Obstructive sleep apnoea is related to melanoma aggressiveness through paraspeckle protein-1 upregulation.

BACKGROUND: In patients with obstructive sleep apnoea (OSA), intermittent hypoxia induces overexpression of paraspeckle component (PSPC)1, a master modulator of transforming growth factor (TGF)-ß signalling, which promotes cell cancer progression through epithelial-mesenchymal transition (EMT) and acquisition of cancer stem cell (CSC)-like features. However, the persistence of intermittent hypoxia-induced effects on PSPC1, and their consequences in cancer patients are not known. To this effect, circulating PSPC1 levels were compared in patients with cutaneous melanoma with or without OSA, and their relationship with tumour aggressiveness along with the in vitro effects of soluble PSPC1 and intermittent hypoxia on melanoma cell aggressiveness mechanisms were assessed. METHODS: In 292 cutaneous melanoma patients, sleep studies and serum levels of PSPC1 and TGF-ß were evaluated. The effect of PSPC1 on expression of EMT and CSC transcription factors was assessed using melanoma cell lines with patient sera under both normoxia and intermittent hypoxia conditions. RESULTS: PSPC1 levels were higher in patients with moderate-severe OSA compared with mild OSA or non-OSA patients. Serum levels of PSPC1 were associated with several cutaneous melanoma clinical aggressiveness indicators. Both intermittent hypoxia exposures and serum from OSA patients upregulated TGF-ß expression and amplified the expression of transcription factors associated with EMT activation and acquisition of CSC characteristics. CONCLUSION: In cutaneous melanoma patients, OSA severity is associated with higher PSPC1 serum levels, which jointly with intermittent hypoxia would enhance the self-reprogramming capabilities of EMT and CSC feature acquisition of melanoma cells, promoting their intrinsic aggressiveness.

Residual pulmonary infiltrates, symptoms and diffusion impairment at 1-year after severe COVID-19 infection have different associated factors.

INTRODUCTION: After severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia, patients may show lung sequelae on radiology and functional impairment at the 1-year follow-up. We aimed to describe the persistence of symptoms, radiological alterations, or reduced diffusing capacity of the lung for carbon monoxide (DLCO ) at 1-year follow-up in patients from the Spanish Registry RECOVID. METHODS: RECOVID collected symptom and radiological and functional lung tests data on hospitalized patients with coronavirus disease 2019 during the acute phase and at the 6- and 12-month follow-up visits. RESULTS: Of the 2500 enrolled survivors (90% admitted to the ward), 1874 had follow-up visits for up to a year. Of these, 42% continued to present with symptoms, 27% had radiological sequelae and 31% had reduced DLCO . Independently associated factors included female sex, asthma and the requirement for invasive or non-invasive mechanical ventilation. Complete radiological resolution was 72.2% at 12 months; associated factors with incomplete recovery were age, male sex, oxygen or respiratory support, corticosteroids and an initial SpO2 /FiO2 <450 or CURB-65 ≥2. Reduced DLCO was observed in 31% of patients at 12 months; associated factors were older age, female sex, smoking habit, SpO2 /FiO2 <450 and CURB-65 ≥2 and the requirement of respiratory support.At 12 months, a proportion of the asymptomatic patients showed reduced DLCO (9.5%), radiological findings (25%) or both (11%). CONCLUSIONS: The factors associated with symptom persistence, incomplete radiological resolution and DLCO <80% differed according to age, sex, comorbidities and respiratory support. The burden of symptoms, reduced DLCO and incomplete radiological resolution were considerable in patients with SARS-CoV-2 pneumonia at the 1-year follow-up after hospitalisation.

