Obstructive sleep apnea (OSA) is a recognized risk factor for the development of diabetic kidney disease (DKD). Our objectives were to compare the urinary albumin-creatinine ratio (UACR) and ...estimated glomerular filtration rate (eGFR) of patients with DKD according to OSA severity, and to evaluate the contribution of sleep parameters to their renal function. In a multicenter, observational, cross-sectional study, 214 patients with DKD were recruited. After a sleep study, UACR and eGFR were measured, as well as serum creatinine, fasting glucose, glycated hemoglobin, insulin resistance, lipid profile and C-reactive protein. UACR was higher in severe OSA patients (920 ± 1053 mg/g) than in moderate (195 ± 232 mg/g, p < 0.001) or mild OSA/non-OSA subjects (119 ± 186 mg/g, p < 0.001). At the same time, eGFR showed an OSA severity-dependent reduction (48 ± 23 vs. 59 ± 21 vs. 73 ± 19 ml/min per 1.73 m
, respectively; p < 0.001). Apnea-hypopnea index (AHI and desaturation index (ODI) were identified as independent predictors for UACR and eGFR, respectively. Therefore, in patients with DKD under optimized treatment, severe OSA is associated with a higher UACR and a lower eGFR, reflecting an additional contribution to the impairment of their renal function, although no causality can be inferred.
Eye diseases are an important group of increasingly prevalent disorders that contribute very significantly to disability and represent a considerable health burden. Some data suggest that several of ...these diseases may be associated with sleep-disordered breathing, mainly obstructive sleep apnea (OSA), due to intermediate mechanisms, such as intermittent hypoxia or sleep fragmentation. The aims of this systematic review were to identify and critically evaluate the current evidence supporting the existence of a possible relationship between OSA and the more relevant eye diseases as well as to evaluate the potential pathogenic mechanisms. There is a body of largely low-level evidence for the association of OSA with glaucoma, nonarteritic ischemic optic neuropathy, central serous chorioretinopathy, and diabetic retinopathy. Meta-analysis of available case-control studies shows that OSA increases the risk of glaucoma (pooled odds ratio: 1.50; 95% confidence interval: 1.25 to 1.80;
< .001), nonarteritic ischemic optic neuropathy (3.62; 1.94 to 6.76;
< .001), and diabetic retinopathy (1.57; 1.09 to 2.27;
= .02). Moreover, several pathogenic pathways have been identified, mainly related to hypoxic damage, mechanical stress, systemic inflammation, oxidative stress, sympathetic tone, and endothelial dysfunction. In contrast, information about the effect of apnea-hypopnea suppression on the development and progression of eye damage is either nonexistent or of a very low level of evidence. In conclusion, OSA has emerged as an additional potential risk factor for many eye diseases, although their link is weak and contradictory, so further examination is required.
García-Sánchez A, Villalaín I, Asencio M, García J, García-Rio F. Sleep apnea and eye diseases: evidence of association and potential pathogenic mechanisms.
. 2022;18(1):265-278.
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).
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.
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).
In this study, nocturnal hypoxemia did not identify stable patients with acute symptomatic PE at increased risk for adverse cardiovascular events.
•If nocturnal hypoxemia is associated with PE prognosis, medical interventions might be worth testing to mitigate outcomes.•We studied 221 patients with acute PE for whom the TSat90 could be calculated and did not receive supplemental oxygen.•TSat90 did not help identify stable PE patients at increased risk of short-term cardiovascular complications.
Obstructive sleep apnoea (OSA) and pulmonary embolism (PE) remain major health issues worldwide. Data from pathophysiological studies suggest that both intermittent hypoxia and sleep fragmentation ...are associated with increased blood coagulability, endothelial dysfunction and venous stasis. There is growing evidence that OSA is potentially prevalent in and a risk factor for PE. Conversely, patients with acute PE have two to four times greater risk of moderate-to-severe OSA. The role of continuous positive airway pressure (CPAP) treatment in improving clinically meaningful outcomes in PE patients remains unclear, although some authors have suggested that CPAP could improve the hypercoagulability state and normalise circadian alterations in some of the coagulation molecules, as observed in patients with OSA. Emerging research highlights the complex interdependent relationships between OSA and PE, emphasising the need for rigorous, well-powered trials that address the impact of OSA and its treatment on the prevention and management of PE. Undoubtedly, these will require closer collaboration between the sleep medicine and clinical/venous thromboembolism communities.
