Mouth Closure and Airflow in Patients With Obstructive Sleep Apnea: A Nonrandomized Clinical Trial.

Importance: Mouth breathing is associated with increased airway resistance, pharyngeal collapsibility, and obstructive sleep apnea (OSA) severity. The common belief is that closing the mouth can mitigate the negative effects of mouth breathing during sleep. However, mouth breathing may serve as an essential route to bypassing obstruction along the nasal route (eg, the velopharynx). Objective: To investigate the role of mouth breathing as an essential route in some patients with OSA and its association with upper airway anatomical factors. Design, Setting, and Participants: This nonrandomized clinical trial included participants diagnosed with OSA who underwent drug-induced sleep endoscopy. Patients were stratified into 3 quantiles based on oral-breathing level (quantile 1: oral airflow < 0.05 L/min; quantile 2: oral airflow 0.05-2.2 L/min; quantile 3: oral airflow > 2.2 L/min). Interventions: Closing the mouth during sleep during alternating breaths by applying pressure to the mentum until teeth are in occlusion. Main Outcomes and Measures: The primary outcome was total inspiratory flow defined as the change in airflow in the transition from mouth relaxed to mouth closed, analyzed overall and by 3 oral-breathing quantiles. The association of velopharyngeal obstruction on the change in total inspiratory airflow was also investigated. Results: Of 66 enrolled patients with OSA, 12 were excluded due to insufficient baseline airflow. The analytic cohort consisted of 54 patients (39 [72%] male; median [IQR] age, 55 [46-64] years; apnea-hypopnea index, 26.9 [17.6-39.9] events/h; and body mass index calculated as weight in kilograms divided by height in meters squared, 28.9 [27.1-31.6]). Mouth closure increased total inspiratory flow by 27.8 percentage points overall (ß, 1.0 [95% CI, 0.4-1.9] L/min). However, outcomes varied based on the degree of baseline oral breathing. No association was found for 10 patients with near-zero mouth breathing (0.9 [95% CI, -0.2 to 2.1] L/min). Airflow improved with mouth closure in 32 patients with moderate levels of mouth breathing (2.0 [95% CI, 1.3-2.7] L/min), whereas it worsened in patients with high levels of mouth breathing (-1.9 [95% CI, -3.1 to -0.6] L/min). Velopharyngeal obstruction was associated with increased mouth breathing (0.6 [95% CI, 0.1-3.0] L/min) and reduced airflow with mouth closure (-1.9 [95% CI, -3.1 to -0.7] L/min). Conclusion and Relevance: Although mouth closure increased inspiratory airflow in the overall cohort of this nonrandomized clinical trial, the outcomes were heterogeneous. In patients who breathe primarily through their mouth during sleep and have velopharyngeal obstruction, airflow worsens with mouth closure. Hence, personalized approaches to treating mouth breathing should be considered. Trial Registration: ClinicalTrials.gov Identifier: NCT06547658.

Diagnostic yield and safety of diagnostic techniques for pulmonary lesions: systematic review, meta-analysis and network meta-analysis.

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.

Clinical characteristics of chylothorax: results from the International Collaborative Effusion database.

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.

Mortalidad a 30 días en neumonías adquiridas en la comunidad graves por SARS-COV-2 y otros virus respiratorios en Chile / Risk of mortality of severe SARS-CoV-2 infection and other causes of viral pneumonia in Chile