SMAD4 Expression in Monocytes as a Potential Biomarker for Atherosclerosis Risk in Patients with Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) patients are at special risk of suffering atherosclerosis, leading to major cardiovascular diseases. Notably, the transforming growth factor (TGF-ß) plays a crucial role in the development and progression of atherosclerosis. In this context, the central regulator of TGF-ß pathway, SMAD4 (small mother against decapentaplegic homolog 4), has been previously reported to be augmented in OSA patients, which levels were even higher in patients with concomitant cardiometabolic diseases. Here, we analyzed soluble and intracellular SMAD4 levels in plasma and monocytes from OSA patients and non-apneic subjects, with or without early subclinical atherosclerosis (eSA). In addition, we used in vitro and ex vivo models to explore the mechanisms underlying SMAD4 upregulation and release. Our study confirmed elevated sSMAD4 levels in OSA patients and identified that its levels were even higher in those OSA patients with eSA. Moreover, we demonstrated that SMAD4 is overexpressed in OSA monocytes and that intermittent hypoxia contributes to SMAD4 upregulation and release in a process mediated by NLRP3. In conclusion, this study highlights the potential role of sSMAD4 as a biomarker for atherosclerosis risk in OSA patients and provides new insights into the mechanisms underlying its upregulation and release to the extracellular space.

Proangiogenic factor midkine is increased in melanoma patients with sleep apnea and induces tumor cell proliferation.

Midkine (MDK) might mediate the proangiogenic effect of intermittent hypoxia (IH) in patients with obstructive sleep apnea (OSA) and cutaneous melanoma (CM). We compare circulating MDK in CM patients with and without OSA, and their relationship with tumor aggressiveness, while exploring in vitro effects of soluble MDK on human lymphatic endothelial (HLEC) and melanoma cell proliferation. In 360 CM patients, sleep studies and MDK serum level measurements were performed. The effect of MDK on cell proliferation was assessed using HLEC and melanoma cell lines with patient sera under both normoxia and IH. MDK levels were higher in severe OSA compared to mild OSA or non-OSA patients, whereas no differences in VEGF levels emerged. In OSA patients, MDK levels correlated with nocturnal hypoxemia and CM mitotic rate. In vitro, MDK promotes HLEC proliferation under IH conditions. Moreover, cultures of the human melanoma cell line C81-61 with sera from patients with the highest MDK levels promoted tumor cell proliferation, which was attenuated after the addition of MDK antibody. These responses were enhanced by IH exposures. In conclusion, in CM patients, OSA severity is associated with higher MDK levels, which, appear to enhance both the lymphangiogenesis as the intrinsic aggressiveness of CM tumor cells.

Soluble PD-L1 is a potential biomarker of cutaneous melanoma aggressiveness and metastasis in obstructive sleep apnoea patients.

Obstructive sleep apnoea (OSA) upregulates the programmed cell death-1 receptor and its ligand (PD-L1) pathway, potentially compromising immunosurveillance. We compared circulating levels of soluble PD-L1 (sPD-L1) in patients with cutaneous melanoma according to the presence and severity of OSA, and evaluated relationships with tumour aggressiveness and invasiveness.In a multicentre observational study, 360 patients with cutaneous melanoma underwent sleep studies, and serum sPD-L1 levels were assayed using ELISA. Cutaneous melanoma aggressiveness indices included mitotic rate, Breslow index, tumour ulceration, Clark level and tumour stage, and sentinel lymph node (SLN) metastasis was recorded as a marker of invasiveness.sPD-L1 levels were higher in severe OSA compared to mild OSA or non-OSA patients. In OSA patients, sPD-L1 levels correlated with Breslow index and were higher in patients with tumour ulceration, advanced primary tumour stages or with locoregional disease. The incorporation of sPD-L1 to the classic risk factors to SLN metastasis led to net improvements in the classification of 27.3%.Thus, sPD-L1 levels are increased in melanoma patients with severe OSA, and, in addition, might serve as a potential biomarker of cutaneous melanoma aggressiveness and invasiveness in this group of subjects.

Biomarkers of carcinogenesis and tumour growth in patients with cutaneous melanoma and obstructive sleep apnoea.

