Hypoxic burden to guide CPAP treatment allocation in patients with obstructive sleep apnoea: a post hoc study of the ISAACC trial.

BACKGROUND: Hypoxic burden (HB) has emerged as a strong predictor of cardiovascular risk in obstructive sleep apnoea (OSA). We aimed to assess the potential of HB to predict the cardiovascular benefit of treating OSA with continuous positive airway pressure (CPAP). METHODS: This was a post hoc analysis of the ISAACC trial (ClinicalTrials.gov: NCT01335087) including non-sleepy patients with acute coronary syndrome (ACS) diagnosed with OSA (apnoea-hypopnoea index ≥15 events·h-1) by respiratory polygraphy. Patients were randomised to CPAP or usual care and followed for a minimum of 1 year. HB was calculated as the total area under all automatically identified desaturations divided by total sleep time. Patients were categorised as having high or low baseline HB according to the median value (73.1%min·h-1). Multivariable Cox regression models were used to assess whether the effect of CPAP on the incidence of cardiovascular outcomes was dependent on the baseline HB level. RESULTS: The population (362 patients assigned to CPAP and 365 patients assigned to usual care) was middle-aged (mean age 59.7 years), overweight/obese and mostly male (84.5%). A significant interaction was found between the treatment arm and the HB categories. In the high HB group, CPAP treatment was associated with a significant reduction in the incidence of cardiovascular events (HR 0.57, 95% CI 0.34-0.96). In the low HB group, CPAP-treated patients exhibited a trend toward a higher risk of cardiovascular outcomes than those receiving usual care (HR 1.33, 95% CI 0.79-2.25). The differential effect of the treatment depending on the baseline HB level followed a dose-response relationship. CONCLUSION: In non-sleepy ACS patients with OSA, high HB levels were associated with a long-term protective effect of CPAP on cardiovascular prognosis.

High-flow nasal cannula oxygen therapy for the treatment of acute respiratory failure secondary to SARS-CoV-2 pneumonia out of ICU.

INTRODUCTION AND OBJECTIVES: High-flow nasal cannula oxygen therapy (HFNC) has been successfully used for the treatment of acute hypoxaemic respiratory failure (AHRF) secondary to SARS-CoV-2 pneumonia and being effective in reducing progression to invasive mechanical ventilation. The objective of this study was to assess the usefulness of HFNC on a hospital ward for the treatment of AHRF secondary to SARS-CoV-2 pneumonia and its impact on the need for intensive care unit (ICU) admission and endotracheal intubation. Other objectives include identifying potential physiological parameters and/or biomarkers for predicting treatment failure and assessing the clinical course and survival. METHODS: Observational study based on data collected prospectively between March 2020 and February 2021 in a single hospital on patients diagnosed with AHRF secondary to SARS-CoV-2 pneumonia who received HFNC outside an ICU. RESULTS: One hundred and seventy-one patients out of 1090 patients hospitalised for SARS-CoV-2 infection. HFNC was set as the ceiling of treatment in 44 cases; 12 survived (27.3%). Among the other 127 patients, intubation was performed in 25.9% of cases with a mortality of 11.8%. Higher creatinine levels (OR 1.942, 95% CI 1.04; 3.732; p = 0.036) and Comorbidity-Age-Lymphocyte-LDH (CALL) score (OR 1.273, 95% CI 1.033; 1.617; p = 0.033) were associated with a higher risk of intubation. High platelet count at HFNC initiation was predictive of good treatment response (OR 0.935, 95% CI 0.884; 0.983; p = 0.012). CONCLUSIONS: HFNC outside an ICU is a treatment with high success rate in patients with AHRF secondary to SARS-CoV-2 pneumonia, including in patients in whom this therapy was deemed to be the ceiling of treatment.

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.