INTRODUCCIÓN: En Chile, los virus respiratorios son una causa frecuente de neumonía adquirida en la comunidad (NAC), con admisión a unidades de paciente crítico en adultos. Los agentes etiológicos asociados son influenza A y B, virus respiratorio sincicial (VRS) y Hantavirus, sumándose el SARS-CoV-2 desde 2020. OBJETIVO: Identificar variables clínicas y de laboratorio asociadas a mortalidad a 30 días en NAC virales graves en un centro del sur de Chile. Metodología: Estudio observacional, se agruparon dos cohortes de pacientes con NAC grave según criterio IDSA/ATS (años 2013-2018, "No COVID-19") y año 2020 ("COVID-19"). Se recolectaron datos sociodemográficos, clínica, laboratorio y mortalidad a 30 días. Se utilizaron pruebas de Chi-cuadrado y Prueba t- student, para variables categóricas y continuas respectivamente. La mortalidad se evaluó mediante regresión logística binaria, con resultados reportados como Odd ratios (ORs). RESULTADOS: La mortalidad a 30 días fue: Hanta virus 54.5%, H1N1 36,8%, 30,4% otras influenza, 25% VRS y 23,6% para COVID-19. Sin diferencia significativa entre el tipo de virus (COVID-19 o NO COVID-19). La mortalidad se asoció con edad > 65 años (OR: 4,6; p 65 años, inmunosupresión, cianosis y uremia al ingreso se asociaron con mayor mortalidad a 30 días en los ingresos por NAC viral grave.

INTRODUCTION: Severe community-acquired pneumonia (CAP) due to respiratory viruses is highly prevalent in Chile. Common etiologies include Influenza A and B, respiratory syncytial virus (RSV), Hantavirus, and SARS-CoV-2 since 2020. OBJECTIVE: To identify clinical and laboratory features associated with 20-day mortality in severe viral CAP in a high complexity health care center in southern Chile. METHODS: The observational study included two cohorts of patients with severe CAP according to IDSA/ATS criteria: the years 2013-2018 (No COVID-19) and the year 2020 (COVID-19). Sociodemographic, clinical, laboratory, and 30-day mortality data were collected. We used Chi-square and Student's T for categorical and continuous variables. We used a binary logistic regression model for mortality analysis, reporting the results as Odd ratios (ORs). RESULTS: Mortality at 30 days was: Hantavirus 54.4%, Influenza H1N1 36.8%, other influenza 30.4%, RSV 25%, and COVID-19 23.6%. We found no significant difference regarding type of virus (COVID-19 or NO COVID-19). Mortality was associated with older age (OR: 4.6; p-value < 0.01), immunosuppression (OR: 5.8; p-value 0.01), and cyanosis (OR: 3.8, p-value 0.02). Conclusion: COVID-19 was not associated with an increased risk of 30-day mortality compared to other common respiratory viruses in our study. Older age, immunosuppression, and cyanosis were associated with higher risk among patients with severe viral CAP.

The U-Shaped Relationship Between Eosinophil Count and Bronchiectasis Severity: The Effect of Inhaled Corticosteroids.

BACKGROUND: Although a proven relationship exists between the blood eosinophil count (BEC) and the severity of both asthma and COPD, its relationship with bronchiectasis has not been well established. The objective of this study was to analyze the relationship between BEC and the number and severity of exacerbations, and patients' responses to inhaled corticosteroid (IC) treatment in bronchiectasis RESEARCH QUESTION: Does an association exist among BEC, the number of exacerbations and severity of bronchiectasis, and IC treatment? STUDY DESIGN AND METHODS: This was a multicenter (43 centers) prospective observational study derived from the Spanish Bronchiectasis Registry. Patients with proven bronchiectasis and a known BEC were included, whereas those with asthma or antieosinophilic treatments were excluded. Patients were divided into four groups according to the BEC at the time of inclusion in the study in a steady-state situation: (1) eosinopenic bronchiectasis (< 50 eosinophils/µL), (2) low number of eosinophils (51-100/µL), (3) normal number of eosinophils (101-300/µL), and (4) eosinophilic bronchiectasis (> 300 eosinophils/µL). RESULTS: Nine hundred twenty-eight patients finally were included: 123 patients (13.3%) with < 50 eosinophils/µL (eosinopenic group), 164 patients (17.7%) with 50-100 eosinophils/µL, 488 patients (52.6%) with 101-300 eosinophils/µL, and 153 patients (16.5%) with > 300 eosinophils/µL (eosinophilic group). BEC showed a significant U-shaped relationship with severity, exacerbations, lung function, microbiologic profile, and IC treatment (these being higher in the eosinopenic group compared with the eosinophilic group). IC treatment significantly decreased the number and severity of exacerbations only in the group of bronchiectasis patients with > 300 eosinophils/µL. INTERPRETATION: A significant U-shaped relationship was found between BEC and severity and exacerbations in bronchiectasis that was more pronounced in the eosinopenic group. IC treatment decreased the number and severity of exacerbations only in the eosinophilic group.