The goal of this study was to assess the relationship between the severity of obstructive sleep apnoea (OSA) and the levels of carcinogenesis- and tumour growth-related biomarkers in patients with cutaneous melanoma.This multicentre observational study included patients who were newly diagnosed with melanoma. The patients were classified as non-OSA (apnoea-hypopnoea index (AHI) 0-5 events·h-1), mild OSA (AHI 5-15 events·h-1) and moderate-severe OSA (AHI >15 events·h-1). ELISAs were performed to analyse the serum levels of hypoxia- and tumour adhesion-related biomarkers (vascular endothelial growth factor (VEGF), interleukin (IL)-8, intracellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM)-1) and markers of tumour aggressiveness (S100 calcium-binding protein B (S100B) and melanoma inhibitory activity (MIA)). A logistic model adjusted for age, sex and body mass index was fitted to each biomarker, and the AHI served as the dependent variable.360 patients were included (52.2% male, median (interquartile range) age 55.5 (43.8-68.0) years and AHI 8.55 (2.8-19.5) events·h-1). The levels of VEGF, IL-8, ICAM-1, S100B and MIA were not related to the severity of OSA. The levels of VCAM-1 were higher in patients with OSA than those without OSA (mild OSA: odds ratio (OR) 2.07, p=0.021; moderate-severe OSA: OR 2.35, p=0.013).In patients with cutaneous melanoma, OSA was associated with elevated circulating levels of VCAM-1 that could indicate the contribution of OSA in tumorigenesis via integrin-based adhesion.

Dysregulation in CD39/CD73 Axis May Trigger the Upsurge of the Immune Suppressive Agent Adenosine in OSA Patients.

INTRODUCTION: Although higher incidence of cancer represents a major burden for obstructive sleep apnea (OSA) patients, the molecular pathways driving this association are not completely understood. Interestingly, adenosinergic signaling has emerged as a powerful immune checkpoint driving tumor development and progression. METHODS: Here, we explored the expression of the adenosinergic ecto-enzymes CD39 and CD73 in T-lymphocytes of OSA patients without any evidence of cancer, as well as their soluble forms in plasma (sCD39 and sCD73), along with adenosine. In addition, we explored the role of intermittent hypoxia (IH) in this context by in vitro models. RESULTS: Our results showed that CD39 is upregulated while CD73 is downregulated in OSA T-cells' membrane. Moreover, our findings suggest that IH, through HIF-1, mediates the upregulation of both CD39 and CD73; and that CD73 downregulation could be mediated by a higher release of sCD73 by OSA T-lymphocytes. Importantly, we found that both sCD39 and sCD73 are upregulated in OSA plasma, suggesting T-lymphocytes as a potential source for plasmatic sCD73. Finally, our data propose the alterations in CD39/CD73 axis could underlie the upsurge of adenosine levels in the plasma of OSA patients. CONCLUSION: Our study reveals a hypoxia-mediated alteration of the CD39/CD73 axis in OSA patients, which could trigger ADO upregulation, thus potentially contributing to the immune suppressive environment and ultimately facilitating tumor development and progression. Therefore, our data highlights the need for new longitudinal studies evaluating CD39 and/or CD73 as potential cancer-risk prognostic biomarkers in OSA patients.

[Home Respiratory Therapies: SEPAR Technical Document for Institutional Decision Support]. / Terapias respiratorias domiciliarias: documento técnico de la Sociedad Española de Neumología y Cirugía Torácica (SEPAR) de apoyo institucional a la toma de decisiones.

Home Respiratory Therapies (HRT) encompass a variety of treatments for patients with chronic respiratory diseases, administered at home over extended periods. The Service Providers of HRT (SPHRT) collaborate with hospital resources to address chronic respiratory diseases, acting as strategic partners. The contracting of HRT in the public health system involves contests where the SPHRT present technical and economic offers. The purpose of this document is to provide a technical basis that can assist professionals, SPHRT, and the administration in making decisions when calling for, evaluating, and deciding on such contests.