Obstructive sleep apnea (OSA) is associated with impaired glycemic control and a higher risk of vascular complications, such as diabetic retinopathy. However, the effect of apnea-hypopnea suppression ...on retinal disease progression is unclear.
To evaluate the efficacy and safety of continuous positive airway pressure (CPAP) for the reduction of retinal lesions in patients with non-proliferative diabetic retinopathy (NPDR) and OSA.
This open-label, parallel-group, randomized controlled trial was conducted between October 2016 and February 2020 at a university hospital in Spain. The date of final follow-up was March 2, 2021. Eighty-three patients with OSA and mild to moderate NPDR receiving stable treatment were randomized to receive CPAP and usual care (43 patients with 79 available eyes) or usual care alone (40 patients with 67 available eyes) for 52 weeks. The primary outcomes were the change in the percentage of eyes with retinal exudates and the number of retinal microhemorrhages from baseline to week 52. We also assessed the effects of both interventions on retinal thickness by means of optical coherence tomography, serum concentrations of glycated hemoglobin, blood pressure, lipid concentrations, sleepiness, and quality of life.
Fifty-two weeks of CPAP treatment was associated with reductions from baseline in the percentage of eyes with hard exudates (overall difference, -21.7%;
= 0.035) and in optical coherence tomography indices of retinal edema, including central subfield thickness and cube volume. However, in patients who met prespecified criteria for CPAP adherence, treatment was also associated with a higher number of retinal microhemorrhages at 52 weeks (intergroup adjusted difference, 6.0 95% confidence interval, 0.6-11.5;
= 0.029), which was directly related to prescribed pressure levels. CPAP treatment also improved glycemic control, sleepiness, and general health-related quality of life.
In patients with OSA and NPDR, long-term CPAP treatment in addition to usual care may result in slower progression of retinal disease, although it could also induce an increase in retinal microhemorrhages. Clinical trial registered with www.clinicaltrials.gov (NCT02874313).
For patients with acute low-risk pulmonary embolism (PE), determined by a validated clinical prognostic score, the additive prognostic significance of computed tomography (CT)-assessed right ...ventricular (RV) enlargement is uncertain.
We performed a systematic review and meta-analysis of studies that enrolled patients with acute low-risk PE to assess the prognostic value of concomitant CT-assessed RV enlargement for 30-day all-cause mortality and PE-related death. We conducted unrestricted searches of PubMed and Embase through December 2019. We used a random-effects model to pool study results; Begg rank correlation method to evaluate for publication bias; and I2 testing to assess for heterogeneity.
Of the 7 cohorts with 2197 participants who had low-risk PE and provided results on the primary outcome, 743 (34%; 95% confidence interval CI, 32–36%) patients had concomitant RV enlargement. Six of 743 (0.8%; 95% CI, 0.3–1.8%) patients with concomitant RV enlargement died 30-days after the diagnosis of PE compared with 3 of 1454 (0.2%, 95% CI, 0–0.6%) without RV enlargement. CT-assessed RV enlargement did not have a significant association with 30-day all-cause mortality (odds ratio OR, 2.6; 95% CI, 0.7–9.4; I2 = 0%; P = 0.15) or PE-related mortality (OR, 2.8; 95% CI, 0.7–12.1; I2 = 0%; P = 0.16).
CT-assessed RV enlargement occurs in a third of PE patients identified as low-risk by clinical scores. Mortality rate in these patients is low, and CT-assessed RV enlargement was not associated with a significantly increased risk of death within 30 days of PE diagnosis.
•The 2019 European Society of Cardiology (ESC) guidelines suggest the routine assessment of the right ventricle (RV) by imaging methods in patients with low-risk pulmonary embolism (PE).•In this meta-analysis of patients with acute symptomatic low-risk PE, the presence of computed tomography-detectable RV enlargement did not show significantly increased risk of short-term death.•Additional studies are required to determine if routine monitoring of RV enlargement is helpful in select subgroups of patients with acute low-risk PE.
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.
•We investigated the prognostic significance of OSA in stable patients with PE.•We found a high prevalence of undiagnosed OSA among patients with acute PE.•Untreated OSA was not a significant predictor of adverse cardiovascular events in patients with acute PE.
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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.
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.
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.
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.
No se ha aclarado suficientemente el papel de la disfunción diafragmática estimada mediante ecografía como predictora del fracaso de la extubación.