Planificación, resultados y anatomía de la vía aérea superior en síndrome de apnea/hipopnea obstructiva del sueño tras avance bimaxilar: 20 casos / Planning, results and anatomy of the upper airway in obstructive sleep apnea/hypopnea syndrome after bimaxillary advancement: 20 cases

OBJETIVOS: El objetivo es presentar el protocolo de trabajo, resultados clínicos y cambios en la vía aérea superior de una cohorte de 20 pacientes con síndrome de apnea/hipopnea obstructiva del sueño, intervenidos de avance maxilomandibular con rotación antihoraria. MATERIAL Y MÉTODOS: Un comité multidisciplinar determina la indicación quirúrgica, que los pacientes consienten. Se llevan a cabo tomografías computarizadas y polisomnografías antes y después de la cirugía, como protocolo habitual de trabajo. El comité ético de investigación clínica regional aprobó el estudio. Longitudes, volúmenes, área mínima, dimensión anteroposterior, dimensión transversal y otras medidas son determinadas en la vía aérea. El análisis estadístico es descriptivo y comparativo por pares con p < 0,05. RESULTADOS: Los movimientos planificados son 10,40 mm de avance y 2,11 mm de impactación anterior. El índice de apnea/hipopnea se reduce 30,50 puntos y la saturación de oxígeno capilar periférica mínima aumenta 5,00 puntos. Los resultados clínica y estadísticamente significativos son: 10,98 mm de acortamiento y 6,26 mm3 de incremento de volumen, especialmente en el compartimento retro-palatal; 91,45 mm2, 3,68 mm y 8,00 mm de aumento de área, dimensión antero-posterior y dimensión transversal respectivamente; el hioides avanza 1,92 mm. CONCLUSIONES: El avance maxilomandibular con rotación antihoraria en síndrome de apnea/hipopnea del sueño moderado-severo logra a corto plazo índice de apnea/hipopnea < 15 en el 80 % y saturación de oxígeno periférica capilar > 85 en el 75 % de nuestra serie. Los principales cambios en vía aérea son: acortamiento, incremento de volumen y áreas, forma elíptica y posicionamiento antero-superior del hioides

OBJECTIVES: To present the working protocol, clinical outcomes and upper airway changes of a 20-patient cohort with moderate-severe obstructive sleep apnea/hypopnea syndrome undergoing maxillo-mandibular advancement with counterclockwise rotation. MATERIAL AND METHODS: A multidisciplinary committee determines the surgical indication, which patients consent. Computed tomographies and polysomnographies are performed before and after surgery, as the usual clinical practice protocol. The clinical investigation ethics institutional review board approved the study. Lengths, volumes, minimum area, antero-posterior dimension, transverse dimension and other measurements are determined in the upper airway. Statistical analysis is descriptive and comparative by pairs with p < 0.05. RESULTS: Planned movements are 10.40 mm of advance and 2.11 mm of anterior impaction. Apnea/hypopnea index reduces by 30.50 points and minimum peripheral capillary oxygen saturation increases by 5.00 points. Clinically and statistical significant findings are: 10.98 mm of shortening and 6.26 mm3 of volume enlargement, especially in the retro-palatal compartment; 91.45 mm2, 3.68 mm and 8.00 mm of area, antero-posterior dimension and transverse dimension widening respectively; hyoid bone advances 1.92 mm. CONCLUSIONS: Maxillo-mandibular advancement with counterclockwise rotation in moderatesevere obstructive sleep apnea/hypopnea syndrome achieves in short-term follow-up apnea/hypopnea index < 15 in 80 % and minimum peripheral capillary oxygen saturation > 85 in 75 % of our series. Main upper airway changes are: shortening, volume and area increase, elliptical shape, and antero-superior hyoid bone movement

Effect of obstructive sleep apnoea and its treatment with continuous positive airway pressure on the prevalence of cardiovascular events in patients with acute coronary syndrome (ISAACC study): a randomised controlled trial.