Nocturnal hypoxemia and prognosis in patients with acute symptomatic pulmonary embolism.

BACKGROUND: Nocturnal hypoxemia has been associated with cardiovascular and non-cardiovascular morbidity and mortality. This study aimed to investigate the prognostic value of nocturnal hypoxemia among patients with hemodynamically stable acute symptomatic pulmonary embolism (PE). METHODS: We performed an ad hoc secondary analysis of clinical data from a prospective cohort study. Nocturnal hypoxemia was measured by the percent sleep registry with oxygen saturation <90% [TSat90]). Outcomes assessed over the 30-days after the diagnosis of PE included PE-related death, other cardiovascular deaths, clinical deterioration requiring an escalation of treatment, recurrent venous thromboembolism (VTE), acute myocardial infarction [AMI], or stroke. RESULTS: Of the 221 hemodynamically stable patients with acute PE from which the TSat90 could be calculated and did not receive supplemental oxygen, the primary outcome occurred in 11 (5.0%; 95% confidence interval [CI], 2.5% to 8.7%) within 30-days after the diagnosis of PE. When categorized by quartiles, TSat90 was not significantly associated with the occurrence of the primary outcome in unadjusted Cox regression analysis (hazard ratio, 0.96; 95% CI, 0.57 to 1.63; P = 0.88), or after adjustment for body mass index (adjusted hazard ratio, 0.97; 95% CI, 0.57 to 1.65; P = 0.92). When examined as a completely continuous variable (between 0 and 100), TSat90 was not associated with a significant increase in the adjusted hazard of 30-day primary outcome rates (hazard ratio, 0.97; 95% CI, 0.86 to 1.10; P = 0.66). CONCLUSIONS: In this study, nocturnal hypoxemia did not identify stable patients with acute symptomatic PE at increased risk for adverse cardiovascular events.

Diagnosis and Treatment of Sleep Apnea in Children: A Future Perspective Is Needed.

Obstructive sleep apnea (OSA) in children is a prevalent, but still, today, underdiagnosed illness, which consists of repetitive episodes of upper airway obstruction during sleep with important repercussions for sleep quality. OSA has relevant consequences in the pediatric population, mainly in the metabolic, cardiovascular (CV), and neurological spheres. However, contrary to adults, advances in diagnostic and therapeutic management have been scarce in the last few years despite the increasing scientific evidence of the deleterious consequences of pediatric OSA. The problem of underdiagnosis and the lack of response to treatment in some groups make an update to the management of OSA in children necessary. Probably, the heterogeneity of OSA is not well represented by the classical clinical presentation and severity parameters (apnea/hypopnea index (AHI)), and new strategies are required. A specific and consensus definition should be established. Additionally, the role of simplified methods in the diagnosis algorithm should be considered. Finally, the search for new biomarkers for risk stratification is needed in this population. In conclusion, new paradigms based on personalized medicine should be implemented in this population.

PSGL-1: a novel immune checkpoint driving T-cell dysfunction in obstructive sleep apnea.

Introduction: Although higher incidence of cancer represents a major burden for obstructive sleep apnea (OSA) patients, the molecular pathways driving this association are not completely understood. Recently, the adhesion receptor P-selectin glycoprotein-1 (PSGL 1) has been identified as a novel immune checkpoint, which are recognized major hallmarks in several types of cancer and have revolutionized cancer therapy. Methods: The expression of PSGL-1 and its ligands VISTA and SIGLEC-5 was assessed in the leucocytes of OSA patients and control subjects exploring the role of intermittent hypoxia (IH) using in vitro models. In addition, PSGL-1 impact on T-cells function was evaluated by ex vivo models. Results: Data showed PSGL-1 expression is upregulated in the T-lymphocytes from patients with severe OSA, indicating a relevant role of hypoxemia mediated by intermittent hypoxia. Besides, results suggest an inhibitory role of PSGL-1 on T-cell proliferation capacity. Finally, the expression of SIGLEC-5 but not VISTA was increased in monocytes from OSA patients, suggesting a regulatory role of intermittent hypoxia. Discussion: In conclusion, PSGL-1 might constitute an additional immune checkpoint leading to T-cell dysfunction in OSA patients, contributing to the disruption of immune surveillance, which might provide biological plausibility to the higher incidence and aggressiveness of several tumors in these patients.