Robotic-assisted bronchoscopy versus CT-guided transthoracic biopsy for diagnosis of pulmonary nodules.

BACKGROUND AND OBJECTIVE: Currently, computed tomography-guided transthoracic biopsy (CTTB) is the most accurate diagnostic approach for pulmonary nodules suspected of malignancy. Traditional bronchoscopy has shown suboptimal diagnostic sensitivity, but the emergence of robotic-assisted bronchoscopy (RAB) has the potential to improve diagnostic accuracy, maximize diagnostic yield and complete mediastinal and hilar staging in a single procedure. We aim to assess the efficacy and diagnostic performance of RAB compared to CTTB for diagnosing pulmonary nodules suspected of lung cancer. METHODS: A multicenter retrospective review of consecutive patients who underwent RAB and CTTB for evaluating pulmonary nodules from January 2019 to March 2021 at Mayo Clinic Florida and Mayo Clinic Rochester, United States. Clinical and demographic information, nodule characteristics, outcomes and complications were compared between RAB and CTTB. RESULTS: A total of 225 patients were included: 113 in the RAB group and 112 in the CTTB group. Overall diagnostic yield was 87.6% for RAB and 88.4% for CTTB. For malignant disease, RAB had a sensitivity of 82.1% and a specificity of 100%, CTTB had a sensitivity of 88.5% and a specificity of 100%. Complication rate was significantly higher for CTTB compared to RAB (17% vs. 4.4%; p = 0.002). CONCLUSION: RAB, when available, can be as accurate as CTTB for sampling pulmonary nodules with similar or reduced complications and should be considered as a means for nodule biopsy, particularly when mediastinal staging is also clinically warranted.

One Year Overview and Follow-Up in a Post-COVID Consultation of Critically Ill Patients.

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.

Evaluación de la salud sexual, mental y sueño en hombres chilenos posterior a infección por SARS-CoV-2 / Sexual, physical, mental and sleep sequelae four months after SARS-CoV-2 disease

BACKGROUND: Long term sequelae can be observed after SARS-CoV2. AIM: To describe the sexual, physical, mental and sleep sequelae four months after SARS-CoV2 diagnosis. PATIENTS AND METHODS: Patients recovering from SARS-CoV2 with different degrees of disease severity were consecutively included and separated in two study groups, namely Group 1 including patients that had an acute respiratory distress syndrome (ARDS) and Group 2 including those with mild or moderate COVID-19. Handgrip strength, respiratory polygraphy (RP), Quality of life using the SF-12 questionnaire, and the international index of erectile (IIEF-5) function were assessed. RESULTS: Twenty patients who had ARDS, and 10 without ARDS were included. Erectile dysfunction was observed in 77 and 10% of patients with and without ARDS, respectively (p < 0.01). The figures for sleep obstructive apnea were 82 and 40% respectively (p = 0.02) and for the physical domain SF-12 score were 39.2 and 47.9 points respectively (p = 0.01). No differences in muscle strength were observed. After a multivariable analysis, previous ARDS due to COVID-19 was independently associated with erectile dysfunction, with an odds ratio of 30.6 (95% confidence intervals, 3.08300.3, p = 0.003). CONCLUSIONS: Among men with ARDS due to COVID-19, the prevalence of erectile dysfunction was high and independently associated with a severe disease four months after discharge.

Sleep health and the circadian rest-activity pattern four months after COVID-19 / Saúde do sono e o padrão circadiano de atividade e repouso quatro meses depois da COVID-19

ABSTRACT 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.