BACKGROUND: Despite the improvement in the prognosis of acute coronary syndrome (ACS), substantial morbidity and mortality remain. We aimed to evaluate the effect of obstructive sleep apnoea (OSA) and its treatment with continuous positive airway pressure (CPAP) on the clinical evolution of patients with ACS. METHODS: We designed a multicentre, open-label, parallel-group, randomised controlled trial of patients with ACS at 15 hospitals in Spain. Eligible non-sleepy patients were men and women aged 18 years and older, admitted to hospital for documented symptoms of ACS. All patients underwent respiratory polygraphy during the first 24-72 h after admission. OSA patients were randomly assigned (1:1) to CPAP treatment plus usual care (CPAP group) or usual care alone (UC group) by a computerised system available 24 h a day. A group of patients with ACS but without OSA was also included as a reference group. Because of the nature of the intervention, the trial intervention could not be masked to either investigators or patients. Patients were monitored and followed for a minimum of 1 year. Patients were examined at the time of inclusion; after 1 month, 3 months, 6 months, 12 months, 18 months, 24 months, 30 months, and 36 months; and every 12 months thereafter, if applicable, during the follow-up period. The primary endpoint was the prevalence of a composite of cardiovascular events (cardiovascular death or non-fatal events [Acute myocardial infarction, non-fatal stroke, hospital admission for heart failure, and new hospitalisations for unstable angina or transient ischaemic attack]) in patients followed up for a minimum of 1 year. The primary analysis was done according to the intention-to-treat principle. This study is registered with Clinicaltrials.gov, NCT01335087 and is now closed. FINDINGS: Between April 25, 2011, and Feb 2, 2018, a total of 2834 patients with ACS had respiratory polygraphy, of whom 2551 (90·01%) were recruited. 1264 (49·55%) patients had OSA and were randomly assigned to the CPAP group (n=633) or the UC group (n=631). 1287 (50·45%) patients did not have OSA, of whom 603 (46·85%) were randomly assigned to the reference group. Patients were followed up for a median of 3·35 years (IQR 1·50-5·31). The prevalence of cardiovascular events was similar in the CPAP and UC groups (98 events [16%] vs 108 events [17%]; hazard ratio [HR] 0·89 [95% CI 0·68-1·17]; p=0·40) during follow-up. Mean time of adherence to CPAP treatment was 2·78 h/night (SD 2·73). The prevalence of cardiovascular events was similar between patients in the reference group (90 [15%] events) and those in the UC group (102 (17%) events) during follow-up (1·01 [0·76-1·35]; p=0·93). The prevalence of cardiovascular events seem not to be related to CPAP compliance or OSA severity. 464 (74%) of 629 patients in the CPAP group had 1538 serious adverse events and 406 (65%) of 626 patients in the UC group had 1764 serious adverse events. INTERPRETATION: Among non-sleepy patients with ACS, the presence of OSA was not associated with an increased prevalence of cardiovascular events and treatment with CPAP did not significantly reduce this prevalence. FUNDING: ResMed (Australia), Fondo de Investigación Sanitaria (Fondo Europeo de Desarrollo Regional), the Spanish Respiratory Society, the Catalonian Cardiology Society, Esteve-Teijin, Oxigen Salud, and ALLER.

Lung function impairment is not associated with the severity of acute coronary syndrome but is associated with a shorter stay in the coronary care unit.

BACKGROUND: Previous population-based studies have suggested that lung function impairment (LFI) could be associated with an increase in the mortality of cardiovascular events. METHODS: We evaluated the association between LFI and the severity and short-term prognosis of acute coronary syndrome (ACS). LFI was established through presence of a forced expiratory volume in one second (FEV1) and/or a forced vital capacity (FVC) less than 80% of predicted. RESULTS: Seventy-one LFI subjects (61.45±10.70 years, 83.10% males) and 247 non-LFI subjects (58.98±11.18 years, 80.57% males) with ACS were included. Subjects with LFI exhibited a higher prevalence of systemic hypertension (57.75% vs. 40.89%, P=0.02) and tobacco exposure (28.50±26.67 vs. 18.21±19.83 pack-years, P=0.007). No significant differences between groups were found regarding the severity of ACS (ejection fraction, Killip class, number of affected vessels, and peak plasma troponin). However, in comparison to non-LFI subjects, a significantly shorter length of stay in the coronary care unit (CCU) was observed in the LFI group (1.83±1.10 vs. 2.24±1.21 days, P=0.01) and this was even shorter in subjects with obstructive LFI (1.62±1.17 days, P=0.009). When considering obstructive sleep apnea (OSA), an interaction with length of stay was found, revealing that OSA subjects with obstructive LFI had the shortest length of stay in the CCU (0.60±0.89 days, P=0.05) also in comparison to non-LFI. CONCLUSIONS: This study indicates a possible association between LFI and a shorter length of stay in the CCU but does not show a significant association with ACS severity.