Recommendations for clinical management of excessive daytime sleepiness in obstructive sleep apnoea - A Delphi consensus study.

STUDY OBJECTIVE: Excessive daytime sleepiness is common with obstructive sleep apnoea and can persist despite efforts to optimise primary airway therapy. The literature lacks recommendations regarding differential diagnosis and management of excessive daytime sleepiness in obstructive sleep apnoea. This study sought to develop expert consensus statements to bridge the gap between existing literature/guidelines and clinical practice. METHODS: A panel of 10 international experts was convened to undertake a modified Delphi process. Statements were developed based on available evidence identified through a scoping literature review, and expert opinion. Consensus was achieved through 3 rounds of iterative, blinded survey voting and revision to statements until a predetermined level of agreement was met (≥80 % voting "strongly agree" or "agree with reservation"). RESULTS: Consensus was achieved for 32 final statements. The panel agreed excessive daytime sleepiness is a patient-reported symptom. The importance of subjective/objective evaluation of excessive daytime sleepiness in the initial evaluation and serial management of obstructive sleep apnoea was recognised. The differential diagnosis of residual excessive daytime sleepiness in obstructive sleep apnoea was discussed. Optimizing airway therapy (eg, troubleshooting issues affecting effectiveness) was addressed. The panel recognised occurrence of residual excessive daytime sleepiness in obstructive sleep apnoea despite optimal airway therapy and the need to evaluate patients for underlying causes. CONCLUSIONS: Excessive daytime sleepiness in patients with obstructive sleep apnoea is a public health issue requiring increased awareness, recognition, and attention. Implementation of these statements may improve patient care, long-term management, and clinical outcomes in patients with obstructive sleep apnoea.

Changes in sleep-disordered breathing from the acute to the stable phase of pulmonary embolism: The ESAET study.

BACKGROUND: /Objective: Sleep-disordered breathing (SDB) may change from the acute to stable phase of some cardiovascular disorders, but little is known whether these dynamic changes also exist in pulmonary embolism (PE). This study aimed to analyze the changes in the apnea-hypopnea index (AHI) from the acute to stable phase of PE as well as the factors associated. PATIENTS/METHODS: We conducted a prospective, longitudinal and multicenter study of consecutive adults requiring hospitalization for non-hypotensive acute PE, with a protocol including clinical, imaging (transthoracic echocardiography [TTE] and computed tomography), blood tests and a sleep study within 48 h of diagnosis of PE. After 3 months of follow-up, the sleep study was repeated. Right ventricular (RV) dysfunction was defined according to TTE criteria. RESULTS: One hundred and eleven patients (mean age [SD]: 63 [15] years; body mass index: 28.4 [4.7] kg/m2) were included. The initial AHI was 24.4 (21.8) events/h (AHI≥5: 82.8 %; AHI≥30: 33.3 %). Seventy-seven patients (69.4 %) had RV dysfunction. In the overall cohort, the AHI decreased by 8.7 events/h from the acute to stable phase (24.4/h vs. 15.7/h; p=0.013). Patients with RV dysfunction showed a greater decrease in AHI (mean decrease 12.3/h vs. 0.43/h). In the multivariable analysis a drop of an AHI≥5 events/hour was independently associated with the presence of initial RV dysfunction (hazard ratio 3.9; 95%CI 1.3 to 12.1). CONCLUSIONS: In hemodynamically stable patients with acute PE, there is a transient but clinically significant decrease in the AHI from the acute to stable phase, particularly when initially presenting with RV dysfunction.