RESUMO Objetivo: Descrever a prevalência e gravidade de transtornos do sono e alterações circadianas em pacientes com COVID-19 quatro meses depois da fase aguda da doença. Métodos: Estudo prospectivo observacional transversal com pacientes com COVID-19 leve, moderada (com necessidade de hospitalização, mas não de ventilação mecânica) ou grave (com SDRA) quatro meses depois da fase aguda da doença. Todos os pacientes foram submetidos a teste domiciliar de apneia do sono e actigrafia de sete dias, além de terem preenchido questionários para avaliar a qualidade do sono e a saúde mental. As diferenças entre os três grupos foram avaliadas por meio de ANOVA e teste do qui-quadrado. Resultados: Foram incluídos no estudo 60 pacientes. Destes, 17 eram do grupo COVID-19 leve, 18 do grupo COVID-19 moderada e 25 do grupo COVID-19 grave. A qualidade do sono, avaliada pela pontuação na escala satisfaction, alertness, timing, efficiency, and duration, foi prejudicada nos três grupos, que também apresentaram alta prevalência de sono não saudável, pelo Índice de Qualidade do Sono de Pittsburgh. A prevalência de insônia, avaliada pelo Insomnia Severity Index, foi elevada nos três grupos. O teste domiciliar de apneia do sono mostrou que a prevalência geral de apneia obstrutiva do sono foi de 60%, e a actigrafia de sete dias mostrou que o tempo total de sono foi < 7 h nos três grupos. Alterações da qualidade de vida e do padrão circadiano de atividade e repouso foram observadas nos três grupos. Conclusões: Sintomas relacionados ao sono, alterações do padrão circadiano de atividade e repouso e comprometimento da saúde mental parecem ser comuns em pacientes com COVID-19 quatro meses depois da fase aguda da doença, sendo a COVID-19 grave associada a uma maior prevalência de apneia obstrutiva do sono.

Asociación e interacciones de la apnea obstructiva del sueño (AOS) y del síndrome de hipoventilación obesidad (SHO) / Metabolic associations of the obstructive sleep apnea (AOS) and hypoventilation obesity syndrome

La apnea obstructiva del sueño (AOS) y el síndrome hipoventilación-obesidad (SHO) son patologías que se encuentran estrechamente asociadas a la obesidad como principal factor de riesgo, hasta un 70% de los pacientes con AOS son obesos. Ambas patologías comparten procesos fisiopatológicos comunes, donde destaca la inflamación sistémica, lo que, sumado a la hipoxia crónica intermitente y la fragmentación del sueño característicos de la AOS, aumenta considerablemente el riesgo de presentar comorbilidades metabólicas como síndrome metabólico, alteraciones en el metabolismo de la glucosa (resistencia a la insulina y diabetes mellitus tipo 2), y hígado graso metabólico. En esta revisión narrativa, se describirán los mecanismos identificados en estas asociaciones, así como la prevalencia y la evidencia sobre el tratamiento de la AOS y del SHO

Obstructive sleep apnea (OSA) and obesity-hypoventilation syndrome (OHS) are pathologies that are closely associated with obesity as the main risk factor, up to 70% of patients with OSA are obese. Both pathologies share common pathophysiological processes, where systemic inflammation stands out, which, added to the intermittent chronic hypoxia and sleep fragmentation characteristic of OSA, considerably increases the risk of presenting metabolic comorbidities such as metabolic syndrome, alterations in the metabolism of the glucose (insulin resistance and type 2 diabetes mellitus), and metabolic fatty liver. In this narrative review, the mechanisms identified in these associations will be described, as well as the prevalence and evidence on the treatment of OSA and OHS

Comparing diagnostic sensitivity of different needle sizes for lymph nodes suspected of lung cancer in endobronchial ultrasound transbronchial needle aspiration: Systematic review and meta-analysis.