Sleep-Disordered Breathing Is Independently Associated With Increased Aggressiveness of Cutaneous Melanoma: A Multicenter Observational Study in 443 Patients.

BACKGROUND: Sleep-disordered breathing (SDB) has been associated with a greater incidence and mortality of cancer, although such findings are inconsistent. However, no large studies are currently available to investigate this association in patients with a specific type of cancer. This study seeks to assess potential relationships between SDB severity and aggressiveness markers of cutaneous melanoma. METHODS: Four hundred and forty-three patients with a diagnosis of melanoma underwent a sleep study within 6 months of diagnosis. General demographics were collected, along with melanoma characteristics and polygraphic parameters consisting of the apnea-hypopnea index (AHI) and indices of both continuous and intermittent night-time oxyhemoglobin desaturation (DI4%). An exploration of independent relationships between SDB and various objective melanoma aggressiveness markers (Breslow index, presence of ulceration, presence of regression, mitotic index, stage of severity, damage to the sentinel lymph, and spreading of the melanoma) was performed. RESULTS: Patients in the upper tertiles of AHI or DI4% were 1.94 (95% CI, 1.14-3.32; P = .022) and 1.93 (95% CI, 1.14-3.26; P = .013) times more likely, respectively, to present with aggressive melanoma (Breslow index > 1 mm) than those in the lowest tertiles of these sleep attributes after adjustment for age, sex, tumor location, and BMI. This association was particularly prominent among patients < 56 years of age with Breslow index > 2 mm. The presence of the additional markers of aggressiveness was also associated with higher AHI and DI4% values. CONCLUSIONS: The severity of SDB was independently associated with greater aggressiveness of cutaneous melanoma, particularly among younger patients.

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.

Predictors of obstructive sleep apnoea in patients admitted for acute coronary syndrome.

Identifying undiagnosed obstructive sleep apnoea (OSA) patients in cardiovascular clinics could improve their management. Aiming to build an OSA predictive model, a broad analysis of clinical variables was performed in a cohort of acute coronary syndrome (ACS) patients.Sociodemographic, anthropometric, life-style and pharmacological variables were recorded. Clinical measures included blood pressure, electrocardiography, echocardiography, blood count, troponin levels and a metabolic panel. OSA was diagnosed using respiratory polygraphy. Logistic regression models and classification and regression trees were used to create predictive models.A total of 978 patients were included (298 subjects with apnoea-hypopnoea index (AHI) <15 events·h-1 and 680 with AHI ≥15 events·h-1). Age, BMI, Epworth sleepiness scale, peak troponin levels and use of calcium antagonists were the main determinants of AHI ≥15 events·h-1 (C statistic 0.71; sensitivity 94%; specificity 24%). Age, BMI, blood triglycerides, peak troponin levels and Killip class ≥II were determinants of AHI ≥30 events·h-1 (C statistic of 0.67; sensitivity 31%; specificity 86%).Although a set of variables associated with OSA was identified, no model could successfully predict OSA in patients admitted for ACS. Given the high prevalence of OSA, the authors propose respiratory polygraphy as a to-be-explored strategy to identify OSA in ACS patients.