Role of Sleep Apnea and Long-Term CPAP Treatment in the Prognosis of Patients With Melanoma: A Prospective Multicenter Study of 443 Patients.

BACKGROUND: OSA has been associated with increased incidence and aggressiveness of melanoma. However, the long-term impact of OSA and CPAP treatment on the prognosis of melanoma remains unexplored. RESEARCH QUESTION: Are OSA and CPAP treatment associated independently with a poor prognosis for cutaneous melanoma? STUDY DESIGN AND METHODS: Four hundred forty-three patients with a diagnosis of cutaneous melanoma (2012-2015) underwent a sleep study within 6 months of diagnosis. The main 5-year outcome of the study was a composite of melanoma recurrence, metastasis, or mortality. Patients were divided into four groups: baseline apnea-hypopnea index (AHI) of fewer than 10 events/h (no OSA; control group), OSA treated with CPAP and good adherence, untreated or poor CPAP adherence in moderate (AHI, 10-29 events/h), and severe OSA (AHI, ≥ 30 events/h). Survival analysis was used to determine the independent role of OSA and CPAP treatment on melanoma composite outcome. RESULTS: Three hundred ninety-one patients (88.2%) were available for analysis at 5-year follow-up (mean age, 65.1 ± 15.2 years; 49% male; Breslow index, 1.7 ± 2.5 mm). One hundred thirty-nine patients had AHI of fewer than 10 events/h (control group); 78 patients with OSA were adherent to CPAP; and 124 and 50 patients had moderate and severe OSA, respectively, without CPAP treatment. Median follow-up was 60 months (interquartile range, 51-74 months). During follow-up, 32 relapses, 53 metastases, and 52 deaths occurred (116 patients showed at least one of the main composite outcomes). After adjusting for age, sex, sentinel lymph nodes affected at diagnosis, BMI, diabetes, nighttime with an oxygen saturation below 90%, Breslow index, Epworth sleepiness scale scores, and melanoma treatment, moderate (hazard ratio [HR], 2.45; 95% CI, 1.09-5.49) and severe OSA (HR, 2.96; 95% CI, 1.36-6.42) were associated with poorer prognosis of melanoma compared with the control group. However, good adherence to CPAP avoided this excess risk (HR, 1.66; 95% CI, 0.71-3.90). INTERPRETATION: Moderate to severe untreated OSA is an independent risk factor for poor prognosis of melanoma. Treatment with CPAP is associated with improved melanoma outcomes compared with untreated moderate to severe OSA.

Persistent Respiratory Failure and Re-Admission in Patients with Chronic Obstructive Pulmonary Disease Following Hospitalization for COVID-19.

Background: Chronic obstructive pulmonary disease (COPD) has been associated with worse clinical evolution/survival during a hospitalization for SARS-CoV2 (COVID-19). The objective of this study was to learn the situation of these patients at discharge as well as the risk of re-admission/mortality in the following 12 months. Methods: We carried out a subanalysis of the RECOVID registry. A multicenter, observational study that retrospectively collected data on severe acute COVID-19 episodes and follow-up visits for up to a year in survivors. The data collection protocol includes general demographic data, smoking, comorbidities, pharmacological treatment, infection severity, complications during hospitalization and required treatment. At discharge, resting oxygen saturation (SpO2), dyspnea according to the mMRC (modified Medical Research Council) scale and long-term oxygen therapy prescription were recorded. The follow-up database included the clinical management visits at 6 and 12 months, where re-admission and mortality were recorded. Results: A total of 2047 patients were included (5.6% had a COPD diagnosis). At discharge, patients with COPD had greater dyspnea and a greater need for prescription home oxygen. After adjusting for age, sex and Charlson comorbidity index, patients with COPD had a greater risk of hospital re-admission due to respiratory causes (HR 2.57 [1.35-4.89], p = 0.004), with no significant differences in survival. Conclusion: Patients with COPD who overcome a serious SARS-CoV2 infection show a worse clinical situation at discharge and a greater risk of re-admission for respiratory causes.