BACKGROUND: Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is a safe and minimally invasive procedure for evaluating hilar and mediastinal lymph nodes. The reported sensitivity and specificity of EBUS-TBNA are 95% and 97%, respectively. A comparison of diagnostic sensitivity for lymph nodes suspected of lung cancer according to needle size in EBUS-TBNA is needed. OBJECTIVES: To compare the diagnostic sensitivity of the 19-G, 21-G, 22-G and 25-G needles for lymph nodes suspected of non-small cell lung cancer (NSCLC) using EBUS-TBNA. METHODS: A literature search from PubMed, EMBASE, LILACS, DOAJ and CENTRAL through October 2020 was performed by two reviewers. The extracted data were evaluated using STATA® and Open Meta Analyst software for meta-analysis with a binary method model to compare sensitivity, specificity and summary receiver operating characteristic curve for each needle size. RESULTS: Fourteen studies including 1296 participants were considered for the analysis. The overall sensitivity of EBUS-TBNA was 88.2% (95% CI 84%, 91%) and 93% (95% CI 88%, 95%) for the 19-G needle, 87.6% (95% CI 79.6%, 92.8%) for the 21-G needle and 85% (95% CI 80%, 88%) for the 22-G needle. The overall sensitivity of EBUS-TBNA for diagnosing NSCLC was 88.3% (95% CI, 81%, 93%) and 92.9% (95% CI, 85%, 97%) for the 19-G needle, 89.4% (95% CI 79.4%, 94.8%) for the 21-G needle and 82.1% (95% CI 66%, 91%) for the 22-G needle. CONCLUSION: The 19-G, 21-G and 22-G needles present a similarly high diagnostic sensitivity in EBUS-TBNA. The 19-G needle provided better sample adequacy for molecular and immunohistochemical testing, improving diagnostic yield in this subgroup.

Risk of complications rise with coronary artery disease and diabetes mellitus after endobronchial valve placement in severe heterogeneous emphysema.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) commonly have comorbidities which may impact both symptoms and prognosis. Endoscopic lung volume reduction (ELVR) with endobronchial valves (EBV) is an innovative, effective and safe treatment for patients with severe emphysema who remain symptomatic despite optimal medical therapy. OBJECTIVES: To evaluate medical comorbidities associated with increased risk of complications after EBV procedure. METHOD: This was a retrospective cohort review of patients with severe, heterogeneous emphysema who underwent Zephyr® EBV installation for ELVR. Demographics, baseline comorbidities, dyspnea scores, data regarding procedure, pulmonary function test, minimal clinically important difference and post-EBV complications were recorded. RESULTS: Of a total 82 participants, 24 were identified as having a post procedure complication. There was a significant difference in the incidence of type 2 diabetes mellitus (T2DM) at baseline (25%) in complication group compared with non-complication group (5.1%) (p value = 0.01). There was also a significant difference between baseline coronary artery disease (CAD) in those with (58.3%) or without (29.3%) complication (p = 0.01). Multivariate analysis of other covariables, identified associations of both CAD and T2DM with a heightened risk of complication (adjusted OR 4.19 CI: 1.23-14.2, p value = 0.02 and adjusted OR of 6.1 CI: 1.3-26.1, p value = 0.02 respectively). CONCLUSIONS: Our study found that patients with severe, heterogeneous emphysema who undergo ELVR utilizing Zephyr® EBV and suffer complications during post-procedure period are more likely to have CAD or T2DM as baseline comorbidity. These data suggest that baseline CAD and T2DM might be predictive of increased risk of complications following ELVR with EBV.

Immunomodulation of T Helper Cells by Tumor Microenvironment in Oral Cancer Is Associated With CCR8 Expression and Rapid Membrane Vitamin D Signaling Pathway.

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.

Takayasu's arteritis and secondary membranous nephropathy: an exceptional association.

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.