Effect of Patient Sex on the Severity of Coronary Artery Disease in Patients with Newly Diagnosis of Obstructive Sleep Apnoea Admitted by an Acute Coronary Syndrome.

BACKGROUND: The cardiovascular consequences of obstructive sleep apnoea (OSA) differ by sex. We hypothesized that sex influences the severity of acute coronary syndrome (ACS) in patients with OSA. OSA was defined as an apnoea-hypopnoea index (AHI)>15 events·h-1. We evaluated the severity of ACS according to the ejection fraction, Killip class, number of diseased vessels, number of stents implanted and plasma peak troponin level. METHODS: We included 663 men (mean±SD, AHI 37±18 events·h-1) and 133 women (AHI 35±18 events·h-1) with OSA. RESULTS: The men were younger than the women (59±11 versus 66±11 years, p<0.0001), exhibited a higher neck circumference (p<0.0001), and were more likely to be smokers and alcohol users than women (p<0.0001, p = 0.0005, respectively). Body mass index and percentage of hypertensive patients or diabetics were similar between sexes. We observed a slight tendency for a higher Killip classification in women, although it was not statistically significant (p = 0.055). For men, we observed that the number of diseased vessels and the number of stents implanted were higher (p = 0.02, p = 0.001, respectively), and a decrease in the ejection fraction (p = 0.002). CONCLUSIONS: This study shows that sex in OSA influences the severity of ACS. Men show a lower ejection fraction and an increased number of diseased vessels and number of stents implanted.

Giant faecaloma causing perforation of the rectum presented as a subcutaneous emphysema, pneumoperitoneum and pneumomediastinum: a case report.

Constipation with faecal impaction is a common condition, which may lead to serious potential complications. Among such complications, stercoral perforation has been rarely reported in the literature. We report a single case of 75-year-old woman, with a massive faecal impaction, which resulted in a rectum perforation, presented as a pneumoperitoneum, pneumomediastinum and subcutaneous emphysema. We present this case to remind physicians that neglected accumulation of faecal matter in the rectum may lead to ischemia and perforation of the colon and rectum. This case illustrates that severe chronic constipation requires adequate management, including disimpaction and aggressive medical treatment. Appropriate operative treatment may be life-saving.

Analysis of latent tuberculosis and mycobacterium avium infection data using mixture models.

BACKGROUND: Estimation of the frequency of latent tuberculosis infection (LTBI) is difficult in areas with low tuberculosis infection rates and high exposure to non-tuberculous mycobacteria (NTM), including BCG vaccination. The objective was to assess LTBI and M avium infection and to estimate their probability based on skin tests responses in an infant population from a region with the aforementioned characteristics. METHODS: A population-based tuberculin skin test (TST) and sensitin (M avium) survey was conducted on seven years old infants in Biscay, a province from The Basque Country (Spain). 2268 schoolchildren received sensitin and 5277 TST. Participation rate was 89%. Commonly used estimation methods were compared with a method based on the fit of mixture models using the Expectation Maximization algorithm. Functions estimating the probabilities of LTBI and M avium infection given the observed skin tests responses were developed for vaccinated and unvaccinated children. RESULTS: LTBI prevalences varied widely according to the estimation method. The mixture model provided prevalences higher than expected although intermediates between those obtained by currently recommended approaches. Exposure to previous BCG vaccine produces an upward shift of an average of about 3 mm on the induration size to attain the same probability of infection. CONCLUSION: Our results confirm the commonplace exposure to NTM which effect should be taken into account when performing and assessing tuberculin surveys. The use of mixture analysis under the empirical Bayes framework allows to better estimate the probability of LTBI in settings with presence of other NTM and high BCG-vaccination coverage. An estimation of the average effect of BCG vaccination on TST induration is also provided. These models maximise information coming from classical tuberculin surveys and could be used together with the newly developed blood tests to improve survey's specificity and cost-effectiveness.

Tuberculina 5UT-PPD RT-23. ¿Se usa correctamente? / Tuberculin 5UT-PPD RT-23. Is it used correctly?

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