Obstructive sleep apnea and systemic hypertension: longitudinal study in the general population: the Vitoria Sleep Cohort.

RATIONALE: Obstructive sleep apnea and systemic hypertension (SH) are highly prevalent. Although their association has been suggested in cross-sectional studies, conflicting evidence has emerged from longitudinal studies. OBJECTIVES: To assess the association between obstructive sleep apnea and SH in the middle-aged general population. METHODS: A total of 2,148 subjects were included in a longitudinal study of the Vitoria Sleep Cohort, a general population sample aged 30-70 years. We analyzed data on office blood pressure, anthropometric measures, health history, and home polygraphy. Out of 1,557 subjects who completed the 7.5-year follow-up, 377 were excluded for having SH at baseline. The odds ratios for the incidence of SH, according to the respiratory disturbance index (RDI) at baseline, were estimated in 1,180 subjects (526 men and 654 women) after adjustment for age; sex; body mass index; neck circumference; fitness level; and alcohol, tobacco, and coffee consumption. The RDI was divided into quartiles (0-2.9, 3-6.9, 7-13.9, and ≥ 14), using the first quartile as reference. MEASUREMENTS AND MAIN RESULTS: The crude odds ratio for incident hypertension increased with higher RDI category with a dose-response effect (P < 0.001), but was not statistically significant after adjustment for age (P = 0.051). Adjustments for sex (P = 0.342), body mass index (P = 0.803), neck circumference (P = 0.885), and fitness level and alcohol, tobacco, and coffee consumption (P = 0.708) further reduced the strength of the association between RDI and SH. No differences were observed between men and women. CONCLUSIONS: Our findings do not suggest an association between obstructive sleep apnea and the incidence of SH in the middle-aged general population. Long-term follow-up longitudinal studies are needed to better ascertain this association.

Untreated obstructive sleep apnea and cardiovascular outcomes in patients with acute symptomatic pulmonary embolism.

There is a paucity of data examining the prognostic significance of untreated obstructive sleep apnea (OSA) in hemodynamically stable patients with acute pulmonary embolism (PE). This prospective cohort study enrolled consecutive non-hypotensive patients with acute PE who underwent an overnight sleep study within 48 h after diagnosis. The patients were divided into 2 groups based on apnea-hypopnea index (AHI): OSA (AHI ≥15) and non-OSA (AHI <15) groups. The study used a composite of fatal or nonfatal cardiovascular events, including PE-related death, other cardiovascular deaths, clinical deterioration requiring an escalation of treatment, recurrent venous thromboembolism, acute myocardial infarction, or stroke within 30-days after the diagnosis of PE as the primary outcome. Between January 1, 2018, and December 31, 2020, 283 eligible patients were prospectively enrolled in 2 academic hospitals, of whom 268 patients completed a sleep study within 7 days of PE diagnosis. OSA was found in 47% (95% confidence interval [CI], 41 to 54%) of patients. The primary outcome occurred in 13 (4.9%) patients within 30-days after the diagnosis of PE. The crude incidence of the composite was not significantly different in the OSA than the non-OSA group (30-day estimate, 6.3% versus 3.5%; P = 0.30). OSA did not significantly predict the incidence of the primary outcome after adjustment for age, sex, body mass index, systolic blood pressure, heart rate, and oxygen saturation (adjusted hazard ratio, 2.15; 95% confidence interval, 0.67-6.87). In this study, untreated OSA was not a significant multivariable predictor of adverse cardiovascular events in patients with acute PE.

Prevalence of High Blood Pressure in Pediatric Patients with Sleep-Disordered Breathing, Reversibility after Treatment: The KIDS TRIAL Study Protocol.