Hipovitaminosis D en población portadora de enfermedad inflamatoria intestinal del Sur de Chile / Vitamin D levels in patients with inflammatory bowel disease

Background: Inflammatory Bowell Diseases (IBD), either ulcerative colitis (UC) or Chron's disease (CD) are commonly associated with intestinal malabsorption, and insufficient levels 1-25 hydroxycholecalciferol (vitamin D). These insufficient levels could be linked with an increased risk of clinical disease activity. Aim: To report vitamin D levels in patients with IBD living in Southern Chile and their possible association with clinical disease activity. Material and Methods: A prospective, observational study in outpatients with IBD living in Los Angeles, Chile. Demographic data and clinical activity using clinical scores were recorded. Vitamin D levels and fecal calprotectin were measured. Results: We studied 44 patients, 32 (73%) with UC and 12 (27%) with CD. The median age at diagnosis was 33 years old. Forty-one (93%) had mild-inactive disease and 3 (7%) a moderate disease. Mean vitamin D levels were 15.2 ± 7.1 ng/ml. Twenty five percent of patients had sufficient levels (> 20 ng/ml), 35% insufficient levels and 40% poor levels. No association between these levels and disease activity was found. Conclusions: These patients with IBD had a high frequency of hypovitaminosis D.

Hypoxemic features of obstructive sleep apnea and the risk of mortality: a cluster analysis.

INTRODUCTION: Patients with moderate to severe obstructive sleep apnea (OSA) have an increased risk of cardiovascular comorbidities and mortality. Although different subtypes of OSA have been described, data about oximetric parameters and their suitability to identify a different phenotype are scant. In this study, we evaluate the association between moderate to severe OSA and oximetric parameters included in the home sleep apnea test (HSAT) and the risks of all-cause mortality, cardiovascular mortality, and cancer mortality. METHODS: Adult patients with moderate to severe OSA from a clinical cohort in Chile were included (SantOSA study). We developed a latent class analysis (LCA) incorporating oximetric measures commonly reported on HSAT. Differences between the groups were evaluated using ANOVA and the chi-squared test. Survival curves were constructed using a Kaplan-Meier (log-rank) model, and adjusted hazard ratios of mortality were calculated using a Cox regression model following a confounder analysis of cardiovascular comorbidities. RESULTS: A total of 889 patients were included in the analysis. LCA identified three different clusters: Cluster 1, "nonhypoxemic" (n = 591); cluster 2, "moderately hypoxemic" (n = 297); and cluster 3, "severely hypoxemic" (n = 115). The mean follow-up was 4.7 years. The hypoxemic groups showed an increased risk of cardiometabolic comorbidities and an independent risk of all-cause mortality (adjusted HR 1.67 (CI 1.0-2.64) p value = 0.027). The moderately hypoxemic group had an adjusted HR of 2.92 (CI 1.00-8.58), p value = 0.05, while the severely hypoxemic group had an adjusted HR of 2.55 (CI 1.08-6.02), p value = 0.031. For cardiovascular mortality, we found an HR of 2.03 (CI 0.50-8.136), p value = 0.31, and for cancer mortality, we found an HR of 5.75 (CI 1.03-32.17), p value = 0.042. CONCLUSION: Oximetric parameters are useful for describing a different phenotype with a high risk of mortality among patients with moderate to severe OSA, beyond the apnea-hypopnea index.

Clinical characteristics and predictors of hospitalization among 7, 108 ambulatory patients with positive RT-PCR for SARS-CoV-2 during the acute pandemic period / Características clínicas e preditores de hospitalização entre 7. 108 pacientes ambulatoriais com RT-PCR positivo para SARS-CoV-2 durante o período de pandemia aguda

ABSTRACT 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.