Realizamos una revisión sistemática y metaanálisis ...de estudios observacionales que incluyeron pacientes intubados sometidos a ventilación mecánica (VM), a los que se realizó una ecografía diafragmática uni- o bilateral para evaluar la disfunción diafragmática antes de la extubación. Se efectuó una búsqueda en las bases de datos Pubmed y Embase entre el primero de enero de 2010 y el 30 de junio de 2019, utilizando los términos diaphragm ultrasound, diaphragm ultrasonography, weaning y extubation. Definimos fracaso del destete como la necesidad de reintubación y soporte con VMI o fracaso de la prueba de respiración espontánea (PRE). Se utilizaron como medidas ecográficas para predecir el fracaso del destete en pacientes intubados sometidos a VM la excursión diafragmática (ED), la fracción de engrosamiento diafragmático (FEG), el tiempo hasta la amplitud del pico inspiratorio del diafragma (TAPI dia), puntuación de ultrasonido pulmonar modificada (PUPm) y el índice de tiempo de excursión diafragmática (ITED). Secundariamente, evaluamos su utilidad para predecir la muerte por cualquier causa, la duración de la estancia hospitalaria y la necesidad de ventilación no invasiva (VMNI) o de oxigenoterapia de alto flujo tras el destete. Para la agregación de datos se utilizó un modelo de efectos aleatorios, la odds ratio (OR) y sus intervalos de confianza (IC) del 95%. La heterogeneidad de los estudios originales se evaluó mediante el estadístico I2. En todos los análisis, los niveles de significación fueron bilaterales y se consideraron significativos los valores de p < 0,05.
Incluimos un total de 18 estudios prospectivos que reclutaron 1.229 pacientes intubados sometidos a VM. El destete fracasó en 254 de los 490 (52%) pacientes con disfunción diafragmática, comparado con 117 de los 739 (16%) pacientes sin disfunción diafragmática. La presencia de disfunción diafragmática evaluada por ecografía se asoció significativamente con el fracaso del destete en los siete primeros días después de la extubación (OR 8,2; IC 95%, 4,7-14,2; p < 0,0001; I2 = 66%). Los resultados fueron consistentes para los estudios que evaluaron el diafragma de forma uni- o bilateral.
La disfunción diafragmática evaluada por ecografía se asocia al fracaso del destete en los siete primeros días después de la extubación.
The evaluation of diaphragmatic dysfunction by ultrasound as a predictor of extubation failure lacks of standardization.
We performed a systematic review and meta-analysis of studies that included patients intubated on mechanical ventilation, and who received unilateral or bilateral diaphragmatic ultrasound to evaluate diaphragmatic dysfunction prior to extubation. We searched the Pubmed and Embase databases from January 1, 2010 to June 30, 2019 using the terms «diaphragm ultrasound, diaphragm ultrasonography», «weaning» and «extubation». We defined weaning failure as the need of intubation with invasive ventilacion or failure in spontaneous breathing trial (SBT). The echographic measures used for predicting weaning failure in intubated patients were diaphragmatic excursion (DE), diaphragm thickening fraction (DTF), time to peak inspiratory amplitude of the diaphragm (TPIA dia), modified lung ultrasound score (LUSm) y el excursion time index (ET index).We evaluated the usefulness of ultrasound-assessed diaphragmatic dysfunction to predict the primary outcome of weaning failure in intubated patients undergoing mechanical ventilation. Secondary outcomes were mortality, hospital stay and the need for noninvasive ventilation or high-flow oxygen therapy after weaning in this group of patients. Random effects model, odds ratio (OR), and 95% confidence intervals (CI) were used for data aggregation. The heterogeneity of the original studies was evaluated using the I2 statistic. In all analyses, significance levels were bilateral and p values < 0.05 were considered significant.
We included a total of 18 prospective studies that recruited 1 229 intubated patients on mechanical ventilation. Weaning failed in 254 of the 490 (52%) patients with diaphragmatic dysfunction, compared with 117 of the 739 (16%) patients without diaphragmatic dysfunction. The presence of ultrasound-assessed diaphragmatic dysfunction was significantly associated with weaning failure within 7 days after extubation (18 cohorts, 1 229 patients; odds ratio OR 8.2; 95% confidence interval CI, 4.7-14,2; p < 0.0001; I2 = 66%). The results were consistent for studies that performed unilateral or bilateral assessment of diaphragmatic function.
Diaphragmatic dysfunction evaluated by ultrasound is significantly associated with weaning failure in the first 7 days after extubation.
