered not only for its benefits in pulmonary function tests but also by its clinically relevant outcomes [corrected].