RESUMO Objetivo: Descrever as características basais de pacientes ambulatoriais com RT-PCR positivo para SARS-CoV-2 e definir se os sintomas de alerta para gravidade (febre, dispneia e dor torácica de início recente) podem prever piora clínica durante o período de isolamento. Métodos: Trata-se de um estudo epidemiológico, observacional e descritivo. Entre março e setembro de 2020, foram incluídos todos os pacientes ambulatoriais com teste positivo para SARS-CoV-2 em um centro médico terciário localizado em Santiago do Chile. Variáveis demográficas, comorbidades, sintomas de alerta para gravidade e outros sintomas foram compilados usando pesquisas de seguimento em intervalos específicos. Também foram calculados o risco de piora clínica (hospitalização) e as razões de risco (RR) ajustadas. Resultados: Foi incluído um total de 7.108 pacientes. A mediana de idade foi de 38 anos (variação: 0-101), e 52% eram homens. No início do estudo, 77% dos pacientes relataram sintomas característicos de infecção por SARS-CoV-2. Os sintomas recentes mais prevalentes foram cefaleia (53%), mialgia (47%) e febre (33%). De acordo com as pesquisas de seguimento, a incidência de sintomas diminuiu durante o período de isolamento; no entanto, 28% dos pacientes ainda apresentavam sintomas no dia 14. O risco de hospitalização para pacientes com febre e dispneia de início recente durante o período de seguimento foi RR = 7,43 (IC95%: 3,85-14,3; p < 0,01) e RR = 5,27 (IC95%: 1,52-18,30; p < 0,01 para ambos), respectivamente. A dor torácica de início recente não mostrou associação com a piora clínica. Conclusões: Nesta amostra de pacientes ambulatoriais com um diagnóstico recente de infecção por SARS-CoV-2, um monitoramento dos sintomas baseado em pesquisa foi útil para identificar aqueles com risco de piora clínica. Febre e dispneia de início recente durante o período de isolamento foram consideradas sintomas de alerta associados ao agravamento clínico e justificam avaliação médica imediata.

Association between cardiovascular mortality and STOP-Bang questionnaire scores in a cohort of hospitalized patients: a prospective study / Associação entre mortalidade cardiovascular e pontuação do questionário STOP-Bang em uma coorte de pacientes hospitalizados: um estudo prospectivo

ABSTRACT 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.

RESUMO Objetivo: A apneia obstrutiva do sono (AOS) está associada a um risco maior de mortalidade e doenças cardiometabólicas. O questionário STOP-Bang é uma ferramenta para rastrear populações em risco de AOS e assim priorizar estudos complementares. Nosso objetivo foi avaliar a utilidade clínica desse questionário na identificação de pacientes com risco aumentado de mortalidade após a alta em uma coorte de pacientes hospitalizados. Métodos: Estudo de coorte prospectivo com pacientes consecutivos internados em uma unidade de medicina interna entre maio e junho de 2017 que foram reavaliados três anos após a alta. No momento basal, coletamos dados sobre comorbidades (hipertensão, obesidade, diabetes e perfil lipídico em jejum) e calculamos as pontuações no STOP-Bang, definindo o risco de OSA (pontuação 0-2, sem risco; pontuação ≥ 3, risco de AOS; e pontuação ≥ 5, risco de AOS moderada a grave), que determinou os grupos de estudo. Também registramos dados sobre mortalidade por todas as causas e mortalidade cardiovascular ao final do período de acompanhamento. Resultados: Foram incluídos 435 pacientes. Desses, 352 (80,9%) e 182 (41,8%) apresentaram pontuações no STOP-Bang ≥ 3 e ≥ 5, respectivamente. Quando comparados com o grupo com pontuação no STOP-Bang de 0-2, os outros dois grupos apresentaram prevalências mais elevadas de obesidade, hipertensão, diabetes e dislipidemia. A análise multivariada mostrou uma associação independente entre mortalidade cardiovascular e pontuação no STOP-Bang ≥ 5 (razão de risco ajustada = 3,12 [IC95%, 1,39-7,03]; p = 0,01). Além disso, doença coronariana prévia também foi associada à mortalidade cardiovascular. Conclusões: Nesta coorte de pacientes hospitalizados, pontuações no STOP-Bang ≥ 5 foram capazes de identificar pacientes com risco aumentado de mortalidade cardiovascular três anos após a alta.

Endoscopic Lung Volume Reduction in Relation to Body Mass Index in Patients with Severe Heterogeneous Emphysema.