Resumen: Introducción: No se ha aclarado suficientemente el papel de la disfunción diafragmática estimada mediante ecografía como predictora del fracaso de la extubación. Métodos: Realizamos una ...revisión sistemática y metaanálisis de estudios observacionales que incluyeron pacientes intubados sometidos a ventilación mecánica (VM), a los que se realizó una ecografía diafragmática uni- o bilateral para evaluar la disfunción diafragmática antes de la extubación. Se efectuó una búsqueda en las bases de datos Pubmed y Embase entre el primero de enero de 2010 y el 30 de junio de 2019, utilizando los términos diaphragm ultrasound, diaphragm ultrasonography, weaning y extubation. Definimos fracaso del destete como la necesidad de reintubación y soporte con VMI o fracaso de la prueba de respiración espontánea (PRE). Se utilizaron como medidas ecográficas para predecir el fracaso del destete en pacientes intubados sometidos a VM la excursión diafragmática (ED), la fracción de engrosamiento diafragmático (FEG), el tiempo hasta la amplitud del pico inspiratorio del diafragma (TAPI dia), puntuación de ultrasonido pulmonar modificada (PUPm) y el índice de tiempo de excursión diafragmática (ITED). Secundariamente, evaluamos su utilidad para predecir la muerte por cualquier causa, la duración de la estancia hospitalaria y la necesidad de ventilación no invasiva (VMNI) o de oxigenoterapia de alto flujo tras el destete. Para la agregación de datos se utilizó un modelo de efectos aleatorios, la odds ratio (OR) y sus intervalos de confianza (IC) del 95%. La heterogeneidad de los estudios originales se evaluó mediante el estadístico I2. En todos los análisis, los niveles de significación fueron bilaterales y se consideraron significativos los valores de p < 0,05. Resultados: Incluimos un total de 18 estudios prospectivos que reclutaron 1.229 pacientes intubados sometidos a VM. El destete fracasó en 254 de los 490 (52%) pacientes con disfunción diafragmática, comparado con 117 de los 739 (16%) pacientes sin disfunción diafragmática. La presencia de disfunción diafragmática evaluada por ecografía se asoció significativamente con el fracaso del destete en los siete primeros días después de la extubación (OR 8,2; IC 95%, 4,7-14,2; p < 0,0001; I2 = 66%). Los resultados fueron consistentes para los estudios que evaluaron el diafragma de forma uni- o bilateral. Conclusiones: La disfunción diafragmática evaluada por ecografía se asocia al fracaso del destete en los siete primeros días después de la extubación. Abstract: Introduction: The evaluation of diaphragmatic dysfunction by ultrasound as a predictor of extubation failure lacks of standardization. Methods: We performed a systematic review and meta-analysis of studies that included patients intubated on mechanical ventilation, and who received unilateral or bilateral diaphragmatic ultrasound to evaluate diaphragmatic dysfunction prior to extubation. We searched the Pubmed and Embase databases from January 1, 2010 to June 30, 2019 using the terms «diaphragm ultrasound, diaphragm ultrasonography», «weaning» and «extubation». We defined weaning failure as the need of intubation with invasive ventilacion or failure in spontaneous breathing trial (SBT). The echographic measures used for predicting weaning failure in intubated patients were diaphragmatic excursion (DE), diaphragm thickening fraction (DTF), time to peak inspiratory amplitude of the diaphragm (TPIA dia), modified lung ultrasound score (LUSm) y el excursion time index (ET index).We evaluated the usefulness of ultrasound-assessed diaphragmatic dysfunction to predict the primary outcome of weaning failure in intubated patients undergoing mechanical ventilation. Secondary outcomes were mortality, hospital stay and the need for noninvasive ventilation or high-flow oxygen therapy after weaning in this group of patients. Random effects model, odds ratio (OR), and 95% confidence intervals (CI) were used for data aggregation. The heterogeneity of the original studies was evaluated using the I2 statistic. In all analyses, significance levels were bilateral and p values < 0.05 were considered significant. Results: We included a total of 18 prospective studies that recruited 1 229 intubated patients on mechanical ventilation. Weaning failed in 254 of the 490 (52%) patients with diaphragmatic dysfunction, compared with 117 of the 739 (16%) patients without diaphragmatic dysfunction. The presence of ultrasound-assessed diaphragmatic dysfunction was significantly associated with weaning failure within 7 days after extubation (18 cohorts, 1 229 patients; odds ratio OR 8.2; 95% confidence interval CI, 4.7-14,2; p < 0.0001; I2 = 66%). The results were consistent for studies that performed unilateral or bilateral assessment of diaphragmatic function. Conclusions: Diaphragmatic dysfunction evaluated by ultrasound is significantly associated with weaning failure in the first 7 days after extubation.
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