Current data support an increase in the prevalence of high blood pressure (HBP) in pediatric patients with sleep-disordered breathing (SDB). Adeno-tonsillectomy has been shown to be an effective treatment for most patients. Our objective was to determine the prevalence of HBP in pediatric patients with SDB and the impact of adeno-tonsillectomy with a multicenter, longitudinal, and prospective study that included 286 children referred for suspected SDB. The diagnosis of SDB was established by polysomnography (PSG) and the diagnosis of HBP by 24-h ambulatory blood pressure monitoring (ABPM). In patients without SDB and SDB without treatment indication, these tests were repeated six months after the baseline visit. For patients with medical treatment for SDB, the tests were repeated six months after the treatment initiation. Finally, in patients with surgery indication, ABPM was performed just before surgical treatment and ABPM and PSG six months after the intervention. The study contributes to elucidating the association between SDB and HBP in pediatric patients. Moreover, it contributes to determining if intervention with adeno-tonsillectomy is associated with BP reduction. The results have direct implications for the management of SDB, providing essential information on treatment indications for existing clinical guidelines. NCT03696654.

Moderate obstructive sleep apnea and cardiovascular outcomes in older adults: a propensity score-matched multicenter study (CPAGE-MODE study).

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) has been associated with cardiovascular events (CVEs), although recent randomized controlled trials have not demonstrated that long-term continuous positive airway pressure (CPAP) prevents CVEs. Our objective was to determine the effect of CPAP on older adults with moderate OSA regarding CVE reduction. METHODS: An observational and multicenter study of a cohort of older adults (> 70 years of age) diagnosed with moderate OSA (apnea-hypopnea index 15.0-29.9 events/h) was conducted. Two groups were formed: (1) CPAP treatment and (2) standard of care. The primary endpoint was CVE occurrence after OSA diagnosis. Association with CPAP treatment was assessed by propensity score matching and inverse weighting probability. Secondary endpoints were incidence of CVE separately and time to first CVE. RESULTS: A total of 614 patients were included. After matching, 236 older adults (111 men, mean age 75.9 ± 4.7 years) with a follow-up of 47 months (interquartile range: 29.6-64.0 months) were considered for primary and secondary endpoint evaluations. Forty-one patients presented at least 1 CVE (17.4%): 20 were in the standard-of-care group (16.9%) and 21 were in the CPAP group (17.8%), with a relative risk of 1.05 (95% confidence interval [CI], 0.60-1.83; P = .43) for CPAP treatment. Inverse probability weighting of the initial 614 patients determined an adjusted relative risk of 1.24 (95% CI, 0.79-1.96; P = .35) for CPAP treatment. No statistical differences were found in secondary endpoint analyses. CONCLUSIONS: CPAP should not be prescribed to reduce CVE probability in older adults with moderate OSA. CITATION: López-Padilla D, Terán-Tinedo J, Cerezo-Lajas A, et al. Moderate obstructive sleep apnea and cardiovascular outcomes in older adults: a propensity score-matched multicenter study (CPAGE-MODE study). J Clin Sleep Med. 2022;18(2):553-561.

[Intermediate Respiratory Care Units: Questions and Answers]. / Unidades de Cuidados Respiratorios Intermedios: preguntas y respuestas.

The intermediate respiratory care units (UCRI) are areas of monitoring and specialized care of patients with acute or chronic-exacerbated respiratory failure, whose severity does not require admission to an intensive care unit, but which due to their complexity cannot be treated in conventional hospitalization. Although the COVID-19 pandemic has proven its usefulness in the management of critical respiratory patients, the historical trajectory of the UCRI comes from many years ago, in which its cost-effectiveness has been demonstrated by far. This document presents a series of questions and answers on the history of the UCRI, in addition to the criteria for admission, infrastructure, human and technical resources, and the types of existing Units. Within the UCRI year 2021-2022 designated by the Spanish Society of Pneumology and Thoracic Surgery, any scientific dissemination linked to the in-depth knowledge of these units is timely, where multidisciplinarity and the work of professionals related to the care of critical respiratory patients converge.