BACKGROUND: In chronic obstructive pulmonary disease (COPD), body mass index (BMI) is significantly lower in the emphysema-dominant type. Endoscopic lung volume reduction (ELVR) is an innovative way of treating severe emphysema. However, the specific associations of low BMI values and outcomes of ELVR is not well-studied. OBJECTIVES: We evaluated associations between initial BMI and changes in major outcomes after endobronchial valve (EBV) placement in patients with heterogeneous severe emphysema. METHODS: In a retrospective cohort study, patients were divided into 2 groups based on their baseline BMI (higher BMI ≥21 kg/m2 [n = 18] and lower BMI <21 kg/m2 [n = 63]). Demographics, procedure data, pulmonary function test and 6-min-walk test (6MWT), dyspnea score (according to the modified Medical Research Council [mMRC] scale), BODE (BMI, airflow obstruction, dyspnea, exercise capacity) index, and complications were recorded. After 6 months, changes in variables (dWeight and dBMI) were recorded. RESULTS: Comparing the 2 groups, we found the following: a dWeight of -2.34 kg and +3.39 kg (p value <0.01) and a dBMI of -0.74 and +1.99 kg/m2, in the higher BMI and lower BMI group, respectively (p value <0.01). Changes in forced expiratory volume <1 s (FEV1), 6MWT, mMRC score, and BODE index were not statistically significant. The most common complication was pneumothorax. The lower BMI group experienced more complications than the higher BMI group (40 vs. 24%). CONCLUSION: Baseline BMI is relevant when selecting candidates for ELVR. Our results show that the COPD patients with a lower BMI gained a significant amount of weight, thus increasing their BMI after the procedure. The rate of complications was higher in the lower BMI group. These findings should alert physicians and encourage nutritional assessment in this population.

Sensitivity and Safety of Electromagnetic Navigation Bronchoscopy for Lung Cancer Diagnosis: Systematic Review and Meta-analysis.

BACKGROUND: Bronchoscopy is a useful tool for the diagnosis of lesions near central airways; however, the diagnostic accuracy of these procedures for peripheral pulmonary lesions (PPLs) is a matter of ongoing debate. In this setting, electromagnetic navigation bronchoscopy (ENB) is a technique used to navigate and obtain samples from these lesions. This systematic review and meta-analysis aims to explore the sensitivity of ENB in patients with PPLs suspected of lung cancer. RESEARCH QUESTION: In patients with peripheral pulmonary lesion suspected of lung cancer, what is the sensitivity and safety of electromagnetic navigation bronchoscopy compared to surgery or longitudinal follow up? STUDY DESIGN AND METHODS: A comprehensive search of several databases was performed. Extracted data included sensitivity of ENB for malignancy, adequacy of the tissue sample, and complications. The study quality was assessed using the QUADAS-2 tool, and the combined data were meta-analyzed using a bivariate method model. A summary receiver operatic characteristic curve (sROC) was created. Finally, the quality of evidence was rated using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Forty studies with a total of 3,342 participants were included in our analysis. ENB reported a pooled sensitivity of 77% (95% CI, 72%-82%; I2 = 80.6%) and a specificity of 100% (95% CI, 99%-100%; I2 = 0%) for malignancy. The sROC showed an area under the curve of 0.955 (P = .03). ENB achieved a sufficient sample for ancillary tests in 90.9% (95% CI, 84.8%-96.9%; I2 = 80.7%). Risk of pneumothorax was 2.0% (95% CI, 1.0-3.0; I2 = 45.2%). We found subgroup differences according to the risk of bias and the number of sampling techniques. Meta-regression showed an association between sensitivity and the mean distance of the sensor tip to the center of the nodule, the number of tissue sampling techniques, and the cancer prevalence in the study. INTERPRETATION: ENB is very safe with good sensitivity for diagnosing malignancy in patients with PPLs. The applicability of our findings is limited because most studies were done with the superDimension navigation system and heterogeneity was high. TRIAL REGISTRY: PROSPERO; No.: CRD42019109449; URL: https://www.crd.york.ac.uk/prospero/.